NUCLEOSIDE PRODRUGS FOR TREATING VIRAL INFECTIONS

CROSS REFERENCE TO RELATED PATENT APPLICATIONS

[0001] This application claims priority under 35 U.S.C. §119(e) of U.S. Provisional Application No. 60/664,897, filed March 23, 2005, the contents of which is incorporated by reference in its entirety.

TECHNICAL FIELD

[0002] The invention relates to the field of pharmaceutical chemistry, in particular to prodrug compounds, compositions and methods for treating viral infections in mammals mediated, at least in part, by a virus in the flaviviridae family of viruses.

BACKGROUND ART

References

[0003] The following publications are cited in this application as superscript numbers:

1. Giangaspero, et al. , Arch. Virol. Suppl. , 7: 53-62 (1993);

2. Giangaspero, et al, Int. J. STD. AIDS, 4(5): 300-302 (1993);

3. Yolken, et al, Lancet, 1(8637): 517-20 (1989);

4. Wilks, et al, Lancet, 1(8629): 107 (1989);

5. Giangaspero, et al, Lancet, 2: 110 (1988);

6. Potts, et al, Lancet, 1(8539): 972-973 (1987);

7. Cornberg, et al, "Hepatitis C: therapeutic perspectives." Forum (Genova), ϋ(2): 154-62 (2001);

8. Dymock, et al , Antivir. Chem. Chemother. ϋ(2):79-96 (2000);

9.- Devos, et al, International Patent Application Publication No. WO 02/18404 A2, published 7 March, 2002;

10. Sommadossi, et al. , International Patent Application Publication No. WO 01/90121, published 23 May, 2001;

11. Carroll, S. S., et al, International Patent Application Publication No. WO 02057287, published 25 July, 2002;

12. Carroll, S. S., et al, International Patent Application Publication No. WO 02057425, published 25 July, 2002;

13. Roberts, et al, U.S. Patent Application Serial No. 10/861,090, filed June 4, 2004.

14. Roberts, et al, U.S. Patent Application Serial No. 10/861,311, filed June 4, 2004.

[0004] All of the above publications and patent applications are herein incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference in its entirety.

State of the Art

[0005] The Flaviviridae family of viruses is composed of three genera: pestivirus, flavivirus and hepacivirus (hepatitis C virus). Of these genera, fiaviviruses and hepaciviruses represent important pathogens of man and are prevalent throughout the world. There are 38 flavi viruses associated with human disease, including the dengue fever viruses, yellow fever virus and Japanese encephalitis virus. Fiaviviruses cause a range of acute febrile illnesses and encephalitic and hemorrhagic diseases. Hepaciviruses currently infect approximately 2 to 3% of the world population and cause persistent infections leading to chronic liver disease, cirrhosis, hepatocellular carcinoma and liver failure. Human pestiviruses have not been as extensively characterized as the animal pestiviruses. However, serological surveys indicate considerable pestivirus exposure in humans. Pestivirus infections in man have been implicated in several diseases including, but not likely limited to, congenital brain injury, infantile gastroenteritis and chronic diarrhea in human immunodeficiency virus (HIV) positive patients. ^1"6

[0006] Currently, there are no antiviral pharmaceutical drugs to prevent or treat pestivirus or flavivirus infections. For hepacivirus, i.e., hepatitis C virus (HCV)

infections, interferon alpha (IFN) is currently the only approved drug in the United States. HCV is a major causative agent for post-transfusion and for sporadic non-A, non-B hepatitis. Infection by HCV is insidious in a high proportion of chronically infected (and infectious) carriers who may not experience clinical symptoms for many years.

[0007] At present, the only acceptable treatment for chronic HCV is interferon (IFN-alpha) and this requires at least six (6) months of treatment and/or ribavirin, which can inhibit viral replication in infected cells and also improve liver function in some people.

[0008] IFN-alpha belongs to a family of naturally occurring small proteins with characteristic biological effects such as antiviral, immunoregulatory and antitumoral activities that are produced and secreted by most animal nucleated cells in response to several diseases, in particular viral infections. IFN-alpha is an important regulator of growth and differentiation affecting cellular communication and immunological control. Treatment of HCV with interferon, however, has limited long term efficacy with a response rate about 25%. In addition, treatment of HCV with interferon has frequently been associated with adverse side effects such as fatigue, fever, chills, headache, myalgias, arthralgias, mild alopecia, psychiatric effects and associated disorders, autoimmune phenomena and associated disorders and thyroid dysfunction. [0009] Ribavirin (1-β-D-ribofuranosyl-l H-l,2,-4-triazole-3-carboxamide), an inhibitor of inosine 5'-monophosphate dehydrogenase (IMPDH), enhances the efficacy of IFN-alpha in the treatment of HCV. Despite the introduction of Ribavirin, more than 50% of the patients do not eliminate the virus with the current standard therapy of interferon-alpha (IFN) and Ribavirin. By now, standard therapy of chronic hepatitis C has been changed to the combination of PEG-IFN plus ribavirin. However, a number of patients still have significant side effects, primarily related to Ribavirin. Ribavirin causes significant hemolysis in 10-20% of patients treated at currently recommended doses, and the drug is both teratogenic and embryotoxic.

[0010] Other approaches are being taken to combat the virus. They include, for example, application of antisense oligonucleotides or ribozymes for inhibiting HCV replication. Furthermore, low-molecular weight compounds that directly

inhibit HCV proteins and interfere with viral replication are considered as attractive strategies to control HCV infection. NS3/4A serine protease, ribonucleic acid (RNA) helicase, RNA-dependent RNA polymerase are considered as potential targets for new drugs. ⁷ ' ⁸

[0011] Devos, et al ⁹ describes purine and pyrimidine nucleoside derivatives and their use as inhibitors of HCV RNA replication. Sommadossi, et al. ¹⁰ describes I ¹ , 2' or 3'-modified nucleosides and their use for treating a host infected with HCV. Carroll, et al. ⁿ ' ⁿ , describes nucleosides as inhibitors of RNA-dependent RNA viral polymerase.

[0012] Recently, Roberts, et al. ¹³ ' ¹⁴ disclosed that certain 7-(2'-substituted-β-D- ribofuranosyl)-4-amino-5-(optionally substituted ethyn-l-yl)-pyrrolo[2,3- d]pyrimidine compounds possess potent activity against HCV.

DETAILED DESCRIPTION

[0013] The embodiments are directed to novel compounds that are useful in the viral infections in mammals mediated, at least in part, by a virus in the flaviviridae family of viruses. Specifically the embodiments are directed to compounds of Formula I:

wherein

Y is selected from the group consisting of a bond, -CH ₂ - or -O-; each of A ⁰ is independently selected from A ¹ , A ² or W ³ with the proviso that the compound of Formula I includes at least one A ¹ ; wherein

A ¹ is:

⁶

A ² is:

-

Y ² is independently a bond, O, N(R ^X ), N(O)(R"), N(OR ^X ), N(0)(0R ^x ), N(N(R ^X )(R ^X )), -S(O) ₀₁₂ -, or -S(O) _m2 -S(O) _m2 -;

R ² is independently H, R ¹ , R ³ or R ⁴ wherein each R ⁴ is independently substituted with 0 to 3 R ³ groups, or taken together at a carbon atom, two R ² groups form a ring of 3 to 8 carbons and the ring may be substituted with 0 to 3 R ³ groups;

W ⁶ is W ³ independently substituted with 1, 2, or 3 A ³ groups;

A ³ is:

Y ¹ is independently O, S, N(R ^X ), N(O)(R ^X ), N(OR"), N(0)(0R ^x ), or N(N(R ^X )(

R ^x ));

W ³ is W ⁴ or W ⁵ ;

W ⁴ is R ⁵ , -QV)R ⁵ , -C(Y')W ⁵ , -SO ₂ R ⁵ , or -SO ₂ W ⁵ ;

W ⁵ is carbocycle or heterocycle wherein W ⁵ is independently substituted with O to 3 R ² groups;

R ⁵ is R ⁴ wherein each R ⁴ is substituted with O to 3 R ³ groups;

R ⁴ is an alkyl of 1 to 18 carbon atoms, alkenyl of 2 to 18 carbon atoms, or alkynyl of 2 to 18 carbon atoms;

R ^x is independently H, R ¹ , W ³ , a protecting group, or the formula:

R ¹ is independently H or an alkyl of 1 to 18 carbon atoms;

R ^y is independently H, W ³ , R ² or a protecting group;

R ³ is R ^3a , R ^3b , R ^3c or R ^3d , provided that when R ³ is bonded to a heteroatom, then R ³ is R ^3c or R ^3d ;

R ^3a is F, Cl, Br, I, -CN, N ₃ , or -NO ₂ ;

R ^3b is Y ¹ ;

R ^3c is -R ^x , -N(R ^X )(R ^X ), -SR ^X , -S(O)R ^X , -S(O) ₂ R", -S(O)(OR ^X ), -S(O) ₂ (OR"), -OC(Y^R", -0C(Y ¹ )0R ^x , -OC(Y ¹ )(N(R ^X )(R ^X )), -SC(Y^R", -SC(Y ¹ )OR ^X , -SC(Y')(N(R ^X )(R ^X )), -N(R ^X )C(Y ¹ )R ^X , -N(R ^X )C(Y ¹ )OR ^X , or -N(R ^X )C(Y ¹ )(N(R ^X )(R ^X ));

R ^3d is -C(Y ^! )R ^X , -C(Y')OR ^X or -C(Y ¹ )(N(R ^X )(R ^X )); ml a, ml c, and mid are independently 0 or 1; m2 is 0, 1 or 2; ml2a is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12; ml2b is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12; ml2c is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12; and pharmaceutically acceptable salts or partial salts thereof; wherein A ⁰ is a prodrug moiety; provided that the prodrug moiety is not selected from the group consisting of acyl, oxyacyl, phosphonate, phosphate esters, phosphate, phosphonamidate, phosphorodiamidate, phosphoramidate monoester, cyclic phosphoramidate, cyclic phosphorodiamidate, phosphoramidate diester, -C(O)CHR ^f NH ₂ , a prodrug moiety of the formula:

a prodrug moiety of the formula:

Rf

wherein R ^e is selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic;

R ^f is selected from the group consisiting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted hetereoaryl, heterocyclic, substituted heterocyclic, and a sidechain of an amino acid; and

R ⁸ is hydrogen or alkyl; and a prodrug moiety of 2,4-dichlorobenzyl. [0014] In one embodiment, Y is -O-. [0015] Another embodiment is directed to compounds of Formula II:

wherein A ⁰ is as defined above; or pharmaceutically acceptable salts or partial salts thereof.

[0016] Compounds of the embodiments can be either active as antiviral agents or can be useful as intermediates in the preparation of antiviral agents as described herein.

[0017] The embodiments are also directed to pharmaceutical compositions comprising a pharmaceutically acceptable diluent and a therapeutically effective amount of a compound as described herein or mixtures of one or more of such compounds.

[0018] The embodiments are still further directed to methods for treating a viral infection mediated at least in part by a virus in the flaviviridae family of viruses, such as HCV, in mammals which methods comprise administering to a mammal,

that has been diagnosed with said viral infection or is at risk of developing said viral infection, a pharmaceutical composition comprising a pharmaceutically acceptable diluent and a therapeutically effective amount of a compound as described herein or mixtures of one or more of such compounds. [0019] In yet another embodiment, methods of treating or preventing viral infections in mammals are provided wherein the compounds of the embodiments are administered in combination with the administration of a therapeutically effective amount of one or more agents active against HCV. Active agents against HCV include, but are not limited to, ribavirin, levovirin, viramidine, thymosin alpha-1, an inhibitor of NS3 serine protease, and inhibitor of inosine monophosphate dehydrogenase, interferon-alpha or pegylated interferon-alpha, either alone or in combination with Ribavirin, levovirin or viramidine. Preferably the additional agent active against HCV is interferon-alpha or pegylated interferon-alpha alone or in combination with Ribavirin, levovirin or viramidine. [0020] Another embodiment provides a use of a compound of Formula I in the manufacture of a medicament for treating and/or inhibiting a viral infection in a mammal which infection is mediated at least in part by a virus in the flaviviridae family of viruses.

MODES FOR CARRYING OUT THE INVENTION

[0021] The present embodiments are directed to prodrug compounds, compositions, and methods for treating flaviviridae viruses, such as hepatitis C virus infections. However, prior to describing the embodiments in detail, the following terms will first be defined:

Definitions

[0022] As used herein and unless otherwise defined herein, the term "alkyl" refers to alkyl groups having from 1 to 30 carbon atoms and more preferably 1 to

20 carbon atoms. This term is exemplified by groups such as methyl, ethyl, n- propyl, wo-propyl, «-butyl, t-butyl, «-pentyl and the like.

[0023] "Substituted alkyl" refers to an alkyl group having from 1 to 3, and preferably 1 to 2, substituents selected from the group consisting of alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino,

aminoacyl, aryl, substituted aryl, aryloxy, substituted aryloxy, cyano, halogen, hydroxyl, nitro, carboxyl, carboxyl esters, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic. [0024] "Alkoxy" refers to the group "alkyl-O-" which includes, by way of example, methoxy, ethoxy, «-propoxy, /so-propoxy, H-butoxy, r-butoxy, sec- butoxy, H-pentoxy and the like.

[0025] "Substituted alkoxy" refers to the group "substituted alkyl-O-". [0026] "Acyl" refers to the groups alkyl-C(O)-, substituted alkyl-C(O)-, alkenyl-C(O)-, substituted alkenyl-C(O)-, alkynyl-C(O)-, substituted alkynyl- C(O)-, cycloalkyl-C(O)-, substituted cycloalkyl-C(O)-, aryl-C(O)-, substituted aryl-C(O)-, heteroaryl-C(O)-, substituted heteroaryl-C(O), heterocyclic-C(O)-, and substituted heterocyclic-C(O)-.

[0027] " Acylamino" refers to the group -C(O)NR ³ R ⁸ where each R ^a is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic and where each R ^a is joined to form together with the nitrogen atom a heterocyclic or substituted heterocyclic ring. [0028] "Acyloxy" refers to the groups alkyl-C(O)O-, substituted alkyl-C(O)O-, alkenyl-C(O)O-, substituted alkenyl-C(O)O-, alkynyl-C(O)O-, substituted alkynyl-C(O)O-, aryl-C(O)O-, substituted aryl-C(O)O-, cycloalkyl-C(O)O-, substituted cycloalkyl-C(O)O-, heteroaryl-C(O)O-, substituted heteroaryl-C(O)O- , heterocyclic-C(O)O-, and substituted heterocyclic-C(O)O-. [0029] "Oxyacyl" refers to the groups alkyl-OC(O)-, substituted alkyl-OC(O)-, alkenyl-OC(O)-, substituted alkenyl-OC(O)-, alkynyl-OC(O)-, substituted alkynyl-OC(O)-, aryl-OC(O)-, substituted aryl-OC(O)-, cycloalkyl-OC(O)-, substituted cycloalkyl-OC(O)-, heteroaryl-OC(O)-, substituted heteroaryl-OC(O)- , heterocyclic-OC(O)-, and substituted heterocyclic-OC(O)-. [0030] Unless otherwise defined herein, the term "alkenyl" refers to hydrocarbyl groups having from 2 to 30 carbon atoms, and preferably 2 to 20 carbon atoms, and having at least 1 and preferably from 1-2 sites of alkenyl unsaturation (>C=C<). Such groups are exemplified by vinyl (ethen-1-yl), allyl, but-3-en-l-yl, and the like.

[0031] "Substituted alkenyl" refers to alkenyl groups having from 1 to 3 substituents, and preferably 1 to 2 substituents, selected from the group consisting of alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aryl, substituted aryl, aryloxy, substituted aryloxy, cyano, halogen, hydroxyl, nitro, carboxyl, carboxyl esters, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic with the proviso that any hydroxyl substitution is not attached to a vinyl (unsaturated) carbon atom. Preferred substituted alkenyl groups are selected from, but not limit to, 2,2-difluoroethen-l-yl, 2-methoxyethen-l-yl, and the like.

[0032] It is understood that the term "substituted alkenyl" includes both E (cis) and Z (trans) isomers as appropriate. The isomers can be pure isomeric compounds or mixtures of E and Z components.

[0033] Unless otherwise defined herein, the term "alkynyl" refers to an unsaturated hydrocarbon having at least 1 site of alkynyl unsaturation (-C≡C-) and having from 2 to 30 carbon atoms and more preferably 2 to 20 carbon atoms. Preferred alkynyl groups are selected from but not limit to ethyn-1-yl, propyn-1- yl, propyn-2-yl, l-methylprop-2-yn-l-yl, butyn-1-yl, butyn-2-yl, butyn-3-yl, and the like.

[0034] "Substituted alkynyl" refers to alkynyl groups having from 1 to 3 substituents, and preferably 1 to 2 substituents, selected from the group consisting of alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aryl, substituted aryl, aryloxy, substituted aryloxy, cyano, halogen, hydroxyl, nitro, carboxyl, carboxyl esters, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic. Preferred substituted alkynyl groups are selected from but not limit to 2-fluoroethyn-l-yl, 3,3,3-trifluoropropyn-l-yl, 3-aminopropyn-l-yl, 3-hydroxypropyn-l-yl, and the like. [0035] "Amino" refers to the group -NH ₂ .

[0036] "Substituted amino" refers to the group -NR'R" where R' and R" are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl,

heterocyclic, substituted heterocyclic and where R' and R" are joined, together with the nitrogen bound thereto to form a heterocyclic or substituted heterocyclic group provided that R' and R" are both not hydrogen. When R' is hydrogen and R" is alkyl, the substituted amino group is sometimes referred to herein as alkylamino. When R' and R" are alkyl, the substituted amino group is sometimes referred to herein as dialkylamino.

[0037] "Aminoacyl" refers to the groups -NR ^b C(O)alkyl, -NR ^b C(O)substituted alkyl, -NR ^b C(O)cycloalkyl, -NR ^b C(O)substituted cycloalkyl, -NR ^b C(O)alkenyl, -NR ^b C(O)substituted alkenyl, -NR ^b C(O)alkynyl, -NR ^b C(O)substituted alkynyl, -NR ^b C(O)aryl, -NR ^b C(O)substituted aryl, -NR ^b C(O)heteroaryl, -NR ^b C(O)substituted heteroaryl, -NR ^b C(O)heterocyclic, and - NR ^b C(O)substituted heterocyclic where R ^b is hydrogen or alkyl. [0038] "Aryl" or "Ar" refers to a monovalent aromatic carbocyclic group of from 6 to 14 carbon atoms having a single ring (e.g., phenyl) or multiple condensed rings (e.g., naphthyl or anthryl) which condensed rings may or may not be aromatic (e.g., 2-benzoxazolinone, 2H-l,4-benzoxazin-3(4H)-one-7-yl, and the like) provided that the point of attachment is at an aromatic carbon atom. Preferred aryls include phenyl and naphthyl.

[0039] "Substituted aryl", including "substituted phenyl", refers to aryl groups or phenyl groups which are substituted with from 1 to 3 substituents, and preferably 1 to 2 substituents, selected from the group consisting of hydroxyl, acyl, acylamino, acyloxy, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amino, substituted amino, aminoacyl, aryl, substituted aryl, aryloxy, substituted aryloxy, cycloalkoxy, substituted cycloalkoxy, carboxyl, carboxyl esters, cyano, thiol, thioalkyl, substituted thioalkyl, thioaryl, substituted thioaryl, thioheteroaryl, substituted thioheteroaryl, thiocycloalkyl, substituted thiocycloalkyl, thioheterocyclic, substituted thioheterocyclic, cycloalkyl, substituted cycloalkyl, halo, nitro, heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic, heteroaryloxy, substituted heteroaryloxy, heterocyclyloxy, and substituted heterocyclyloxy.

[0040] "Aryloxy" refers to the group aryl-O- that includes, by way of example, phenoxy, naphthoxy, and the like.

[0041] "Substituted aryloxy" refers to substituted aryl-O- groups.

[0042] "CarboxyP'and "carboxylic acid" refers to -COOH or salts thereof.

[0043] "Carboxyl esters" refers to the groups -C(O)O-alkyl,

-C(O)O-substituted alkyl, -C(O)O-aryl, and -C(O)O-substituted aryl wherein alkyl, substituted alkyl, aryl and substituted aryl are as defined herein.

[0044] "Cyano" refers to the group -CN.

[0045] "Cycloalkyl" refers to cyclic alkyl groups of from 3 to 10 carbon atoms having single or multiple cyclic rings one or more of which may be aromatic or heteroaromatic provided that the point of attachment is through a cycloalkyl ring atom. Such groups include, by way of example, adamantyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclooctyl, and the like.

[0046] "Substituted cycloalkyl" refers to a saturated or unsaturated, but not aromatic, cycloalkyl having from 1 to 5 substituents selected from the group consisting of oxo (=0), thioxo (=S), alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aryl, substituted aryl, aryloxy, substituted aryloxy, cyano, halogen, hydroxyl, nitro, carboxyl, carboxyl esters, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic.

[0047] "Cycloalkoxy" refers to -O-cycloalkyl groups.

[0048] "Substituted cycloalkoxy" refers to -O-substituted cycloalkyl groups.

[0049] "Formyl" refers to HC(O)-.

[0050] "Halo" or "halogen" refers to fluoro, chloro, bromo, and iodo and preferably is fluoro or chloro.

[0051] "Heteroaryl" refers to an aromatic group of from 1 to 10 carbon atoms and 1 to 4 heteroatoms selected from the group consisting of oxygen, nitrogen, sulfur in the ring. The sulfur and nitrogen heteroatoms atoms may also be present in their oxidized forms, such as >N(O), >S(O) and >S(O) ₂ . Such heteroaryl groups can have a single ring (e.g., pyridyl or furyl) or multiple condensed rings

(e.g., indolizinyl or benzothienyl) wherein the condensed rings may or may not be aromatic and/or contain a heteroatom provided that the point of attachment is through an atom of the aromatic heteroaryl group. Preferred heteroaryls include pyridyl, pyrrolyl, thienyl, indolyl, thiophenyl, and furyl.

[0052] "Substituted heteroaryl" refers to heteroaryl groups that are substituted with from 1 to 3 substituents selected from the same group of substituents defined for substituted aryl.

[0053] "Heteroaryloxy" refers to the group -O-heteroaryl and "substituted heteroaryloxy" refers to the group -O-substituted heteroaryl.

[0054] "Heterocycle" or "heterocyclic" or "heterocycloalkyl" refers to a saturated or unsaturated group (but not heteroaryl) having a single ring or multiple condensed rings, from 1 to 10 carbon atoms and from 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen, sulfur, >S(O), and

>S(O) ₂ within the ring wherein, in fused ring systems, one or more the rings can be cycloalkyl, aryl or heteroaryl provided that the point of attachment is through the heterocyclic ring.

[0055] "Substituted heterocyclic" or "substituted heterocycloalkyl" refers to heterocycle groups that are substituted with from 1 to 3 of the same substituents as defined for substituted cycloalkyl.

[0056] Examples of heterocycles and heteroaryls include, but are not limited to, azetidine, pyrrole, imidazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, indolizine, isoindole, indole, dihydroindole, indazole, purine, quinolizine, isoquinoline, quinoline, phthalazine, naphthylpyridine, quinoxaline, quinazoline, cinnoline, pteridine, carbazole, carboline, phenanthridine, acridine, phenanthroline, isothiazole, phenazine, isoxazole, phenoxazine, phenothiazine, imidazolidine, imidazoline, piperidine, piperazine, indoline, phthalimide,

1 ,2,3,4-tetrahydroisoquinoline, 4,5,6,7-tetrahydrobenzo[b]thiophene, thiazole, thiazolidine, thiophene, benzo[b]thiophene, morpholinyl, thiomorpholinyl (also referred to as thiamorpholinyl), piperidinyl, pyrrolidine, tetrahydrofuranyl, and the like.

[0057] "Heterocyclyloxy" refers to the group -O-heterocyclic and "substituted heterocyclyloxy" refers to the group -O-substituted heterocyclic.

[0058] "Hydroxy" refers to the group -OH.

[0059] "Nitro" refers to the group -NO ₂ .

[0060] "Phosphate" refers to the groups -OP(O)(OH) ₂ (monophosphate or phospho), -OP(O)(OH)OP(O)(OH) ₂ (diphosphate or diphospho) and

-OP(O)(OH)OP(O)(OH)OP(O)(OH) ₂ (triphosphate or triphospho) or salts thereof

including partial salts thereof. It is understood, of course, that the initial oxygen of the mono-, di-, and triphosphate (phospho, diphospho and triphospho) includes the oxygen atom at, for example, the 5-position of the ribose sugar. [0061] "Phosphate esters" refers to the mono-, di- and tri-phosphate groups described above wherein one or more of the hydroxyl groups is replaced by an alkoxy group.

[0062] "Phosphonate" refers to the groups -OP(O)(R^(OH) or -OP(O)(R ⁱ )(OR ⁱ ) or salts thereof including partial salts thereof, wherein each R ¹ is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, carboxylic acid, and carboxyl ester. It is understood, of course, that the initial oxygen of the phosphonate includes the oxygen atom at, for example, the 5- position of the ribose sugar.

[0063] "Phosphorodiamidate" refers to the group: o

Il , (Rn) ₂ N -P-;

(Rn) ₂ N wherein each R ⁿ may be the same or different and each is hydrogen, alkyl, substituted alkyl, cycloalkyl, or substituted cycloalkyl. A particularly preferred phosphorodiamidate is the following group: o

Il , H ₂ N-P^

NH ₂

[0064] "Phosphoramidate monoester" refers to the group below, where R ^f and R ^ε are as defined above. In a preferred embodiment R ^f is derived from an L- amino acid.

[0065] "Phosphoramidate diester" refers to the group below, where R ^e , R ^f and R ⁸ are as defined above. In a preferred embodiment R is derived from an L- amino acid.

[0066] "Cyclic phosphoramidate" refers to the group below, where « is 1 to 3, more preferably n is 1 to 2.

[0067] "Cyclic phosphorodiamidate" refers to the group below, where n is 1 to 3, more preferably n is 1 to 2.

[0068] "Phosphonamidate" refers to the group below, where R ⁰ is hydrogen, alkyl, substituted alkyl, cycloalkyl, or substituted cycloalkyl.

[0069] "Thiol" refers to the group -SH.

[0070] "Thioalkyl" or "alkylthioether" or "thioalkoxy" refers to the group

-S-alkyl.

[0071] "Substituted thioalkyl" or "substituted alkylthioether" or "substituted thioalkoxy" refers to the group -S-substituted alkyl.

[0072] "Thiocycloalkyl" refers to the groups -S-cycloalkyl and "substituted thiocycloalkyl" refers to the group -S-substituted cycloalkyl.

[0073] "Thioaryl" refers to the group -S-aryl and "substituted thioaryl" refers to the group -S-substituted aryl.

[0074] "Thioheteroaryl" refers to the group -S-heteroaryl and "substituted thioheteroaryl" refers to the group -S-substituted heteroaryl.

[0075] "Thioheterocyclic" refers to the group -S-heterocyclic and "substituted thioheterocyclic" refers to the group -S-substituted heterocyclic.

[0076] The term "amino acid sidechain" refers to the R ^J substituent of α-amino acids of the formula R ^k NHCH(R ^j )COOH wherein R ^j is selected from the group consisting of hydrogen, alkyl, substituted alkyl, and aryl; and R ^k is hydrogen or together with R ^J and the nitrogen and carbon atoms bound thereto respectively form a heterocyclic ring. Preferably, the α-amino acid sidechain is the sidechain one of the twenty naturally occurring L amino acids.

[0077] The term "prodrug" as used herein refers to any compound that when administered to a biological system generates the drug substance, i.e. active ingredient, as a result of spontaneous chemical reaction(s), enzyme catalyzed chemical reaction(s), photolysis, and/or metabolic chemical reaction(s). A prodrug is thus a covalently modified analog or latent form of a therapeutically- active compound.

[0078] "Prodrug moiety" means a labile functional group which separates from the active inhibitory compound during metabolism, systemically, inside a cell, by hydrolysis, enzymatic cleavage, or by some other process (Bundgaard, Hans, "Design and Application of Prodrugs" in Textbook of Drug Design and Development (1991), P. Krogsgaard-Larsen and H. Bundgaard, Eds. Harwood Academic Publishers, pp. 113-191, herein incorporated by reference in its entirety). Enzymes which are capable of an enzymatic activation mechanism with the phosphonate prodrug compounds of the embodiments include, but are not limited to, amidases, esterases, microbial enzymes, phospholipases, cholinesterases, and phosphases. Prodrug moieties can serve to enhance solubility, absorption, and lipophilicity to optimize drug delivery, bioavailability and efficacy.

[0079] Exemplary prodrug moieties include the hydrolytically sensitive or labile acyloxymethyl esters -CH ₂ OC(=O)R ^d and acyloxymethyl carbonates -CH ₂ OC(=O)OR ^d where R ^d is C ₁ -QaIlCyI, d-C ₆ substituted alkyl, C ₆ -C _2O aryl or C ₆ -C ₂₀ substituted aryl. The acyloxyalkyl ester was first used as a prodrug strategy for carboxylic acids and then applied to phosphates and phosphonates by Farquhar et al (1983) J Pharm. ScL 72: 324; also US Patent Nos. 4816570, 4968788, 5663159 and 5792756; all of which are incorporated herein by reference in their entirety. In certain compounds of the embodiments, a prodrug moiety is part of a phosphonate group. Subsequently, the acyloxyalkyl ester was used to deliver phosphonic acids across cell membranes and to enhance oral bioavailability. A close variant of the acyloxyalkyl ester, the alkoxycarbonyloxyalkyl ester (carbonate), may also enhance oral bioavailability as a prodrug moiety in the compounds of the combinations of the embodiments. An exemplary acyloxymethyl ester is pivaloyloxymethoxy, (POM)

-CH ₂ OC(=O)C(CH ₃ ) ₃ . An exemplary acyloxymethyl carbonate prodrug moiety is pivaloyloxymethylcarbonate (POC) -CH ₂ OC(=O)OC(CH ₃ ) ₃ . [0080] The phosphonate group may be a phosphonate prodrug moiety. The prodrug moiety may be sensitive to hydrolysis, such as, but not limited to a pivaloyloxymethyl carbonate (POC) or POM group. Alternatively, the prodrug moiety may be sensitive to enzymatic potentiated cleavage, such as a lactate ester or a phosphonamidate-ester group.

[0081] Aryl esters of phosphorus groups, especially phenyl esters, are reported to enhance oral bioavailability (DeLambert et al (1994) J Med. Chem. 37: 498, herein incorporated by reference in its entirety). Phenyl esters containing a carboxylic ester ortho to the phosphate have also been described (Khamnei and Torrence, (1996) J. Med. Chem. 39:4109-4115, herein incorporated by reference in its entirety). Benzyl esters are reported to generate the parent phosphonic acid. In some cases, substituents at the ort/zo-or/rørα-position may accelerate the hydrolysis. Benzyl analogs with an acylated phenol or an alkylated phenol may generate the phenolic compound through the action of enzymes, e.g. esterases, oxidases, etc., which in turn undergoes cleavage at the benzylic C-O bond to generate the phosphoric acid and the quinone methide intermediate. Examples of this class of prodrugs are described by Mitchell et al (1992) J Chem. Soc. Perkin Trans. /2345; Brook et al WO 91/19721, all of which are herein incorporated by reference in their entirety. Still other benzylic prodrugs have been described containing a carboxylic ester-containing group attached to the benzylic methylene (Glazier et al WO 91/19721, herein incorporated by reference in its entirety). Thio-containing prodrugs are reported to be useful for the intracellular delivery of phosphonate drugs. These proesters contain an ethylthio group in which the thiol group is either esterified with an acyl group or combined with another thiol group to form a disulfide. Deesterification or reduction of the disulfide generates the free thio intermediate which subsequently breaks down to the phosphoric acid and episulfide (Puech et al (1993) Antiviral Res., 22: 155-174; Benzaria et al (1996) J. Med. Chem. 39: 4958, all of which are herein incorporated by reference in their entirety). Cyclic phosphonate esters have also been described as prodrugs of phosphorus-containing compounds (Erion et al, US Patent No. 6312662, herein incorporated by reference in its entirety).

[0082] The term "pharmaceutically acceptable salt" refers to pharmaceutically acceptable salts of a compound, which salts are derived from a variety of organic and inorganic counter ions well known in the art and include, by way of example only, sodium, potassium, calcium, magnesium, ammonium, tetraalkylammonium, and the like; and when the molecule contains a basic functionality, salts of organic or inorganic acids, such as hydrochloride, hydrobromide, tartrate, mesylate, acetate, maleate, oxalate, and the like. [0083] The term "pharmaceutically acceptable partial salts" refers to compounds having a substituent capable of having more than one group form a salt but less than the maximum amount of such groups actually form a salt. For example, a diphospho group can form a plurality of salts and, if only partially ionized, the resulting group is sometimes referred to herein as a partial salt. "Carbocycle" means a saturated, unsaturated or aromatic ring having 3 to 7 carbon atoms as a monocycle or 7 to 12 carbon atoms as a bicycle. Monocyclic carbocycles have 3 to 6 ring atoms, still more typically 5 or 6 ring atoms. Bicyclic carbocycles have 7 to 12 ring atoms, e.g. arranged as a bicyclo [4,5], [5,5], [5,6] or [6,6] system, or 9 or 10 ring atoms arranged as a bicyclo [5,6] or [6,6] system. Examples of monocyclic carbocycles include cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopent-l-enyl, l-cyclopent-2-enyl, l-cyclopent-3- enyl, cyclohexyl, 1-cyclohex-l-enyl, l-cyclohex-2-enyl, l-cyclohex-3-enyl, phenyl, spiryl, and naphthyl.

[0084] "Carbocycle" means a saturated, unsaturated or aromatic ring having 3 to 7 carbon atoms as a monocycle or 7 to 12 carbon atoms as a bicycle. Monocyclic carbocycles have 3 to 6 ring atoms, still more typically 5 or 6 ring atoms. Bicyclic carbocycles have 7 to 12 ring atoms, e.g. arranged as a bicyclo [4,5], [5,5], [5,6] or [6,6] system, or 9 or 10 ring atoms arranged as a bicyclo [5,6] or [6,6] system. Examples of monocyclic carbocycles include cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopent-l-enyl, l-cyclopent-2-enyl, l-cyclopent-3- enyl, cyclohexyl, 1-cyclohex-l-enyl, l-cyclohex-2-enyl, l-cyclohex-3-enyl, phenyl, spiryl, and naphthyl.

[0085] "Linker" or "link" means a chemical moiety comprising a covalent bond or a chain of atoms that covalently attaches a phosphonate group to a drug. Linkers include portions of substituents A ¹ and A enumerated in Formulas I and

II which include moieties such as: repeating units of alkyloxy (e.g. polyethylenoxy, PEG, polymethyleneoxy) and alkylamino (e.g. polyethyleneamino, Jeffamine™); and diacid ester and amides including succinate, succinamide, diglycolate, malonate, and caproamide. [0086] The term "crural" refers to molecules which have the property of non- superimposability of the mirror image partner, while the term "achiral" refers to molecules which are superimposable on their mirror image partner. [0087] The term "stereoisomers" refers to compounds which have identical chemical constitution, but differ with regard to the arrangement of the atoms or groups in space.

[0088] "Diastereomer" refers to a stereoisomer with two or more centers of chirality and whose molecules are not mirror images of one another. Diastereomers have different physical properties, e.g. melting points, boiling points, spectral properties, and reactivities. Mixtures of diastereomers may separate under high resolution analytical procedures such as electrophoresis and chromatography.

[0089] "Enantiomers" refer to two stereoisomers of a compound which are non- superimposable mirror images of one another.

[0090] Stereochemical definitions and conventions used herein generally follow S. P. Parker, Ed., McGraw-Hill Dictionary of Chemical Terms (1984) McGraw- Hill Book Company, New York; and Eliel, E. and Wilen, S., Stereochemistry of Organic Compounds (1994) John Wiley & Sons, Inc., New York. Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes d and 1, D and L, or (+) and (-) are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or 1 meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these stereoisomers are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric mixture. A 50:50 mixture of enantiomers is referred to as a racemic mixture or a racemate, which may occur

where there has been no stereoselection or stereospecificity in a chemical reaction or process. The terms "racemic mixture" and "racemate" refer to an equimolar mixture of two enantiomeric species, devoid of optical activity. [0091] It is understood that in all substituted groups defined above, polymers arrived at by defining substituents with further substituents to themselves (e.g., substituted aryl having a substituted aryl group as a substituent which is itself substituted with a substituted aryl group, etc.) are not intended for inclusion herein. In such cases, the maximum number of such substituents is three. That is to say that each of the above definitions is constrained by a limitation that, for example, substituted aryl groups are limited to -substituted aryl-(substituted aryl)-substituted aryl.

[0092] Similarly, it is understood that the above definitions are not, intended to include impermissible substitution patterns (e.g., methyl substituted with 5 fluoro groups or a hydroxyl group alpha to ethenylic or acetylenic unsaturation). Such impermissible substitution patterns are well known to the skilled artisan. [0093] In the context of the present embodiments, embodiments of protecting groups include prodrug moieties and chemical protecting groups. [0094] Protecting groups are available, commonly known and used, and are optionally used to prevent side reactions with the protected group during synthetic procedures, i.e. routes or methods to prepare the compounds of the embodiments. For the most part the decision as to which groups to protect, when to do so, and the nature of the chemical protecting group "PRT" will be dependent upon the chemistry of the reaction to be protected against (e.g., acidic, basic, oxidative, reductive or other conditions) and the intended direction of the synthesis. The" PRT groups do not need to be, and generally are not, the same if the compound is substituted with multiple PRT. In general, PRT will be used to protect functional groups such as carboxyl, hydroxyl, or amino groups and to thus prevent side reactions or to otherwise facilitate the synthetic efficiency. The order of deprotection to yield free, deprotected groups is dependent upon the intended direction of the synthesis and the reaction conditions to be encountered, and may occur in any order as determined by the artisan. [0095] Various functional groups of the compounds of the embodiments may be protection. For example, protecting groups for -OH groups (whether

hydroxyl, carboxylic acid, phosphonic acid, or other functions) are embodiments of "ether- or ester-forming groups". Ether- or ester-forming groups are capable of functioning as chemical protecting groups in the synthetic schemes set forth herein. However, some hydroxyl and thio protecting groups are neither ether- nor ester-forming groups, as will be understood by those skilled in the art, and are included with amides, discussed below.

[0096] A very large number of hydroxyl protecting groups and amide-forming groups and corresponding chemical cleavage reactions are described in "Protective Groups in Organic Chemistry", Theodora W. Greene (John Wiley & Sons, Inc., New York, 1991, ISBN 0-471-62301-6) ("Greene"), herein incorporated by reference in its entirety. See also Kocienski, Philip J.; "Protecting Groups" (Georg Thieme Verlag Stuttgart, New York, 1994), which is incorporated by reference in its entirety herein. In particular Chapter 1 , Protecting Groups: An Overview, pages 1-20, Chapter 2, Hydroxyl Protecting Groups, pages 21-94, Chapter 3, Diol Protecting Groups, pages 95-117, Chapter 4, Carboxyl Protecting Groups, pages 118-154, Chapter 5, Carbonyl Protecting Groups, pages 155-184. For protecting groups for carboxylic acid, phosphonic acid, phosphonate, sulfonic acid and other protecting groups for acids see Greene as set forth below. Such groups include by way of example and not limitation, esters, amides, hydrazides, and the like.

Ether- and Ester-forming protecting groups

[0097] Ester-forming groups include: (1) phosphonate ester-forming groups, such as phosphonamidate esters, phosphorothioate esters, phosphonate esters, and phosphon-bis-amidates; (2) carboxyl ester-forming groups, and (3) sulphur ester- forming groups, such as sulphonate, sulfate, and sulfinate. [0098] The phosphonate moieties of the compounds of the embodiments may or may not be prodrug moieties, i.e. they may or may not be susceptible to hydrolytic or enzymatic cleavage or modification. Certain phosphonate moieties are stable under most or nearly all metabolic conditions. For example, a dialkylphosphonate, wherein the alkyl groups comprise two or more carbons, can have appreciable stability in vivo due to a slow rate of hydrolysis.

[0099] Within the context of phosphonate prodrug moieties, a large number of structurally-diverse prodrugs have been described for phosphonic acids (Freeman and Ross in Progress in Medicinal Chemistry 34: 112-147 (1997) , herein incorporated by reference in its entirety, and are included within the scope of the present embodiments. An exemplary embodiment of a phosphonate ester- forming group is the phenyl carbocycle in substructure A ₃ having the formula:

wherein ml is 1, 2, 3, 4, 5, 6, 7 or 8, and the phenyl carbocycle is substituted with 0 to 3 R ₂ groups. Also, in this embodiment, where Y ₁ is O, a lactate ester is formed.

Alternatively, where Y ₁ is N(R ₂ ), N(OR ₂ ) or N(N(R ₂ ) ₂ , then phosphonamidate esters result. R ₁ may be H or Ci-C ₁₂ alkyl. The corollary exemplary substructure A is included in the embodiments with Y , R and R substituents.

[0100] In its ester-forming role, a protecting group typically is bound to any acidic group such as, by way of example and not limitation, a -CO2H or

-C(S)OH group, thereby resulting in -Cθ2R ^x where R ^x is defined herein. Also,

R ^x for example includes the enumerated ester groups of WO 95/07920, herein incorporated by reference in its entirety.

[0101] Examples of protecting groups include, but are not limited to:

C3-C12 heterocycle (described above) or aryl. These aromatic groups optionally are polycyclic or monocyclic. Examples include phenyl, spiryl, 2- and 3-pyrrolyl, 2- and 3-thienyl, 2- and 4-imidazolyl, 2-, 4- and 5-oxazolyl, 3- and 4-isoxazolyl, 2-, 4- and 5- thiazolyl, 3-, 4- and 5-isothiazolyl, 3- and 4-pyrazolyl, 1-, 2-, 3- and 4-pyridinyl, and 1-, 2-, 4- and 5-pyrimidinyl,

C3-C12 heterocycle or aryl substituted with halo, R ¹ , R'-O-Ci-Ci2 alkylene, C]- C ₁ 2 alkoxy, CN, NO2, OH, carboxy, carboxyester, thiol, thioester, C ₁ -C12 haloalkyl (1-6 halogen atoms), C ₂ -C ₁ 2 alkenyl or C2-C12 alkynyl. Such groups include 2-, 3- and 4-

alkoxyphenyl (Ci -C 12 alkyl), 2-, 3- and 4-methoxyphenyl, 2-, 3- and 4-ethoxyphenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-diethoxyphenyl, 2- and 3-carboethoxy-4- hydroxyphenyl, 2- and 3-ethoxy-4-hydroxyphenyl, 2- and 3-ethoxy-5-hydroxyphenyl, 2- and 3-ethoxy-6-hydroxyphenyl, 2-, 3- and 4-O-acetylphenyl, 2-, 3- and 4- dimethylaminophenyl, 2-, 3- and 4-methylmercaptophenyl, 2-, 3- and 4-halophenyl (including 2-, 3- and 4-fluorophenyl and 2-, 3- and 4-chlorophenyl), 2,3-, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-dimethylphenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-biscarboxyethylphenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-dimethoxyphenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- and 3,5- dihalophenyl (including 2,4-difluorophenyl and 3,5-difluorophenyl), 2-, 3- and 4- haloalkylphenyl (1 to 5 halogen atoms, C1-C ₁ 2 alkyl including 4-trifluoromethylphenyl), 2-, 3- and 4-cyanophenyl, 2-, 3- and 4-nitrophenyl, 2-, 3- and 4-haloalkylbenzyl (1 to 5 halogen atoms, Ci -C 12 alkyl including 4-trifluoromethylbenzyl and 2-, 3- and 4- trichloromethylphenyl and 2-, 3- and 4-trichloromethylphenyl), 4-N-methylpiperidinyl, 3-N-methylpiperidinyl, 1-ethylpiperazinyl, benzyl, alkylsalicylphenyl (C1-C4 alkyl, including 2-, 3- and 4-ethylsalicylphenyl), 2-,3- and 4-acetylphenyl, 1,8- dihydroxynaphthyl (-C10H6-OH) and aryloxy ethyl [C6-C9 aryl (including phenoxy ethyl)], 2,2'-dihydroxybiphenyl, 2-, 3- and 4-N,N-dialkylaminophenol, -CO^CH ₂ - N(CH3)2, trimethoxybenzyl, triethoxybenzyl, 2-alkyl pyridinyl (C ₁ .4 alkyl);

; C4 _ C8 esters of 2- carboxyphenyl; and C1-C4 alkylene-C3-C6 aryl (including benzyl, -CH ₂ -pyrrolyl, -CH ₂ - thienyl, -CH2-imidazolyl, -CH2-oxazolyl, -CH2-isoxazolyl, -CH2-thiazolyl, -CH ₂ - isothiazolyl, -CH2-pyrazolyl, -CH2-pyridinyl and -CH2-pyrimidinyl) substituted in the aryl moiety by 3 to 5 halogen atoms or 1 to 2 atoms or groups selected from halogen, Q- C ₁₂ alkoxy (including methoxy and ethoxy), cyano, nitro, OH, C ₁ -C12 haloalkyl (1 to 6 halogen atoms; including -CH2CCI3), Ci -C ₁ 2 alkyl (including methyl and ethyl), C2-C12 alkenyl or C ₂ -Ci ₂ alkynyl; alkoxy ethyl [Ci-C ₆ alkyl including -CH ₂ -CH ₂ -O-CH ₃ (methoxy ethyl)]; alkyl substituted by any of the groups set forth above for aryl, in particular OH or by 1 to 3 halo atoms (including -CH ₃ , -CH(CH ₃ ) ₂ , -C(CH ₃ ) ₃ , - CH ₂ CH ₃ , -(CH ₂ ) ₂ CH ₃ , -(CH ₂ ) ₃ CH ₃ , -(CH ₂ ) ₄ CH ₃ , -(CH ₂ ) ₅ CH3,CH ₂ CH ₂ F, -CH ₂ CH ₂ Cl,

-CH ₂ CF ₃ , and -CH ₂ CCl ₃ ); ; -N-2-propylmorpholino, 2,3-dihydro-6- hydroxyindene, sesamol, catechol monoester, -CH ₂ -C(O)-N(R ¹ ) ₂ , -CH ₂ -S(O)(R ¹ ), - CH ₂ -S(O) ₂ (R ¹ ), -CH ₂ -CH(OC(O)CH ₂ R ¹ )-CH ₂ (OC(O)CH ₂ R ¹ ), cholesteryl, enolpyruvate (HOOC-C(=CH ₂ )-), glycerol; a 5 or 6 carbon monosaccharide, disaccharide or oligosaccharide (3 to 9 monosaccharide residues); triglycerides such as α-D-β-diglycerides (wherein the fatty acids composing glyceride lipids generally are naturally occurring saturated or unsaturated C6- ₂ 6, Cό-is or Cό-io fatty acids such as linoleic, lauric, myristic, palmitic, stearic, oleic, palmitoleic, linolenic and the like fatty acids) linked to acyl of the parental compounds herein through a glyceryl oxygen of the triglyceride; phospholipids linked to the carboxyl group through the phosphate of the phospholipid; phthalidyl (shown in Fig. 1 of Clayton et al., Antimicrob. Agents Chemo. (1974) 5(6):670-671; cyclic carbonates such as (5-Rd-2-oxo-l,3-dioxolen-4-yl) methyl esters (Sakamoto et al., Chem. Pharm. Bull. (1984) 32(6)2241-2248), herein incorporated by reference in its entirety, wherein Rd is Ri, R4 or aryl; and

-CH ₂ C(O)N O

[0102] The hydroxy 1 groups of the compounds of the embodiments optionally are substituted with one of groups III, IV or V disclosed in WO 94/21604, herein incorporated by reference in its entirety, or with isopropyl. [0103] As further embodiments, Table A lists examples of protecting group ester moieties that for example can be bonded via oxygen to -C(O)O- and - P(O)(O-) ₂ groups. Several amidates also are shown, which are bound directly to -C(O)- or -P(O)2. Esters of structures 1-5, 8-10 and 16, 17, 19-22 are synthesized by reacting the compound herein having a free hydroxyl with the corresponding halide (chloride or acyl chloride and the like) and N ,N- dicyclohexyl-N-morpholine carboxamidine (or another base such as DBU, triethylamine, CsCO ₃ , N,N-dimethylaniline and the like) in DMF (or other

solvent such as acetonitrile or N-methylpyrrolidone). When the compound to be protected is a phosphonate, the esters of structures 5-7, 11, 12, 21, and 23-26 are synthesized by reaction of the alcohol or alkoxide salt (or the corresponding amines in the case of compounds such as 13, 14 and 15) with the monochlorophosphonate or dichlorophosphonate (or another activated phosphonate).

# - chiral center is (R), (S) or racemate.

[0104] Other esters that are suitable for use herein are described in EP 632048, herein incorporated by reference in its entirety.

[0105] Protecting groups also includes "double ester" forming profunctionalities such as

-CH2θC(O)OCH3, -CH2SCOCH3, -CH2θCON(CH3)2, or alkyl- or aryl- acyloxyalkyl groups of the structure -CH(R ¹ or W ⁵ )O((CO)R ³⁷ ) or -CH(R ¹ or W ⁵ )((CO)OR ³⁸ ) (linked to oxygen of the acidic group) wherein R ³⁷ and R ³⁸ are alkyl, aryl, or alkylaryl groups (see U.S. Patent No. 4,968,788, herein incorporated by reference in its entirety). Frequently R ³⁷ and R ³⁸ are bulky groups such as branched alkyl, ortho-substituted aryl, meta-substituted aryl, or combinations thereof, including normal, secondary, iso- and tertiary alkyls of 1-6 carbon atoms. An example is the pivaloyloxymethyl group. These are of particular use with prodrugs for oral administration. Examples of such useful protecting groups are alkylacyloxymethyl esters and their derivatives, including -CH(CH2CH2θCH ₃ )OC(O)C(CH ₃ )3,

-CH ₂ OC(O)CI ₀ HI ₅ , -CH ₂ OC(O)C(CH ₃ ) ₃ , -CH(CH ₂ OCH ₃ )OC(O)C(CH ₃ ) ₃ , -CH(CH(CH ₃ ) ₂ )OC(O)C(CH ₃ ) ₃ , -CH ₂ OC(O)CH ₂ CH(CH ₃ ) ₂ , -CH ₂ OC(O)C ₆ Hi 1, -CH ₂ OC(O)C ₆ H ₅ , -CH ₂ OC(O)CI ₀ HI ₅ , -CH ₂ OC(O)CH ₂ CH ₃ , -CH ₂ OC(O)CH(CH ₃ ) ₂ , -CH ₂ OC(O)C(CH ₃ ) ₃ and -CH ₂ OC(O)CH ₂ C ₆ H ₅ .

[0106] For prodrug purposes, the ester typically chosen is one heretofore used for antibiotic drugs, in particular the cyclic carbonates, double esters, or the phthalidyl, aryl or alkyl esters.

[0107] In some embodiments the protected acidic group is an ester of the acidic group and is the residue of a hydroxyl-containing functionality. In other embodiments, an amino compound is used to protect the acid functionality. The residues of suitable hydroxyl or amino-containing functionalities are set forth above or are found in WO 95/07920. Of particular interest are the residues of amino acids, amino acid esters, polypeptides, or aryl alcohols. Typical amino acid, polypeptide and carboxyl-esterified amino acid residues are described on pages 11-18 and related text of WO 95/07920 as groups Ll or L2. WO 95/07920

expressly teaches the amidates of phosphonic acids, but it will be understood that such amidates are formed with any of the acid groups set forth herein and the amino acid residues set forth in WO 95/07920.

[0108] Typical esters for protecting acidic functionalities are also described in WO 95/07920, again understanding that the same esters can be formed with the acidic groups herein as with the phosphonate of the '920 publication. Typical ester groups are defined at least on WO 95/07920 pages 89-93 (under R.31 or R35) ₅ the table on page 105, and pages 21-23 (as R). Of particular interest are esters of unsubstituted aryl such as phenyl or arylalkyl such benzyl, or hydroxy-, halo-, alkoxy-, carboxy- and/or alkylestercarboxy-substituted aryl or alkylaryl, especially phenyl, ortho-ethoxyphenyl, or C1-C4 alkylestercarboxyphenyl (salicylate C ₁ -C12 alkylesters).

[0109] The protected acidic groups, particularly when using the esters or amides of WO 95/07920, are useful as prodrugs for oral administration. However, it is not essential that the acidic group be protected in order for the compounds of the embodiments to be effectively administered by the oral route. When the compounds of the embodiments having protected groups, in particular amino acid amidates or substituted and unsubstituted aryl esters are administered systemically or orally they are capable of hydrolytic cleavage in vivo to yield the free acid.

[0110] One or more of the acidic hydroxyls are protected. If more than one acidic hydroxyl is protected then the same or a different protecting group is employed, e.g., the esters may be different or the same, or a mixed amidate and ester may be used.

[0111] Typical hydroxy protecting groups described in Greene (pages 14-118) include substituted methyl and alkyl ethers, substituted benzyl ethers, silyl ethers, esters including sulfonic acid esters, and carbonates. For example:

• Ethers (methyl, t-butyl, allyl);

• Substituted Methyl Ethers (Methoxymethyl, Methylthiomethyl, t-Butylthiomethyl, (Phenyldimethylsilyl)methoxymethyl, Benzyloxymethyl, p- Methoxybenzyloxymethyl, (4-Methoxyphenoxy)methyl, Guaiacolmethyl, t- Butoxymethyl, 4-Pentenyloxymethyl, Siloxymethyl, 2-Methoxyethoxymethyl, 2,2,2- Trichloroethoxymethyl, Bis(2-chloroethoxy)methyl, 2-(Trimethylsilyl)ethoxymethyl,

Tetrahydropyranyl, 3-Bromotetrahydropyranyl, Tetrahydropthiopyranyl, 1- Methoxycyclohexyl, 4-Methoxytetrahydropyranyl, 4-Methoxytetrahydrothiopyranyl, 4-Methoxytetrahydropthiopyranyl S.S-Dioxido, 1 -[(2-Chloro-4-methyl)phenyl]-4- methoxypiperidin-4-yl, l,4-Dioxan-2-yl, Tetrahydrofuranyl, Tetrahydrothiofuranyl, 2,3,3a,4,5,6,7,7a-Octahydro-7,8,8-trimethyl-4,7-methanobenzo flιran-2-yl));

• Substituted Ethyl Ethers ( 1 -Ethoxyethyl, 1 -(2-Chloroethoxy)ethyl, 1 -Methyl- 1 - methoxy ethyl, 1 -Methyl- 1 -benzyloxyethyl, 1 -Methyl- 1 -benzyloxy-2-fluoroethyl, 2,2,2-Trichloroethyl, 2-Trimethylsilylethyl, 2-(Phenylselenyl)ethyl,

• j7-Chlorophenyl,p-Methoxyphenyl, 2,4-Dinitrophenyl, Benzyl);

• Substituted Benzyl Ethers (p-Methoxybenzyl, 3,4-Dimethoxybenzyl, o-Nitrobenzyl, /?-Nitrobenzyl, /?-Halobenzyl, 2,6-Dichlorobenzyl, /?-Cyanobenzyl, p-Phenylbenzyl, 2- and 4-Picolyl, 3-Methyl-2-picolyl N-Oxido, Diphenylmethyl, p,p'- Dinitrobenzhydryl, 5-Dibenzosuberyl, Triphenylmethyl, α-Naphthyldiphenylmethyl, /»-methoxyphenyldiphenylmethyl, Di(/?-methoxyphenyl)phenylmethyl, Tri(p- methoxyphenyl)methyl, 4-(4'-Bromophenacyloxy)phenyldiphenylmethyl, 4,4',4"- Tris(4,5-dichlorophthalimidophenyl)methyl, 4,4',4"- Tris(levulinoyloxyphenyl)methyl, 4,4',4"-Tris(benzoyloxyphenyl)methyl, 3- (Imidazol- 1 -ylmethyl)bis(4',4"-dimethoxyphenyl)methyl, 1 , 1 -Bis(4-methoxyphenyl)- l'-pyrenylmethyl, 9-Anthryl, 9-(9-Phenyl)xanthenyl, 9-(9-Phenyl-10-oxo)anthryl, l,3-Benzodithiolan-2-yl, Benzisothiazolyl S.S-Dioxido);

• Silyl Ethers (Trimethylsilyl, Triethylsilyl, Triisopropylsilyl, Dimethylisopropylsilyl, Diethylisopropylsilyl, Dimethylthexylsilyl, t-Butyldimethylsilyl, t- Butyldiphenylsilyl, Tribenzylsilyl, Tri-p-xylylsilyl, Triphenylsilyl, Diphenylmethylsilyl, t-Butylmethoxyphenylsilyl);

• Esters (Formate, Benzoylformate, Acetate, Chloroacetate, Dichloroacetate, Trichloroacetate, Trifluoroacetate, Methoxyacetate, Triphenylmethoxyacetate, Phenoxyacetate, p-Chlorophenoxyacetate, /7-poly-Phenylacetate, 3-Phenylpropionate, 4-Oxopentanoate (Levulinate), 4,4-(Ethylenedithio)pentanoate, Pivaloate, Adamantoate, Crotonate, 4-Methoxycrotonate, Benzoate, /7-Phenylbenzoate, 2,4,6- Trimethylbenzoate (Mesitoate));

• Carbonates (Methyl, 9-Fluorenylmethyl, Ethyl, 2,2,2-Trichloroethyl, 2- (Trimethylsilyl)ethyl, 2-(Phenylsulfonyl)ethyl, 2-(Triphenylphosphonio)ethyl, Isobutyl, Vinyl, Allyl, p-Nitrophenyl, Benzyl, />-Methoxybenzyl, 3,4-

Dimethoxybenzyl, o-Nitrobenzyl, p-Nitrobenzyl, S-Benzyl Thiocarbonate, 4-Ethoxy- 1-naphthyl, Methyl Dithiocarbonate);

• Groups With Assisted Cleavage (2-Iodobenzoate, 4-Azidobutyrate, 4-Nitro-4- methylpentanoate, o-(Dibromomethyl)benzoate, 2-Formylbenzenesulfonate, 2- (Methylthiomethoxy)ethyl Carbonate, 4-(Methylthiomethoxy)butyrate, 2- (Methylthiomethoxymethyl)benzoate); Miscellaneous Esters (2,6-Dichloro-4- methylphenoxyacetate, 2,6-Dichloro-4-(l ,1 ,3,3 tetramethylbutyl)phenoxyacetate, 2,4-Bis( 1 , 1 -dimethylpropyl)phenoxyacetate, Chlorodiphenylacetate, Isobutyrate, Monosuccinate, (E)-2-Methyl-2-butenoate (Tigloate), o-(Methoxycarbonyl)benzoate, /7-poly-Benzoate, α-Naphthoate, Nitrate, Alkyl N,N,N',N'- Tetramethylphosphorodiamidate, iV-Phenylcarbamate, Borate, Dimethylphosphinothioyl, 2,4-Dinitrophenylsulfenate); and

• Sulfonates (Sulfate, Methanesulfonate (Mesylate), Benzylsulfonate, Tosylate). [0112] Typical 1,2-diol protecting groups (thus, generally where two OH groups are taken together with the protecting functionality) are described in Greene at pages 118-142 and include Cyclic Acetals and Ketals (Methylene, εthylidene, 1 -t-Butylethylidene, 1-Phenylethylidene, (4- Methoxyphenyl)ethylidene, 2,2,2-Trichloroethylidene, Acetonide (Isopropylidene), Cyclopentylidene, Cyclohexylidene, Cycloheptylidene, Benzylidene,/»-Methoxybenzylidene, 2,4-Dimethoxybenzylidene, 3,4- Dimethoxybenzylidene, 2-Nitrobenzylidene); Cyclic Ortho Esters (Methoxymethylene, Ethoxymethylene, Dimethoxymethylene, 1- Methoxyethylidene, 1-Ethoxyethylidine, 1 ,2-Dimethoxyethylidene, α- Methoxybenzylidene, l-(jV _> N-Dimethylamino)ethylidene Derivative, α -(N ₁ N- Dimethylamino)benzylidene Derivative, 2-Oxacyclopentylidene); Silyl Derivatives (Di-t-butylsilylene Group, 1,3-(1, 1,3,3-

Tetraisopropyldisiloxanylidene), and Tetra-t-butoxydisiloxane-1 ,3-diylidene), Cyclic Carbonates, Cyclic Boronates, Ethyl Boronate and Phenyl Boronate. [0113] More typically, 1,2-diol protecting groups include those shown in Table B, still more typically, epoxides, acetonides, cyclic ketals and aryl acetals.

Table B

wherein R ⁹ is Ci-Cό alkyl.

Amino protecting groups

[0114] Another set of protecting groups include any of the typical amino protecting groups described by Greene at pages 315-385. They include:

• Carbamates: (methyl and ethyl, 9-fluorenylmethyl, 9(2-sulfo)fluorenylmethyl, 9-(2,7- dibromo)fluorenylmethyl, 2,7-di-t-butyl-[9-( 10, 10-dioxo- 10,10,10,10- tetrahydrothioxanthyl)]methyl, 4-methoxyphenacyl);

• Substituted Ethyl: (2,2,2-trichoroethyl, 2-trimethylsilylethyl, 2-phenylethyl, 1-(1- adamantyl)- 1 -methylethyl, 1 , 1 -dimethyl-2-haloethyl, 1 , 1 -dimethyl-2,2-dibromoethyl, 1 , 1 -dimethyl-2,2,2-trichloroethyl, 1 -methyl- 1 -(4-biphenylyl)ethyl, 1 -(3 ,5-di-t- butylphenyl)-l -methylethyl, 2-(2'- and 4'-pyridyl)ethyl, 2-(N, N- dicyclohexylcarboxamido)ethyl, t-butyl, 1-adamantyl, vinyl, allyl, 1-isopropylallyl, cinnamyl, 4-nitrocinnamyl, 8-quinolyl, JV-hydroxypiperidinyl, alkyldithio, benzyl, p- methoxybenzyl, /7-nitrobenzyl, /7-bromobenzyl, /?-chlorobenzyl, 2,4-dichlorobenzyl, 4-methylsulfϊnylbenzyl, 9-anthrylmethyl, diphenylmethyl);

• Groups With Assisted Cleavage: (2-methylthioethyl, 2-methylsulfonylethyl, 2-(p- toluenesulfonyl)ethyl, [2-(l,3-dithianyl)]methyl, 4-methylthiophenyl, 2,4- dimethylthiophenyl, 2-phosphonioethyl, 2-triphenylphosphonioisopropyl, 1,1- dimethyl-2-cyanoethyl, w-choro-p-acyloxybenzyl, /?-(dihydroxyboryl)benzyl, 5- benzisoxazolylmethyl, 2-(trifluoromethyl)-6-chromonylmethyl);

• Groups Capable of Photolytic Cleavage: (m-nitrophenyl, 3,5-dimethoxybenzyl, o- nitrobenzyl, 3,4-dimethoxy-6-nitrobenzyl, phenyl(o-nitrophenyl)methyl); Urea-Type Derivatives (phenothiazinyl-(lθ)-carbonyl, iV-p-toluenesulfonylaminocarbonyl, N'-

pheny laminothiocarbony 1) ;

• Miscellaneous Carbamates: (Y-amyl, S-benzyl thiocarbamate, j?-cyanobenzyl, cyclobutyl, cyclohexyl, cyclopentyl, cyclopropylmethyl, /7-decyloxybenzyl, diisopropylmethyl, 2,2-dimethoxycarbonylvinyl, o-(N,N- dimethylcarboxamido)benzyl, 1 , 1 -dimethyl-3 -(N, N-dimethylcarboxamido)propyl, 1,1-dimethylpropynyl, di(2-pyridyl)methyl, 2-fiiranylmethyl, 2-Iodoethyl, Isobornyl, Isobutyl, Isonicotinyl,/»-(/?'-Methoxyphenylazo)benzyl, 1-methylcyclobutyl, 1- methylcyclohexyl, 1 -methyl- 1 -cyclopropylmethyl, 1 -methyl- 1 -(3,5- dimethoxyphenyl)ethyl, 1 -methyl- 1 -(p-phenylazophenyl)ethyl, 1 -methyl- 1 - phenylethyl, 1 -methyl- l-(4-pyridyl)ethyl, phenyl, ^-(phenylazo)benzyl, 2,4,6-tri-t- butylphenyl, 4-(trimethylammonium)benzyl, 2,4,6-trimethylbenzyl);

• Amides: (N-formyl, N-acetyl, N-choroacetyl, N-trichoroacetyl, N-trifluoroacetyl, N- phenylacetyl, N-3 -pheny lpropionyl, N-picolinoyl, N-3-pyridylcarboxamide, N- benzoylphenylalanyl, N-benzoyl, N-p-phenylbenzoyl);

• Amides With Assisted Cleavage: (N-o-nitrophenylacetyl, N-o-nitrophenoxyacetyl, N- acetoacetyl, (N'-dithiobenzyloxycarbonylamino)acetyl, N-3-(p- hydroxyphenyl)propionyl, N-3-(o-nitrophenyl)propionyl, N-2-methyl-2-(o- nitrophenoxy)propionyl, N-2-methyl-2-(o-phenylazophenoxy)propionyl, N-4- chlorobutyryl, N-3-methyl-3-nitrobutyryl, N-o-nitrocinnamoyl, N-acetylmethionine, N-o-nitrobenzoyl, N-o-(benzoyloxymethyl)benzoyl, 4,5-diphenyl-3-oxazolin-2-one);

• Cyclic Imide Derivatives: (N-phthalimide, N-dithiasuccinoyl, N-2,3- diphenylmaleoyl, N-2,5-dimethylpyrτolyl, N- 1,1, 4,4- tetramethyldisilylazacyclopentane adduct, 5-substituted l,3-dimethyl-l,3,5- triazacyclohexan-2-one, 5-substituted l,3-dibenzyl-l,3-5-triazacyclohexan-2-one, 1- substituted 3 , 5 -dinitro-4-pyridonyl) ;

• N-Alkyl and N-Aryl Amines: (N-methyl, N-allyl, N-[2-(trimethylsilyl)ethoxy]methyl, N-3-acetoxypropyl, N-(I -isopropyl-4-nitro-2-oxo-3-pyrrolin-3-yl), Quaternary Ammonium Salts, N-benzyl, N-di(4-methoxyphenyl)methyl, N-5-dibenzosuberyl, N- triphenylmethyl, N-(4-methoxyphenyl)diphenylmethyl, N-9-phenylfluorenyl, N-2,7- dichloro-9-fluorenylmethylene, N-ferrocenylmethyl, N-2-picolylamine N-oxide);

• Imine Derivatives: (N- 1 , 1 -dimethylthiomethylene, N-benzylidene, N-/?- methoxybenylidene, N-diphenylmethylene, N- [(2-pyridyl)mesityl]methylene, N,(N^V-dimethylaminomethylene, N _^ /V-isopropylidene, N-p-nitrobenzylidene, N-

salicylidene, JV-5-chlorosalicylidene, JV-(5-chloro-2- hydroxyphenyl)phenylmethylene, JV-cyclohexylidene);

• Enamine Derivatives: (N-(5,5-dimethyl-3-oxo-l-cyclohexenyl));

• JV-Metal Derivatives (JV-borane derivatives, JV-diphenylborinic acid derivatives, JV- [phenyl(pentacarbonylchromium- or -tungsten)]carbenyl, JV-copper or JV-zinc chelate);

• N-N Derivatives: (JV-nitro, JV-nitroso, JV-oxide);

• N-P Derivatives: (JV-diphenylphosphinyl, JV-dimethylthiophosphinyl, JV- diphenylthiophosphinyl, iV-dialkyl phosphoryl, JV-dibenzyl phosphoryl, JV-diphenyl phosphoryl);

• N-Si Derivatives, N-S Derivatives, and N-Sulfenyl Derivatives: (iV-benzenesulfenyl, JV-o-nitrobenzenesulfenyl, 7V-2,4-dinitrobenzenesulfenyl, N- pentachlorobenzenesulfenyl, iV-2-nitro-4-methoxybenzenesulfenyl, JV- triphenylmethylsulfenyl, JV-3-nitropyridinesulfenyl); and JV-sulfonyl Derivatives (JV- /?-toluenesulfony 1, JV-benzenesulfonyl, JV-2,3 ,6-trimethyl-4-methoxybenzenesulfonyl, JV-2,4,6-trimethoxybenzenesulfonyl, N-2,6-dimethyl-4-methoxybenzenesulfonyl, JV- pentamethylbenzenesulfonyl, JV-2,3 ,5 ,6,-tetramethyl-4-methoxybenzenesulfonyl, JV- 4-methoxybenzenesulfonyl, JV-2,4,6-trimethylbenzenesulfonyl, JV-2,6-dimethoxy-4- methylbenzenesulfonyl, JV-2,2,5,7,8-pentamethylchroman-6-sulfonyl, JV- methanesulfonyl, JV-β-trimethylsilyethanesulfonyl, JV-9-anthracenesulfonyl, JV-4- (4',8'-dimethoxynaphthylmethyl)benzenesulfonyl, JV-benzylsulfonyl, JV- trifluoromethylsulfonyl, JV-phenacylsulfonyl).

[0115] Protected amino groups include carbamates, amides and amidines, e.g. -NHC(O)OR ¹ , -NHC(O)R ¹ or -N=CR ¹ N(R ¹ ^. Another protecting group, also useful as a prodrug for amino or -NH(R ⁵ ), is:

See for example Alexander, J. et al (1996) J. Med. Chem. 39:480-486, herein incorporated by reference in its entirety.

Amino acid and polypeptide protecting group and conjugates [0116] An amino acid or polypeptide protecting group of a compound of the embodiments has the structure R ¹⁵ NHCH(R ¹⁶ )C(O)-, where R ¹⁵ is H, an amino acid or polypeptide residue, or R ⁵ , and R ¹⁶ is defined below. [0117] R ¹⁶ is lower alkyl or lower alkyl (Ci-C ₆ ) substituted with amino, carboxyl, amide, carboxyl ester, hydroxyl, C ₆ -C ₇ aryl, guanidinyl, imidazolyl, indolyl, sulfhydryl, sulfoxide, and/or alkylphosphate. R ¹⁶ also is taken together with the amino acid α-N to form a proline residue (R ¹⁶ = -CH ₂ )3-). However, R ¹⁶ is generally the side group of a naturally-occurring amino acid such as H, -CH3, - CH(CH ₃ ) ₂ , -CH ₂ -CH(CH ₃ ) ₂ , -CHCH ₃ -CH ₂ -CH ₃ , -CH ₂ -C ₆ H ₅ , -CH ₂ CH ₂ -S-CH ₃ , -CH ₂ OH, -CH(OH)-CH ₃ , -CH ₂ -SH, -CH ₂ -C ₆ H ₄ OH, -CH ₂ -CO-NH ₂ , -CH ₂ -CH ₂ - CO-NH ₂ , -CH ₂ -COOH, -CH ₂ -CH ₂ -COOH, -(CH ₂ ) ₄ -NH ₂ and -(CH ₂ ) ₃ -NH- C(NH ₂ )-NH ₂ . R ¹⁶ also includes l-guanidinoprop-3-yl, benzyl, 4-hydroxybenzyl, imidazol-4-yl, indol-3-yl, methoxyphenyl and ethoxyphenyl. [0118] Another set of protecting groups include the residue of an amino- containing compound, in particular an amino acid, a polypeptide, a protecting group, -NHSO2R, NHC(O)R, -N(R)2, NH2 or -NH(R)(H), whereby for example a carboxylic acid is reacted, i.e. coupled, with the amine to form an amide, as in C(O)NR ₂ . A phosphonic acid may be reacted with the amine to form a phosphonamidate, as in -P(O)(OR)(NR ₂ ).

[Ol 19] Amino acids have the structure R ¹⁷ C(O)CH(R ¹⁶ )NH-, where R ¹⁷ is -OH, -OR, an amino acid or a polypeptide residue. Amino acids are low molecular weight compounds, on the order of less than about 1000 MW and which contain at least one amino or imino group and at least one carboxyl group. Generally the amino acids will be found in nature, i.e., can be detected in biological material such as bacteria or other microbes, plants, animals or man. Suitable amino acids typically are alpha amino acids, i.e. compounds characterized by one amino or imino nitrogen atom separated from the carbon atom of one carboxyl group by a single substituted or unsubstituted alpha carbon atom. Of particular interest are hydrophobic residues such as mono-or di-alkyl or aryl amino acids, cycloalkylamino acids and the like. These residues contribute to cell permeability by increasing the partition coefficient of the parental drug. In some instances, the residue does not contain a sulfhydryl or guanidino substituent.

[0120] Naturally-occurring amino acid residues are those residues found naturally in plants, animals or microbes, especially proteins thereof. Polypeptides most typically will be substantially composed of such naturally-occurring amino acid residues. These amino acids are glycine, alanine, valine, leucine, isoleucine, serine, threonine, cysteine, methionine, glutamic acid, aspartic acid, lysine, hydroxylysine, arginine, histidine, phenylalanine, tyrosine, tryptophan, proline, asparagine, glutamine and hydroxyproline. Additionally, non-natural amino acids, for example, valanine, phenylglycine and homoarginine are also included. Commonly encountered amino acids that are not gene-encoded may also be used in the present embodiments. All of the amino acids used in the present embodiments may be either the D- or L- optical isomer. In addition, other peptidomimetics are also useful in the present embodiments. For a general review, see Spatola, A. F., in Chemistry and Biochemistry of Amino Acids, Peptides and Proteins, B. Weinstein, eds., Marcel Dekker, New York, p. 267 (1983), herein incorporated by reference in its entirety.

[0121] When protecting groups are single amino acid residues or polypeptides they optionally are substituted at R ³ of substituents A ¹ , A ² or A ³ in Formula I, or substituted at R ₃ of substituents Ai, A ₂ or A ₃ in Formula II. These conjugates are generally produced by forming an amide bond between a carboxyl group of the amino acid (or C-terminal amino acid of a polypeptide for example). Alternatively, conjugates are formed between R ³ (Formula I) or R ₃ (Formula II) and an amino group of an amino acid or polypeptide. Generally, only one of any site in the scaffold drug-like compound is amidated with an amino acid as described herein, although it is within the scope of the embodiments to introduce amino acids at more than one permitted site. Usually, a carboxyl group of R ³ is amidated with an amino acid. In general, the α-amino or α-carboxyl group of the amino acid or the terminal amino or carboxyl group of a polypeptide are bonded to the scaffold, parental functionalities. Carboxyl or amino groups in the amino acid side chains generally may be used to form the amide bonds with the parental compound or these groups may need to be protected during synthesis of the conjugates as described further below.

[0122] With respect to the carboxyl-containing side chains of amino acids or polypeptides it will be understood that the carboxyl group optionally will be

blocked, e.g. by R ¹ , esterified with R ⁵ or amidated. Similarly, the amino side chains R ¹⁶ optionally will be blocked with R ¹ or substituted with R ⁵ . [0123] Such ester or amide bonds with side chain amino or carboxyl groups, like the esters or amides with the parental molecule, optionally are hydrolyzable in vivo or in vitro under acidic (about pH <3) or basic (about pH >10) conditions. Alternatively, they are substantially stable in the gastrointestinal tract of humans but are hydrolyzed enzymatically in blood or in intracellular environments. The esters or amino acid or polypeptide amidates also are useful as intermediates for the preparation of the parental molecule containing free amino or carboxyl groups. The free acid or base of the parental compound, for example, is readily formed from the esters or amino acid or polypeptide conjugates of the embodiments by conventional hydrolysis procedures.

[0124] When an amino acid residue contains one or more chiral centers, any of the D, L, meso, threo, or erythro (as appropriate) racemates, scalemates or mixtures thereof may be used. In general, if the intermediates are to be hydrolyzed non-enzymatically (as would be the case where the amides are used as chemical intermediates for the free acids or free amines), D isomers are useful. On the other hand, L isomers are more versatile since they can be susceptible to both non-enzymatic and enzymatic hydrolysis, and are more efficiently transported by amino acid or dipeptidyl transport systems in the gastrointestinal tract.

[0125] Examples of suitable amino acids whose residues are represented by R ^x or R ^y include the following:

Glycine;

Aminopolycarboxylic acids, e.g., aspartic acid, β-hydroxyaspartic acid, glutamic acid, β -hydroxyglutamic acid, β-methylaspartic acid, β-methylglutamic acid, β, β- dimethylaspartic acid, γ-hydroxyglutamic acid, β, γ-dihydroxyglutamic acid, β - phenylglutamic acid, γ-methyleneglutamic acid, 3-aminoadipic acid, 2-aminopimelic acid, 2-aminosuberic acid, and 2-aminosebacic acid;

Amino acid amides, such as glutamine and asparagine;

Polyamino- or polybasic-monocarboxylic acids such as arginine, lysine, β - aminoalanine, γ -aminobutyrine, ornithine, citruline, homoarginine, homocitrulline, hydroxylysine, allohydroxylsine, and diaminobutyric acid;

Other basic amino acid residues, such as histidine;

Diaminodicarboxylic acids such as α, α'-diaminosuccinic acid, α, α'- diaminoglutaric acid, α, α'-diaminoadipic acid, α, α'-diaminopimelic acid, α, α'-diamino- β-hydroxypimelic acid, α, α'-diaminosuberic acid, α, α'-diaminoazelaic acid, and α, α'- diaminosebacic acid;

Imino acids such as proline, hydroxyproline, allohydroxyproline, γ- methylproline, pipecolic acid, 5-hydroxypipecolic acid, and azetidine-2-carboxylic acid;

A mono- or di-alkyl (typically Ci-Cs branched or normal) amino acid such as alanine, valine, leucine, allylglycine, butyrine, norvaline, norleucine, heptyline, α- methylserine, α-amino-α-methyl-γ-hydroxyvaleric acid, α-amino- α-methyl-δ- hydroxyvaleric acid, α-amino- α-methyl-ε-hydroxycaproic acid, isovaline, α- methylglutamic acid, α-aminoisobutyric acid, α-aminodiethylacetic acid, α- aminodiisopropylacetic acid, α-aminodi-n-propylacetic acid, α-aminodiisobutylacetic acid, α-aminodi-n-butylacetic acid, α-aminoethylisopropylacetic acid, α-amino-n- propylacetic acid, α-aminodiisoamyacetic acid, α-methylaspartic acid, α-methylglutamic acid, 1-aminocyclopropane-l-carboxylic acid, iso leucine, alloiso leucine, tert-leucine, β- methyltryptophan and α-amino- β-ethyl-β-phenylpropionic acid; β-phenylserinyl;

Aliphatic α-amino-β-hydroxy acids such as serine, β-hydroxyleucine, β- hydroxynorleucine, β -hydroxynorvaline, and α-amino-β-hydroxystearic acid; α-Amino, α-, γ-, δ- or ε-hydroxy acids such as homoserine, δ -hydroxynorvaline, γ-hydroxynorvaline and ε-hydroxynorleucine residues; canavine and canaline; γ - hydroxyornithine;

2-hexosaminic acids such as D-glucosaminic acid or D-galactosaminic acid; α-Amino-β-thiols such as penicillamine, β-thiolnorvaline or β-thiolbutyrine;

Other sulfur containing amino acid residues including cysteine; homocystine, β- phenylmethionine, methionine, S-allyl-L-cysteine sulfoxide, 2-thiolhistidine, cystathionine, and thiol ethers of cysteine or homocysteine;

Phenylalanine, tryptophan and ring-substituted α-amino acids such as the phenyl- or cyclohexylamino acids α-aminophenylacetic acid, α-aminocyclohexylacetic acid and α-amino-β-cyclohexylpropionic acid; phenylalanine analogues and derivatives comprising aryl, lower alkyl, hydroxy, guanidino, oxyalkylether, nitro, sulfur or halo- substituted phenyl (e.g., tyrosine, methyltyrosine and o-chloro-, p-chloro-, 3,4-dichloro,

O- ^■ , w- or/7-methyl-, 2,4,6-trimethyl-, 2-ethoxy-5-nitro-, 2-hydroxy-5-nitro- and p-nitro- phenylalanine); furyl-, thienyl-, pyridyl-, pyrimidinyl-, purinyl- or naphthyl-alanines; and tryptophan analogues and derivatives including kynurenine, 3-hydroxykynurenine, 2- hydroxytryptophan and 4-carboxytryptophan; α-Amino substituted amino acids including sarcosine (N-methylglycine), N- benzylglycine, N-methylalanine, N-benzylalanine, N-methylphenylalanine, N- benzylphenylalanine, N-methyl valine and N-benzyl valine; and α-Hydroxy and substituted α -hydroxy amino acids including serine, threonine, allothreonine, phosphoserine and phosphothreonine.

[0126] Polypeptides are polymers of amino acids in which a carboxyl group of one amino acid monomer is bonded to an amino or imino group of the next amino acid monomer by an amide bond. Polypeptides include dipeptides, low molecular weight polypeptides (about 1500-5000 MW) and proteins. Proteins optionally contain about 3, 5, 10, 50, 75, 100 or more residues, and suitably are substantially sequence-homologous with human, animal, plant or microbial proteins. They include enzymes (e.g., hydrogen peroxidase) as well as immunogens such as KLH, or antibodies or proteins of any type against which one wishes to raise an immune response. The nature and identity of the polypeptide may vary widely.

[0127] The polypeptide amidates are useful as immunogens in raising antibodies against either the polypeptide (if it is not immunogenic in the animal to which it is administered) or against the epitopes on the remainder of the compound of the embodiments.

[0128] Antibodies capable of binding to the parental non-peptidyl compound are used to separate the parental compound from mixtures, for example in diagnosis or manufacturing of the parental compound. The conjugates of parental compound and polypeptide generally are more immunogenic than the polypeptides in closely homologous animals, and therefore make the polypeptide more immunogenic for facilitating raising antibodies against it. Accordingly, the polypeptide or protein may be immunogenic in an animal typically used to raise antibodies, e.g., rabbit, mouse, horse, or rat. The polypeptide optionally contains a peptidolytic enzyme cleavage site at the peptide bond between the first and second residues adjacent to the acidic heteroatom. Such cleavage sites are

flanked by enzymatic recognition structures, e.g. a particular sequence of residues recognized by a peptidolytic enzyme.

[0129] Peptidolytic enzymes for cleaving the polypeptide conjugates of the embodiments are well known, and in particular include carboxypeptidases, which digest polypeptides by removing C-terminal residues, and are specific in many instances for particular C-terminal sequences. Such enzymes and their substrate requirements in general are well known. For example, a dipeptide (having a given pair of residues and a free carboxyl terminus) is covalently bonded through its α-amino group to the phosphorus or carbon atoms of the compounds herein. In certain embodiments, a phosphonate group substituted with an amino acid or peptide will be cleaved by the appropriate peptidolytic enzyme, leaving the carboxyl of the proximal amino acid residue to autocatalytically cleave the phosphonoamidate bond.

[0130] Suitable dipeptidyl groups (designated by their single letter code) are AA, AR, AN, AD, AC, AE, AQ, AG, AH, AI, AL, AK, AM, AF, AP, AS, AT, AW, AY, AV, RA, RR, RN, RD, RC, RE, RQ, RG, RH, RI, RL, RK, RM, RF, RP, RS, RT, RW, RY, RV, NA, NR, NN, ND, NC, NE, NQ, NG, NH, NI, NL, NK, NM, NF, NP, NS, NT, NW, NY, NV, DA, DR, DN, DD, DC, DE, DQ, DG, DH, DI, DL, DK, DM, DF, DP, DS, DT, DW, DY, DV, CA, CR, CN, CD, CC, CE, CQ, CG, CH, CI, CL, CK, CM, CF, CP, CS, CT, CW, CY, CV, EA, ER, EN, ED, EC, EE, EQ, EG, EH, EI, EL, EK, EM, EF, EP, ES, ET, EW, EY, EV, QA, QR, QN, QD, QC, QE, QQ, QG, QH, QI, QL, QK, QM, QF, QP, QS, QT, QW, QY, QV, GA, GR, GN, GD, GC, GE, GQ, GG, GH, GI, GL, GK, GM, GF, GP, GS, GT, GW, GY, GV, HA, HR, HN, HD, HC, HE, HQ, HG, HH, HI, HL, HK, HM, HF, HP, HS, HT, HW, HY, HV, IA, IR, IN, ID, IC, IE, IQ, IG, IH, II, IL, IK, IM, IF, IP, IS, IT, IW, IY, IV, LA, LR, LN, LD, LC, LE, LQ, LG, LH, LI, LL, LK, LM, LF, LP, LS, LT, LW, LY, LV, KA, KR, KN, KD, KC, KE, KQ, KG, KH, KI, KL, KK, KM, KF, KP, KS, KT, KW, KY, KV, MA, MR, MN, MD, MC, ME, MQ, MG, MH, MI, ML, MK, MM, MF, MP, MS, MT, MW, MY, MV, FA, FR, FN, FD, FC, FE, FQ, FG, FH, FI, FL, FK, FM, FF, FP, FS, FT, FW, FY, FV, PA, PR, PN, PD, PC, PE, PQ, PG, PH, PI, PL, PK, PM, PF, PP, PS, PT, PW, PY, PV, SA, SR, SN, SD, SC, SE, SQ, SG, SH, SI, SL, SK, SM, SF, SP, SS, ST, SW, SY, SV, TA, TR, TN, TD, TC, TE, TQ, TG, TH, TI, TL, TK, TM, TF, TP,

TS, TT, TW, TY, TV, WA, WR, WN, WD, WC, WE, WQ, WG, WH, WI, WL, WK, WM, WF, WP, WS, WT, WW, WY, WV, YA, YR, YN, YD, YC, YE, YQ, YG, YH, YI, YL, YK, YM, YF, YP, YS, YT, YW, YY, YV, VA, VR, VN, VD, VC, VE, VQ, VG, VH, VI, VL, VK, VM, VF, VP, VS, VT, VW, VY, and VV. [0131] Tripeptide residues are also useful as protecting groups. When a phosphonate is to be protected, the sequence -X ⁴ -pro-X ⁵ - (where X ⁴ is any amino acid residue and X ⁵ is an amino acid residue, a carboxyl ester of proline, or hydrogen) will be cleaved by luminal carboxypeptidase to yield X ⁴ with a free carboxyl, which in turn is expected to autocatalytically cleave the phosphonoamidate bond. The carboxy group of X ⁵ optionally is esterified with benzyl.

[0132] Dipeptide or tripeptide species can be selected on the basis of known transport properties and/or susceptibility to peptidases that can affect transport to intestinal mucosal or other cell types. Dipeptides and tripeptides lacking an α- amino group are transport substrates for the peptide transporter found in brush border membrane of intestinal mucosal cells (Bai, J.P.F., (1992) Pharm Res. 9:969-978. Transport competent peptides can thus be used to enhance bioavailability of the amidate compounds. Di- or tripeptides having one or more amino acids in the D configuration may be compatible with peptide transport. Amino acids in the D configuration can be used to reduce the susceptibility of a di- or tripeptide to hydrolysis by proteases common to the brush border such as aminopeptidase N. In addition, di- or tripeptides alternatively are selected on the basis of their relative resistance to hydrolysis by proteases found in the lumen of the intestine. For example, tripeptides or polypeptides lacking asp and/or glu are poor substrates for aminopeptidase A, di- or tripeptides lacking amino acid residues on the N-terminal side of hydrophobic amino acids (leu, tyr, phe, val, trp) are poor substrates for endopeptidase, and peptides lacking a pro residue at the penultimate position at a free carboxyl terminus are poor substrates for carboxypeptidase P. Similar considerations can also be applied to the selection of peptides that are either relatively resistant or relatively susceptible to hydrolysis by cytosolic, renal, hepatic, serum or other peptidases. Such poorly cleaved polypeptide amidates are immunogens or are useful for bonding to proteins in order to prepare immunogens.

Recursive Substituents

[0133] Selected substituents within the compounds of the embodiments are present to a recursive degree. In this context, "recursive substituent" means that a substituent may recite another instance of itself. Because of the recursive nature of such substituents, theoretically, a large number of compounds may be present in any given embodiment. For example, R ^x contains a R ^y substituent. R ^y can be R ² , which in turn can be R ³ . IfR ³ is selected to be R ^3c , then a second instance of R ^x can be selected. One of ordinary skill in the art of medicinal chemistry understands that the total number of such substituents is reasonably limited by the desired properties of the compound intended. Such properties include, by of example and not limitation, physical properties such as molecular weight, solubility or log P, application properties such as activity against the intended target, and practical properties such as ease of synthesis. [0134] By way of example and not limitation, W ³ , R ^y and R ³ are all recursive substituents in certain embodiments. Typically, each of these may independently occur about 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0, times in a given embodiment. More typically, each of these may independently occur about 12 or fewer times in a given embodiment. More typically yet, W ³ will occur about 0 to 8 times, R ^y will occur about 0 to 6 times and R will occur about 0 to 10 times in a given embodiment. Even more typically, W ³ will occur about 0 to 6 times, R ^y will occur about 0 to 4 times and R ³ will occur about 0 to 8 times in a given embodiment.

[0135] Recursive substituents are an intended aspect of the embodiments. One of ordinary skill in the art of medicinal chemistry understands the versatility of such substituents. To the degree that recursive substituents are present in an embodiment, the total number will be determined as set forth above.

Preferred Embodiments:

[0136] In one embodiment Y ² is Y ^2a , wherein Y ^2a is O, N(R") or S. In another embodiment Y ² is Y ^2b , wherein Y ^2b is O or N(R ^X ). In another embodiment Y ² is Y ^2c , wherein Y ^2c is O, N(R ^y ) or S. In another embodiment Y ² is Y ^2d where Y ^2d is O or N(R ^y ). In another embodiment Y ² is a bond. In another embodiment Y ² is O. In another embodiment Y ² is -N(H)-.

[0137] In one embodiment Y ¹ is Y ^la wherein Y ^la is O or S. In another embodiment Y ¹ is O.

[0138] In one embodiment R ^y is R ² .

[0139] In one embodiment R is H. In another embodiment R is R .

[0140] In one embodiment R ¹ is H.

[0141] In one embodiment ml 2a is 1. In another embodiment ml 2a is ml2d, wherein ml 2d is 1, 2, 3, 4, 5, 6, 7, or 8. In another embodiment ml 2d is 1.

[0142] In one embodiment ml 2b is 1. In one embodiment ml 2b is 0.

[0143] In one embodiment m2 is 0.

[0144] In one embodiment W ⁶ is W ³ -A ³ .

[0145] In one embodiment W ³ is W ⁵ . In another embodiment W ³ is W ^5a . In another embodiment W ³ is W ⁴ .

[0146] In one embodiment W ⁵ is W ^5a , wherein W ^5a is a carbocycle independently substituted with 0 or 1 R ² groups. In one embodiment W ⁵ is W ⁵ , wherein W ^5b is a carbocycle or heterocycle optionally substituted with 1 , 2, or 3

R ² groups.

[0147] The W ⁵ , W ^5a and W ^5b carbocycles and W ⁵ , W ^5a and W ^5b heterocycles may be a saturated, an unsaturated or an aromatic ring comprising a mono- or bicyclic carbocycle or heterocycle. W ⁵ , W ^5a and W ^5b may have 3 to 10 ring atoms, e.g., 3 to 7 ring atoms. The W ⁵ , W ^5a and W ⁵ rings are saturated when containing 3 ring atoms, saturated or mono-unsaturated when containing 4 ring atoms, saturated, or mono- or di-unsaturated when containing 5 ring atoms, and saturated, mono- or di-unsaturated, or aromatic when containing 6 ring atoms.

[0148] A W ⁵ , W ^5a or W ^5b heterocycle may be a monocycle having 3 to 7 ring members (2 to 6 carbon atoms and 1 to 3 heteroatoms selected from N, O, P, and

S) or a bicycle having 7 to 10 ring members (4 to 9 carbon atoms and 1 to 3 heteroatoms selected from N, O, P, and S). W ⁵ , W ^5a and W ^5b heterocyclic monocycles may have 3 to 6 ring atoms (2 to 5 carbon atoms and 1 to 2 heteroatoms selected from N, O, and S); or 5 or 6 ring atoms (3 to 5 carbon atoms. and 1 to 2 heteroatoms selected from N and S). W ⁵ , W ^5a and W ^5b heterocyclic bicycles have 7 to 10 ring atoms (6 to 9 carbon atoms and 1 to 2 heteroatoms selected from N, O, and S) arranged as a bicyclo [4,5], [5,5], [5,6], or [6,6] system; or 9 to 10 ring atoms (8 to 9 carbon atoms and 1 to 2 hetero atoms

selected from N and S) arranged as a bicyclo [5,6] or [6,6] system. The W ⁵ , W ^5a and W ^5b heterocycle may be bonded to Y ² through a carbon, nitrogen, sulfur or other atom by a stable covalent bond.

[0149] The W ⁵ , W ^5a and W ^5b heterocycles include for example, pyridyl, dihydropyridyl isomers, piperidine, pyridazinyl, pyrimidinyl, pyrazinyl, s- triazinyl, oxazolyl, imidazolyl, thiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, furanyl, thiofuranyl, thienyl, and pyrrolyl. W ⁵ , W ^5a and W ^5b also include, but are not limited to, examples such as:

0150] Substituted W ⁵ carbocycles include, for example:

[0151] In one embodiment each A ⁰ is independently selected from A ¹ , A ² or W ³ wwiitthh tthhee pprroovviissoo tthhaatt tthhee ccoommppound of formula I includes at least one A ¹ ; In another embodiment A ⁰ is A ¹ .

[0152] In one embodiment, A is of the formula:

⁶

where W ⁶ is W ³ -A ³ . In another embodiment of A ¹ having the formula above, W ⁶ is W ³ -A ³ and at least one Y ² is a bond. In another embodiment W ⁶ is W ³ -A ³ , each Y ² is a bond and ml 2a is 1. In another embodiment of A ¹ having the formula above, W ⁶ is W ^5a -A ³ , each Y ² is a bond and ml 2b is 1. In another embodiment of A ¹ having the formula above W ⁶ is W ^5a -A ³ , each Y ² is a bond and ml 2a and ml 2b are 1.

[0153] In one embodiment, A 2 is of the formula:

*

wherein W is W ⁵ . In another embodiment of A ² having the formula above, W ³ is W ⁵ and at least one Y is a bond. In another embodiment of A ² having the formula above,

W ³ is W ⁵ and at least one Y ² is a bond and m 12b is 1. In another embodiment of A ² having the formula above, W ³ is W ⁵ and each Y ² is a bond. In another embodiment of A ² having the formula above, W ³ is W ^5b , each Y ² is a bond and ml 2b is 0. In another embodiment of A ² having the formula above, W ³ is W ^5b , each Y ² is a bond, ml 2b is 1, and ml 2a is 1. In another embodiment of A ² having the formula above, W ³ is W ⁴ . In another embodiment of A ² having the formula above, W ³ is W ⁴ and at least one Y ² is a bond. In another embodiment of A ² having the formula above W ³ is W ⁴ and at least one

Y ² is a bond and ml 2b is 1.

[0154] In another embodiment, A ² is selected from phenyl, substituted phenyl, benzyl, substituted benzyl, pyridinyl and substituted pyridinyl.

[0155] Embodiments of A ³ include phenyl phosphonamidate amino acid, e.g. alanate esters and phenyl phosphonate-lactate esters. The chiral carbon of the amino acid and lactate moieties may be either the R or S configuration or the racemic mixture.

[0156] In one embodiment, A ³ is of the formula:

wherein m2 is 0. In another embodiment of A having the formula above m2 is 0 and ml 2b is 1. In another embodiment of A ³ having the formula above m2 and ml 2b are ( and Y ¹ is Y ^la , and Y ² is Y ^2a , where Y ^la and Y ^2a are defined above.

[0157] In one embodiment, A ³ is of the formula:

In another embodiment of A ³ having the formula above, Y ^2b is O and ml 2a is 1. In another embodiment of A ³ having the formula above ml 2a is ml2d, wherein ml2d is defined as above. In another embodiment of A ³ having the formula above ml 2a is ml2d and R ² is H. In another embodiment of A ³ having the formula above ml 2a is 1, and R ² is

H.

[0158] In one embodiment, A is of the formula:

In another embodiment A is of the formula above wherein W is W . In another

"X "X embodiment A is of the formula above wherein ml 2b is 1. In another embodiment A is of the formula above wherein ml 2b is 1 Y ¹ is Y ^la and Y ² is Y ^2a as defined above. In another embodiment A ³ is of the formula above wherein ml 2b is 1 Y is O and Y is Y ^a . [0159] In another embodiment, A ³ is of the formula:

In another embodiment A ³ is of the formula above, wherein R ² is R ¹ and ml 2a is ml2d. In another embodiment of A ³ having the formula above, R ² is H and ml 2a is ml2d. In another embodiment A ³ is of the formula above, wherein R ² is R ¹ and ml 2a is ml2d.

[0160] In another embodiment A ³ is of the formula:

In another embodiment of A ³ having the formula above, ml2d is 1, 2, 3, 4, 5, 6, 7 or 8 and R ¹ is H. In another embodiment of A ³ having the formula above, ml2d is 1. [0161] In another embodiment A ³ is of the formula:

[0162] In another embodiment A ³ is of the formula:

In another embodiment of A ³ having the formula above there are zero R ² substituents on the phenoxy group.

[0163] In one embodiment A ³ is of the formula:

In another embodiment of A ³ having the formula above, W ⁵ is phenyl.

[0164] Not withstanding other disclosure herein which describes the role or presence of phosphonates in the compounds of the embodiments, in another embodiment, A ³ is A ^3a which is of the formula:

In this embodiment, any A ³ group may be A ^3a .

[0165] In another aspect of the embodiments, A ³ is of the formula:

ml 2a is other than 0 and at least one phosphonate group present in the compound is not bonded directly to W ³ . More typically, the phosphonate is not bonded directly to W ⁵ . In such an embodiment, the phosphorous atom of the phosphonate is not bonded directly to a carbon atom of a ring.

[0166] Embodiments of R ^x include esters, carbamates, carbonates, thioesters, amides, thioamides, and urea groups. In one embodiment R ^x is of the formula:

In another embodiment of R* having the formula above, one R ² is H, ml 2a is 1, Y ¹ is Y ^la , and Y ² is Y ^2c , wherein Y ^la and Y ^2c are as defined above. In another embodiment of R ^x having the formula above, one R ² is H, ml 2a is 1, Y ¹ is Y ^la , and Y ² is Y ^2d , wherein Y ^2d is as defined above. In another embodiment of R ^x having the formula above, one R ² is H, ml 2a is 1, Y ¹ is O, and Y ² is O. In another embodiment of R ^x having the formula above, one R ² is H, ml 2a is 1, Y ¹ is O, Y ² is O, and R ^y is R ² .

[0167] In another embodiment R ^x is of the formula:

[0168] In one embodiment, A ³ is of the formula:

and R ^x is of the formula:

[0169] In one embodiment, A 3 is of the formula:

and R ^x is of the formula:

[0170] In one embodiment, A 3 is of the formula:

and R ^x is of the formula:

[0171] In one embodiment, A ³ is of the formula:

and R ^x is of the formula:

In another embodiment, where A ³ and R ^x are of the formulae shown above, in A ³ ml 2a

[0172] In one embodiment, A ³ is of the formula:

and R ^x is of the formula:

In another embodiment, where A and R ^x are of the formulae shown above, in A ml2d is 1, and R ^y is R ² . In another embodiment, where A ³ and R ^x are of the formulae shown above, A ³ is of the formula:

[0173] In one embodiment, A is of the formula:

and R ^x is of the formula:

In another embodiment, where A ³ and R ^x are of the formulae shown above, A ³ is of the formula:

In another embodiment, where A ³ and R ^x are of the formulae shown above, A ³ is of the formula:

In another embodiment, where A and R ^x are of the formulae shown above, A is of the formula:

In another embodiment, where A ³ and R ^x are of the formulae shown above, A ³ is of the formula:

In another embodiment, where A ³ and R ^x are of the formulae shown above, A is of the formula:

[0174] In one embodiment, A ¹ is of the formula:

and A is of the formula:

[0175] In another embodiment, A ¹ is of the formula:

A is of the formula:

and R ^x is of the formula:

In another embodiment, where A ¹ , A ³ and R ^x are of the formulae shown above, A ¹ is of the formula:

and A ³ is of the formula:

In another embodiment, where A ¹ , A ³ and R ^x are of the formulae shown above, A ¹ is of the formula:

and A ³ is of the formula:

In another embodiment, where A ¹ , A ³ and R ^x are of the formulae shown above, A ¹ is of the formula:

and A is of the formula:

[0176] In one embodiment, at least one A is of the formula:

[0177] In one embodiment, at least one A ⁰ is of the formula:

[0178] In one embodiment, A ¹ is of the formula:

and A ³ is of the formula:

³

[0179] In another embodiment, A is of the formula:

and A is of the formula:

and R ^x is of the formula:

In another embodiment, where A ¹ , A ³ and R ^x are of the formulae shown above, A ¹ is of the formula:

and A ³ is of the formula:

In another embodiment, where A , A ³ and R ^x are of the formulae shown above, A ¹ is of the formula:

and A is of the formula:

In another embodiment, where A ¹ , A ³ and R ^x are of the formulae shown above, A ³ is of the formula:

In another embodiment, where A ¹ , A ³ and R ^x are of the formulae shown above, A ¹ is of the formula:

and A ³ is of the formula:

In another embodiment of A ³ shown above, Y ^2b is O and W ³ is phenyl.

In another embodiment, where A ¹ , A ³ and R ^x are of the formulae shown above, A ³ is of the formula:

In another embodiment, where A , A and R ^x are of the formulae shown above, A is of the formula:

[0180] In one embodiment, at least one A ⁰ is of the formula:

Exemplary Enumerated Compounds.

[0181] By way of example and not limitation, embodiments are named below in tabular format (Table 100). These embodiments are of the general formula

"MBF":

MBF

[0182] Each embodiment of MBF is depicted as a substituted nucleus (Sc) in which the nucleus is designated by a number and each substituent is designated in order by letter or number. Tables 1.1 to 1.2 are a schedule of nuclei used in forming the embodiments of Table 100. Each nucleus (Sc) is given a number designation from Tables 1.1 to 1.2 and this designation appears first in each embodiment name. Similarly, Tables 10.1 to 10.19 and 20.1 to 20.36 list the selected linking groups (Lg) and prodrug (Pd ¹ and Pd ² ) substituents, again by letter or number designation, respectively.

[0183] Accordingly, each named embodiment of Table 100 is depicted by a number designating the nucleus from Table 1.1-1.5, followed by a letter designating the linking group (Lg) from Table 10.1-10.19, and two numbers designating the two prodrug groups (Pd ¹ and Pd ² ) from Table 20.1-20.36. In graphical tabular form, each embodiment of Table 100 appears as a name having the syntax:

Thus, ignoring stereochemistry, structure 10, Scheme 2, Scheme Section A, is represented by 5.AB.247.247.

5.AB.247.247

[0184] Each Sc group is shown having a tilda ("-")• The tilda is the point of covalent attachment of Sc to Lg. Q ¹ and Q ² of the linking groups (Lg), it should be understood, do not represent groups or atoms but are simply connectivity designations. Q ¹ is the site of the covalent bond to the nucleus (Sc) and Q ² is the site of the covalent bond to the phosphorous atom of formula MBF. Each prodrug group (Pd ¹ and Pd ² ) are covalently bonded to the phosphorous atom of

MBF at the tilda symbol ("~"). Some embodiments of Tables 10.1-10.19 and 20.1-20.36 may be designated as a combination of letters and numbers (Table 10.1 - 10.19) or number and letter (Table 20.1 -20.36). For example there are Table 10 entries for BJl and BJ2. In any event, entries of Table 10.1-10.19 always begin with a letter and those of Table 20.1-20.36 always begin with a number. When a nucleus (Sc) is shown enclosed within square brackets ("[]") and a covalent bond extends outside the brackets, the point of covalent attachment of Sc to Lg may be at any substitutable site on SC. Selection of the point of attachment is described herein. By way of example and not limitation, the point of attachment is selected from those depicted in the schemes and examples.

AF

AG

Table 10.4 No table 10.4

Table 10.5

Table 10.6

BM

Table 10.7

BT

Table 10.9

CE

CG

Table 10.10

Table 10.11

Table 10.12

DD

Table 10.13

Table 10.15

Table 10.17

EN

Table 10.19

Table 20.1

Table 20.3

Table 20.4

Table 20.5

Table 20.6

Table 20.7

Table 20.8

Table 20.9

Table 20.10

Table 20.11

Table 20.12

Table 20.13

Table 20.14

Table 20.15

Table 20.16

Table 20.17

Table 20.18

Table 20.19

Table 20.20

Table 20.21

Table 20.22

Table 20.23

Table 20.24

Table 20.26

160 161 162

163 164 165

166 167 168

169 170 171

Table 20.27

172 173

174 175

176 177

179

Table 20.28

185

Table 20.29

186 187

188 189

190 191

193

Table 20.30

199

Table 20.31

200

201

202

203

207

206

Table 20.32

212

Table 20.33

214

215

216

221

220

Table 20.34

226

Table 20.36

240 241

242 243

Table 100

Prodrugs of l.B l.B.228.228; l.B.228.229; l.B.228.230; l.B.228.231; l.B.228.236; l.B.228.237; l.B.228.238; l.B.228.239; l.B.228.154; l.B.228.157; l.B.228.166; l.B.228.169; l.B.228.172; l.B.228.175; l.B.228.240; l.B.228.244; l.B.229.228; l.B.229.229; l.B.229.230; l.B.229.231; l.B.229.236; l.B.229.237; l.B.229.238; l.B.229.239; l.B.229.154; l.B.229.157; l.B.229.166; l.B.229.169; l.B.229.172; l.B.229.175; l.B.229.240; l.B.229.244; l.B.230.228; l.B.230.229; l.B.230.230; l.B.230.231; l.B.230.236; l.B.230.237; l.B.230.238; l.B.230.239; l.B.230.154; l.B.230.157; l.B.230.166; l.B.230.169; l.B.230.172; l.B.230.175; l.B.230.240; l.B.230.244; l.B.231.228; l.B.231.229; l.B.231.230; l.B.231.231; l.B.231.236; l.B.231.237; l.B.231.238; l.B.231.239; l.B.231.154; l.B.231.157; l.B.231.166; l.B.231.169; l.B.231.172; l.B.231.175; l.B.231.240; l.B.231.244; l.B.236.228; l.B.236.229; l.B.236.230; l.B.236.231; l.B.236.236; l.B.236.237; l.B.236.238; l.B.236.239; l.B.236.154; l.B.236.157; l.B.236.166; l.B.236.169; l.B.236.172; l.B.236.175; l.B.236.240; l.B.236.244; l.B.237.228; l.B.237.229; l.B.237.230; l.B.237.231; l.B.237.236; l.B.237.237; l.B.237.238; l.B.237.239; l.B.237.154; l.B.237.157; l.B.237.166; l.B.237.169; l.B.237.172; l.B.237.175; l.B.237.240; l.B.237.244; l.B.238.228; l.B.238.229; l.B.238.230; l.B.238.231; l.B.238.236; l.B.238.237; l.B.238.238; l.B.238.239; l.B.238.154; l.B.238.157; l.B.238.166; l.B.238.169; l.B.238.172; l.B.238.175; l.B.238.240; l.B.238.244; l.B.239.228; l.B.239.229; l.B.239.230; l.B.239.231; l.B.239.236; l.B.239.237; l.B.239.238; l.B.239.239; l.B.239.154; l.B.239.157; l.B.239.166; l.B.239.169; l.B.239.172; l.B.239.175; l.B.239.240; l.B.239.244; l.B.154.228; l.B.154.229; l.B.154.230; l.B.154.231; l.B.154.236; l.B.154.237; l.B.154.238; l.B.154.239; l.B.154.154; l.B.154.157; l.B.154.166; l.B.154.169; l.B.154.172; l.B.154.175; l.B.154.240; l.B.154.244; l.B.157.228; l.B.157.229; l.B.157.230; l.B.157.231; l.B.157.236; l.B.157.237; l.B.157.238; l.B.157.239; l.B.157.154; l.B.157.157; l.B.157.166; l.B.157.169; l.B.157.172; l.B.157.175; l.B.157.240; l.B.157.244; l.B.166.228; l.B.166.229; l.B.166.230; l.B.166.231; l.B.166.236; l.B.166.237; l.B.166.238; l.B.166.239; l.B.166.154; l.B.166.157; l.B.166.166; l.B.166.169; l.B.166.172; l.B.166.175; l.B.166.240; l.B.166.244; l.B.169.228; l.B.169.229; l.B.169.230; l.B.169.231; l.B.169.236; l.B.169.237; l.B.169.238; l.B.169.239; l.B.169.154; l.B.169.157; l.B.169.166; l.B.169.169; l.B.169.172; l.B.169.175; l.B.169.240; l.B.169.244; l.B.172.228; l.B.172.229; l.B.172.230; l.B.172.231; l.B.172.236; l.B.172.237; l.B.172.238; l.B.172.239; l.B.172.154; l.B.172.157; l.B.172.166; l.B.172.169; l.B.172.172; l.B.172.175; l.B.172.240; l.B.172.244; l.B.175.228; l.B.175.229; l.B.175.230; l.B.175.231; l.B.175.236; l.B.175.237; l.B.175.238; l.B.175.239; l.B.175.154; l.B.175.157; l.B.175.166; l.B.175.169; l.B.175.172; l.B.175.175; l.B.175.240; l.B.175.244; l.B.240.228; l.B.240.229; l.B.240.230; l.B.240.231; l.B.240.236; l.B.240.237; l.B.240.238; l.B.240.239; l.B.240.154; l.B.240.157; l.B.240.166; l.B.240.169; l.B.240.172; l.B.240.175; l.B.240.240; l.B.240.244; l.B.244.228; l.B.244.229; l.B.244.230; l.B.244.231; l.B.244.236; l.B.244.237; l.B.244.238; l.B.244.239; l.B.244.154; l.B.244.157; l.B.244.166; l.B.244.169; l.B.244.172; l.B.244.175; l.B.244.240; l.B.244.244;

Prodrugs of l.D l.D.228.228; l.D.228.229; l.D.228.230; l.D.228.231; l.D.228.236; l.D.228.237; l.D.228.238; l.D.228.239; l.D.228.154; l.D.228.157; l.D.228.166; l.D.228.169; l.D.228.172; l.D.228.175; l.D.228.240; l.D.228.244; l.D.229.228; l.D.229.229; l.D.229.230; l.D.229.231; l.D.229.236; l.D.229.237; l.D.229.238; l.D.229.239; l.D.229.154; l.D.229.157; l.D.229.166; l.D.229.169; l.D.229.172; l.D.229.175; l.D.229.240; l.D.229.244; l.D.230.228; l.D.230.229; l.D.230.230; l.D.230.231; l.D.230.236; l.D.230.237; l.D.230.238; l.D.230.239; l.D.230.154; l.D.230.157; l.D.230.166; l.D.230.169; l.D.230.172; l.D.230.175; l.D.230.240; l.D.230.244; l.D.231.228; l.D.231.229; l.D.231.230; l.D.231.231; l.D.231.236; l.D.231.237; l.D.231.238; l.D.231.239; l.D.231.154; l.D.231.157; l.D.231.166; l.D.231.169; l.D.231.172; l.D.231.175; l.D.231.240; l.D.231.244; l.D.236.228; l.D.236.229; l.D.236.230; l.D.236.231; l.D.236.236; l.D.236.237; l.D.236.238; l.D.236.239; l.D.236.154; l.D.236.157; l.D.236.166; l.D.236.169; l.D.236.172; l.D.236.175; l.D.236.240; l.D.236.244; l.D.237.228; l.D.237.229; l.D.237.230; l.D.237.231; l.D.237.236; l.D.237.237; l.D.237.238; l.D.237.239; l.D.237.154; l.D.237.157; l.D.237.166; l.D.237.169; l.D.237.172; l.D.237.175; l.D.237.240; l.D.237.244; l.D.238.228; l.D.238.229; l.D.238.230; l.D.238.231; l.D.238.236; l.D.238.237; l.D.238.238; l.D.238.239; l.D.238.154; l.D.238.157; l.D.238.166; l.D.238.169; l.D.238.172; l.D.238.175; l.D.238.240; l.D.238.244; l.D.239.228; l.D.239.229; l.D.239.230; l.D.239.231; l.D.239.236; l.D.239.237; l.D.239.238; l.D.239.239; l.D.239.154; l.D.239.157; l.D.239.166; l.D.239.169; l.D.239.172; l.D.239.175; l.D.239.240; l.D.239.244; l.D.154.228; l.D.154.229; l.D.154.230; l.D.154.231; l.D.154.236; l.D.154.237; l.D.154.238; l.D.154.239; l.D.154.154; l.D.154.157; l.D.154.166; l.D.154.169; l.D.154.172; l.D.154.175; l.D.154.240; l.D.154.244; l.D.157.228; l.D.157.229; l.D.157.230; l.D.157.231; l.D.157.236; l.D.157.237; l.D.157.238; l.D.157.239; l.D.157.154; l.D.157.157; l.D.157.166; l.D.157.169; l.D.157.172; l.D.157.175; l.D.157.240; l.D.157.244; l.D.166.228; l.D.166.229; l.D.166.230; l.D.166.231; l.D.166.236; l.D.166.237; l.D.166.238; l.D.166.239; l.D.166.154; l.D.166.157; l.D.166.166; l.D.166.169; l.D.166.172; l.D.166.175; l.D.166.240; l.D.166.244; l.D.169.228; l.D.169.229; l.D.169.230; l.D.169.231; l.D.169.236; l.D.169.237; l.D.169.238; l.D.169.239; l.D.169.154; l.D.169.157; l.D.169.166; l.D.169.169; l.D.169.172; l.D.169.175; l.D.169.240; l.D.169.244; l.D.172.228; l.D.172.229; l.D.172.230; l.D.172.231; l.D.172.236; l.D.172.237; l.D.172.238; l.D.172.239; l.D.172.154; l.D.172.157; l.D.172.166; l.D.172.169; l.D.172.172; l.D.172.175; l.D.172.240; l.D.172.244; l.D.175.228; l.D.175.229; l.D.175.230; l.D.175.231; l.D.175.236; l.D.175.237; l.D.175.238; l.D.175.239; l.D.175.154; l.D.175.157; l.D.175.166; l.D.175.169; l.D.175.172; l.D.175.175; l.D.175.240; l.D.175.244; l.D.240.228; l.D.240.229; l.D.240.230; l.D.240.231; l.D.240.236; l.D.240.237; l.D.240.238; l.D.240.239; l.D.240.154; l.D.240.157; l.D.240.166; l.D.240.169; l.D.240.172; l.D.240.175; l.D.240.240; l.D.240.244; l.D.244.228; l.D.244.229; l.D.244.230; l.D.244.231; l.D.244.236; l.D.244.237; l.D.244.238; l.D.244.239; l.D.244.154; l.D.244.157; l.D.244.166; l.D.244.169; l.D.244.172; l.D.244.175; l.D.244.240; l.D.244.244;

Prodrugs of l.AB l.AB.228.228; l.AB.228.229; l.AB.228.230; l.AB.228.231; l.AB.228.236; l.AB.228.237; l.AB.228.238; l.AB.228.239; l.AB.228.154; l.AB.228.157; l.AB.228.166; l.AB.228.169; l.AB.228.172; l.AB.228.175; l.AB.228.240; l.AB.228.244; l.AB.229.228; l.AB.229.229; l.AB.229.230; l.AB.229.231; l.AB.229.236; l.AB.229.237; l.AB.229.238; l.AB.229.239; l.AB.229.154; l.AB.229.157; l.AB.229.166; l.AB.229.169; l.AB.229.172; l.AB.229.175; l.AB.229.240; l.AB.229.244; l.AB.230.228; l.AB.230.229; l.AB.230.230; l.AB.230.231; l.AB.230.236; l.AB.230.237; l.AB.230.238; l.AB.230.239; l.AB.230.154; l.AB.230.157; l.AB.230.166; l.AB.230.169; l.AB.230.172; l.AB.230.175; l.AB.230.240; l.AB.230.244; l.AB.231.228; l.AB.231.229; l.AB.231.230; l.AB.231.231; l.AB.231.236; l.AB.231.237; l.AB.231.238; l.AB.231.239; l.AB.231.154; l.AB.231.157; l.AB.231.166; l.AB.231.169; l.AB.231.172; l.AB.231.175; l.AB.231.240; l.AB.231.244; l.AB.236.228; l.AB.236.229; l.AB.236.230; l.AB.236.231; l.AB.236.236; l.AB.236.237; l.AB.236.238; l.AB.236.239; l.AB.236.154; l.AB.236.157; l.AB.236.166; l.AB.236.169; l.AB.236.172; l.AB.236.175; l.AB.236.240; l.AB.236.244; l.AB.237.228; l.AB.237.229; l.AB.237.230; l.AB.237.231; l.AB.237.236; l.AB.237.237; l.AB.237.238; l.AB.237.239; l.AB.237.154; l.AB.237.157; l.AB.237.166; l.AB.237.169; l.AB.237.172; l.AB.237.175; l.AB.237.240; l.AB.237.244; l.AB.238.228; l.AB.238.229; l.AB.238.230; l.AB.238.231; l.AB.238.236; l.AB.238.237; l.AB.238.238; l.AB.238.239; l.AB.238.154; l.AB.238.157; l.AB.238.166; l.AB.238.169; l.AB.238.172; l.AB.238.175; l.AB.238.240; l.AB.238.244; l.AB.239.228; l.AB.239.229; l.AB.239.230; l.AB.239.231; l.AB.239.236; l.AB.239.237; l.AB.239.238; l.AB.239.239; l.AB.239.154; l.AB.239.157; l.AB.239.166; l.AB.239.169; l.AB.239.172; l.AB.239.175; l.AB.239.240; l.AB.239.244; l.AB.154.228; l.AB.154.229; l.AB.154.230; l.AB.154.231; l.AB.154.236; l.AB.154.237; l.AB.154.238; l.AB.154.239; l.AB.154.154; l.AB.154.157; l.AB.154.166; l.AB.154.169; l.AB.154.172; l.AB.154.175; l.AB.154.240; l.AB.154.244; l.AB.157.228; l.AB.157.229; l.AB.157.230; l.AB.157.231; l.AB.157.236; l.AB.157.237; l.AB.157.238; l.AB.157.239; l.AB.157.154; l.AB.157.157; l.AB.157.166; l.AB.157.169; l.AB.157.172; l.AB.157.175; l.AB.157.240; l.AB.157.244; l.AB.166.228; l.AB.166.229; l.AB.166.230; l.AB.166.231; l.AB.166.236; l.AB.166.237; l.AB.166.238; l.AB.166.239; l.AB.166.154; l.AB.166.157; l.AB.166.166; l.AB.166.169; l.AB.166.172; l.AB.166.175; l.AB.166.240; l.AB.166.244; l.AB.169.228; l.AB.169.229; l.AB.169.230; l.AB.169.231; l.AB.169.236; l.AB.169.237; l.AB.169.238; l.AB.169.239; l.AB.169.154; l.AB.169.157; l.AB.169.166; l.AB.169.169; l.AB.169.172; l.AB.169.175; l.AB.169.240; l.AB.169.244; l.AB.172.228; l.AB.172.229; l.AB.172.230; l.AB.172.231; l.AB.172.236; l.AB.172.237; l.AB.172.238; l.AB.172.239; l.AB.172.154; l.AB.172.157; l.AB.172.166; l.AB.172.169; l.AB.172.172; l.AB.172.175; l.AB.172.240; l.AB.172.244; l.AB.175.228; l.AB.175.229; l.AB.175.230; l.AB.175.231; l.AB.175.236; l.AB.175.237; l.AB.175.238; l.AB.175.239; l.AB.175.154; l.AB.175.157; l.AB.175.166; l.AB.175.169; l.AB.175.172; l.AB.175.175; l.AB.175.240; l.AB.175.244; l.AB.240.228;

l.AB.240.229; l.AB.240.230; l.AB.240.231; l.AB.240.236; l.AB.240.237; l.AB.240.238; l.AB.240.239; l.AB.240.154; l.AB.240.157; l.AB.240.166; l.AB.240.169; l.AB.240.172; l.AB.240.175; l.AB.240.240; l.AB.240.244; l.AB.244.228; l.AB.244.229; l.AB.244.230; l.AB.244.231; l.AB.244.236; l.AB.244.237; l.AB.244.238; l.AB.244.239; l.AB.244.154; l.AB.244.157; l.AB.244.166; l.AB.244.169; l.AB.244.172; l.AB.244.175; l.AB.244.240; l.AB.244.244;

Prodrugs of l.BI l.BI.228.228; l.BI.228.229; l.BI.228.230; l.BI.228.231; l.BI.228.236; l.BI.228.237; l.BI.228.238; l.BI.228.239; l.BI.228.154; l.BI.228.157; l.BI.228.166; l.BI.228.169; l.BI.228.172; l.BI.228.175; l.BI.228.240; l.BI.228.244; l.BI.229.228; l.BI.229.229; l.BI.229.230; l.BI.229.231; l.BI.229.236; l.BI.229.237; l.BI.229.238; l.BI.229.239; l.BI.229.154; l.BI.229.157; l.BI.229.166; l.BI.229.169; l.BI.229.172; l.BI.229.175; l.BI.229.240; l.BI.229.244; l.BI.230.228; l.BI.230.229; l.BI.230.230; l.BI.230.231; l.BI.230.236; l.BI.230.237; l.BI.230.238; l.BI.230.239; l.BI.230.154; l.BI.230.157; l.BI.230.166; l.BI.230.169; l.BI.230.172; l.BI.230.175; l.BI.230.240; l.BI.230.244; l.BI.231.228; l.BI.231.229; l.BI.231.230; l.BI.231.231; l.BI.231.236; l.BI.231.237; l.BI.231.238; l.BI.231.239; l.BI.231.154; l.BI.231.157; l.BI.231.166; l.BI.231.169; l.BI.231.172; l.BI.231.175; l.BI.231.240; l.BI.231.244; l.BI.236.228; l.BI.236.229; l.BI.236.230; l.BI.236.231; l.BI.236.236; l.BI.236.237; l.BI.236.238; l.BI.236.239; l.BI.236.154; l.BI.236.157; l.BI.236.166; l.BI.236.169; l.BI.236.172; l.BI.236.175; l.BI.236.240; l.BI.236.244; l.BI.237.228; l.BI.237.229; l.BI.237.230; l.BI.237.231; l.BI.237.236; l.BI.237.237; l.BI.237.238; l.BI.237.239; l.BI.237.154; l.BI.237.157; l.BI.237.166; l.BI.237.169; l.BI.237.172; l.BI.237.175; l.BI.237.240; l.BI.237.244; l.BI.238.228; l.BI.238.229; l.BI.238.230; l.BI.238.231; l.BI.238.236; l.BI.238.237; l.BI.238.238; l.BI.238.239; l.BI.238.154; l.BI.238.157; l.BI.238.166; l.BI.238.169; l.BI.238.172; l.BI.238.175; l.BI.238.240; l.BI.238.244; l.BI.239.228; l.BI.239.229; l.BI.239.230; l.BI.239.231; l.BI.239.236; l.BI.239.237; l.BI.239.238; l.BI.239.239; l.BI.239.154; l.BI.239.157; l.BI.239.166; l.BI.239.169; l.BI.239.172; l.BI.239.175; l.BI.239.240; l.BI.239.244; l.BI.154.228; l.BI.154.229; l.BI.154.230; l.BI.154.231; l.BI.154.236; l.BI.154.237; l.BI.154.238; l.BI.154.239; l.BI.154.154; l.BI.154.157; l.BI.154.166; l.BI.154.169; l.BI.154.172; l.BI.154.175; l.BI.154.240; l.BI.154.244; l.BI.157.228; l.BI.157.229; l.BI.157.230; l.BI.157.231; l.BI.157.236; l.BI.157.237; l.BI.157.238; l.BI.157.239; l.BI.157.154; l.BI.157.157; l.BI.157.166; l.BI.157.169; l.BI.157.172; l.BI.157.175; l.BI.157.240; l.BI.157.244; l.BI.166.228; l.BI.166.229; l.BI.166.230; l.BI.166.231; l.BI.166.236; l.BI.166.237; l.BI.166.238; l.BI.166.239; l.BI.166.154; l.BI.166.157; l.BI.166.166; l.BI.166.169; l.BI.166.172; l.BI.166.175; l.BI.166.240; l.BI.166.244; l.BI.169.228; l.BI.169.229; l.BI.169.230; l.BI.169.231; l.BI.169.236; l.BI.169.237; l.BI.169.238; l.BI.169.239; l.BI.169.154; l.BI.169.157; l.BI.169.166; l.BI.169.169; l.BI.169.172; l.BI.169.175; l.BI.169.240; l.BI.169.244; l.BI.172.228; l.BI.172.229; l.BI.172.230; l.BI.172.231; l.BI.172.236; l.BI.172.237; l.BI.172.238; l.BI.172.239; l.BI.172.154; l.BI.172.157; l.BI.172.166; l.BI.172.169; l.BI.172.172; l.BI.172.175; l.BI.172.240; l.BI.172.244; l.BI.175.228; l.BI.175.229; l.BI.175.230; l.BI.175.231; l.BI.175.236; l.BI.175.237; l.BI.175.238; l.BI.175.239; l.BI.175.154; l.BI.175.157; l.BI.175.166; l.BI.175.169; l.BI.175.172; l.BI.175.175;

l.BI.175.240; l.BI.175.244; l.BI.240.228; l.BI.240.229; l.BI.240.230; l.BI.240.231; l.BI.240.236; l.BI.240.237; l.BI.240.238; l.BI.240.239; l.BI.240.154; l.BI.240.157; l.BI.240.166; l.BI.240.169; l.BI.240.172; l.BI.240.175; l.BI.240.240; l.BI.240.244; l.BI.244.228; l.BI.244.229; l.BI.244.230; l.BI.244.231; l.BI.244.236; l.BI.244.237; l.BI.244.238; l.BI.244.239; l.BI.244.154; l.BI.244.157; l.BI.244.166; l.BI.244.169; l.BI.244.172; l.BI.244.175; l.BI.244.240; l.BI.244.244;

Prodrugs of 1.1

1.1.228.228; 1.1.228.229; 1.1.228.230; 1.1.228.231; 1.1.228.236; 1.1.228.237; 1.1.228.238; 1.1.228.239; 1.1.228.154; 1.1.228.157; 1.1.228.166; 1.1.228.169; 1.1.228.172; 1.1.228.175; 1.1.228.240; 1.1.228.244; 1.1.229.228; 1.1.229.229; 1.1.229.230; 1.1.229.231; 1.1.229.236; 1.1.229.237; 1.1.229.238; 1.1.229.239; 1.1.229.154; 1.1.229.157; 1.1.229.166; 1.1.229.169; 1.1.229.172; 1.1.229.175; 1.1.229.240; 1.1.229.244; 1.1.230.228; 1.1.230.229; 1.1.230.230; 1.1.230.231; 1.1.230.236; 1.1.230.237; 1.1.230.238; 1.1.230.239; 1.1.230.154; 1.1.230.157; 1.1.230.166; 1.1.230.169; 1.1.230.172; 1.1.230.175; 1.1.230.240; 1.1.230.244; 1.1.231.228; 1.1.231.229; 1.1.231.230; 1.1.231.231; 1.1.231.236; 1.1.231.237; 1.1.231.238; 1.1.231.239; 1.1.231.154; 1.1.231.157; 1.1.231.166; 1.1.231.169; 1.1.231.172; 1.1.231.175; 1.1.231.240; 1.1.231.244; 1.1.236.228; 1.1.236.229; 1.1.236.230; 1.1.236.231; 1.1.236.236; 1.1.236.237; 1.1.236.238; 1.1.236.239; 1.1.236.154; 1.1.236.157; 1.1.236.166; 1.1.236.169; 1.1.236.172; 1.1.236.175; 1.1.236.240; 1.1.236.244; 1.1.237.228; 1.1.237.229; 1.1.237.230; 1.1.237.231; 1.1.237.236; 1.1.237.237; 1.1.237.238; 1.1.237.239; 1.1.237.154; 1.1.237.157; 1.1.237.166; 1.1.237.169; 1.1.237.172; 1.1.237.175; 1.1.237.240; 1.1.237.244; 1.1.238.228; 1.1.238.229; 1.1.238.230; 1.1.238.231; 1.1.238.236; 1.1.238.237; 1.1.238.238; 1.1.238.239; 1.1.238.154; 1.1.238.157; 1.1.238.166; 1.1.238.169; 1.1.238.172; 1.1.238.175; 1.1.238.240; 1.1.238.244; 1.1.239.228; 1.1.239.229; 1.1.239.230; 1.1.239.231; 1.1.239.236; 1.1.239.237; 1.1.239.238; 1.1.239.239; 1.1.239.154; 1.1.239.157; 1.1.239.166; 1.1.239.169; 1.1.239.172; 1.1.239.175; 1.1.239.240; 1.1.239.244; 1.1.154.228; 1.1.154.229; 1.1.154.230; 1.1.154.231; 1.1.154.236; 1.1.154.237; 1.1.154.238; 1.1.154.239; 1.1.154.154; 1.1.154.157; 1.1.154.166; 1.1.154.169; 1.1.154.172; 1.1.154.175; 1.1.154.240; 1.1.154.244; 1.1.157.228; 1.1.157.229; 1.1.157.230; 1.1.157.231; 1.1.157.236; 1.1.157.237; 1.1.157.238; 1.1.157.239; 1.1.157.154; 1.1.157.157; 1.1.157.166; 1.1.157.169; 1.1.157.172; 1.1.157.175; 1.1.157.240; 1.1.157.244; 1.1.166.228; 1.1.166.229; 1.1.166.230; 1.1.166.231; 1.1.166.236; 1.1.166.237; 1.1.166.238; 1.1.166.239; 1.1.166.154; 1.1.166.157; 1.1.166.166; 1.1.166.169; 1.1.166.172; 1.1.166.175; 1.1.166.240; 1.1.166.244; 1.1.169.228; 1.1.169.229; 1.1.169.230; 1.1.169.231; 1.1.169.236; 1.1.169.237; 1.1.169.238; 1.1.169.239; 1.1.169.154; 1.1.169.157; 1.1.169.166; 1.1.169.169; 1.1.169.172; 1.1.169.175; 1.1.169.240; 1.1.169.244; 1.1.172.228; 1.1.172.229; 1.1.172.230; 1.1.172.231; 1.1.172.236; 1.1.172.237; 1.1.172.238; 1.1.172.239; 1.1.172.154; 1.1.172.157; 1.1.172.166; 1.1.172.169; 1.1.172.172; 1.1.172.175; 1.1.172.240; 1.1.172.244; 1.1.175.228; 1.1.175.229; 1.1.175.230; 1.1.175.231; 1.1.175.236; 1.1.175.237; 1.1.175.238; 1.1.175.239; 1.1.175.154; 1.1.175.157; 1.1.175.166; 1.1.175.169; 1.1.175.172; 1.1.175.175; 1.1.175.240; 1.1.175.244; 1.1.240.228; 1.1.240.229; 1.1.240.230; 1.1.240.231; 1.1.240.236; 1.1.240.237; 1.1.240.238; 1.1.240.239; 1.1.240.154; 1.1.240.157; 1.1.240.166; 1.1.240.169; 1.1.240.172; 1.1.240.175; 1.1.240.240; 1.1.240.244; 1.1.244.228; 1.1.244.229; 1.1.244.230; 1.1.244.231; 1.1.244.236; 1.1.244.237; 1.1.244.238; 1.1.244.239; 1.1.244.154; 1.1.244.157; 1.1.244.166; 1.1.244.169; 1.1.244.172; 1.1.244.175; 1.1.244.240; 1.1.244.244;

Prodrugs of l.T l.J.228.228; l.J.228.229; l.J.228.230; l.J.228.231; l.J.228.236; l.J.228.237; l.J.228.238; l.J.228.239; l.J.228.154; l.J.228.157; l.J.228.166; l.J.228.169; l.J.228.172; l.J.228.175; l.J.228.240; l.J.228.244; l.J.229.228; l.J.229.229; l.J.229.230; l.J.229.231; l.J.229.236; l.J.229.237; l.J.229.238; l.J.229.239; l.J.229.154; l.J.229.157; l.J.229.166; l.J.229.169; l.J.229.172; l.J.229.175; l.J.229.240; l.J.229.244; l.J.230.228; l.J.230.229; l.J.230.230; l.J.230.231; l.J.230.236; l.J.230.237; l.J.230.238; l.J.230.239; l.J.230.154; l.J.230.157; l.J.230.166; l.J.230.169; l.J.230.172; l.J.230.175; l.J.230.240; l.J.230.244; l.J.231.228; l.J.231.229; l.J.231.230; l.J.231.231; l.J.231.236; l.J.231.237; l.J.231.238; l.J.231.239; l.J.231.154; l.J.231.157; l.J.231.166; l.J.231.169; l.J.231.172; l.J.231.175; l.J.231.240; l.J.231.244; l.J.236.228; l.J.236.229; l.J.236.230; l.J.236.231; l.J.236.236; l.J.236.237; l.J.236.238; l.J.236.239; l.J.236.154; l.J.236.157; l.J.236.166; l.J.236.169; l.J.236.172; l.J.236.175; l.J.236.240; l.J.236.244; l.J.237.228; l.J.237.229; l.J.237.230; l.J.237.231; l.J.237.236; l.J.237.237; l.J.237.238; l.J.237.239; l.J.237.154; l.J.237.157; l.J.237.166; l.J.237.169; l.J.237.172; l.J.237.175; l.J.237.240; l.J.237.244; l.J.238.228; l.J.238.229; l.J.238.230; l.J.238.231; l.J.238.236; l.J.238.237; l.J.238.238; l.J.238.239; l.J.238.154; l.J.238.157; l.J.238.166; l.J.238.169; l.J.238.172; l.J.238.175; l.J.238.240; l.J.238.244; l.J.239.228; l.J.239.229; l.J.239.230; l.J.239.231; l.J.239.236; l.J.239.237; l.J.239.238; l.J.239.239; l.J.239.154; l.J.239.157; l.J.239.166; l.J.239.169; l.J.239.172; l.J.239.175; l.J.239.240; l.J.239.244; l.J.154.228; l.J.154.229; l.J.154.230; l.J.154.231; l.J.154.236; l.J.154.237; l.J.154.238; l.J.154.239; l.J.154.154; l.J.154.157; l.J.154.166; l.J.154.169; l.J.154.172; l.J.154.175; l.J.154.240; l.J.154.244; l.J.157.228; l.J.157.229; l.J.157.230; l.J.157.231; l.J.157.236; l.J.157.237; l.J.157.238; l.J.157.239; l.J.157.154; l.J.157.157; l.J.157.166; l.J.157.169; l.J.157.172; l.J.157.175; l.J.157.240; l.J.157.244; l.J.166.228; l.J.166.229; l.J.166.230; l.J.166.231; l.J.166.236; l.J.166.237; l.J.166.238; l.J.166.239; l.J.166.154; l.J.166.157; l.J.166.166; l.J.166.169; l.J.166.172; l.J.166.175; l.J.166.240; l.J.166.244; l.J.169.228; l.J.169.229; l.J.169.230; l.J.169.231; l.J.169.236; l.J.169.237; l.J.169.238; l.J.169.239; l.J.169.154; l.J.169.157; l.J.169.166; l.J.169.169; l.J.169.172; l.J.169.175; l.J.169.240; l.J.169.244; l.J.172.228; l.J.172.229; l.J.172.230; l.J.172.231; l.J.172.236; l.J.172.237; l.J.172.238; l.J.172.239; l.J.172.154; l.J.172.157; l.J.172.166; l.J.172.169; l.J.172.172; l.J.172.175; l.J.172.240; l.J.172.244; l.J.175.228; l.J.175.229; l.J.175.230; l.J.175.231; l.J.175.236; l.J.175.237; l.J.175.238; l.J.175.239; l.J.175.154; l.J.175.157; l.J.175.166; l.J.175.169; l.J.175.172; l.J.175.175; l.J.175.240; l.J.175.244; l.J.240.228; l.J.240.229; l.J.240.230; l.J.240.231; l.J.240.236; l.J.240.237; l.J.240.238; l.J.240.239; l.J.240.154; l.J.240.157; l.J.240.166; l.J.240.169; l.J.240.172; l.J.240.175; l.J.240.240; l.J.240.244; l.J.244.228; l.J.244.229; l.J.244.230; l.J.244.231; l.J.244.236; l.J.244.237; l.J.244.238; l.J.244.239; l.J.244.154; l.J.244.157; l.J.244.166; l.J.244.169; l.J.244.172; l.J.244.175; l.J.244.240; l.J.244.244;

Prodrugsof l.L l.L.228.228; l.L.228.229; l.L.228.230; l.L.228.231; l.L.228.236; l.L.228.237; l.L.228.238; l.L.228.239; l.L.228.154; l.L.228.157; l.L.228.166; l.L.228.169; l.L.228.172; l.L.228.175; l.L.228.240; l.L.228.244; l.L.229.228; l.L.229.229; l.L.229.230; l.L.229.231; l.L.229.236; l.L.229.237; l.L.229.238; l.L.229.239; l.L.229.154; l.L.229.157; l.L.229.166; l.L.229.169; l.L.229.172; l.L.229.175; l.L.229.240; l.L.229.244; l.L.230.228; l.L.230.229; l.L.230.230; l.L.230.231;

l.L.230.236; l.L.230.237; l.L.230.238; l.L.230.239; l.L.230.154; l.L.230.157; l.L.230.166; l.L.230.169; l.L.230.172; l.L.230.175; l.L.230.240; l.L.230.244; l.L.231.228; l.L.231.229; l.L.231.230; l.L.231.231; l.L.231.236; l.L.231.237; l.L.231.238; l.L.231.239; l.L.231.154; l.L.231.157; l.L.231.166; l.L.231.169; l.L.231.172; l.L.231.175; l.L.231.240; l.L.231.244; l.L.236.228; l.L.236.229; l.L.236.230; l.L.236.231; l.L.236.236; l.L.236.237; l.L.236.238; l.L.236.239; l.L.236.154; l.L.236.157; l.L.236.166; l.L.236.169; l.L.236.172; l.L.236.175; l.L.236.240; l.L.236.244; l.L.237.228; l.L.237.229; l.L.237.230; l.L.237.231; l.L.237.236; l.L.237.237; l.L.237.238; l.L.237.239; l.L.237.154; l.L.237.157; l.L.237.166; l.L.237.169; l.L.237.172; l.L.237.175; l.L.237.240; l.L.237.244; l.L.238.228; l.L.238.229; l.L.238.230; l.L.238.231; l.L.238.236; l.L.238.237; l.L.238.238; l.L.238.239; l.L.238.154; l.L.238.157; l.L.238.166; l.L.238.169; l.L.238.172; l.L.238.175; l.L.238.240; l.L.238.244; l.L.239.228; l.L.239.229; l.L.239.230; l.L.239.231; l.L.239.236; l.L.239.237; l.L.239.238; l.L.239.239; l.L.239.154; l.L.239.157; l.L.239.166; l.L.239.169; l.L.239.172; l.L.239.175; l.L.239.240; l.L.239.244; l.L.154.228; l.L.154.229; l.L.154.230; l.L.154.231; l.L.154.236; l.L.154.237; l.L.154.238; l.L.154.239; l.L.154.154; l.L.154.157; l.L.154.166; l.L.154.169; l.L.154.172; l.L.154.175; l.L.154.240; l.L.154.244; l.L.157.228; l.L.157.229; l.L.157.230; l.L.157.231; l.L.157.236; l.L.157.237; l.L.157.238; l.L.157.239; l.L.157.154; l.L.157.157; l.L.157.166; l.L.157.169; l.L.157.172; l.L.157.175; l.L.157.240; l.L.157.244; l.L.166.228; l.L.166.229; l.L.166.230; l.L.166.231; l.L.166.236; l.L.166.237; l.L.166.238; l.L.166.239; l.L.166.154; l.L.166.157; l.L.166.166; l.L.166.169; l.L.166.172; l.L.166.175; l.L.166.240; l.L.166.244; l.L.169.228; l.L.169.229; l.L.169.230; l.L.169.231; l.L.169.236; l.L.169.237; l.L.169.238; 1..L.169..239; l.L.169.154; l.L.169.157; l.L.169.166; l.L.169.169; l.L.169.172; l.L.169.175; l.L.169.240; l.L.169.244; l.L.172.228; l.L.172.229; l.L.172.230; l.L.172.231; l.L.172.236; l.L.172.237; l.L.172.238; l.L.172.239; l.L.172.154; l.L.172.157; l.L.172.166; l.L.172.169; l.L.172.172; l.L.172.175; l.L.172.240; l.L.172.244; l.L.175.228; l.L.175.229; l.L.175.230; l.L.175.231; l.L.175.236; l.L.175.237; l.L.175.238; l.L.175.239; l.L.175.154; l.L.175.157; l.L.175.166; l.L.175.169; l.L.175.172; l.L.175.175; l.L.175.240; l.L.175.244; l.L.240.228; l.L.240.229; l.L.240.230; l.L.240.231; l.L.240.236; l.L.240.237; l.L.240.238; l.L.240.239; l.L.240.154; l.L.240.157; l.L.240.166; l.L.240.169; l.L.240.172; l.L.240.175; l.L.240.240; l.L.240.244; l.L.244.228; l.L.244.229; l.L.244.230; l.L.244.231; l.L.244.236; l.L.244.237; l.L.244.238; l.L.244.239; l.L.244.154; l.L.244.157; l.L.244.166; l.L.244.169; l.L.244.172; l.L.244.175; l.L.244.240; l.L.244.244;

Prodrugs of l.O

1.O.228.228; 1.O.228.229; 1.O.228.230; 1.O.228.231; 1.O.228.236; 1.O.228.237; 1.O.228.238; 1.O.228.239; 1.O.228.154; 1.O.228.157; 1.O.228.166; 1.O.228.169; 1.O.228.172; 1.O.228.175; 1.O.228.240; 1.O.228.244; 1.O.229.228; 1.O.229.229; 1.O.229.230; 1.O.229.231; 1.O.229.236; 1.O.229.237; 1.O.229.238; 1.O.229.239; 1.O.229.154; 1.O.229.157; 1.O.229.166; 1.O.229.169; 1.O.229.172; 1.O.229.175; 1.O.229.240; 1.O.229.244; 1.O.230.228; 1.O.230.229; 1.O.230.230; 1.O.230.231; 1.O.230.236; 1.O.230.237; 1.O.230.238; 1.O.230.239; 1.O.230.154; 1.O.230.157;

1.O.230.166; 1.O.230.169; 1.O.230.172; 1.O.230.175; 1.O.230.240; 1.O.230.244; 1.O.231.228; 1.O.231.229; 1.O.231.230; 1.O.231.231; 1.O.231.236; 1.O.231.237; 1.O.231.238; 1.O.231.239; 1.O.231.154; 1.O.231.157; 1.O.231.166; 1.O.231.169; 1.O.231.172; 1.O.231.175; 1.O.231.240; 1.O.231.244; 1.O.236.228; 1.O.236.229; 1.O.236.230; 1.O.236.231; 1.O.236.236; 1.O.236.237; 1.O.236.238; 1.O.236.239; 1.O.236.154; 1.O.236.157; 1.O.236.166; 1.O.236.169; 1.O.236.172; 1.O.236.175; 1.O.236.240; 1.O.236.244; 1.O.237.228; 1.O.237.229; 1.O.237.230; 1.O.237.231; 1.O.237.236; 1.O.237.237; 1.O.237.238; 1.O.237.239; 1.O.237.154; 1.O.237.157; 1.O.237.166; 1.O.237.169; 1.O.237.172; 1.O.237.175; 1.O.237.240; 1.O.237.244; 1.O.238.228; 1.O.238.229; 1.O.238.230; 1.O.238.231; 1.O.238.236; 1.O.238.237; 1.O.238.238; 1.O.238.239; 1.O.238.154; 1.O.238.157; 1.O.238.166; 1.O.238.169; 1.O.238.172; 1.O.238.175; 1.O.238.240; 1.O.238.244; 1.O.239.228; 1.O.239.229; 1.O.239.230; 1.O.239.231; 1.O.239.236; 1.O.239.237; 1.O.239.238; 1.O.239.239; 1.O.239.154; 1.O.239.157; 1.O.239.166; 1.O.239.169; 1.O.239.172; 1.O.239.175; 1.O.239.240; 1.O.239.244; 1.O.154.228; 1.O.154.229; 1.O.154.230; 1.O.154.231; 1.O.154.236; 1.O.154.237; 1.O.154.238; 1.O.154.239; 1.O.154.154; 1.O.154.157; 1.O.154.166; 1.O.154.169; 1.O.154.172; 1.O.154.175; 1.O.154.240; 1.O.154.244; 1.O.157.228; 1.O.157.229; 1.O.157.230; 1.O.157.231; 1.O.157.236; 1.O.157.237; 1.O.157.238; 1.O.157.239; 1.O.157.154; 1.O.157.157; 1.O.157.166; 1.O.157.169; 1.O.157.172; 1.O.157.175; 1.O.157.240; 1.O.157.244; 1.O.166.228; 1.O.166.229; 1.O.166.230; 1.O.166.231; 1.O.166.236; 1.O.166.237; 1.O.166.238; 1.O.166.239; 1.O.166.154; 1.O.166.157; 1.O.166.166; 1.O.166.169; 1.O.166.172; 1.O.166.175; 1.O.166.240; 1.O.166.244; 1.O.169.228; 1.O.169.229; 1.O.169.230; 1.O.169.231; 1.O.169.236; 1.O.169.237; 1.O.169.238; 1.O.169.239; 1.O.169.154; 1.O.169.157; 1.O.169.166; 1.O.169.169; 1.O.169.172; 1.O.169.175; 1.O.169.240; 1.O.169.244; 1.O.172.228; 1.O.172.229; 1.O.172.230; 1.O.172.231; 1.O.172.236; 1.O.172.237; 1.O.172.238; 1.O.172.239; 1.O.172.154; 1.O.172.157; 1.O.172.166; 1.O.172.169; 1.O.172.172; 1.O.172.175; 1.O.172.240; 1.O.172.244; 1.O.175.228; 1.O.175.229; 1.O.175.230; 1.O.175.231; 1.O.175.236; 1.O.175.237; 1.O.175.238; 1.O.175.239; 1.O.175.154; 1.O.175.157; 1.O.175.166; 1.O.175.169; 1.O.175.172; 1.O.175.175; 1.O.175.240; 1.O.175.244; 1.O.240.228; 1.O.240.229; 1.O.240.230; 1.O.240.231; 1.O.240.236; 1.O.240.237; 1.O.240.238; 1.O.240.239; 1.O.240.154; 1.O.240.157; 1.O.24Q.166; 1.O.240.169; 1.O.240.172; 1.O.240.175; 1.O.240.240; 1.O.240.244; 1.O.244.228; 1.O.244.229; 1.O.244.230; 1.O.244.231; 1.O.244.236; 1.O.244.237; 1.O.244.238; 1.O.244.239; 1.O.244.154; 1.O.244.157; 1.O.244.166; 1.O.244.169; 1.O.244.172; 1.O.244.175; 1.O.244.240; 1.O.244.244;

Prodrugs of l.P l.P.228.228; l.P.228.229; l.P.228.230; l.P.228.231; l.P.228.236; l.P.228.237; l.P.228.238; l.P.228.239; l.P.228.154; l.P.228.157; l.P.228.166; l.P.228.169; l.P.228.172; l.P.228.175; l.P.228.240; l.P.228.244; l.P.229.228; l.P.229.229; l.P.229.230; l.P.229.231; l.P.229.236; l.P.229.237; l.P.229.238; l.P.229.239; l.P.229.154; l.P.229.157; l.P.229.166; l.P.229.169; l.P.229.172; l.P.229.175; l.P.229.240; l.P.229.244; l.P.230.228; l.P.230.229; l.P.230.230; l.P.230.231; l.P.230.236; l.P.230.237; l.P.230.238; l.P.230.239; l.P.230.154; l.P.230.157; l.P.230.166; l.P.230.169; l.P.230.172; l.P.230.175; l.P.230.240; l.P.230.244;

l.P.231.228; l.P.231.229; l.P.231.230; l.P.231.231; l.P.231.236; l.P.231.237; l.P.231.238; l.P.231.239; l.P.231.154; l.P.231.157; l.P.231.166; l.P.231.169; l.P.231.172; l.P.231.175; l.P.231.240; l.P.231.244; l.P.236.228; l.P.236.229; l.P.236.230; l.P.236.231; l.P.236.236; l.P.236.237; l.P.236.238; l.P.236.239; l.P.236.154; l.P.236.157; l.P.236.166; l.P.236.169; l.P.236.172; l.P.236.175; l.P.236.240; l.P.236.244; l.P.237.228; l.P.237.229; l.P.237.230; l.P.237.231; l.P.237.236; l.P.237.237; l.P.237.238; l.P.237.239; l.P.237.154; l.P.237.157; l.P.237.166; l.P.237.169; l.P.237.172; l.P.237.175; l.P.237.240; l.P.237.244; l.P.238.228; l.P.238.229; l.P.238.230; l.P.238.231; l.P.238.236; l.P.238.237; l.P.238.238; l.P.238.239; l.P.238.154; l.P.238.157; l.P.238.166; l.P.238.169; l.P.238.172; l.P.238.175; l.P.238.240; l.P.238.244; l.P.239.228; l.P.239.229; l.P.239.230; l.P.239.231; l.P.239.236; l.P.239.237; l.P.239.238; l.P.239.239; l.P.239.154; l.P.239.157; l.P.239.166; l.P.239.169; l.P.239.172; l.P.239.175; l.P.239.240; l.P.239.244; l.P.154.228; l.P.154.229; l.P.154.230; l.P.154.231; l.P.154.236; l.P.154.237; l.P.154.238; l.P.154.239; l.P.154.154; l.P.154.157; l.P.154.166; l.P.154.169; l.P.154.172; l.P.154.175; l.P.154.240; l.P.154.244; l.P.157.228; l.P.157.229; l.P.157.230; l.P.157.231; l.P.157.236; l.P.157.237; l.P.157.238; l.P.157.239; l.P.157.154; l.P.157.157; l.P.157.166; l.P.157.169; l.P.157.172; l.P.157.175; l.P.157.240; l.P.157.244; l.P.166.228; l.P.166.229; l.P.166.230; l.P.166.231; l.P.166.236; l.P.166.237; l.P.166.238; l.P.166.239; l.P.166.154; l.P.166.157; l.P.166.166; l.P.166.169; l.P.166.172; l.P.166.175; l.P.166.240; l.P.166.244; l.P.169.228; l.P.169.229; l.P.169.230; l.P.169.231; l.P.169.236; l.P.169.237; l.P.169.238; l.P.169.239; l.P.169.154; l.P.169.157; l.P.169.166; l.P.169.169; l.P.169.172; l.P.169.175; l.P.169.240; l.P.169.244; l.P.172.228; l.P.172.229; l.P.172.230; l.P.172.231; 1..P .172.236; l.P.172.237; l.P.172.238; l.P.172.239; l.P.172.154; l.P.172.157; l.P.172.166; l.P.172.169; l.P.172.172; l.P.172.175; l.P.172.240; l.P.172.244; l.P.175.228; l.P.175.229; l.P.175.230; l.P.175.231; l.P.175.236; l.P.175.237; l.P.175.238; l.P.175.239; l.P.175.154; l.P.175.157; l.P.175.166; l.P.175.169; l.P.175.172; l.P.175.175; l.P.175.240; l.P.175.244; l.P.240.228; l.P.240.229; l.P.240.230; l.P.240.231; l.P.240.236; l.P.240.237; l.P.240.238; l.P.240.239; l.P.240.154; l.P.240.157; l.P.240.166; l.P.240.169; l.P.240.172; l.P.240.175; l.P.240.240; l.P.240.244; l.P.244.228; l.P.244.229; l.P.244.230; l.P.244.231; l.P.244.236; l.P.244.237; l.P.244.238; l.P.244.239; l.P.244.154; l.P.244.157; l.P.244.166; l.P.244.169; l.P.244.172; l.P.244.175; l.P.244.240; l.P.244.244;

Prodrugs of l.U l.U.228.228; l.U.228.229; l.U.228.230; l.U.228.231; l.U.228.236; l.U.228.237; l.U.228.238; l.U.228.239; l.U.228.154; l.U.228.157; l.U.228.166; l.U.228.169; l.U.228.172; l.U.228.175; l.U.228.240; l.U.228.244; l.U.229.228; l.U.229.229; l.U.229.230; l.U.229.231; l.U.229.236; l.U.229.237; l.U.229.238; l.U.229.239; l.U.229.154; l.U.229.157; l.U.229.166; l.U.229.169; l.U.229.172; l.U.229.175; l.U.229.240; l.U.229.244; l.U.230.228; l.U.230.229; l.U.230.230; l.U.230.231; l.U.230.236; l.U.230.237; l.U.230.238; l.U.230.239; l.U.230.154; l.U.230.157; l.U.230.166; l.U.230.169; l.U.230.172; l.U.230.175; l.U.230.240; l.U.230.244; l.U.231.228; l.U.231.229; l.U.231.230; l.U.231.231; l.U.231.236; l.U.231.237;

l.U.231.238; l.U.231.239; l.U.231.154; l.U.231.157; l.U.231.166; l.U.231.169; l.U.231.172; l.U.231.175; l.U.231.240; l.U.231.244; l.U.236.228; l.U.236.229; l.U.236.230; l.U.236.231; l.U.236.236; l.U.236.237; l.U.236.238; l.U.236.239; l.U.236.154; l.U.236.157; l.U.236.166; l.U.236.169; l.U.236.172; l.U.236.175; l.U.236.240; l.U.236.244; l.U.237.228; l.U.237.229; l.U.237.230; l.U.237.231; l.U.237.236; l.U.237.237; l.U.237.238; l.U.237.239; l.U.237.154; l.U.237.157; l.U.237.166; l.U.237.169; l.U.237.172; l.U.237.175; l.U.237.240; l.U.237.244; l.U.238.228; l.U.238.229; l.U.238.230; l.U.238.231; l.U.238.236; l.U.238.237; l.U.238.238; l.U.238.239; l.U.238.154; l.U.238.157; l.U.238.166; l.U.238.169; l.U.238.172; l.U.238.175; l.U.238.240; l.U.238.244; l.U.239.228; l.U.239.229; l.U.239.230; l.U.239.231; l.U.239.236; l.U.239.237; l.U.239.238; l.U.239.239; l.U.239.154; l.U.239.157; l.U.239.166; l.U.239.169; l.U.239.172; l.U.239.175; l.U.239.240; l.U.239.244; l.U.154.228; l.U.154.229; l.U.154.230; l.U.154.231; l.U.154.236; l.U.154.237; l.U.154.238; l.U.154.239; l.U.154.154; l.U.154.157; l.U.154.166; l.U.154.169; l.U.154.172; l.U.154.175; l.U.154.240; l.U.154.244; l.U.157.228; l.U.157.229; l.U.157.230; l.U.157.231; l.U.157.236; l.U.157.237; l.U.157.238; l.U.157.239; l.U.157.154; l.U.157.157; l.U.157.166; l.U.157.169; l.U.157.172; l.U.157.175; l.U.157.240; l.U.157.244; l.U.166.228; l.U.166.229; l.U.166.230; l.U.166.231; l.U.166.236; l.U.166.237; l.U.166.238; l.U.166.239; l.U.166.154; l.U.166.157; l.U.166.166; l.U.166.169; l.U.166.172; l.U.166.175; l.U.166.240; l.U.166.244; l.U.169.228; l.U.169.229; l.U.169.230; l.U.169.231; l.U.169.236; l.U.169.237; l.U.169.238; l.U.169.239; l.U.169.154; l.U.169.157; l.U.169.166; l.U.169.169; l.U.169.172; l.U.169.175; l.U.169.240; l.U.169.244; l.U.172.228; l.U.172.229; l.U.172.230; l.U.172.231; LU .172.236; l.U.172.237; l.U.172.238; l.U.172.239; l.U.172.154; l.U.172.157; l.U.172.166; l.U.172.169; l.U.172.172; l.U.172.175; l.U.172.240; l.U.172.244; l.U.175.228; l.U.175.229; l.U.175.230; l.U.175.231; l.U.175.236; l.U.175.237; l.U.175.238; l.U.175.239; l.U.175.154; l.U.175.157; l.U.175.166; l.U.175.169; l.U.175.172; l.U.175.175; l.U.175.240; l.U.175.244; l.U.240.228; l.U.240.229; l.U.240.230; l.U.240.231; l.U.240.236; l.U.240.237; l.U.240.238; l.U.240.239; l.U.240.154; l.U.240.157; l.U.240.166; l.U.240.169; l.U.240.172; l.U.240.175; l.U.240.240; l.U.240.244; l.U.244.228; l.U.244.229; l.U.244.230; l.U.244.231; l.U.244.236; l.U.244.237; l.U.244.238; l.U.244.239; l.U.244.154; l.U.244.157; l.U.244.166; l.U.244.169; l.U.244.172; l.U.244.175; l.U.244.240; l.U.244.244;

Prodrugs of l.CD l.CD.228.228; l.CD.228.229; l.CD.228.230; l.CD.228.231; l.CD.228.236; l.CD.228.237; l.CD.228.238; l.CD.228.239; l.CD.228.154; l.CD.228.157; l.CD.228.166; l.CD.228.169; l.CD.228.172; l.CD.228.175; l.CD.228.240; l.CD.228.244; l.CD.229.228; l.CD.229.229; l.CD.229.230; l.CD.229.231; l.CD.229.236; l.CD.229.237; l.CD.229.238; l.CD.229.239; l.CD.229.154; l.CD.229.157; l.CD.229.166; l.CD.229.169; I. CD.229.172; l.CD.229.175; l.CD.229.240; l.CD.229.244; l.CD.230.228; l.CD.230.229; l.CD.230.230; l.CD.230.231; l.CD.230.236; l.CD.230.237; l.CD.230.238; l.CD.230.239; l.CD.230.154; l.CD.230.157; l.CD.230.166; l.CD.230.169; l.CD.230.172; l.CD.230.175; l.CD.230.240; l.CD.230.244; l.CD.231.228; l.CD.231.229;

l.CD.231.230; l.CD.231.231; l.CD.231.236; l.CD.231.237; l.CD.231.238; l.CD.231.239; l.CD.231.154; l.CD.231.157; l.CD.231.166; l.CD.231.169; l.CD.231.172; l.CD.231.175; l.CD.231.240; l.CD.231.244; l.CD.236.228; l.CD.236.229; l.CD.236.230; l.CD.236.231; l.CD.236.236; l.CD.236.237; l.CD.236.238; l.CD.236.239; l.CD.236.154; l.CD.236.157; l.CD.236.166; l.CD.236.169; l.CD.236.172; l.CD.236.175; l.CD.236.240; l.CD.236.244; l.CD.237.228; l.CD.237.229; l.CD.237.230; l.CD.237.231; l.CD.237.236; l.CD.237.237; l.CD.237.238; l.CD.237.239; l.CD.237.154; l.CD.237.157; l.CD.237.166; l.CD.237.169; l.CD.237.172; l.CD.237.175; l.CD.237.240; l.CD.237.244; l.CD.238.228; l.CD.238.229; l.CD.238.230; l.CD.238.231; l.CD.238.236; l.CD.238.237; l.CD.238.238; l.CD.238.239; l.CD.238.154; l.CD.238.157; l.CD.238.166; l.CD.238.169; l.CD.238.172; l.CD.238.175; l.CD.238.240; l.CD.238.244; l.CD.239.228; l.CD.239.229; l.CD.239.230; l.CD.239.231; l.CD.239.236; l.CD.239.237; l.CD.239.238; l.CD.239.239; l.CD.239.154; l.CD.239.157; l.CD.239.166; l.CD.239.169; l.CD.239.172; l.CD.239.175; l.CD.239.240; l.CD.239.244; l.CD.154.228; l.CD.154.229; l.CD.154.230; l.CD.154.231; l.CD.154.236; l.CD.154.237; l.CD.154.238; l.CD.154.239; l.CD.154.154; l.CD.154.157; l.CD.154.166; l.CD.154.169; l.CD.154.172; l.CD.154.175; l.CD.154.240; l.CD.154.244; l.CD.157.228; l.CD.157.229; l.CD.157.230; l.CD.157.231; l.CD.157.236; l.CD.157.237; l.CD.157.238; l.CD.157.239; l.CD.157.154; l.CD.157.157; l.CD.157.166; l.CD.157.169; l.CD.157.172; l.CD.157.175; l.CD.157.240; l.CD.157.244; l.CD.166.228; l.CD.166.229; l.CD.166.230; l.CD.166.231; l.CD.166.236; l.CD.166.237; l.CD.166.238; l.CD.166.239; l.CD.166.154; l.CD.166.157; l.CD.166.166; l.CD.166.169; l.CD.166.172; l.CD.166.175; l.CD.166.240; l.CD.166.244; l.CD.169.228; l.CD.169.229; l.CD.169.230; l.CD.169.231; l.CD.169.236; l.CD.169.237; l.CD.169.238; l.CD.169.239; l.CD.169.154; l.CD.169.157; l.CD.169.166; l.CD.169.169; l.CD.169.172; l.CD.169.175; l.CD.169.240; l.CD.169.244; l.CD.172.228; l.CD.172.229; l.CD.172.230; l.CD.172.231; l.CD.172.236; l.CD.172.237; l.CD.172.238; l.CD.172.239; l.CD.172.154; l.CD.172.157; l.CD.172.166; l.CD.172.169; l.CD.172.172; l.CD.172.175; l.CD.172.240; l.CD.172.244; l.CD.175.228; l.CD.175.229; l.CD.175.230; l.CD.175.231; l.CD.175.236; l.CD.175.237; l.CD.175.238; l.CD.175.239; l.CD.175.154; l.CD.175.157; l.CD.175.166; l.CD.175.169; l.CD.175.172; l.CD.175.175; l.CD.175.240; l.CD.175.244; l.CD.240.228; l.CD.240.229; l.CD.240.230; l.CD.240.231; l.CD.240.236; l.CD.240.237; l.CD.240.238; l.CD.240.239; l.CD.240.154; l.CD.240.157; l.CD.240.166; l.CD.240.169; l.CD.240.172; l.CD.240.175; l.CD.240.240; l.CD.240.244; l.CD.244.228; l.CD.244.229; l.CD.244.230; l.CD.244.231; l.CD.244.236; l.CD.244.237; l.CD.244.238; l.CD.244.239; l.CD.244.154; l.CD.244.157; l.CD.244.166; l.CD.244.169; l.CD.244.172; l.CD.244.175; l.CD.244.240; l.CD.244.244;

Prodrugs of l.EB l.EB.228.228; l.EB.228.229; l.EB.228.230; l.EB.228.231; l.EB.228.236; l.EB.228.237; l.EB.228.238; l.EB.228.239; l.EB.228.154; l.EB.228.157; l.EB.228.166;

l.EB.228.169; l.EB.228.172; l.EB.228.175; l.EB.228.240; l.EB.228.244; l.EB.229.228; l.EB.229.229; l.EB.229.230; l.EB.229.231; l.EB.229.236; l.EB.229.237; l.EB.229.238; l.EB.229.239; l.EB.229.154; l.EB.229.157; l.EB.229.166; l.EB.229.169; l.EB.229.172; l.EB.229.175; l.EB.229.240; l.EB.229.244; l.EB.230.228; l.EB.230.229; l.EB.230.230; l.EB.230.231; l.EB.230.236; l.EB.230.237; l.EB.230.238; l.EB.230.239; l.EB.230.154; l.EB.230.157; l.EB.230.166; l.EB.230.169; l.EB.230.172; l.EB.230.175; l.EB.230.240; l.EB.230.244; l.EB.231.228; l.EB.231.229; l.EB.231.230; l.EB.231.231; l.EB.231.236; l.EB.231.237; l.EB.231.238; l.EB.231.239; l.EB.231.154; l.EB.231.157; l.EB.231.166; l.EB.231.169; l.EB.231.172; l.EB.231.175; l.EB.231.240; l.EB.231.244; l.EB.236.228; l.EB.236.229; l.EB.236.230; l.EB.236.231; l.EB.236.236; l.EB.236.237; l.EB.236.238; l.EB.236.239; l.EB.236.154; l.EB.236.157; l.EB.236.166; l.EB.236.169; l.EB.236.172; l.EB.236.175; l.EB.236.240; l.EB.236.244; l.EB.237.228; l.EB.237.229; l.EB.237.230; l.EB.237.231; l.EB.237.236; l.EB.237.237; l.EB.237.238; l.EB.237.239; l.EB.237.154; l.EB.237.157; l.EB.237.166; l.EB.237.169; l.EB.237.172; l.EB.237.175; l.EB.237.240; l.EB.237.244; l.EB.238.228; l.EB.238.229; l.EB.238.230; l.EB.238.231; l.EB.238.236; l.EB.238.237; l.EB.238.238; l.EB.238.239; l.EB.238.154; l.EB.238.157; l.EB.238.166; l.EB.238.169; l.EB.238.172; l.EB.238.175; l.EB.238.240; l.EB.238.244; l.EB.239.228; l.EB.239.229; l.EB.239.230; l.EB.239.231; l.EB.239.236; l.EB.239.237; l.EB.239.238; l.EB.239.239; l.EB.239.154; l.EB.239.157; l.EB.239.166; l.EB.239.169; l.EB.239.172; l.EB.239.175; l.EB.239.240; l.EB.239.244; l.EB.154.228; l.EB.154.229; l.EB.154.230; l.EB.154.231; l.EB.154.236; l.EB.154.237; l.EB.154.238; l.EB.154.239; l.EB.154.154; l.EB.154.157; l.EB.154.166; l.EB.154.169; l.EB.154.172; l.EB.154.175; l.EB.154.240; l.EB.154.244; l.EB.157.228; l.EB.157.229; l.EB.157.230; l.EB.157.231; l.EB.157.236; l.EB.157.237; l.EB.157.238; l.EB.157.239; l.EB.157.154; l.EB.157.157; l.EB.157.166; l.EB.157.169; l.EB.157.172; l.EB.157.175; l.EB.157.240; l.EB.157.244; l.EB.166.228; l.EB.166.229; l.EB.166.230; l.EB.166.231; l.EB.166.236; l.EB.166.237; l.EB.166.238; l.EB.166.239; l.EB.166.154; l.EB.166.157; l.EB.166.166; l.EB.166.169; l.EB.166.172; l.EB.166.175; l.EB.166.240; l.EB.166.244; l.EB.169.228; l.EB.169.229; l.EB.169.230; l.EB.169.231; l.EB.169.236; l.EB.169.237; l.EB.169.238; l.EB.169.239; l.EB.169.154; l.EB.169.157; l.EB.169.166; l.EB.169.169; l.EB.169.172; l.EB.169.175; l.EB.169.240; l.EB.169.244; l.EB.172.228; l.EB.172.229; l.EB.172.230; l.EB.172.231; l.EB.172.236; l.EB.172.237; l.EB.172.238; l.EB.172.239; l.EB.172.154; l.EB.172.157; l.EB.172.166; l.EB.172.169; l.EB.172.172; l.EB.172.175; l.EB.172.240; l.EB.172.244; l.EB.175.228; l.EB.175.229; l.EB.175.230; l.EB.175.231; l.EB.175.236; l.EB.175.237; l.EB.175.238; l.EB.175.239; l.EB.175.154; l.EB.175.157; l.EB.175.166; l.EB.175.169; l.EB.175.172; l.EB.175.175; l.EB.175.240; l.EB.175.244; l.EB.240.228; l.EB.240.229; l.EB.240.230; l.EB.240.231; l.EB.240.236; l.EB.240.237; l.EB.240.238; l.EB.240.239; l.EB.240.154; l.EB.240.157; l.EB.240.166; l.EB.240.169; l.EB.240.172; l.EB.240.175; l.EB.240.240; l.EB.240.244; l.EB.244.228; l.EB.244.229; l.EB.244.230; l.EB.244.231; l.EB.244.236; l.EB.244.237; l.EB.244.238; l.EB.244.239; l.EB.244.154; l.EB.244.157; l.EB.244.166; l.EB.244.169; l.EB.244.172; l.EB.244.175; l.EB.244.240; l.EB.244.244;

Prodrugs of 2.B

2.B.228.228; 2.B.228.229; 2.B.228.230; 2.B.228.231; 2.B.228.236; 2.B.228.237; 2.B.228.238; 2.B.228.239; 2.B.228.154; 2.B.228.157; 2.B.228.166; 2.B.228.169; 2.B.228.172; 2.B.228.175; 2.B.228.240; 2.B.228.244; 2.B.229.228; 2.B.229.229;

2.B.229.230; 2.B.229.231; 2.B.229.236; 2.B.229.237; 2.B.229.238; 2.B.229.239; 2.B.229.154; 2.B.229.157; 2.B.229.166; 2.B.229.169; 2.B.229.172; 2.B.229.175; 2.B.229.240; 2.B.229.244; 2.B.230.228; 2.B.230.229; 2.B.230.230; 2.B.230.231; 2.B.230.236; 2.B.230.237; 2.B.230.238; 2.B.230.239; 2.B.230.154; 2.B.230.157; 2.B.230.166; 2.B.230.169; 2.B.230.172; 2.B.230.175; 2.B.230.240; 2.B.230.244; 2.B.231.228; 2.B.231.229; 2.B.231.230; 2.B.231.231; 2.B.231.236; 2.B.231.237; 2.B.231.238; 2.B.231.239; 2.B.231.154; 2.B.231.157; 2.B.231.166; 2.B.231.169; 2.B.231.172; 2.B.231.175; 2.B.231.240; 2.B.231.244; 2.B.236.228; 2.B.236.229; 2.B.236.230; 2.B.236.231; 2.B.236.236; 2.B.236.237; 2.B.236.238; 2.B.236.239; 2.B.236.154; 2.B.236.157; 2.B.236.166; 2.B.236.169; 2.B.236.172; 2.B.236.175; 2.B.236.240; 2.B.236.244; 2.B.237.228; 2.B.237.229; 2.B.237.230; 2.B.237.231; 2.B.237.236; 2.B.237.237; 2.B.237.238; 2.B.237.239; 2.B.237.154; 2.B.237.157; 2.B.237.166; 2.B.237.169; 2.B.237.172; 2.B.237.175; 2.B.237.240; 2.B.237.244; 2.B.238.228; 2.B.238.229; 2.B.238.230; 2.B.238.231; 2.B.238.236; 2.B.238.237; 2.B.238.238; 2.B.238.239; 2.B.238.154; 2.B.238.157; 2.B.238.166; 2.B.238.169; 2.B.238.172; 2.B.238.175; 2.B.238.240; 2.B.238.244; 2.B.239.228; 2.B.239.229; 2.B.239.230; 2.B.239.231; 2.B.239.236; 2.B.239.237; 2.B.239.238; 2.B.239.239; 2.B.239.154; 2.B.239.157; 2.B.239.166; 2.B.239.169; 2.B.239.172; 2.B.239.175; 2.B.239.240; 2.B.239.244; 2.B.154.228; 2.B.154.229; 2.B.154.230; 2.B.154.231; 2.B.154.236; 2.B.154.237; 2.B.154.238; 2.B.154.239; 2.B.154.154; 2.B.154.157; 2.B.154.166; 2.B.154.169; 2.B.154.172; 2.B.154.175; 2.B.154.240; 2.B.154.244; 2.B.157.228; 2.B.157.229; 2.B.157.230; 2.B.157.231; 2.B.157.236; 2.B.157.237; 2.B.157.238; 2.B.157.239; 2.B.157.154; 2.B.157.157; 2.B.157.166; 2.B.157.169; 2.B.157.172; 2.B.157.175; 2.B.157.240; 2.B.157.244; 2.B.166.228; 2.B.166.229; 2.B.166.230; 2.B.166.231; 2.B.166.236; 2.B.166.237; 2.B.166.238; 2.B.166.239; 2.B.166.154; 2.B.166.157; 2.B.166.166; 2.B.166.169; 2.B.166.172; 2.B.166.175; 2.B.166.240; 2.B.166.244; 2.B.169.228; 2.B.169.229; 2.B.169.230; 2.B.169.231; 2.B.169.236; 2.B.169.237; 2.B.169.238; 2.B.169.239; 2.B.169.154; 2.B.169.157; 2.B.169.166; 2.B.169.169; 2.B.169.172; 2.B.169.175; 2.B.169.240; 2.B.169.244; 2.B.172.228; 2.B.172.229; 2.B.172.230; 2.B.172.231; 2.B.172.236; 2.B.172.237; 2.B.172.238; 2.B.172.239; 2.B.172.154; 2.B.172.157; 2.B.172.166; 2.B.172.169; 2.B.172.172; 2.B.172.175; 2.B.172.240; 2.B.172.244; 2.B.175.228; 2.B.175.229; 2.B.175.230; 2.B.175.231; 2.B.175.236; 2.B.175.237; 2.B.175.238; 2.B.175.239; 2.B.175.154; 2.B.175.157; 2.B.175.166; 2.B.175.169; 2.B.175.172; 2.B.175.175; 2.B.175.240; 2.B.175.244; 2.B.240.228; 2.B.240.229; 2.B.240.230; 2.B.240.231; 2.B.240.236; 2.B.240.237; 2.B.240.238; 2.B.240.239; 2.B.240.154; 2.B.240.157; 2.B.240.166; 2.B.240.169; 2.B.240.172; 2.B.240.175; 2.B.240.240; 2.B.240.244; 2.B.244.228; 2.B.244.229; 2.B.244.230; 2.B.244.231; 2.B.244.236; 2.B.244.237; 2.B.244.238; 2.B.244.239; 2.B.244.154; 2.B.244.157; 2.B.244.166; 2.B.244.169; 2.B.244.172; 2.B.244.175; 2.B.244.240; 2.B.244.244;

Prodrugs of 2.D

2.D.228.228; 2.D.228.229; 2.D.228.230; 2.D.228.231; 2.D.228.236; 2.D.228.237; 2.D.228.238; 2.D.228.239; 2.D.228.154; 2.D.228.157; 2.D.228.166; 2.D.228.169; 2.D.228.172; 2.D.228.175; 2.D.228.240; 2.D.228.244; 2.D.229.228; 2.D.229.229; 2.D.229.230; 2.D.229.231; 2.D.229.236; 2.D.229.237; 2.D.229.238; 2.D.229.239;

2.D.229.154; 2.D.229.157; 2.D.229.166; 2.D.229.169; 2.D.229.172; 2.D.229.175; 2.D.229.240; 2.D.229.244; 2.D.230.228; 2.D.230.229; 2.D.230.230; 2.D.230.231; 2.D.230.236; 2.D.230.237; 2.D.230.238; 2.D.230.239; 2.D.230.154; 2.D.230.157; 2.D.230.166; 2.D.230.169; 2.D.230.172; 2.D.230.175; 2.D.230.240; 2.D.230.244; 2.D.231.228; 2.D.231.229; 2.D.231.230; 2.D.231.231; 2.D.231.236; 2.D.231.237; 2.D.231.238; 2.D.231.239; 2.D.231.154; 2.D.231.157; 2.D.231.166; 2.D.231.169; 2.D.231.172; 2.D.231.175; 2.D.231.240; 2.D.231.244; 2.D.236.228; 2.D.236.229; 2.D.236.230; 2.D.236.231; 2.D.236.236; 2.D.236.237; 2.D.236.238; 2.D.236.239; 2.D.236.154; 2.D.236.157; 2.D.236.166; 2.D.236.169; 2.D.236.172; 2.D.236.175; 2.D.236.240; 2.D.236.244; 2.D.237.228; 2.D.237.229; 2.D.237.230; 2.D.237.231; 2.D.237.236; 2.D.237.237; 2.D.237.238; 2.D.237.239; 2.D.237.154; 2.D.237.157; 2.D.237.166; 2.D.237.169; 2.D.237.172; 2.D.237.175; 2.D.237.240; 2.D.237.244; 2.D.238.228; 2.D.238.229; 2.D.238.230; 2.D.238.231; 2.D.238.236; 2.D.238.237; 2.D.238.238; 2.D.238.239; 2.D.238.154; 2.D.238.157; 2.D.238.166; 2.D.238.169; 2.D.238.172; 2.D.238.175; 2.D.238.240; 2.D.238.244; 2.D.239.228; 2.D.239.229; 2.D.239.230; 2.D.239.231; 2.D.239.236; 2.D.239.237; 2.D.239.238; 2.D.239.239; 2.D.239.154; 2.D.239.157; 2.D.239.166; 2.D.239.169; 2.D.239.172; 2.D.239.175; 2.D.239.240; 2.D.239.244; 2.D.154.228; 2.D.154.229; 2.D.154.230; 2.D.154.231; 2.D.154.236; 2.D.154.237; 2.D.154.238; 2.D.154.239; 2.D.154.154; 2.D.154.157; 2.D.154.166; 2.D.154.169; 2.D.154.172; 2.D.154.175; 2.D.154.240; 2.D.154.244; 2.D.157.228; 2.D.157.229; 2.D.157.230; 2.D.157.231; 2.D.157.236; 2.D.157.237; 2.D.157.238; 2.D.157.239; 2.D.157.154; 2.D.157.157; 2.D.157.166; 2.D.157.169; 2.D.157.172; 2.D.157.175; 2.D.157.240; 2.D.157.244; 2.D.166.228; 2.D.166.229; 2.D.166.230; 2.D.166.231; 2.D.166.236; 2.D.166.237; 2.D.166.238; 2.D.166.239; 2.D.166.154; 2.D.166.157; 2.D.166.166; 2.D.166.169; 2.D.166.172; 2.D.166.175; 2.D.166.240; 2.D.166.244; 2.D.169.228; 2.D.169.229; 2.D.169.230; 2.D.169.231; 2.D.169.236; 2.D.169.237; 2.D.169.238; 2.D.169.239; 2.D.169.154; 2.D.169.157; 2.D.169.166; 2.D.169.169; 2.D.169.172; 2.D.169.175; 2.D.169.240; 2.D.169.244; 2.D.172.228; 2.D.172.229; 2.D.172.230; 2.D.172.231; 2.D.172.236; 2.D.172.237; 2.D.172.238; 2.D.172.239; 2.D.172.154; 2.D.172.157; 2.D.172.166; 2.D.172.169; 2.D.172.172; 2.D.172.175; 2.D.172.240; 2.D.172.244; 2.D.175.228; 2.D.175.229; 2.D.175.230; 2.D.175.231; 2.D.175.236; 2.D.175.237; 2.D.175.238; 2.D.175.239; 2.D.175.154; 2.D.175.157; 2.D.175.166; 2.D.175.169; 2.D.175.172; 2.D.175.175; 2.D.175.240; 2.D.175.244; 2.D.240.228; 2.D.240.229; 2.D.240.230; 2.D.240.231; 2.D.240.236; 2.D.240.237; 2.D.240.238; 2.D.240.239; 2.D.240.154; 2.D.240.157; 2.D.240.166; 2.D.240.169; 2.D.240.172; 2.D.240.175; 2.D.240.240; 2.D.240.244; 2.D.244.228; 2.D.244.229; 2.D.244.230; 2.D.244.231; 2.D.244.236; 2.D.244.237; 2.D.244.238; 2.D.244.239; 2.D.244.154; 2.D.244.157; 2.D.244.166; 2.D.244.169; 2.D.244.172; 2.D.244.175; 2.D.244.240; 2.D.244.244;

Prodrugs of 2.AB

2.AB.228.228; 2.AB.228.229; 2.AB.228.230; 2.AB.228.231; 2.AB.228.236; 2.AB.228.237; 2.AB.228.238; 2.AB.228.239; 2.AB.228.154; 2.AB.228.157; 2.AB.228.166; 2.AB.228.169; 2.AB.228.172; 2.AB.228.175; 2.AB.228.240; 2.AB.228.244; 2.AB.229.228; 2.AB.229.229; 2.AB.229.230; 2.AB.229.231; 2.AB.229.236; 2.AB.229.237; 2.AB.229.238; 2.AB.229.239; 2.AB.229.154;

2.AB.229.157; 2.AB.229.166; 2.AB.229.169; 2.AB.229.172; 2.AB.229.175; 2.AB.229.240; 2.AB.229.244; 2.AB.230.228; 2.AB.230.229; 2.AB.230.230; 2.AB.230.231; 2.AB.230.236; 2.AB.230.237; 2.AB.230.238; 2.AB.230.239; 2.AB.230.154; 2.AB.230.157; 2.AB.230.166; 2.AB.230.169; 2.AB.230.172; 2.AB.230.175; 2.AB.230.240; 2.AB.230.244; 2.AB.231.228; 2.AB.231.229; 2.AB.231.230; 2.AB.231.231; 2.AB.231.236; 2.AB.231.237; 2.AB.231.238; 2.AB.231.239; 2.AB.231.154; 2.AB.231.157; 2.AB.231.166; 2.AB.231.169; 2.AB.231.172; 2.AB.231.175; 2.AB.231.240; 2.AB.231.244; 2.AB.236.228; 2.AB.236.229; 2.AB.236.230; 2.AB.236.231; 2.AB.236.236; 2.AB.236.237; 2.AB.236.238; 2.AB.236.239; 2.AB.236.154; 2.AB.236.157; 2.AB.236.166; 2.AB.236.169; 2.AB.236.172; 2.AB.236.175; 2.AB.236.240; 2.AB.236.244; 2.AB.237.228; 2.AB.237.229; 2.AB.237.23Q; 2.AB.237.231; 2.AB.237.236; 2.AB.237.237; 2.AB.237.238; 2.AB.237.239; 2.AB.237.154; 2.AB.237.157; 2.AB.237.166; 2.AB.237.169; 2.AB.237.172; 2.AB.237.175; 2.AB.237.240; 2.AB.237.244; 2.AB.238.228; 2.AB.238.229; 2.AB.238.230; 2.AB.238.231; 2.AB.238.236; 2.AB.238.237; 2.AB.238.238; 2.AB.238.239; 2.AB.238.154; 2.AB.238.157; 2.AB.238.166; 2.AB.238.169; 2.AB.238.172; 2.AB.238.175; 2.AB.238.240; 2.AB.238.244; 2.AB.239.228; 2.AB.239.229; 2.AB.239.230; 2.AB.239.231; 2.AB.239.236; 2.AB.239.237; 2.AB.239.238; 2.AB.239.239; 2.AB.239.154; 2.AB.239.157; 2.AB.239.166; 2.AB.239.169; 2.AB.239.172; 2.AB.239.175; 2.AB.239.240; 2.AB.239.244; 2.AB.154.228; 2.AB.154.229; 2.AB.154.230; 2.AB.154.231; 2.AB.154.236; 2.AB.154.237; 2.AB.154.238; 2.AB.154.239; 2.AB.154.154; 2.AB.154.157; 2.AB.154.166; 2.AB.154.169; 2.AB.154.172; 2.AB.154.175; 2.AB.154.240; 2.AB.154.244; 2.AB.157.228; 2.AB.157.229; 2.AB.157.230; 2.AB.157.231; 2.AB.157.236; 2.AB.157.237; 2.AB.157.238; 2.AB.157.239; 2.AB.157.154; 2.AB.157.157; 2.AB.157.166; 2.AB.157.169; 2.AB.157.172; 2.AB.157.175; 2.AB.157.240; 2.AB.157.244; 2.AB.166.228; 2.AB.166.229; 2.AB.166.230; 2.AB.166.231; 2.AB.166.236; 2.AB.166.237; 2.AB.166.238; 2.AB.166.239; 2.AB.166.154; 2.AB.166.157; 2.AB.166.166; 2.AB.166.169; 2.AB.166.172; 2.AB.166.175; 2.AB.166.240; 2.AB.166.244; 2.AB.169.228; 2.AB.169.229; 2.AB.169.230; 2.AB.169.231; 2.AB.169.236; 2.AB.169.237; 2.AB.169.238; 2.AB.169.239; 2.AB.169.154; 2.AB.169.157; 2.AB.169.166; 2.AB.169.169; 2.AB.169.172; 2.AB.169.175; 2.AB.169.240; 2.AB.169.244; 2.AB.172.228; 2.AB.172.229; 2.AB.172.230; 2.AB.172.231; 2.AB.172.236; 2.AB.172.237; 2.AB.172.238; 2.AB.172.239; 2.AB.172.154; 2.AB.172.157; 2.AB.172.166; 2.AB.172.169; 2.AB.172.172; 2.AB.172.175; 2.AB.172.240; 2.AB.172.244; 2.AB.175.228; 2.AB.175.229; 2.AB.175.230; 2.AB.175.231; 2.AB.175.236; 2.AB.175.237; 2.AB.175.238; 2.AB.175.239; 2.AB.175.154; 2.AB.175.157; 2.AB.175.166; 2.AB.175.169; 2.AB.175.172; 2.AB.175.175; 2.AB.175.240; 2.AB.175.244; 2.AB.240.228; 2.AB.240.229; 2.AB.240.230; 2.AB.240.231; 2.AB.240.236; 2.AB.240.237; 2.AB.240.238; 2.AB.240.239; 2.AB.240.154; 2.AB.240.157; 2.AB.240.166; 2.AB.240.169; 2.AB.240.172; 2.AB.240.175; 2.AB.240.240; 2.AB.240.244; 2.AB.244.228; 2.AB.244.229; 2.AB.244.230; 2.AB.244.231; 2.AB.244.236; 2.AB.244.237; 2.AB.244.238; 2.AB.244.239; 2.AB.244.154; 2.AB.244.157;

2.AB.244.166; 2.AB.244.169; 2.AB.244.172; 2.AB.244.175; 2.AB.244.240; 2.AB.244.244;

Prodrugs of 2.BI

2.BI.228.228; 2.BI.228.229; 2.BI.228.230; 2.BI.228.231; 2.BI.228.236; 2.BI.228.237; 2.BI.228.238; 2.BI.228.239; 2.BI.228.154; 2.BI.228.157; 2.BI.228.166; 2.BI.228.169; 2.BI.228.172; 2.BI.228.175; 2.BI.228.240; 2.BI.228.244; 2.BI.229.228; 2.BI.229.229; 2.BI.229.230; 2.BI.229.231; 2.BI.229.236; 2.BI.229.237; 2.BI.229.238; 2.BI.229.239; 2.BI.229.154; 2.BI.229.157; 2.BI.229.166; 2.BI.229.169; 2.BI.229.172; 2.BI.229.175; 2.BI.229.240; 2.BI.229.244; 2.BI.230.228; 2.BI.230.229; 2.BI.230.230; 2.BI.230.231; 2.BI.230.236; 2.BI.230.237; 2.BI.230.238; 2.BI.230.239; 2.BI.230.154; 2.BI.230.157; 2.BI.230.166; 2.BI.230.169; 2.BI.230.172; 2.BI.230.175; 2.BI.230.240; 2.BI.230.244; 2.BI.231.228; 2.BI.231.229; 2.BI.231.230; 2.BI.231.231; 2.BI.231.236; 2.BI.231.237; 2.BI.231.238; 2.BI.231.239; 2.BI.231.154; 2.BI.231.157; 2.BI.231.166; 2.BI.231.169; 2.BI.231.172; 2.BI.231.175; 2.BI.231.240; 2.BI.231.244; 2.BI.236.228; 2.BI.236.229; 2.BI.236.230; 2.BI.236.231; 2.BI.236.236; 2.BI.236.237; 2.BI.236.238; 2.BI.236.239; 2.BI.236.154; 2.BI.236.157; 2.BI.236.166; 2.BI.236.169; 2.BI.236.172; 2.BI.236.175; 2.BI.236.240; 2.BI.236.244; 2.BI.237.228; 2.BI.237.229; 2.BI.237.230; 2.BI.237.231; 2.BI.237.236; 2.BI.237.237; 2.BI.237.238; 2.BI.237.239; 2.BI.237.154; 2.BI.237.157; 2.BI.237.166; 2.BI.237.169; 2.BI.237.172; 2.BI.237.175; 2.BI.237.240; 2.BI.237.244; 2.BI.238.228; 2.BI.238.229; 2.BI.238.230; 2.BI.238.231; 2.BI.238.236; 2.BI.238.237; 2.BI.238.238; 2.BI.238.239; 2.BI.238.154; 2.BI.238.157; 2.BI.238.166; 2.BI.238.169; 2.BI.238.172; 2.BI.238.175; 2.BI.238.240; 2.BI.238.244; 2.BI.239.228; 2.BI.239.229; 2.BI.239.230; 2.BI.239.231; 2.BI.239.236; 2.BI.239.237; 2.BI.239.238; 2.BI.239.239; 2.BI.239.154; 2.BI.239.157; 2.BI.239.166; 2.BI.239.169; 2.BI.239.172; 2.BI.239.175; 2.BI.239.240; 2.BI.239.244; 2.BI.154.228; 2.BI.154.229; 2.BI.154.230; 2.BI.154.231; 2.BI.154.236; 2.BI.154.237; 2.BI.154.238; 2.BI.154.239; 2.BI.154.154; 2.BI.154.157; 2.BI.154.166; 2.BI.154.169; 2.BI.154.172; 2.BI.154.175; 2.BI.154.240; 2.BI.154.244; 2.BI.157.228; 2.BI.157.229; 2.BI.157.230; 2.BI.157.231; 2.BI.157.236; 2.BI.157.237; 2.BI.157.238; 2.BI.157.239; 2.BI.157.154; 2.BI.157.157; 2.BI.157.166; 2.BI.157.169; 2.BI.157.172; 2.BI.157.175; 2.BI.157.240; 2.BI.157.244; 2.BI.166.228; 2.BI.166.229; 2.BI.166.230; 2.BI.166.231; 2.BI.166.236; 2.BI.166.237; 2.BI.166.238; 2.BI.166.239; 2.BI.166.154; 2.BI.166.157; 2.BI.166.166; 2.BI.166.169; 2.BI.166.172; 2.BI.166.175; 2.BI.166.240; 2.BI.166.244; 2.BI.169.228; 2.BI.169.229; 2.BI.169.230; 2.BI.169.231; 2.BI.169.236; 2.BI.169.237; 2.BI.169.238; 2.BI.169.239; 2.BI.169.154; 2.BI.169.157; 2.BI.169.166; 2.BI.169.169; 2.BI.169.172; 2.BI.169.175; 2.BI.169.240; 2.BI.169.244; 2.BI.172.228; 2.BI.172.229; 2.BI.172.230; 2.BI.172.231; 2.BI.172.236; 2.BI.172.237; 2.BI.172.238; 2.BI.172.239; 2.BI.172.154; 2.BI.172.157; 2.BI.172.166; 2.BI.172.169; 2.BI.172.172; 2.BI.172.175; 2.BI.172.240; 2.BI.172.244; 2.BI.175.228; 2.BI.175.229; 2.BI.175.230; 2.BI.175.231; 2.BI.175.236; 2.BI.175.237; 2.BI.175.238; 2.BI.175.239; 2.BI.175.154; 2.BI.175.157; 2.BI.175.166; 2.BI.175.169; 2.BI.175.172; 2.BI.175.175; 2.BI.175.240; 2.BI.175.244; 2.BI.240.228; 2.BI.240.229; 2.BI.240.230; 2.BI.240.231; 2.BI.240.236; 2.BI.240.237; 2.BI.240.238; 2.BI.240.239; 2.BI.240.154; 2.BI.240.157; 2.BI.240.166; 2.BI.240.169; 2.BI.240.172; 2.BI.240.175; 2.BI.240.240; 2.BI.240.244; 2.BI.244.228; 2.BI.244.229; 2.BI.244.230; 2.BI.244.231; 2.BI.244.236; 2.BI.244.237;

2.BI.244.238; 2.BI.244.239; 2.BI.244.154; 2.BI.244.157; 2.BI.244.166; 2.BI.244.169; 2.BI.244.172; 2.BI.244.175; 2.BI.244.240; 2.BI.244.244;

Prodrugs of2.1

2.1.228.228; 2.1.228.229; 2.1.228.230; 2.1.228.231; 2.1.228.236; 2.1.228.237; 2.1.228.238; 2.1.228.239; 2.1.228.154; 2.1.228.157; 2.1.228.166; 2.1.228.169; 2.1.228.172; 2.1.228.175; 2.1.228.240; 2.1.228.244; 2.1.229.228; 2.1.229.229; 2.1.229.230; 2.1.229.231; 2.1.229.236; 2.1.229.237; 2.1.229.238; 2.1.229.239; 2.1.229.154; 2.1.229.157; 2.1.229.166; 2.1.229.169; 2.1.229.172; 2.1.229.175; 2.1.229.240; 2.1.229.244; 2.1.230.228; 2.1.230.229; 2.1.230.230; 2.1.230.231; 2.1.230.236; 2.1.230.237; 2.1.230.238; 2.1.230.239; 2.1.230.154; 2.1.230.157; 2.1.230.166; 2.1.230.169; 2.1.230.172; 2.1.230.175; 2.1.230.240; 2.1.230.244; 2.1.231.228; 2.1.231.229; 2.1.231.230; 2.1.231.231; 2.1.231.236; 2.1.231.237; 2.1.231.238; 2.1.231.239; 2.1.231.154; 2.1.231.157; 2.1.231.166; 2.1.231.169; 2.1.231.172; 2.1.231.175; 2.1.231.240; 2.1.231.244; 2.1.236.228; 2.1.236.229; 2.1.236.230; 2.1.236.231; 2.1.236.236; 2.1.236.237; 2.1.236.238; 2.1.236.239; 2.1.236.154; 2.1.236.157; 2.1.236.166; 2.1.236.169; 2.1.236.172; 2.1.236.175; 2.1.236.240; 2.1.236.244; 2.1.237.228; 2.1.237.229;2.1.237.230; 2.1.237.231; 2.1.237.236; 2.1.237.237; 2.1.237.238; 2.1.237.239; 2.1.237.154; 2.1.237.157; 2.1.237.166; 2.1.237.169; 2.1.237.172; 2.1.237.175; 2.1.237.240; 2.1.237.244; 2.1.238.228; 2.1.238.229; 2.1.238.230; 2.1.238.231; 2.1.238.236; 2.1.238.237; 2.1.238.238; 2.1.238.239; 2.1.238.154; 2.1.238.157; 2.1.238.166; 2.1.238.169; 2.1.238.172; 2.1.238.175; 2.1.238.240; 2.1.238.244; 2.1.239.228; 2.1.239.229; 2.1.239.230; 2.1.239.231; 2.1.239.236; 2.1.239.237; 2.1.239.238; 2.1.239.239; 2.1.239.154; 2.1.239.157; 2.1.239.166; 2.1.239.169; 2.1.239.172; 2.1.239.175; 2.1.239.240; 2.1.239.244; 2.1.154.228; 2.1.154.229; 2.1.154.230; 2.1.154.231; 2.1.154.236; 2.1.154.237; 2.1.154.238; 2.1.154.239; 2.1.154.154; 2.1.154.157; 2.1.154.166; 2.1.154.169; 2.1.154.172; 2.1.154.175; 2.1.154.240; 2.1.154.244; 2.1.157.228; 2.1.157.229; 2.1.157.230; 2.1.157.231; 2.1.157.236; 2.1.157.237; 2.1.157.238; 2.1.157.239; 2.1.157.154; 2.1.157.157; 2.1.157.166; 2.1.157.169; 2.1.157.172; 2.1.157.175; 2.1.157.240; 2.1.157.244; 2.1.166.228; 2.1.166.229; 2.1.166.230; 2.1.166.231; 2.1.166.236; 2.1.166.237; 2.1.166.238; 2.1.166.239; 2.1.166.154; 2.1.166.157; 2.1.166.166; 2.1.166.169; 2.1.166.172; 2.1.166.175; 2.1.166.240; 2.1.166.244; 2.1.169.228; 2.1.169.229; 2.1.169.230; 2.1.169.231; 2.1.169.236; 2.1.169.237; 2.1.169.238; 2.1.169.239; 2.1.169.154; 2.1.169.157; 2.1.169.166; 2.1.169.169; 2.1.169.172; 2.1.169.175; 2.1.169.240; 2.1.169.244; 2.1.172.228; 2.1.172.229; 2.1.172.230; 2.1.172.231; 2.1.172.236; 2.1.172.237; 2.1.172.238; 2.1.172.239; 2.1.172.154; 2.1.172.157; 2.1.172.166; 2.1.172.169; 2.1.172.172; 2.1.172.175; 2.1.172.240; 2.1.172.244; 2.1.175.228; 2.1.175.229; 2.1.175.230; 2.1.175.231; 2.1.175.236; 2.1.175.237; 2.1.175.238; 2.1.175.239; 2.1.175.154; 2.1.175.157; 2.1.175.166; 2.1.175.169; 2.1.175.172; 2.1.175.175; 2.1.175.240; 2.1.175.244; 2.1.240.228; 2.1.240.229; 2.1.240.230; 2.1.240.231; 2.1.240.236; 2.1.240.237; 2.1.240.238; 2.1.240.239; 2.1.240.154; 2.1.240.157; 2.1.240.166; 2.1.240.169; 2.1.240.172; 2.1.240.175; 2.1.240.240; 2.1.240.244; 2.1.244.228; 2.1.244.229; 2.1.244.230; 2.1.244.231; 2.1.244.236; 2.1.244.237; 2.1.244.238; 2.1.244.239; 2.1.244.154; 2.1.244.157; 2.1.244.166; 2.1.244.169; 2.1.244.172; 2.1.244.175; 2.1.244.240; 2.1.244.244;

Prodrugs of 2.T

2.J.228.228; 2.J.228.229; 2.J.228.230; 2.J.228.231; 2.J.228.236; 2.J.228.237; 2.J.228.238; 2J.228.239; 2.J.228.154; 2.J.228.157; 2.J.228.166; 2.J.228.169; 2.J.228.172; 2.J.228.175; 2.J.228.240; 2.J.228.244; 2.J.229.228; 2.J.229.229; 2.J.229.230; 2.J.229.231;

2.J.229.236; 2.J.229.237; 2.J.229.238; 2.J.229.239; 2.J.229.154; 2.J.229.157; 2.J.229.166; 2.J.229.169; 2.J.229.172; 2.J.229.175; 2.J.229.240; 2.J.229.244; 2.J.230.228; 2.J.230.229; 2.J.230.230; 2J.230.231; 2.J.230.236; 2.J.230.237; 2.J.230.238; 2.J.230.239; 2.J.230.154; 2.J.230.157; 2.J.230.166; 2.J.230.169; 2.J.230.172; 2.J.230.175; 2.J.230.240; 2 J.230.244; 2.J.231.228; 2J.231.229; 2.J.231.230; 2J.231.231; 2J.231.236; 2J.231.237; 2J.231.238; 2J.231.239; 2J.231.154; 2J.231.157; 2J.231.166; 2J.231.169; 2J.231.172; 2J.231.175; 2J.231.240; 2J.231.244; 2J.236.228; 2J.236.229; 2J.236.230; 2J.236.231; 2J.236.236; 2J.236.237; 2J.236.238; 2J.236.239; 2J.236.154; 2 J.236.157; 2J.236.166; 2.J.236.169; 2J.236.172; 2 J.236.175; 2.J.236.240; 2J.236.244; 2.J.237.228; 2.J.237.229; 2J.237.230; 2J.237.231; 2J.237.236; 2J.237.237; 2J.237.238; 2J.237.239; 2 J.237.154; 2J.237.157; 2.J.237.166; 2J.237.169; 2J.237.172; 2J.237.175; 2J.237.240; 2J.237.244; 2J.238.228; 2J.238.229; 2.J.238.230; 2J.238.231; 2J.238.236; 2J.238.237; 2J.238.238; 2J.238.239; 2J.238.154; 2J.238.157; 2J.238.166; 2 J.238.169; 2J.238.172; 2J.238.175; 2J.238.240; 2J.238.244; 2J.239.228; 2J.239.229; 2J.239.230; 2J.239.231; 2J.239.236; 2J.239.237; 2J.239.238; 2J.239.239; 2J.239.154; 2J.239.157; 2 J.239.166; 2J.239.169; 2J.239.172; 2J.239.175; 2J.239.240; 2J.239.244; 2J.154.228; 2J.154.229; 2J.154.230; 2J.154.231; 2J.154.236; 2J.154.237; 2 J.154.238; 2.J.154.239; 2 J.154.154; 2J.154.157; 2J.154.166; 2J.154.169; 2J.154.172; 2J.154.175; 2 J.154.240; 2 J.154.244; 2J.157.228; 2J.157.229; 2J.157.230; 2J.157.231; 2 J.157.236; 2J.157.237; 2 J.157.238; 2J.157.239; 2J.157.154; 2J.157.157; 2 J.157.166; 2 J.157.169; 2.J.157.172; 2J.157.175; 2J.157.240; 2J.157.244; 2J.166.228; 2J.166.229; 2 J.166.230; 2J.166.231; 2 J.166.236; 2J.166.237; 2J.166.238; 2 J.166.239; 2 J.166.154; 2J.166.157; 2.J.166.166; 2 J.166.169; 2J.166.172; 2J.166.175; 2J.166.240; 2J.166.244; 2J.169.228; 2 J.169.229; 2J.169.230; 2J.169.231; 2J.169.236; 2J.169.237; 2J.169.238; 2 J.169.239; 2J.169.154; 2 J.169.157; 2J.169.166; 2J.169.169; 2J.169.172; 2J.169.175; 2J.169.240; 2 J.169.244; 2J.172.228; 2J.172.229; 2J.172.230; 2J.172.231; 2J.172.236; 2J.172.237; 2 J.172.238; 2 J.172.239; 2J.172.154; 2.J.172.157; 2J.172.166; 2J.172.169; 2J.172.172; 2 J.172.175; 2J.172.240; 2J.172.244; 2J.175.228; 2J.175.229; 2J.175.230; 2J.175.231; 2 J.175.236; 2J.175.237; 2J.175.238; 2.J.175.239; 2J.175.154; 2J.175.157; 2J.175.166; 2J.175.169; 2J.175.172; 2J.175.175; 2J.175.240; 2J.175.244; 2J.240.228; 2J.240.229; 2J.240.230; 2J.240.231; 2J.240.236; 2.J.240.237; 2J.240.238; 2J.240.239; 2J.240.154; 2J.240.157; 2 J.240.166; 2J.240.169; 2J.240.172; 2J.240.175; 2J.240.240; 2J.240.244; 2.J.244.228; 2J.244.229; 2J.244.230; 2J.244.231; 2J.244.236; 2J.244.237; 2J.244.238; 2.J.244.239; 2J.244.154; 2J.244.157; 2J.244.166; 2J.244.169; 2J.244.172; 2J.244.175; 2.J.244.240; 2J.244.244;

Prodrugs of 2.L

2.L.228.228; 2.L.228.229; 2.L.228.230; 2.L.228.231; 2.L.228.236; 2.L.228.237; 2.L.228.238; 2.L.228.239; 2.L.228.154; 2.L.228.157; 2.L.228.166; 2.L.228.169; 2.L.228.172; 2.L.228.175; 2.L.228.240; 2.L.228.244; 2.L.229.228; 2.L.229.229; 2.L.229.230; 2.L.229.231; 2.L.229.236; 2.L.229.237; 2.L.229.238; 2.L.229.239; 2.L.229.154; 2.L.229.157; 2.L.229.166; 2.L.229.169; 2.L.229.172; 2.L.229.175; 2.L.229.240; 2.L.229.244; 2.L.230.228; 2.L.230.229; 2.L.230.230; 2.L.230.231; 2.L.230.236; 2.L.230.237; 2.L.230.238; 2.L.230.239; 2.L.230.154; 2.L.230.157; 2.L.230.166; 2.L.230.169; 2.L.230.172; 2.L.230.175; 2.L.230.240; 2.L.230.244; 2.L.231.228; 2.L.231.229; 2.L.231.230; 2.L.231.231; 2.L.231.236; 2.L.231.237; 2.L.231.238; 2.L.231.239; 2.L.231.154; 2.L.231.157; 2.L.231.166; 2.L.231.169;

2.L.231.172; 2.L.231.175; 2.L.231.240; 2.L.231.244; 2.L.236.228; 2.L.236.229; 2.L.236.230; 2.L.236.231; 2.L.236.236; 2.L.236.237; 2.L.236.238; 2.L.236.239; 2.L.236.154; 2.L.236.157; 2.L.236.166; 2.L.236.169; 2.L.236.172; 2.L.236.175; 2.L.236.240; 2.L.236.244; 2.L.237.228; 2.L.237.229; 2.L.237.230; 2.L.237.231; 2.L.237.236; 2.L.237.237; 2.L.237.238; 2.L.237.239; 2.L.237.154; 2.L.237.157; 2.L.237.166; 2.L.237.169; 2.L.237.172; 2.L.237.175; 2.L.237.240; 2.L.237.244; 2.L.238.228; 2.L.238.229; 2.L.238.230; 2.L.238.231; 2.L.238.236; 2.L.238.237; 2.L.238.238; 2.L.238.239; 2.L.238.154; 2.L.238.157; 2.L.238.166; 2.L.238.169; 2.L.238.172; 2.L.238.175; 2.L.238.240; 2.L.238.244; 2.L.239.228; 2.L.239.229; 2.L.239.230; 2.L.239.231; 2.L.239.236; 2.L.239.237; 2.L.239.238; 2.L.239.239; 2.L.239.154; 2.L.239.157; 2.L.239.166; 2.L.239.169; 2.L.239.172; 2.L.239.175; 2.L.239.240; 2.L.239.244; 2.L.154.228; 2.L.154.229; 2.L.154.230; 2.L.154.231; 2.L.154.236; 2.L.154.237; 2.L.154.238; 2.L.154.239; 2.L.154.154; 2.L.154.157; 2.L.154.166; 2.L.154.169; 2.L.154.172; 2.L.154.175; 2.L.154.240; 2.L.154.244; 2.L.157.228; 2.L.157.229; 2.L.157.230; 2.L.157.231; 2.L.157.236; 2.L.157.237; 2.L.157.238; 2.L.157.239; 2.L.157.154; 2.L.157.157; 2.L.157.166; 2.L.157.169; 2.L.157.172; 2.L.157.175; 2.L.157.240; 2.L.157.244; 2.L.166.228; 2.L.166.229; 2.L.166.230; 2.L.166.231; 2.L.166.236; 2.L.166.237; 2.L.166.238; 2.L.166.239; 2.L.166.154; 2.L.166.157; 2.L.166.166; 2.L.166.169; 2.L.166.172; 2.L.166.175; 2.L.166.240; 2.L.166.244; 2.L.169.228; 2.L.169.229; 2.L.169.230; 2.L.169.231; 2.L.169.236; 2.L.169.237; 2.L.169.238; 2.L.169.239; 2.L.169.154; 2.L.169.157; 2.L.169.166; 2.L.169.169; 2.L.169.172; 2.L.169.175; 2.L.169.240; 2.L.169.244; 2.L.172.228; 2.L.172.229; 2.L.172.230; 2.L.172.231; 2.L.172.236; 2.L.172.237; 2.L.172.238; 2.L.172.239; 2.L.172.154; 2.L.172.157; 2.L.172.166; 2.L.172.169; 2.L.172.172; 2.L.172.175; 2.L.172.240; 2.L.172.244; 2.L.175.228; 2.L.175.229; 2.L.175.230; 2.L.175.231; 2.L.175.236; 2.L.175.237; 2.L.175.238; 2.L.175.239; 2.L.175.154; 2.L.175.157; 2.L.175.166; 2.L.175.169; 2.L.175.172; 2.L.175.175; 2.L.175.240; 2.L.175.244; 2.L.240.228; 2.L.240.229; 2.L.240.230; 2.L.240.231; 2.L.240.236; 2.L.240.237; 2.L.240.238; 2.L.240.239; 2.L.240.154; 2.L.240.157; 2.L.240.166; 2.L.240.169; 2.L.240.172; 2.L.240.175; 2.L.240.240; 2.L.240.244; 2.L.244.228; 2.L.244.229; 2.L.244.230; 2.L.244.231; 2.L.244.236; 2.L.244.237; 2.L.244.238; 2.L.244.239; 2.L.244.154; 2.L.244.157; 2.L.244.166; 2.L.244.169; 2.L.244.172; 2.L.244.175; 2.L.244.240; 2.L.244.244;

Prodrugs of 2.O

2.O.228.228; 2.O.228.229; 2.O.228.230; 2.O.228.231; 2.O.228.236; 2.O.228.237; 2.O.228.238; 2.O.228.239; 2.O.228.154; 2.O.228.157; 2.O.228.166; 2.O.228.169; 2.O.228.172; 2.O.228.175; 2.O.228.240; 2.O.228.244; 2.O.229.228; 2.O.229.229; 2.O.229.230; 2.O.229.231; 2.O.229.236; 2.O.229.237; 2.O.229.238; 2.O.229.239; 2.O.229.154; 2.O.229.157; 2.O.229.166; 2.O.229.169; 2.O.229.172; 2.O.229.175; 2.O.229.240; 2.O.229.244; 2.O.230.228; 2.O.230.229; 2.O.230.230; 2.O.230.231; 2.O.230.236; 2.O.230.237; 2.O.230.238; 2.O.230.239; 2.O.230.154; 2.O.230.157; 2.O.230.166; 2.O.230.169; 2.O.230.172; 2.O.230.175; 2.O.230.240; 2.O.230.244; 2.O.231.228; 2.O.231.229; 2.O.231.230; 2.O.231.231; 2.O.231.236; 2.O.231.237; 2.O.231.238; 2.O.231.239; 2.O.231.154; 2.O.231.157; 2.O.231.166; 2.O.231.169; 2.O.231.172; 2.O.231.175; 2.O.231.240; 2.O.231.244; 2.O.236.228; 2.O.236.229;

2.O.236.230; 2.O.236.231; 2.O.236.236; 2.O.236.237; 2.O.236.238; 2.O.236.239; 2.O.236.154; 2.O.236.157; 2.O.236.166; 2.O.236.169; 2.O.236.172; 2.O.236.175; 2.O.236.240; 2.O.236.244; 2.O.237.228; 2.O.237.229; 2.O.237.230; 2.O.237.231; 2.O.237.236; 2.O.237.237; 2.O.237.238; 2.O.237.239; 2.O.237.154; 2.O.237.157; 2.O.237.166; 2.O.237.169; 2.O.237.172; 2.O.237.175; 2.O.237.240; 2.O.237.244; 2.O.238.228; 2.O.238.229; 2.O.238.230; 2.O.238.231; 2.O.238.236; 2.O.238.237; 2.O.238.238; 2.O.238.239; 2.O.238.154; 2.O.238.157; 2.O.238.166; 2.O.238.169; 2.O.238.172; 2.O.238.175; 2.O.238.240; 2.O.238.244; 2.O.239.228; 2.O.239.229; 2.O.239.230; 2.O.239.231; 2.O.239.236; 2.O.239.237; 2.O.239.238; 2.O.239.239; 2.O.239.154; 2.O.239.157; 2.O.239.166; 2.O.239.169; 2.O.239.172; 2.O.239.175; 2.O.239.240; 2.O.239.244; 2.O.154.228; 2.O.154.229; 2.O.154.230; 2.O.154.231; 2.O.154.236; 2.O.154.237; 2.O.154.238; 2.O.154.239; 2.O.154.154; 2.O.154.157; 2.O.154.166; 2.O.154.169; 2.O.154.172; 2.O.154.175; 2.O.154.240; 2.O.154.244; 2.O.157.228; 2.O.157.229; 2.O.157.230; 2.O.157.231; 2.O.157.236; 2.O.157.237; 2.O.157.238; 2.O.157.239; 2.O.157.154; 2.O.157.157; 2.O.157.166; 2.O.157.169; 2.O.157.172; 2.O.ϊ57.175; 2.O.157.240; 2.O.157.244; 2.O.166.228; 2.O.166.229; 2.O.166.230; 2.O.166.231; 2.O.166.236; 2.O.166.237; 2.O.166.238; 2.O.166.239; 2.O.166.154; 2.O.166.157; 2.O.166.166; 2.O.166.169; 2.O.166.172; 2.O.166.175; 2.O.166.240; 2.O.166.244; 2.O.169.228; 2.O.169.229; 2.O.169.230; 2.O.169.231; 2.O.169.236; 2.O.169.237; 2.O.169.238; 2.O.169.239; 2.O.169.154; 2.O.169.157; 2.O.169.166; 2.O.169.169; 2.O.169.172; 2.O.169.175; 2.O.169.240; 2.O.169.244; 2.O.172.228; 2.O.172.229; 2.O.172.230; 2.O.172.231; 2.O.172.236; 2.O.172.237; 2.O.172.238; 2.O.172.239; 2.O.172.154; 2.O.172.157; 2.O.172.166; 2.O.172.169; 2.O.172.172; 2.O.172.175; 2.O.172.240; 2.O.172.244; 2.O.175.228; 2.O.175.229; 2.O.175.230; 2.O.175.231; 2.O.175.236; 2.O.175.237; 2.O.175.238; 2.O.175.239; 2.O.175.154; 2.O.175.157; 2.O.175.166; 2.O.175.169; 2.O.175.172; 2.O.175.175; 2.O.175.240; 2.O.175.244; 2.O.240.228; 2.O.240.229; 2.O.240.230; 2.O.240.231; 2.O.240.236; 2.O.240.237; 2.O.240.238; 2.O.240.239; 2.O.240.154; 2.O.240.157; 2.O.240.166; 2.O.240.169; 2.O.240.172; 2.O.240.175; 2.O.240.240; 2.O.240.244; 2.O.244.228; 2.O.244.229; 2.O.244.230; 2.O.244.231; 2.O.244.236; 2.O.244.237; 2.O.244.238; 2.O.244.239; 2.O.244.154; 2.O.244.157; 2.O.244.166; 2.O.244.169; 2.O.244.172; 2.O.244.175; 2.O.244.240; 2.O.244.244;

Prodrugs of 2.P

2.P.228.228; 2.P.228.229; 2.P.228.230; 2.P.228.231; 2.P.228.236; 2.P.228.237; 2.P.228.238; 2.P.228.239; 2.P.228.154; 2.P.228.157; 2.P.228.166; 2.P.228.169; 2.P.228.172; 2.P.228.175; 2.P.228.240; 2.P.228.244; 2.P.229.228; 2.P.229.229; 2.P.229.230; 2.P.229.231; 2.P.229.236; 2.P.229.237; 2.P.229.238; 2.P.229.239; 2.P.229.154; 2.P.229.157; 2.P.229.166; 2.P.229.169; 2.P.229.172; 2.P.229.175; 2.P.229.240; 2.P.229.244; 2.P.230.228; 2.P.230.229; 2.P.230.230; 2.P.230.231; 2.P.230.236; 2.P.230.237; 2.P.230.238; 2.P.230.239; 2.P.230.154; 2.P.230.157; 2.P.230.166; 2.P.230.169; 2.P.230.172; 2.P.230.175; 2.P.230.240; 2.P.230.244; 2.P.231.228; 2.P.231.229; 2.P.231.230; 2.P.231.231; 2.P.231.236; 2.P.231.237; 2.P.231.238; 2.P.231.239; 2.P.231.154; 2.P.231.157; 2.P.231.166; 2.P.231.169; 2.P.231.172; 2.P.231.175; 2.P.231.240; 2.P.231.244; 2.P.236.228; 2.P.236.229; 2.P.236.230; 2.P.236.231; 2.P.236.236; 2.P.236.237; 2.P.236.238; 2.P.236.239;

2.P.236.154; 2.P.236.157; 2.P.236.166; 2.P.236.169; 2.P.236.172; 2.P.236.175; 2.P.236.240; 2.P.236.244; 2.P.237.228; 2.P.237.229; 2.P.237.230; 2.P.237.231; 2.P.237.236; 2.P.237.237; 2.P.237.238; 2.P.237.239; 2.P.237.154; 2.P.237.157; 2.P.237.166; 2.P.237.169; 2.P.237.172; 2.P.237.175; 2.P.237.240; 2.P.237.244; 2.P.238.228; 2.P.238.229; 2.P.238.230; 2.P.238.231; 2.P.238.236; 2.P.238.237; 2.P.238.238; 2.P.238.239; 2.P.238.154; 2.P.238.157; 2.P.238.166; 2.P.238.169; 2.P.238.172; 2.P.238.175; 2.P.238.240; 2.P.238.244; 2.P.239.228; 2.P.239.229; 2.P.239.230; 2.P.239.231; 2.P.239.236; 2.P.239.237; 2.P.239.238; 2.P.239.239; 2.P.239.154; 2.P.239.157; 2.P.239.166; 2.P.239.169; 2.P.239.172; 2.P.239.175; 2.P.239.240; 2.P.239.244; 2.P.154.228; 2.P.154.229; 2.P.154.230; 2.P.154.231; 2.P.154.236; 2.P.154.237; 2.P.154.238; 2.P.154.239; 2.P.154.154; 2.P.154.157; 2.P.154.166; 2.P.154.169; 2.P.154.172; 2.P.154.175; 2.P.154.240; 2.P.154.244; 2.P.157.228; 2.P.157.229; 2.P.157.230; 2.P.157.231; 2.P.157.236; 2.P.157.237; 2.P.157.238; 2.P.157.239; 2.P.157.154; 2.P.157.157; 2.P.157.166; 2.P.157.169; 2.P.157.172; 2.P.157.175; 2.P.157.240; 2.P.157.244; 2.P.166.228; 2.P.166.229; 2.P.166.230; 2.P.166.231; 2.P.166.236; 2.P.166.237; 2.P.166.238; 2.P.166.239; 2.P.166.154; 2.P.166.157; 2.P.166.166; 2.P.166.169; 2.P.166.172; 2.P.166.175; 2.P.166.240; 2.P.166.244; 2.P.169.228; 2.P.169.229; 2.P.169.230; 2.P.169.231; 2.P.169.236; 2.P.169.237; 2.P.169.238; 2.P.169.239; 2.P.169.154; 2.P.169.157; 2.P.169.166; 2.P.169.169; 2.P.169.172; 2.P.169.175; 2.P.169.240; 2.P.169.244; 2.P.172.228; 2.P.172.229; 2.P.172.230; 2.P.172.231; 2.P.172.236; 2.P.172.237; 2.P.172.238; 2.P.172.239; 2.P.172.154; 2.P.172.157; 2.P.172.166; 2.P.172.169; 2.P.172.172; 2.P.172.175; 2.P.172.240; 2.P.172.244; 2.P.175.228; 2.P.175.229; 2.P.175.230; 2.P.175.231; 2.P.175.236; 2.P.175.237; 2.P.175.238; 2.P.175.239; 2.P.175.154; 2.P.175.157; 2.P.175.166; 2.P.175.169; 2.P.175.172; 2.P.175.175; 2.P.175.240; 2.P.175.244; 2.P.240.228; 2.P.240.229; 2.P.240.230; 2.P.240.231; 2.P.240.236; 2.P.240.237; 2.P.240.238; 2.P.240.239; 2.P.240.154; 2.P.240.157; 2.P.240.166; 2.P.240.169; 2.P.240.172; 2.P.240.175; 2.P.240.240; 2.P.240.244; 2.P.244.228; 2.P.244.229; 2.P.244.230; 2.P.244.231; 2.P.244.236; 2.P.244.237; 2.P.244.238; 2.P.244.239; 2.P.244.154; 2.P.244.157; 2.P.244.166; 2.P.244.169; 2.P.244.172; 2.P.244.175; 2.P.244.240; 2.P.244.244;

Prodrugs of 2.U

2.U.228.228; 2.U.228.229; 2.U.228.230; 2.U.228.231; 2.U.228.236; 2.U.228.237; 2.U.228.238; 2.U.228.239; 2.U.228.154; 2.U.228.157; 2.U.228.166; 2.U.228.169; 2.U.228.172; 2.U.228.175; 2.U.228.240; 2.U.228.244; 2.U.229.228; 2.U.229.229; 2.U.229.230; 2.U.229.231; 2.U.229.236; 2.U.229.237; 2.U.229.238; 2.U.229.239; 2.U.229.154; 2.U.229.157; 2.U.229.166; 2.U.229.169; 2.U.229.172; 2.U.229.175; 2.U.229.240; 2.U.229.244; 2.U.230.228; 2.U.230.229; 2.U.230.230; 2.U.230.231; 2.U.230.236; 2.U.230.237; 2.U.230.238; 2.U.230.239; 2.U.230.154; 2.U.230.157; 2.U.230.166; 2.U.230.169; 2.U.230.172; 2.U.230.175; 2.U.230.240; 2.U.230.244; 2.U.231.228; 2.U.231.229; 2.U.231.230; 2.U.231.231; 2.U.231.236; 2.U.231.237; 2.U.231.238; 2.U.231.239; 2.U.231.154; 2.U.231.157; 2.U.231.166; 2.U.231.169; 2.U.231.172; 2.U.231.175; 2.U.231.240; 2.U.231.244; 2.U.236.228; 2.U.236.229; 2.U.236.230; 2.U.236.231; 2.U.236.236; 2.U.236.237; 2.U.236.238; 2.U.236.239; 2.U.236.154; 2.U.236.157; 2.U.236.166; 2.U.236.169; 2.U.236.172; 2.U.236.175;

2.U.236.240; 2.U.236.244; 2.U.237.228; 2.U.237.229; 2.U.237.230; 2.U.237.231; 2.U.237.236; 2.U.237.237; 2.U.237.238; 2.U.237.239; 2.U.237.154; 2.U.237.157; 2.U.237.166; 2.U.237.169; 2.U.237.172; 2.U.237.175; 2.U.237.240; 2.U.237.244; 2.U.238.228; 2.U.238.229; 2.U.238.230; 2.U.238.231; 2.U.238.236; 2.U.238.237; 2.U.238.238; 2.U.238.239; 2.U.238.154; 2.U.238.157; 2.U.238.166; 2.U.238.169; 2.U.238.172; 2.U.238.175; 2.U.238.240; 2.U.238.244; 2.U.239.228; 2.U.239.229; 2.U.239.230; 2.U.239.231; 2.U.239.236; 2.U.239.237; 2.U.239.238; 2.U.239.239; 2.U.239.154; 2.U.239.157; 2.U.239.166; 2.U.239.169; 2.U.239.172; 2.U.239.175; 2.U.239.240; 2.U.239.244; 2.U.154.228; 2.U.154.229; 2.U.154.230; 2.U.154.231; 2.U.154.236; 2.U.154.237; 2.U.154.238; 2.U.154.239; 2.U.154.154; 2.U.154.157; 2.U.154.166; 2.U.154.169; 2.U.154.172; 2.U.154.175; 2.U.154.240; 2.U.154.244; 2.U.157.228; 2.U.157.229; 2.U.157.230; 2.U.157.231; 2.U.157.236; 2.U.157.237; 2.U.157.238; 2.U.157.239; 2.U.157.154; 2.U.157.157; 2.U.157.166; 2.U.157.169; 2.U.157.172; 2.U.157.175; 2.U.157.240; 2.U.157.244; 2.U.166.228; 2.U.166.229; 2.U.166.230; 2.U.166.231; 2.U.166.236; 2.U.166.237; 2.U.166.238; 2.U.166.239; 2.U.166.154; 2.U.166.157; 2.U.166.166; 2.U.166.169; 2.U.166.172; 2.U.166.175; 2.U.166.240; 2.U.166.244; 2.U.169.228; 2.U.169.229; 2.U.169.230; 2.U.169.231; 2.U.169.236; 2.U.169.237; 2.U.169.238; 2.U.169.239; 2.U.169.154; 2.U.169.157; 2.U.169.166; 2.U.169.169; 2.U.169.172; 2.U.169.175; 2.U.169.240; 2.U.169.244; 2.U.172.228; 2.U.172.229; 2.U.172.230; 2.U.172.231; 2.U.172.236; 2.U.172.237; 2.U.172.238; 2.U.172.239; 2.U.172.154; 2.U.172.157; 2.U.172.166; 2.U.172.169; 2.U.172.172; 2.U.172.175; 2.U.172.240; 2.U.172.244; 2.U.175.228; 2.U.175.229; 2.U.175.230; 2.U.175.231; 2.U.175.236; 2.U.175.237; 2.U.175.238; 2.U.175.239; 2.U.175.154; 2.U.175.157; 2.U.175.166; 2.U.175.169; 2.U.175.172; 2.U.175.175; 2.U.175.240; 2.U.175.244; 2.U.240.228; 2.U.240.229; 2.U.240.230; 2.U.240.231; 2.U.240.236; 2.U.240.237; 2.U.240.238; 2.U.240.239; 2.U.240.154; 2.U.240.157; 2.U.240.166; 2.U.240.169; 2.U.240.172; 2.U.240.175; 2.U.240.240; 2.U.240.244; 2.U.244.228; 2.U.244.229; 2.U.244.230; 2.U.244.231; 2.U.244.236; 2.U.244.237; 2.U.244.238; 2.U.244.239; 2.U.244.154; 2.U.244.157; 2.U.244.166; 2.U.244.169; 2.U.244.172; 2.U.244.175; 2.U.244.240; 2.U.244.244;

Prodrugs of 2.CD

2.CD.228.228; 2.CD.228.229; 2.CD.228.230; 2.CD.228.231; 2.CD.228.236; 2.CD.228.237; 2.CD.228.238; 2.CD.228.239; 2.CD.228.154; 2.CD.228.157; 2.CD.228.166; 2.CD.228.169; 2.CD.228.172; 2.CD.228.175; 2.CD.228.240; 2.CD.228.244; 2.CD.229.228; 2.CD.229.229; 2.CD.229.230; 2.CD.229.231; 2.CD.229.236; 2.CD.229.237; 2.CD.229.238; 2.CD.229.239; 2.CD.229.154; 2.CD.229.157; 2.CD.229.166; 2.CD.229.169; 2.CD.229.172; 2.CD.229.175; 2.CD.229.240; 2.CD.229.244; 2.CD.230.228; 2.CD.230.229; 2.CD.230.230; 2.CD.230.231; 2.CD.230.236; 2.CD.230.237; 2.CD.230.238; 2.CD.230.239; 2.CD.230.154; 2.CD.230.157; 2.CD.230.166; 2.CD.230.169; 2.CD.230.172; 2.CD.230.175; 2.CD.230.240; 2.CD.230.244; 2.CD.231.228; 2.CD.231.229; 2.CD.231.230; 2.CD.231.231; 2.CD.231.236; 2.CD.231.237; 2.CD.231.238; 2.CD.231.239; 2.CD.231.154; 2.CD.231.157; 2.CD.231.166; 2.CD.231.169; 2.CD.231.172; 2.CD.231.175; 2.CD.231.240; 2.CD.231.244; 2.CD.236.228; 2.CD.236.229; 2.CD.236.230; 2.CD.236.231; 2.CD.236.236; 2.CD.236.237;

2.CD.236.238; 2.CD.236.239; 2.CD.236.154; 2.CD.236.157; 2.CD.236.166; 2.CD.236.169; 2.CD.236.172; 2.CD.236.175; 2.CD.236.240; 2.CD.236.244; 2.CD.237.228; 2.CD.237.229; 2.CD.237.230; 2.CD.237.231; 2.CD.237.236; 2.CD.237.237; 2.CD.237.238; 2.CD.237.239; 2.CD.237.154; 2.CD.237.157; 2.CD.237.166; 2.CD.237.169; 2.CD.237.172; 2.CD.237.175; 2.CD.237.240; 2.CD.237.244; 2.CD.238.228; 2.CD.238.229; 2.CD.238.230; 2.CD.238.231; 2.CD.238.236; 2.CD.238.237; 2.CD.238.238; 2.CD.238.239; 2.CD.238.154; 2.CD.238.157; 2.CD.238.166; 2.CD.238.169; 2.CD.238.172; 2.CD.238.175; 2.CD.238.240; 2.CD.238.244; 2.CD.239.228; 2.CD.239.229; 2.CD.239.230; 2.CD.239.231; 2.CD.239.236; 2.CD.239.237; 2.CD.239.238; 2.CD.239.239; 2.CD.239.154; 2.CD.239.157; 2.CD.239.166; 2.CD.239.169; 2.CD.239.172; 2.CD.239.175; 2.CD.239.240; 2.CD.239.244; 2.CD.154.228; 2.CD.154.229; 2.CD.154.230; 2.CD.154.231; 2.CD.154.236; 2.CD.154.237; 2.CD.154.238; 2.CD.154.239; 2.CD.154.154; 2.CD.154.157; 2.CD.154.166; 2.CD.154.169; 2.CD.154.172; 2.CD.154.175; 2.CD.154.240; 2.CD.154.244; 2.CD.157.228; 2.CD.157.229; 2.CD.157.230; 2.CD.157.231; 2.CD.157.236; 2.CD.157.237; 2.CD.157.238; 2.CD.157.239; 2.CD.157.154; 2.CD.157.157; 2.CD.157.166; 2.CD.157.169; 2.CD.157.172; 2.CD.157.175; 2.CD.157.240; 2.CD.157.244; 2.CD.166.228; 2.CD.166.229; 2.CD.166.230; 2.CD.166.231; 2.CD.166.236; 2.CD.166.237; 2.CD.166.238; 2.CD.166.239; 2.CD.166.154; 2.CD.166.157; 2.CD.166.166; 2.CD.166.169; 2.CD.166.172; 2.CD.166.175; 2.CD.166.240; 2.CD.166.244; 2.CD.169.228; 2.CD.169.229; 2.CD.169.230; 2.CD.169.231; 2.CD.169.236; 2.CD.169.237; 2.CD.169.238; 2.CD.169.239; 2.CD.169.154; 2.CD.169.157; 2.CD.169.166; 2.CD.169.169; 2.CD.169.172; 2.CD.169.175; 2.CD.169.240; 2.CD.169.244; 2.CD.172.228; 2.CD.172.229; 2.CD.172.230; 2.CD.172.231; 2.CD.172.236; 2.CD.172.237; 2.CD.172.238; 2.CD.172.239; 2.CD.172.154; 2.CD.172.157; 2.CD.172.166; 2.CD.172.169; 2.CD.172.172; 2.CD.172.175; 2.CD.172.240; 2.CD.172.244; 2.CD.175.228; 2.CD.175.229; 2.CD.175.230; 2.CD.175.231; 2.CD.175.236; 2.CD.175.237; 2.CD.175.238; 2.CD.175.239; 2.CD.175.154; 2.CD.175.157; 2.CD.175.166; 2.CD.175.169; 2.CD.175.172; 2.CD.175.175; 2.CD.175.240; 2.CD.175.244; 2.CD.240.228; 2.CD.240.229; 2.CD.240.230; 2.CD.240.231; 2.CD.240.236; 2.CD.240.237; 2.CD.240.238; 2.CD.240.239; 2.CD.240.154; 2.CD.240.157; 2.CD.240.166; 2.CD.240.169; 2.CD.240.172; 2.CD.240.175; 2.CD.240.240; 2.CD.240.244; 2.CD.244.228; 2.CD.244.229; 2.CD.244.230; 2.CD.244.231; 2.CD.244.236; 2.CD.244.237; 2.CD.244.238; 2.CD.244.239; 2.CD.244.154; 2.CD.244.157; 2.CD.244.166; 2.CD.244.169; 2.CD.244.172; 2.CD.244.175; 2.CD.244.240; 2.CD.244.244;

Prodrugs of 2.EB

2.EB.228.228; 2.EB.228.229; 2.EB.228.230; 2.EB.228.231; 2.EB.228.236; 2.EB.228.237; 2.EB.228.238; 2.EB.228.239; 2.EB.228.154; 2.EB.228.157; 2.EB.228.166; 2.EB.228.169; 2.EB.228.172; 2.EB.228.175; 2.EB.228.240; 2.EB.228.244; 2.EB.229.228; 2.EB.229.229; 2.EB.229.230; 2.EB.229.231; 2.EB.229.236; 2.EB.229.237; 2.EB.229.238; 2.EB.229.239; 2.EB.229.154; 2.EB.229.157; 2.EB.229.166; 2.EB.229.169; 2.EB.229.172; 2.EB.229.175; 2.EB.229.240; 2.EB.229.244; 2.EB.230.228; 2.EB.230.229; 2.EB.230.230;

2.EB.230.231; 2.EB.230.236; 2.EB.230.237; 2.EB.230.238; 2.EB.230.239; 2.EB.230.154; 2.EB.230.157; 2.EB.230.166; 2.EB.230.169; 2.EB.230.172; 2.EB.230.175; 2.EB.230.240; 2.EB.230.244; 2.EB.231.228; 2.EB.231.229; 2.EB.231.230; 2.EB.231.231; 2.EB.231.236; 2.EB.231.237; 2.EB.231.238; 2.EB.231.239; 2.EB.231.154; 2.EB.231.157; 2.EB.231.166; 2.EB.231.169; 2.EB.231.172; 2.EB.231.175; 2.EB.231.240; 2.EB.231.244; 2.EB.236.228; 2.EB.236.229; 2.EB.236.230; 2.EB.236.231; 2.EB.236.236; 2.EB.236.237; 2.EB.236.238; 2.EB.236.239; 2.EB.236.154; 2.EB.236.157; 2.EB.236.166; 2.EB.236.169; 2.EB.236.172; 2.EB.236.175; 2.EB.236.240; 2.EB.236.244; 2.EB.237.228; 2.EB.237.229; 2.EB.237.230; 2.EB.237.231; 2.EB.237.236; 2.EB.237.237; 2.EB.237.238; 2.EB.237.239; 2.EB.237.154; 2.EB.237.157; 2.EB.237.166; 2.EB.237.169; 2.EB.237.172; 2.EB.237.175; 2.EB.237.240; 2.EB.237.244; 2.EB.238.228; 2.EB.238.229; 2.EB.238.230; 2.EB.238.231; 2.EB.238.236; 2.EB.238.237; 2.EB.238.238; 2.EB.238.239; 2.EB.238.154; 2.EB.238.157; 2.EB.238.166; 2.EB.238.169; 2.EB.238.172; 2.EB.238.175; 2.EB.238.240; 2.EB.238.244; 2.EB.239.228; 2.EB.239.229; 2.EB.239.230; 2.EB.239.231; 2.EB.239.236; 2.EB.239.237; 2.EB.239.238; 2.EB.239.239; 2.EB.239.154; 2.EB.239.157; 2.EB.239.166; 2.EB.239.169; 2.EB.239.172; 2.EB.239.175; 2.EB.239.240; 2.EB.239.244; 2.EB.154.228; 2.EB.154.229; 2.EB.154.230; 2.EB.154.231; 2.EB.154.236; 2.EB.154.237; 2.EB.154.238; 2.EB.154.239; 2.EB.154.154; 2.EB.154.157; 2.EB.154.166; 2.EB.154.169; 2.EB.154.172; 2.EB.154.175; 2.EB.154.240; 2.EB.154.244; 2.EB.157.228; 2.EB.157.229; 2.EB.157.230; 2.EB.157.231; 2.EB.157.236; 2.EB.157.237; 2.EB.157.238; 2.EB.157.239; 2.EB.157.154; 2.EB.157.157; 2.EB.157.166; 2.EB.157.169; 2.EB.157.172; 2.EB.157.175; 2.EB.157.240; 2.EB.157.244; 2.EB.166.228; 2.EB.166.229; 2.EB.166.230; 2.EB.166.231; 2.EB.166.236; 2.EB.166.237; 2.EB.166.238; 2.EB.166.239; 2.EB.166.154; 2.EB.166.157; 2.EB.166.166; 2.EB.166.169; 2.EB.166.172; 2.EB.166.175; 2.EB.166.240; 2.EB.166.244; 2.EB.169.228; 2.EB.169.229; 2.EB.169.230; 2.EB.169.231; 2.EB.169.236; 2.EB.169.237; 2.EB.169.238; 2.EB.169.239; 2.EB.169.154; 2.EB.169.157; 2.EB.169.166; 2.EB.169.169; 2.EB.169.172; 2.EB.169.175; 2.EB.169.240; 2.EB.169.244; 2.EB.172.228; 2.EB.172.229; 2.EB.172.230; 2.EB.172.231; 2.EB.172.236; 2.EB.172.237; 2.EB.172.238; 2.EB.172.239; 2.EB.172.154; 2.EB.172.157; 2.EB.172.166; 2.EB.172.169; 2.EB.172.172; 2.EB.172.175; 2.EB.172.240; 2.EB.172.244; 2.EB.175.228; 2.EB.175.229; 2.EB.175.230; 2.EB.175.231; 2.EB.175.236; 2.EB.175.237; 2.EB.175.238; 2.EB.175.239; 2.EB.175.154; 2.EB.175.157; 2.EB.175.166; 2.EB.175.169; 2.EB.175.172; 2.EB.175.175; 2.EB.175.240; 2.EB.175.244; 2.EB.240.228; 2.EB.240.229; 2.EB.240.230; 2.EB.240.231; 2.EB.240.236; 2.EB.240.237; 2.EB.240.238; 2.EB.240.239; 2.EB.240.154; 2.EB.240.157; 2.EB.240.166; 2.EB.240.169; 2.EB.240.172; 2.EB.240.175; 2.EB.240.240; 2.EB.240.244; 2.EB.244.228; 2.EB.244.229; 2.EB.244.230; 2.EB.244.231; 2.EB.244.236; 2.EB.244.237; 2.EB.244.238; 2.EB.244.239; 2.EB.244.154; 2.EB.244.157; 2.EB.244.166; 2.EB.244.169; 2.EB.244.172; 2.EB.244.175; 2.EB.244.240; 2.EB.244.244;

Prodrugs of 3.B

3.B.228.228; 3.B.228.229; 3.B.228.230; 3.B.228.231; 3.B.228.236; 3.B.228.237; 3.B.228.238; 3.B.228.239; 3.B.228.154; 3.B.228.157; 3.B.228.166; 3.B.228.169; 3.B.228.172; 3.B.228.175; 3.B.228.240; 3.B.228.244; 3.B.229.228; 3.B.229.229; 3.B.229.230; 3.B.229.231; 3.B.229.236; 3.B.229.237; 3.B.229.238; 3.B.229.239; 3.B.229.154; 3.B.229.157; 3.B.229.166; 3.B.229.169; 3.B.229.172; 3.B.229.175; 3.B.229.240; 3.B.229.244; 3.B.230.228; 3.B.230.229; 3.B.230.230; 3.B.230.231; 3.B.230.236; 3.B.230.237; 3.B.230.238; 3.B.230.239; 3.B.230.154; 3.B.230.157;

3.B.230.166; 3.B.230.169; 3.B.230.172; 3.B.230.175; 3.B.230.240; 3.B.230.244; 3.B.231.228; 3.B.231.229; 3.B.231.230; 3.B.231.231; 3.B.231.236; 3.B.231.237; 3.B.231.238; 3.B.231.239; 3.B.231.154; 3.B.231.157; 3.B.231.166; 3.B.231.169; 3.B.231.172; 3.B.231.175; 3.B.231.240; 3.B.231.244; 3.B.236.228; 3.B.236.229; 3.B.236.230; 3.B.236.231; 3.B.236.236; 3.B.236.237; 3.B.236.238; 3.B.236.239; 3.B.236.154; 3.B.236.157; 3.B.236.166; 3.B.236.169; 3.B.236.172; 3.B.236.175; 3.B.236.240; 3.B.236.244; 3.B.237.228; 3.B.237.229; 3.B.237.230; 3.B.237.231; 3.B.237.236; 3.B.237.237; 3.B.237.238; 3.B.237.239; 3.B.237.154; 3.B.237.157; 3.B.237.166; 3.B.237.169; 3.B.237.172; 3.B.237.175; 3.B.237.240; 3.B.237.244; 3.B.238.228; 3.B.238.229; 3.B.238.230; 3.B.238.231; 3.B.238.236; 3.B.238.237; 3.B.238.238; 3.B.238.239; 3.B.238.154; 3.B.238.157; 3.B.238.166; 3.B.238.169; 3.B.238.172; 3.B.238.175; 3.B.238.240; 3.B.238.244; 3.B.239.228; 3.B.239.229; 3.B.239.230; 3.B.239.231; 3.B.239.236; 3.B.239.237; 3.B.239.238; 3.B.239.239; 3.B.239.154; 3.B.239.157; 3.B.239.166; 3.B.239.169; 3.B.239.172; 3.B.239.175; 3.B.239.240; 3.B.239.244; 3.B.154.228; 3.B.154.229; 3.B.154.230; 3.B.154.231; 3.B.154.236; 3.B.154.237; 3.B.154.238; 3.B.154.239; 3.B.154.154; 3.B.154.157; 3.B.154.166; 3.B.154.169; 3.B.154.172; 3.B.154.175; 3.B.154.240; 3.B.154.244; 3.B.157.228; 3.B.157.229; 3.B.157.230; 3.B.157.231; 3.B.157.236; 3.B.157.237; 3.B.157.238; 3.B.157.239; 3.B.157.154; 3.B.157.157; 3.B.157.166; 3.B.157.169; 3.B.157.172; 3.B.157.175; 3.B.157.240; 3.B.157.244; 3.B.166.228; 3.B.166.229; 3.B.166.230; 3.B.166.231; 3.B.166.236; 3.B.166.237; 3.B.166.238; 3.B.166.239; 3.B.166.154; 3.B.166.157; 3.B.166.166; 3.B.166.169; 3.B.166.172; 3.B.166.175; 3.B.166.240; 3.B.166.244; 3.B.169.228; 3.B.169.229; 3.B.169.230; 3.B.169.231; 3.B.169.236; 3.B.169.237; 3.B.169.238; 3.B.169.239; 3.B.169.154; 3.B.169.157; 3.B.169.166; 3.B.169.169; 3.B.169.172; 3.B.169.175; 3.B.169.240; 3.B.169.244; 3.B.172.228; 3.B.172.229; 3.B.172.230; 3.B.172.231; 3.B.172.236; 3.B.172.237; 3.B.172.238; 3.B.172.239; 3.B.172.154; 3.B.172.157; 3.B.172.166; 3.B.172.169; 3.B.172.172; 3.B.172.175; 3.B.172.240; 3.B.172.244; 3.B.175.228; 3.B.175.229; 3.B.175.230; 3.B.175.231; 3.B.175.236; 3.B.175.237; 3.B.175.238; 3.B.175.239; 3.B.175.154; 3.B.175.157; 3.B.175.166; 3.B.175.169; 3.B.175.172; 3.B.175.175; 3.B.175.240; 3.B.175.244; 3.B.240.228; 3.B.240.229; 3.B.240.230; 3.B.240.231; 3.B.240.236; 3.B.240.237; 3.B.240.238; 3.B.240.239; 3.B.240.154; 3.B.240.157; 3.B.240.166; 3.B.240.169; 3.B.240.172; 3.B.240.175; 3.B.240.240; 3.B.240.244; 3.B.244.228; 3.B.244.229; 3.B.244.230; 3.B.244.231; 3.B.244.236; 3.B.244.237; 3.B.244.238; 3.B.244.239; 3.B.244.154; 3.B.244.157; 3.B.244.166; 3.B.244.169; 3.B.244.172; 3.B.244.175; 3.B.244.240; 3.B.244.244;

Prodrugs of 3.D

3.D.228.228; 3.D.228.229; 3.D.228.230; 3.D.228.231; 3.D.228.236; 3.D.228.237; 3.D.228.238; 3.D.228.239; 3.D.228.154; 3.D.228.157; 3.D.228.166; 3.D.228.169; 3.D.228.172; 3.D.228.175; 3.D.228.240; 3.D.228.244; 3.D.229.228; 3.D.229.229; 3.D.229.230; 3.D.229.231; 3.D.229.236; 3.D.229.237; 3.D.229.238; 3.D.229.239; 3.D.229.154; 3.D.229.157; 3.D.229.166; 3.D.229.169; 3.D.229.172; 3.D.229.175; 3.D.229.240; 3.D.229.244; 3.D.230.228; 3.D.230.229; 3.D.230.230; 3.D.230.231; 3.D.230.236; 3.D.230.237; 3.D.230.238; 3.D.230.239; 3.D.230.154; 3.D.230.157; 3.D.230.166; 3.D.230.169; 3.D.230.172; 3.D.230.175; 3.D.230.240; 3.D.230.244;

3.D.231.228; 3.D.231.229; 3.D.231.230; 3.D.231.231; 3.D.231.236; 3.D.231.237; 3.D.231.238; 3.D.231.239; 3.D.231.154; 3.D.231.157; 3.D.231.166; 3.D.231.169; 3.D.231.172; 3.D.231.175; 3.D.231.240; 3.D.231.244; 3.D.236.228; 3.D.236.229; 3.D.236.230; 3.D.236.231; 3.D.236.236; 3.D.236.237; 3.D.236.238; 3.D.236.239; 3.D.236.154; 3.D.236.157; 3.D.236.166; 3.D.236.169; 3.D.236.172; 3.D.236.175; 3.D.236.240; 3.D.236.244; 3.D.237.228; 3.D.237.229; 3.D.237.230; 3.D.237.231; 3.D.237.236; 3.D.237.237; 3.D.237.238; 3.D.237.239; 3.D.237.154; 3.D.237.157; 3.D.237.166; 3.D.237.169; 3.D.237.172; 3.D.237.175; 3.D.237.240; 3.D.237.244; 3.D.238.228; 3.D.238.229; 3.D.238.230; 3.D.238.231; 3.D.238.236; 3.D.238.237; 3.D.238.238; 3.D.238.239; 3.D.238.154; 3.D.238.157; 3.D.238.166; 3.D.238.169; 3.D.238.172; 3.D.238.175; 3.D.238.240; 3.D.238.244; 3.D.239.228; 3.D.239.229; 3.D.239.230; 3.D.239.231; 3.D.239.236; 3.D.239.237; 3.D.239.238; 3.D.239.239; 3.D.239.154; 3.D.239.157; 3.D.239.166; 3.D.239.169; 3.D.239.172; 3.D.239.175; 3.D.239.240; 3.D.239.244; 3.D.154.228; 3.D.154.229; 3.D.154.230; 3.D.154.231; 3.D.154.236; 3.D.154.237; 3.D.154.238; 3.D.154.239; 3.D.154.154; 3.D.154.157; 3.D.154.166; 3.D.154.169; 3.D.154.172; 3.D.154.175; 3.D.154.240; 3.D.154.244; 3.D.157.228; 3.D.157.229; 3.D.157.230; 3.D.157.231; 3.D.157.236; 3.D.157.237; 3.D.157.238; 3.D.157.239; 3.D.157.154; 3.D.157.157; 3.D.157.166; 3.D.157.169; 3.D.157.172; 3.D.157.175; 3.D.157.240; 3.D.157.244; 3.D.166.228; 3.D.166.229; 3.D.166.230; 3.D.166.231; 3.D.166.236; 3.D.166.237; 3.D.166.238; 3.D.166.239; 3.D.166.154; 3.D.166.157; 3.D.166.166; 3.D.166.169; 3.D.166.172; 3.D.166.175; 3.D.166.240; 3.D.166.244; 3.D.169.228; 3.D.169.229; 3.D.169.230; 3.D.169.231; 3.D.169.236; 3.D.169.237; 3.D.169.238; 3.D.169.239; 3.D.169.154; 3.D.169.157; 3.D.169.166; 3.D.169.169; 3.D.169.172; 3.D.169.175; 3.D.169.240; 3.D.169.244; 3.D.172.228; 3.D.172.229; 3.D.172.230; 3.D.172.231; 3.D.172.236; 3.D.172.237; 3.D.172.238; 3.D.172.239; 3.D.172.154; 3.D.172.157; 3.D.172.166; 3.D.172.169; 3.D.172.172; 3.D.172.175; 3.D.172.240; 3.D.172.244; 3.D.175.228; 3.D.175.229; 3.D.175.230; 3.Dλ75.231; 3.D.175.236; 3.D.175.237; 3.D.175.238; 3.D.175.239; 3.D.175.154; 3.D.175.157; 3.D.175.166; 3.D.175.169; 3.D.175.172; 3.D.175.175; 3.D.175.240; 3.D.175.244; 3.D.240.228; 3.D.240.229; 3.D.240.230; 3.D.240.231; 3.D.240.236; 3.D.240.237; 3.D.240.238; 3.D.240.239; 3.D.240.154; 3.D.240.157; 3.D.240.166; 3.D.240.169; 3.D.240.172; 3.D.240.175; 3.D.240.240; 3.D.240.244; 3.D.244.228; 3.D.244.229; 3.D.244.230; 3.D.244.231; 3.D.244.236; 3.D.244.237; 3.D.244.238; 3.D.244.239; 3.D.244.154; 3.D.244.157; 3.D.244.166; 3.D.244.169; 3.D.244.172; 3.D.244.175; 3.D.244.240; 3.D.244.244;

Prodrugs of 3.AB

3.AB.228.228; 3.AB.228.229; 3.AB.228.230; 3.AB.228.231; 3.AB.228.236; 3.AB.228.237; 3.AB.228.238; 3.AB.228.239; 3.AB.228.154; 3.AB.228.157; 3.AB.228.166; 3.AB.228.169; 3.AB.228.172; 3.AB.228.175; 3.AB.228.240; 3.AB.228.244; 3.AB.229.228; 3.AB.229.229; 3.AB.229.230; 3.AB.229.231; 3.AB.229.236; 3.AB.229.237; 3.AB.229.238; 3.AB.229.239; 3.AB.229.154; 3.AB.229.157; 3.AB.229.166; 3.AB.229.169; 3.AB.229.172; 3.AB.229.175; 3.AB.229.240; 3.AB.229.244; 3.AB.230.228; 3.AB.230.229; 3.AB.230.230; 3.AB.230.231; 3.AB.230.236; 3.AB.230.237; 3.AB.230.238; 3.AB.230.239; 3.AB.230.154; 3.AB.230.157; 3.AB.230.166; 3.AB.230.169; 3.AB.230.172;

3.AB.230.175; 3.AB.230.240; 3.AB.230.244; 3.AB.231.228; 3.AB.231.229; 3.AB.231.230; 3.AB.231.231; 3.AB.231.236; 3.AB.231.237; 3.AB.231.238; 3.AB.231.239; 3.AB.231.154; 3.AB.231.157; 3.AB.231.166; 3.AB.231.169; 3.AB.231.172; 3.AB.231.175; 3.AB.231.240; 3.AB.231.244; 3.AB.236.228; 3.AB.236.229; 3.AB.236.230; 3.AB.236.231; 3.AB.236.236; 3.AB.236.237; 3.AB.236.238; 3.AB.236.239; 3.AB.236.154; 3.AB.236.157; 3.AB.236.166; 3.AB.236.169; 3.AB.236.172; 3.AB.236.175; 3.AB.236.240; 3.AB.236.244; 3.AB.237.228; 3.AB.237.229; 3.AB.237.230; 3.AB.237.231; 3.AB.237.236; 3.AB.237.237; 3.AB.237.238; 3.AB.237.239; 3.AB.237.154; 3.AB.237.157; 3.AB.237.166; 3.AB.237.169; 3.AB.237.172; 3.AB.237.175; 3.AB.237.240; 3.AB.237.244; 3.AB.238.228; 3.AB.238.229; 3.AB.238.230; 3.AB.238.231; 3.AB.238.236; 3.AB.238.237; 3.AB.238.238; 3.AB.238.239; 3.AB.238.154; 3.AB.238.157; 3.AB.238.166; 3.AB.238.169; 3.AB.238.172; 3.AB.238.175; 3.AB.238.240; 3.AB.238.244; 3.AB.239.228; 3.AB.239.229; 3.AB.239.230; 3.AB.239.231; 3.AB.239.236; 3.AB.239.237; 3.AB.239.238; 3.AB.239.239; 3.AB.239.154; 3.AB.239.157; 3.AB.239.166; 3.AB.239.169; 3.AB.239.172; 3.AB.239.175; 3.AB.239.240; 3.AB.239.244; 3.AB.154.228; 3.AB.154.229; 3.AB.154.230; 3.AB.154.231; 3.AB.154.236; 3.AB.154.237; 3.AB.154.238; 3.AB.154.239; 3.AB.154.154; 3.AB.154.157; 3.AB.154.166; 3.AB.154.169; 3.AB.154.172; 3.AB.154.175; 3.AB.154.240; 3.AB.154.244; 3.AB.157.228; 3.AB.157.229; 3.AB.157.230; 3.AB.157.231; 3.AB.157.236; 3.AB.157.237; 3.AB.157.238; 3.AB.157.239; 3.AB.157.154; 3.AB.157.157; 3.AB.157.166; 3.AB.157.169; 3.AB.157.172; 3.AB.157.175; 3.AB.157.240; 3.AB.157.244; 3.AB.166.228; 3.AB.166.229; 3.AB.166.230; 3.AB.166.231; 3.AB.166.236; 3.AB.166.237; 3.AB.166.238; 3.AB.166.239; 3.AB.166.154; 3.AB.166.157; 3.AB.166.166; 3.AB.166.169; 3.AB.166.172; 3.AB.166.175; 3.AB.166.240; 3.AB.166.244; 3.AB.169.228; 3.AB.169.229; 3.AB.169.230; 3.AB.169.231; 3.AB.169.236; 3.AB.169.237; 3.AB.169.238; 3.AB.169.239; 3.AB.169.154; 3.AB.169.157; 3.AB.169.166; 3.AB.169.169; 3.AB.169.172; 3.AB.169.175; 3.AB.169.240; 3.AB.169.244; 3.AB.172.228; 3.AB.172.229; 3.AB.172.230; 3.AB.172.231; 3.AB.172.236; 3.AB.172.237; 3.AB.172.238; 3.AB.172.239; 3.AB.172.154; 3.AB.172.157; 3.AB.172.166; 3.AB.172.169; 3.AB.172.172; 3.AB.172.175; 3.AB.172.240; 3.AB.172.244; 3.AB.175.228; 3.AB.175.229; 3.AB.175.230; 3.AB.175.231; 3.AB.175.236; 3.AB.175.237; 3.AB.175.238; 3.AB.175.239; 3.AB.175.154; 3.AB.175.157; 3.AB.175.166; 3.AB.175.169; 3.AB.175.172; 3.AB.175.175; 3.AB.175.240; 3.AB.175.244; 3.AB.240.228; 3.AB.240.229; 3.AB.240.230; 3.AB.240.231; 3.AB.240.236; 3.AB.240.237; 3.AB.240.238; 3.AB.240.239; 3.AB.240.154; 3.AB.240.157; 3.AB.240.166; 3.AB.240.169; 3.AB.240.172; 3.AB.240.175; 3.AB.240.240; 3.AB.240.244; 3.AB.244.228; 3.AB.244.229; 3.AB.244.230; 3.AB.244.231; 3.AB.244.236; 3.AB.244.237; 3.AB.244.238; 3.AB.244.239; 3.AB.244.154; 3.AB.244.157; 3.AB.244.166; 3.AB.244.169; 3.AB.244.172; 3.AB.244.175; 3.AB.244.240; 3.AB.244.244;

Prodrues of 3.BI

3.BI.228.228; 3.BI.228.229; 3.BI.228.230; 3.BI.228.231; 3.BI.228.236; 3.BI.228.237; 3.BI.228.238; 3.BI.228.239; 3.BI.228.154; 3.BI.228.157; 3.BI.228.166; 3.BI.228.169; 3.BI.228.172; 3.BI.228.175; 3.BI.228.240; 3.BI.228.244; 3.BI.229.228; 3.BI.229.229; 3.BI.229.230; 3.BI.229.231; 3.BI.229.236; 3.BI.229.237; 3.BI.229.238; 3.BI.229.239; 3.BI.229.154; 3.BI.229.157; 3.BI.229.166; 3.BI.229.169; 3.BI.229.172; 3.BI.229.175; 3.BI.229.240; 3.BI.229.244; 3.BI.230.228; 3.BI.230.229; 3.BI.230.230; 3.BI.230.231; 3.BI.230.236; 3.BI.230.237; 3.BI.230.238; 3.BI.230.239; 3.BI.230.154; 3.BI.230.157; 3.BI.230.166; 3.BI.230.169; 3.BI.230.172; 3.BI.230.175; 3.BI.230.240; 3.BI.230.244; 3.BI.231.228; 3.BI.231.229; 3.BI.231.230; 3.BI.231.231; 3.BI.231.236; 3.BI.231.237; 3.BI.231.238; 3.BI.231.239; 3.BI.231.154; 3.BI.231.157; 3.BI.231.166; 3.BI.231.169; 3.BI.231.172; 3.BI.231.175; 3.BI.231.240; 3.BI.231.244; 3.BI.236.228; 3.BI.236.229; 3.BI.236.230; 3.BI.236.231; 3.BI.236.236; 3.BI.236.237; 3.BI.236.238; 3.BI.236.239; 3.BI.236.154; 3.BI.236.157; 3.BI.236.166; 3.BI.236.169; 3.BI.236.172; 3.BI.236.175; 3.BI.236.240; 3.BI.236.244; 3.BI.237.228; 3.BI.237.229; 3.BI.237.230; 3.BI.237.231; 3.BI.237.236; 3.BI.237.237; 3.BI.237.238; 3.BI.237.239; 3.BI.237.154; 3.BI.237.157; 3.BI.237.166; 3.BI.237.169; 3.BI.237.172; 3.BI.237.175; 3.BI.237.240; 3.BI.237.244; 3.BI.238.228; 3.BI.238.229; 3.BI.238.230; 3.BI.238.231; 3.BI.238.236; 3.BI.238.237; 3.BI.238.238; 3.BI.238.239; 3.BI.238.154; 3.BI.238.157; 3.BI.238.166; 3.BI.238.169; 3.BI.238.172; 3.BI.238.175; 3.BI.238.240; 3.BI.238.244; 3.BI.239.228; 3.BI.239.229; 3.BI.239.230; 3.BI.239.231; 3.BI.239.236; 3.BI.239.237; 3.BI.239.238; 3.BI.239.239; 3.BI.239.154; 3.BI.239.157; 3.BI.239.166; 3.BI.239.169; 3.BI.239.172; 3.BI.239.175; 3.BI.239.240; 3.BI.239.244; 3.BI.154.228; 3.BI.154.229; 3.BI.154.230; 3.BI.154.231; 3.BI.154.236; 3.BI.154.237; 3.BI.154.238; 3.BI.154.239; 3.BI.154.154; 3.BI.154.157; 3.BI.154.166; 3.BI.154.169; 3.BI.154.172; 3.BI.154.175; 3.BI.154.240; 3.BI.154.244; 3.BI.157.228; 3.BI.157.229; 3.BI.157.230; 3.BI.157.231; 3.BI.157.236; 3.BI.157.237; 3.BI.157.238; 3.BI.157.239; 3.BI.157.154; 3.BI.157.157; 3.BI.157.166; 3.BI.157.169; 3.BI.157.172; 3.BI.157.175; 3.BI.157.240; 3.BI.157.244; 3.BI.166.228; 3.BI.166.229; 3.BI.166.230; 3.BI.166.231; 3.BI.166.236; 3.BI.166.237; 3.BI.166.238; 3.BI.166.239; 3.BI.166.154; 3.BI.166.157; 3.BI.166.166; 3.BI.166.169; 3.BI.166.172; 3.BI.166.175; 3.BI.166.240; 3.BI.166.244; 3.BI.169.228; 3.BI.169.229; 3.BI.169.230; 3.BI.169.231; 3.BI.169.236; 3.BI.169.237; 3.BI.169.238; 3.BI.169.239; 3.BI.169.154; 3.BI.169.157; 3.BI.169.166; 3.BI.169.169; 3.BI.169.172; 3.BI.169.175; 3.BI.169.240; 3.BI.169.244; 3.BI.172.228; 3.BI.172.229; 3.BI.172.230; 3.BI.172.231; 3.BI.172.236; 3.BI.172.237; 3.BI.172.238; 3.BI.172.239; 3.BI.172.154; 3.BI.172.157; 3.BI.172.166; 3.BI.172.169; 3.BI.172.172; 3.BI.172.175; 3.BI.172.240; 3.BI.172.244; 3.BI.175.228; 3.BI.175.229; 3.BI.175.230; 3.BI.175.231; 3.BI.175.236; 3.BI.175.237; 3.BI.175.238; 3.BI.175.239; 3.BI.175.154; 3.BI.175.157; 3.BI.175.166; 3.BI.175.169; 3.BI.175.172; 3.BI.175.175; 3.BI.175.240; 3.BI.175.244; 3.BI.240.228; 3.BI.240.229; 3.BI.240.230; 3.BI.240.231; 3.BI.240.236; 3.BI.240.237; 3.BI.240.238; 3.BI.240.239; 3.BI.240.154; 3.BI.240.157; 3.BI.240.166; 3.BI.240.169; 3.BI.240.172; 3.BI.240.175; 3.BI.240.240; 3.BI.240.244; 3.BI.244.228; 3.BI.244.229; 3.BI.244.230; 3.BI.244.231; 3.BI.244.236; 3.BI.244.237; 3.BI.244.238; 3.BI.244.239; 3.BI.244.154; 3.BI.244.157; 3.BI.244.166; 3.BI.244.169; 3.BI.244.172; 3.BI.244.175; 3.BI.244.240; 3.BI.244.244;

Prodrugs of 3.1

3.1.228.228; 3.1.228.229; 3.1.228.230; 3.1.228.231; 3.1.228.236; 3.1.228.237; 3.1.228.238; 3.1.228.239; 3.1.228.154; 3.1.228.157; 3.1.228.166; 3.1.228.169; 3.1.228.172; 3.1.228.175; 3.1.228.240; 3.1.228.244; 3.1.229.228; 3.1.229.229; 3.1.229.230; 3.1.229.231; 3.1.229.236; 3.1.229.237; 3.1.229.238; 3.1.229.239; 3.1.229.154; 3.1.229.157; 3.1.229.166; 3.1.229.169; 3.1.229.172; 3.1.229.175; 3.1.229.240; 3.1.229.244; 3.1.230.228; 3.1.230.229; 3.1.230.230; 3.1.230.231; 3.1.230.236; 3.1.230.237; 3.1.230.238; 3.1.230.239; 3.1.230.154; 3.1.230.157; 3.1.230.166; 3.1.230.169; 3.1.230.172; 3.1.230.175; 3.1.230.240; 3.1.230.244; 3.1.231.228; 3.1.231.229; 3.1.231.230; 3.1.231.231; 3.1.231.236; 3.1.231.237; 3.1.231.238; 3.1.231.239; 3.1.231.154; 3.1.231.157; 3.1.231.166; 3.1.231.169; 3.1.231.172; 3.1.231.175; 3.1.231.240; 3.1.231.244; 3.1.236.228; 3.1.236.229; 3.1.236.230; 3.1.236.231; 3.1.236.236; 3.1.236.237; 3.1.236.238; 3.1.236.239; 3.1.236.154; 3.1.236.157; 3.1.236.166; 3.1.236.169; 3.1.236.172; 3.1.236.175; 3.1.236.240; 3.1.236.244; 3.1.237.228; 3.1.237.229; 3.1.237.230; 3.1.237.231; 3.1.237.236; 3.1.237.237; 3.1.237.238; 3.1.237.239; 3.1.237.154; 3.1.237.157; 3.1.237.166; 3.1.237.169; 3.1.237.172; 3.1.237.175; 3.1.237.240; 3.1.237.244; 3.1.238.228; 3.1.238.229; 3.1.238.230; 3.1.238.231; 3.1.238.236; 3.1.238.237; 3.1.238.238; 3.1.238.239; 3.1.238.154; 3.1.238.157; 3.1.238.166; 3.1.238.169; 3.1.238.172; 3.1.238.175; 3.1.238.240; 3.1.238.244; 3.1.239.228; 3.1.239.229; 3.1.239.230; 3.1.239.231; 3.1.239.236; 3.1.239.237; 3.1.239.238; 3.1.239.239; 3.1.239.154; 3.1.239.157; 3.1.239.166; 3.1.239.169; 3.1.239.172; 3.1.239.175; 3.1.239.240; 3.1.239.244; 3.1.154.228; 3.1.154.229; 3.1.154.230; 3.1.154.231; 3.1.154.236; 3.1.154.237; 3.1.154.238; 3.1.154.239; 3.1.154.154; 3.1.154.157; 3.1.154.166; 3.1.154.169; 3.1.154.172; 3.1.154.175; 3.1.154.240; 3.1.154.244; 3.1.157.228; 3.1.157.229; 3.1.157.230; 3.1.157.231; 3.1.157.236; 3.1.157.237; 3.1.157.238; 3.1.157.239; 3.1.157.154; 3.1.157.157; 3.1.157.166; 3.1.157.169; 3.1.157.172; 3.1.157.175; 3.1.157.240; 3.1.157.244; 3.1.166.228; 3.1.166.229; 3.1.166.230; 3.1.166.231; 3.1.166.236; 3.1.166.237; 3.1.166.238; 3.1.166.239; 3.1.166.154; 3.1.166.157; 3.1.166.166; 3.1.166.169; 3.1.166.172; 3.1.166.175; 3.1.166.240; 3.1.166.244; 3.1.169.228; 3.1.169.229; 3.1.169.230; 3.1.169.231; 3.1.169.236; 3.1.169.237; 3.1.169.238; 3.1.169.239; 3.1.169.154; 3.1.169.157; 3.1.169.166; 3.1.169.169; 3.1.169.172; 3.1.169.175; 3.1.169.240; 3.1.169.244; 3.1.172.228; 3.1.172.229; 3.1.172.230; 3.1.172.231; 3.1.172.236; 3.1.172.237; 3.1.172.238; 3.1.172.239; 3.1.172.154; 3.1.172.157; 3.1.172.166; 3.1.172.169; 3.1.172.172; 3.1.172.175; 3.1.172.240; 3.1.172.244; 3.1.175.228; 3.1.175.229; 3.1.175.230; 3.1.175.231; 3.1.175.236; 3.1.175.237; 3.1.175.238; 3.1.175.239; 3.1.175.154; 3.1.175.157; 3.1.175.166; 3.1.175.169; 3.1.175.172; 3.1.175.175; 3.1.175.240; 3.1.175.244; 3.1.240.228; 3.1.240.229; 3.1.240.230; 3.1.240.231; 3.1.240.236; 3.1.240.237; 3.1.240.238; 3.1.240.239; 3.1.240.154; 3.1.240.157; 3.1.240.166; 3.1.240.169; 3.1.240.172; 3.1.240.175; 3.1.240.240; 3.1.240.244; 3.1.244.228; 3.1.244.229; 3.1.244.230; 3.1.244.231; 3.1.244.236; 3.1.244.237; 3.1.244.238; 3.1.244.239; 3.1.244.154; 3.1.244.157; 3.1.244.166; 3.1.244.169; 3.1.244.172; 3.1.244.175; 3.1.244.240; 3.1.244.244;

Prodrugs of 3.T

3.J.228.228; 3.J.228.229; 3.J.228.230; 3.J.228.231; 3.J.228.236; 3.J.228.237; 3.J.228.238; 3.J.228.239; 3.J.228.154; 3J.228.157; 3.J.228.166; 3.J.228.169; 3.J.228.172; 3.J.228.175; 3.J.228.240; 3.J.228.244; 3.J.229.228; 3.J.229.229; 3.J.229.230; 3.J.229.231; 3.J.229.236; 3.J.229.237; 3.J.229.238; 3.J.229.239; 3.J.229.154; 3.J.229.157; 3.J.229.166; 3.J.229.169; 3.J.229.172; 3.J.229.175; 3.J.229.240; 3.J.229.244; 3.J.230.228; 3J.230.229; 3.J.230.230; 3J.230.231; 3J.230.236; 3J.230.237; 3J.230.238; 3J.230.239; 3J.230.154; 3J.230.157; 3J.230.166; 3 J.230.169; 3 J.230.172; 3J.230.175; 3 J.230.240; 3J.230.244;

3.J.231.228; 3.J.231.229; 3J.231.230; 3.J.231.231; 3.J.231.236; 3.J.231.237; 3.J.231.238; 3.J.231.239; 3J.231.154; 3J.231.157; 3J.231.166; 3J.231.169; 3J.231.172; 3J.231.175; 3.J.231.240; 3J.231.244; 3J.236.228; 3J.236.229; 3J.236.230; 3J.236.231; 3J.236.236; 3J.236.237; 3J.236.238; 3J.236.239; 3J.236.154; 3J.236.157; 3J.236.166; 3J.236.169; 3J.236.172; 3 J.236.175; 3J.236.240; 3 J.236.244; 3J.237.228; 3J.237.229; 3 J.237.230; 3J.237.231; 3 J.237.236; 3J.237.237; 3J.237.238; 3J.237.239; 3J.237.154; 3J.237.157; 3J.237.166; 3J.237.169; 3J.237.172; 3J.237.175; 3J.237.240; 3J.237.244; 3J.238.228; 3J.238.229; 3 J.238.230; 3J.238.231; 3J.238.236; 3 J.238.237; 3 J.238.238; 3J.238.239; 3J.238.154; 3J.238.157; 3J.238.166; 3J.238.169; 3J.238.172; 3J.238.175; 3J.238.240; 3J.238.244; 3J.239.228; 3J.239.229; 3J.239.230; 3J.239.231; 3J.239.236; 3J.239.237; 3J.239.238; 3J.239.239; 3J.239.154; 3J.239.157; 3 J.239.166; 3J.239.169; 3J.239.172; 3 J.239.175; 3.J.239.240; 3J.239.244; 3J.154.228; 3J.154.229; 3 J.154.230; 3J.154.231; 3J.154.236; 3J.154.237; 3J.154.238; 3.J.154.239; 3 J.154.154; 3 J.154.157; 3J.154.166; 3 J.154.169; 3 J.154.172; 3J.154.175; 3.J.154.240; 3J.154.244; 3 J.157.228; 3 J.157.229; 3J.157.230; 3 J.157.231; 3J.157.236; 3J.157.237; 3 J.157.238; 3.J.157.239; 3 J.157.154; 3J.157.157; 3J.157.166; 3J.157.169; 3J.157.172; 3 J.157.175; 3J.157.240; 3J.157.244; 3 J.166.228; 3 J.166.229; 3J.166.230; 3J.166.231; 3 J.166.236; 3.J.166.237; 3 J.166.238; 3J.166.239; 3 J.166.154; 3 J.166.157; 3J.166.166; 3J.166.169; 3J.166.172; 3 J.166.175; 3 J.166.240; 3J.166.244; 3 J.169.228; 3J.169.229; 3 J.169.230; 3J.169.231; 3 J.169.236; 3 J.169.237; 3.J.169.238; 3 J.169.239; 3 J.169.154; 3J.169.157; 3 J.169.166; 3 J.169.169; 3J.169.172; 3 J.169.175; 3 J.169.240; 3 J.169.244; 3J.172.228; 3 J.172.229; 3J.172.230; 3J.172.231; 3J.172.236; 3J.172.237; 3 J.172.238; 3J.172.239; 3 J.172.154; 3J.172.157; 3J.172.166; 3 J.172.169; 3J.172.172; 3J.172.175; 3.J.172.240; 3 J.172.244; 3J.175.228; 3 J.175.229; 3J.175.230; 3J.175.231; 3.J.175.236; 3J.175.237; 3 J.175.238; 3J.175.239; 3J.175.154; 3 J.175.157; 3 J.175.166; 3 J.175.169; 3J.175.172; 3 J.175.175; 3J.175.240; 3 J.175.244; 3J.240.228; 3J.240.229; 3 J.240.230; 3 J.240.231; 3J.240.236; 3J.240.237; 3 J.240.238; 3J.240.239; 3.J.240.154; 3J.240.157; 3 J.240.166; 3J.240.169; 3 J.240.172; 3J.240.175; 3J.240.240; 3J.240.244; 3J.244.228; 3J.244.229; 3J.244.230; 3J.244.231; 3J.244.236; 3.J.244.237; 3.J.244.238; 3J.244.239; 3J.244.154; 3J.244.157; 3J.244.166; 3 J.244.169; 3J.244.172; 3J.244.175; 3J.244.240; 3J.244.244;

Prodrugs of 3.L

3.L.228.228; 3.L.228.229; 3.L.228.230; 3.L.228.231; 3.L.228.236; 3.L.228.237; 3.L.228.238; 3.L.228.239; 3.L.228.154; 3.L.228.157; 3.L.228.166; 3.L.228.169; 3.L.228.172; 3.L.228.175; 3.L.228.240; 3.L.228.244; 3.L.229.228; 3.L.229.229; 3.L.229.230; 3.L.229.231; 3.L.229.236; 3.L.229.237; 3.L.229.238; 3.L.229.239; 3.L.229.154; 3.L.229.157; 3.L.229.166; 3.L.229.169; 3.L.229.172; 3.L.229.175; 3.L.229.240; 3.L.229.244; 3.L.230.228; 3.L.230.229; 3.L.230.230; 3.L.230.231; 3.L.230.236; 3.L.230.237; 3.L.230.238; 3.L.230.239; 3.L.230.154; 3.L.230.157; 3.L.230.166; 3.L.230.169; 3.L.230.172; 3.L.230.175; 3.L.230.240; 3.L.230.244; 3.L.231.228; 3.L.231.229; 3.L.231.230; 3.L.231.231; 3.L.231.236; 3.L.231.237; 3.L.231.238; 3.L.231.239; 3.L.231.154; 3.L.231.157; 3.L.231.166; 3.L.231.169; 3.L.231.172; 3.L.231.175; 3.L.231.240; 3.L.231.244; 3.L.236.228; 3.L.236.229; 3.L.236.230; 3.L.236.231; 3.L.236.236; 3.L.236.237; 3.L.236.238; 3.L.236.239; 3.L.236.154; 3.L.236.157; 3.L.236.166; 3.L.236.169; 3.L.236.172; 3.L.236.175; 3.L.236.240; 3.L.236.244; 3.L.237.228; 3.L.237.229; 3.L.237.230; 3.L.237.231;

3.L.237.236; 3.L.237.237; 3.L.237.238; 3.L.237.239; 3.L.237.154; 3.L.237.157; 3.L.237.166; 3.L.237.169; 3.L.237.172; 3.L.237.175; 3.L.237.240; 3.L.237.244; 3.L.238.228; 3.L.238.229; 3.L.238.230; 3.L.238.231; 3.L.238.236; 3.L.238.237; 3.L.238.238; 3.L.238.239; 3.L.238.154; 3.L.238.157; 3.L.238.166; 3.L.238.169; 3.L.238.172; 3.L.238.175; 3.L.238.240; 3.L.238.244; 3.L.239.228; 3.L.239.229; 3.L.239.230; 3.L.239.231; 3.L.239.236; 3.L.239.237; 3.L.239.238; 3.L.239.239; 3.L.239.154; 3.L.239.157; 3.L.239.166; 3.L.239.169; 3.L.239.172; 3.L.239.175; 3.L.239.240; 3.L.239.244; 3.L.154.228; 3.L.154.229; 3.L.154.230; 3.L.154.231; 3.L.154.236; 3.L.154.237; 3.L.154.238; 3.L.154.239; 3.L.154.154; 3.L.154.157; 3.L.154.166; 3.L.154.169; 3.L.154.172; 3.L.154.175; 3.L.154.240; 3.L.154.244; 3.L.157.228; 3.L.157.229; 3.L.157.230; 3.L.157.231; 3.L.157.236; 3.L.157.237; 3.L.157.238; 3.L.157.239; 3.L.157.154; 3.L.157.157; 3.L.157.166; 3.L.157.169; 3.L.157.172; 3.L.157.175; 3.L.157.240; 3.L.157.244; 3.L.166.228; 3.L.166.229; 3.L.166.230; 3.L.166.231; 3.L.166.236; 3.L.166.237; 3.L.166.238; 3.L.166.239; 3.L.166.154; 3.L.166.157; 3.L.166.166; 3.L.166.169; 3.L.166.172; 3.L.166.175; 3.L.166.240; 3.L.166.244; 3.L.169.228; 3.L.169.229; 3.L.169.230; 3.L.169.231; 3.L.169.236; 3.L.169.237; 3.L.169.238; 3.L.169.239; 3.L.169.154; 3.L.169.157; 3.L.169.166; 3.L.169.169; 3.L.169.172; 3.L.169.175; 3.L.169.240; 3.L.169.244; 3.L.172.228; 3.L.172.229; 3.L.172.230; 3.L.172.231; 3.L.172.236; 3.L.172.237; 3.L.172.238; 3.L.172.239; 3.L.172.154; 3.L.172.157; 3.L.172.166; 3.L.172.169; 3.L.172.172; 3.L.172.175; 3.L.172.240; 3.L.172.244; 3.L.175.228; 3.L.175.229; 3.L.175.230; 3.L.175.231; 3.L.175.236; 3.L.175.237; 3.L.175.238; 3.L.175.239; 3.L.175.154; 3.L.175.157; 3.L.175.166; 3.L.175.169; 3.L.175.172; 3.L.175.175; 3.L.175.240; 3.L.175.244; 3.L.240.228; 3.L.240.229; 3.L.240.230; 3.L.240.231; 3.L.240.236; 3.L.240.237; 3.L.240.238; 3.L.240.239; 3.L.240.154; 3.L.240.157; 3.L.240.166; 3.L.240.169; 3.L.240.172; 3.L.240.175; 3.L.240.240; 3.L.240.244; 3.L.244.228; 3.L.244.229; 3.L.244.230; 3.L.244.231; 3.L.244.236; 3.L.244.237; 3.L.244.238; 3.L.244.239; 3.L.244.154; 3.L.244.157; 3.L.244.166; 3.L.244.169; 3.L.244.172; 3.L.244.175; 3.L.244.240; 3.L.244.244;

Prodrugs of 3.O

3.O.228.228; 3.O.228.229; 3.O.228.230; 3.O.228.231; 3.O.228.236; 3.O.228.237; 3.O.228.238; 3.O.228.239; 3.O.228.154; 3.O.228.157; 3.O.228.166; 3.O.228.169; 3.O.228.172; 3.O.228.175; 3.O.228.240; 3.O.228.244; 3.O.229.228; 3.O.229.229; 3.O.229.230; 3.O.229.231; 3.O.229.236; 3.O.229.237; 3.O.229.238; 3.O.229.239; 3.O.229.154; 3.O.229.157; 3.O.229.166; 3.O.229.169; 3.O.229.172; 3.O.229.175; 3.O.229.240; 3.O.229.244; 3.O.230.228; 3.O.230.229; 3.O.230.230; 3.O.230.231; 3.O.230.236; 3.O.230.237; 3.O.230.238; 3.O.230.239; 3.O.230.154; 3.O.230.157; 3.O.230.166; 3.O.230.169; 3.O.230.172; 3.O.230.175; 3.O.230.240; 3.O.230.244; 3.O.231.228; 3.O.231.229; 3.O.231.230; 3.O.231.231; 3.O.231.236; 3.O.231.237; 3.O.231.238; 3.O.231.239; 3.O.231.154; 3.O.231.157; 3.O.231.166; 3.O.231.169; 3.O.231.172; 3.O.231.175; 3.O.231.240; 3.O.231.244; 3.O.236.228; 3.O.236.229; 3.O.236.230; 3.O.236.231; 3.O.236.236; 3.O.236.237; 3.O.236.238; 3.O.236.239; 3.O.236.154; 3.O.236.157; 3.O.236.166; 3.O.236.169; 3.O.236.172; 3.O.236.175; 3.O.236.240; 3.O.236.244; 3.O.237.228; 3.O.237.229; 3.O.237.230; 3.O.237.231; 3.O.237.236; 3.O.237.237; 3.O.237.238; 3.O.237.239; 3.O.237.154; 3.O.237.157;

3.O.237.166; 3.O.237.169; 3.O.237.172; 3.O.237.175; 3.O.237.240; 3.O.237.244; 3.O.238.228; 3.O.238.229; 3.O.238.230; 3.O.238.231; 3.O.238.236; 3.O.238.237; 3.O.238.238; 3.O.238.239; 3.O.238.154; 3.O.238.157; 3.O.238.166; 3.O.238.169; 3.O.238.172; 3.O.238.175; 3.O.238.240; 3.O.238.244; 3.O.239.228; 3.O.239.229; 3.O.239.230; 3.O.239.231; 3.O.239.236; 3.O.239.237; 3.O.239.238; 3.O.239.239; 3.O.239.154; 3.O.239.157; 3.O.239.166; 3.O.239.169; 3.O.239.172; 3.O.239.175; 3.O.239.240; 3.O.239.244; 3.O.154.228; 3.O.154.229; 3.O.154.230; 3.O.154.231; 3.O.154.236; 3.O.154.237; 3.O.154.238; 3.O.154.239; 3.O.154.154; 3.O.154.157; 3.O.154.166; 3.O.154.169; 3.O.154.172; 3.O.154.175; 3.O.154.240; 3.O.154.244; 3.O.157.228; 3.O.157.229; 3.O.157.230; 3.O.157.231; 3.O.157.236; 3.O.157.237; 3.O.157.238; 3.O.157.239; 3.O.157.154; 3.O.157.157; 3.O.157.166; 3.O.157.169; 3.O.157.172; 3.O.157.175; 3.O.157.240; 3.O.157.244; 3.O.166.228; 3.O.166.229; 3.O.166.230; 3.O.166.231; 3.O.166.236; 3.O.166.237; 3.O.166.238; 3.O.166.239; 3.O.166.154; 3.O.166.157; 3.O.166.166; 3.O.166.169; 3.O.166.172; 3.O.166.175; 3.O.166.240; 3.O.166.244; 3.O.169.228; 3.O.169.229; 3.O.169.230; 3.O.169.231; 3.O.169.236; 3.O.169.237; 3.O.169.238; 3.O.169.239; 3.O.169.154; 3.O.169.157; 3.O.169.166; 3.O.169.169; 3.O.169.172; 3.O.169.175; 3.O.169.240; 3.O.169.244; 3.O.172.228; 3.O.172.229; 3.O.172.230; 3.O.172.231; 3.O.172.236; 3.O.172.237; 3.O.172.238; 3.O.172.239; 3.O.172.154; 3.O.172.157; 3.O.172.166; 3.O.172.169; 3.O.172.172; 3.O.172.175; 3.O.172.240; 3.O.172.244; 3.O.175.228; 3.O.175.229; 3.O.175.230; 3.O.175.231; 3.O.175.236; 3.O.175.237; 3.O.175.238; 3.O.175.239; 3.O.175.154; 3.O.175.157; 3.O.175.166; 3.O.175.169; 3.O.175.172; 3.O.175.175; 3.O.175.240; 3.O.175.244; 3.O.240.228; 3.O.240.229; 3.O.240.230; 3.O.240.231; 3.O.240.236; 3.O.240.237; 3.O.240.238; 3.O.240.239; 3.O.240.154; 3.O.240.157; 3.O.240.166; 3.O.240.169; 3.O.240.172; 3.O.240.175; 3.O.240.240; 3.O.240.244; 3.O.244.228; 3.O.244.229; 3.O.244.230; 3.O.244.231; 3.O.244.236; 3.O.244.237; 3.O.244.238; 3.O.244.239; 3.O.244.154; 3.O.244.157; 3.O.244.166; 3.O.244.169; 3.O.244.172; 3.O.244.175; 3.O.244.240; 3.O.244.244;

Prodrugs of 3.P

3.P.228.228; 3.P.228.229; 3.P.228.230; 3.P.228.231; 3.P.228.236; 3.P.228.237; 3.P.228.238; 3.P.228.239; 3.P.228.154; 3.P.228.157; 3.P.228.166; 3.P.228.169; 3.P.228.172; 3.P.228.175; 3.P.228.240; 3.P.228.244; 3.P.229.228; 3.P.229.229; 3.P.229.230; 3.P.229.231; 3.P.229.236; 3.P.229.237; 3.P.229.238; 3.P.229.239; 3.P.229.154; 3.P.229.157; 3.P.229.166; 3.P.229.169; 3.P.229.172; 3.P.229.175; 3.P.229.240; 3.P.229.244; 3.P.230.228; 3.P.230.229; 3.P.230.230; 3.P.230.231; 3.P.230.236; 3.P.230.237; 3.P.230.238; 3.P.230.239; 3.P.230.154; 3.P.230.157; 3.P.230.166; 3.P.230.169; 3.P.230.172; 3.P.230.175; 3.P.230.240; 3.P.230.244; 3.P.231.228; 3.P.231.229; 3.P.231.230; 3.P.231.231; 3.P.231.236; 3.P.231.237; 3.P.231.238; 3.P.231.239; 3.P.231.154; 3.P.231.157; 3.P.231.166; 3.P.231.169; 3.P.231.172; 3.P.231.175; 3.P.231.240; 3.P.231.244; 3.P.236.228; 3.P.236.229; 3.P.236.230; 3.P.236.231; 3.P.236.236; 3.P.236.237; 3.P.236.238; 3.P.236.239; 3.P.236.154; 3.P.236.157; 3.P.236.166; 3.P.236.169; 3.P.236.172; 3.P.236.175; 3.P.236.240; 3.P.236.244; 3.P.237.228; 3.P.237.229; 3.P.237.230; 3.P.237.231; 3.P.237.236; 3.P.237.237; 3.P.237.238; 3.P.237.239; 3.P.237.154; 3.P.237.157; 3.P.237.166; 3.P.237.169; 3.P.237.172; 3.P.237.175; 3.P.237.240; 3.P.237.244;

3.P.238.228; 3.P.238.229; 3.P.238.230; 3.P.238.231; 3.P.238.236; 3.P.238.237; 3.P.238.238; 3.P.238.239; 3.P.238.154; 3.P.238.157; 3.P.238.166; 3.P.238.169; 3.P.238.172; 3.P.238.175; 3.P.238.240; 3.P.238.244; 3.P.239.228; 3.P.239.229; 3.P.239.230; 3.P.239.231; 3.P.239.236; 3.P.239.237; 3.P.239.238; 3.P.239.239; 3.P.239.154; 3.P.239.157; 3.P.239.166; 3.P.239.169; 3.P.239.172; 3.P.239.175; 3.P.239.240; 3.P.239.244; 3.P.154.228; 3.P.154.229; 3.P.154.230; 3.P.154.231; 3.P.154.236; 3.P.154.237; 3.P.154.238; 3.P.154.239; 3.P.154.154; 3.P.154.157; 3.P.154.166; 3.P.154.169; 3.P.154.172; 3.P.154.175; 3.P.154.240; 3.P.154.244; 3.P.157.228; 3.P.157.229; 3.P.157.230; 3.P.157.231; 3.P.157.236; 3.P.157.237; 3.P.157.238; 3.P.157.239; 3.P.157.154; 3.P.157.157; 3.P.157.166; 3.P.157.169; 3.P.157.172; 3.P.157.175; 3.P.157.240; 3.P.157.244; 3.P.166.228; 3.P.166.229; 3.P.166.230; 3.P.166.231; 3.P.166.236; 3.P.166.237; 3.P.166.238; 3.P.166.239; 3.P.166.154; 3.P.166.157; 3.P.166.166; 3.P.166.169; 3.P.166.172; 3.P.166.175; 3.P.166.240; 3.P.166.244; 3.P.169.228; 3.P.169.229; 3.P.169.230; 3.P.169.231; 3.P.169.236; 3.P.169.237; 3.P.169.238; 3.P.169.239; 3.P.169.154; 3.P.169.157; 3.P.169.166; 3.P.169.169; 3.P.169.172; 3.P.169.175; 3.P.169.240; 3.P.169.244; 3.P.172.228; 3.P.172.229; 3.P.172.230; 3.P.172.231; 3.P.172.236; 3.P.172.237; 3.P.172.238; 3.P.172.239; 3.P.172.154; 3.P.172.157; 3.P.172.166; 3.P.172.169; 3.P.172.172; 3.P.172.175; 3.P.172.240; 3.P.172.244; 3.P.175.228; 3.P.175.229; 3.P.175.230; 3.P.175.231; 3.P.175.236; 3.P.175.237; 3.P.175.238; 3.P.175.239; 3.P.175.154; 3.P.175.157; 3.P.175.166; 3.P.175.169; 3.P.175.172; 3.P.175.175; 3.P.175.240; 3.P.175.244; 3.P.240.228; 3.P.240.229; 3.P.240.230; 3.P.240.231; 3.P.240.236; 3.P.240.237; 3.P.240.238; 3.P.240.239; 3.P.240.154; 3.P.240.157; 3.P.240.166; 3.P.240.169; 3.P.240.172; 3.P.240.175; 3.P.240.240; 3.P.240.244; 3.P.244.228; 3.P.244.229; 3.P.244.230; 3.P.244.231; 3.P.244.236; 3.P.244.237; 3.P.244.238; 3.P.244.239; 3.P.244.154; 3.P.244.157; 3.P.244.166; 3.P.244.169; 3.P.244.172; 3.P.244.175; 3.P.244.240; 3.P.244.244;

Prodrugs of 3.U

3.U.228.228; 3.U.228.229; 3.U.228.230; 3.U.228.231; 3.U.228.236; 3.U.228.237; 3.U.228.238; 3.U.228.239; 3.U.228.154; 3.U.228.157; 3.U.228.166; 3.U.228.169; 3.U.228.172; 3.U.228.175; 3.U.228.240; 3.U.228.244; 3.U.229.228; 3.U.229.229; 3.U.229.230; 3.U.229.231; 3.U.229.236; 3.U.229.237; 3.U.229.238; 3.U.229.239; 3.U.229.154; 3.U.229.157; 3.U.229.166; 3.U.229.169; 3.U.229.172; 3.U.229.175; 3.U.229.240; 3.U.229.244; 3.U.230.228; 3.U.230.229; 3.U.230.230; 3.U.230.231; 3.U.230.236; 3.U.230.237; 3.U.230.238; 3.U.230.239; 3.U.230.154; 3.U.230.157; 3.U.230.166; 3.U.230.169; 3.U.230.172; 3.U.230.175; 3.U.230.240; 3.U.230.244; 3.U.231.228; 3.U.231.229; 3.U.231.230; 3.U.231.231; 3.U.231.236; 3.U.231.237; 3.U.231.238; 3.U.231.239; 3.U.231.154; 3.U.231.157; 3.U.231.166; 3.U.231.169; 3.U.231.172; 3.U.231.175; 3.U.231.240; 3.U.231.244; 3.U.236.228; 3.U.236.229; 3.U.236.230; 3.U.236.231; 3.U.236.236; 3.U.236.237; 3.U.236.238; 3.U.236.239; 3.U.236.154; 3.U.236.157; 3.U.236.166; 3.U.236.169; 3.U.236.172; 3.U.236.175; 3.U.236.240; 3.U.236.244; 3.U.237.228; 3.U.237.229; 3.U.237.230; 3.U.237.231; 3.U.237.236; 3.U.237.237; 3.U.237.238; 3.U.237.239; 3.U.237.154; 3.U.237.157; 3.U.237.166; 3.U.237.169; 3.U.237.172; 3.U.237.175; 3.U.237.240; 3.U.237.244; 3.U.238.228; 3.U.238.229; 3.U.238.230; 3.U.238.231; 3.U.238.236; 3.U.238.237;

3.U.238.238; 3.U.238.239; 3.U.238.154; 3.U.238.157; 3.U.238.166; 3.U.238.169; 3.U.238.172; 3.U.238.175; 3.U.238.240; 3.U.238.244; 3.U.239.228; 3.U.239.229; 3.U.239.230; 3.U.239.231; 3.U.239.236; 3.U.239.237; 3.U.239.238; 3.U.239.239; 3.U.239.154; 3.U.239.157; 3.U.239.166; 3.U.239.169; 3.U.239.172; 3.U.239.175; 3.U.239.240; 3.U.239.244; 3.U.154.228; 3.U.154.229; 3.U.154.230; 3.U.154.231; 3.U.154.236; 3.U.154.237; 3.U.154.238; 3.U.154.239; 3.U.154.154; 3.U.154.157; 3.U.154.166; 3.U.154.169; 3.U.154.172; 3.U.154.175; 3.U.154.240; 3.U.154.244; 3.U.157.228; 3.U.157.229; 3.U.157.230; 3.U.157.231; 3.U.157.236; 3.U.157.237; 3.U.157.238; 3.U.157.239; 3.U.157.154; 3.U.157.157; 3.U.157.166; 3.U.157.169; 3.U.157.172; 3.U.157.175; 3.U.157.240; 3.U.157.244; 3.U.166.228; 3.U.166.229; 3.U.166.230; 3.U.166.231; 3.U.166.236; 3.U.166.237; 3.U.166.238; 3.U.166.239; 3.U.166.154; 3.U.166.157; 3.U.166.166; 3.U.166.169; 3.U.166.172; 3.U.166.175; 3.U.166.240; 3.U.166.244; 3.U.169.228; 3.U.169.229; 3.U.169.230; 3.U.169.231; 3.U.169.236; 3.U.169.237; 3.U.169.238; 3.U.169.239; 3.U.169.154; 3.U.169.157; 3.U.169.166; 3.U.169.169; 3.U.169.172; 3.U.169.175; 3.U.169.240; 3.U.169.244; 3.U.172.228; 3.U.172.229; 3.U.172.230; 3.U.172.231; 3.U.172.236; 3.U.172.237; 3.U.172.238; 3.U.172.239; 3.U.172.154; 3.U.172.157; 3.U.172.166; 3.U.172.169; 3.U.172.172; 3.U.172.175; 3.U.172.240; 3.U.172.244; 3.U.175.228; 3.U.175.229; 3.U.175.230; 3.U.175.231; 3.U.175.236; 3.U.175.237; 3.U.175.238; 3.U.175.239; 3.U.175.154; 3.U.175.157; 3.U.175.166; 3.U.175.169; 3.U.175.172; 3.U.175.175; 3.U.175.240; 3.U.175.244; 3.U.240.228; 3.U.240.229; 3.U.240.230; 3.U.240.231; 3.U.240.236; 3.U.240.237; 3.U.240.238; 3.U.240.239; 3.U.240.154; 3.U.240.157; 3.U.240.166; 3.U.240.169; 3.U.240.172; 3.U.240.175; 3.U.240.240; 3.U.240.244; 3.U.244.228; 3.U.244.229; 3.U.244.230; 3.U.244.231; 3.U.244.236; 3.U.244.237; 3.U.244.238; 3.U.244.239; 3.U.244.154; 3.U.244.157; 3.U.244.166; 3.U.244.169; 3.U.244.172; 3.U.244.175; 3.U.244.240; 3.U.244.244;

Prodrugs of 3.CD

3.CD.228.228; 3.CD.228.229; 3.CD.228.230; 3.CD.228.231; 3.CD.228.236; 3.CD.228.237; 3.CD.228.238; 3.CD.228.239; 3.CD.228.154; 3.CD.228.157; 3.CD.228.166; 3.CD.228.169; 3.CD.228.172; 3.CD.228.175; 3.CD.228.240; 3.CD.228.244; 3.CD.229.228; 3.CD.229.229; 3.CD.229.230; 3.CD.229.231; 3.CD.229.236; 3.CD.229.237; 3.CD.229.238; 3.CD.229.239; 3.CD.229.154; 3.CD.229.157; 3.CD.229.166; 3.CD.229.169; 3.CD.229.172; 3.CD.229.175; 3.CD.229.240; 3.CD.229.244; 3.CD.230.228; 3.CD.230.229; 3.CD.230.230; 3.CD.230.231; 3.CD.230.236; 3.CD.230.237; 3.CD.230.238; 3.CD.230.239; 3.CD.230.154; 3.CD.230.157; 3.CD.230.166; 3.CD.230.169; 3.CD.230.172; 3.CD.230.175; 3.CD.230.240; 3.CD.230.244; 3.CD.231.228; 3.CD.231.229; 3.CD.231.230; 3.CD.231.231; 3.CD.231.236; 3.CD.231.237; 3.CD.231.238; 3.CD.231.239; 3.CD.231.154; 3.CD.231.157; 3.CD.231.166; 3.CD.231.169; 3.CD.231.172; 3.CD.231.175; 3.CD.231.240; 3.CD.231.244; 3.CD.236.228; 3.CD.236.229; 3.CD.236.230; 3.CD.236.231; 3.CD.236.236; 3.CD.236.237; 3.CD.236.238; 3.CD.236.239; 3.CD.236.154; 3.CD.236.157; 3.CD.236.166; 3.CD.236.169; 3.CD.236.172; 3.CD.236.175; 3.CD.236.240; 3.CD.236.244; 3.CD.237.228; 3.CD.237.229; 3.CD.237.230; 3.CD.237.231; 3.CD.237.236; 3.CD.237.237; 3.CD.237.238; 3.CD.237.239; 3.CD.237.154; 3.CD.237.157;

3.CD.237.166; 3.CD.237.169; 3.CD.237.172; 3.CD.237.175; 3.CD.237.240; 3.CD.237.244; 3.CD.238.228; 3.CD.238.229; 3.CD.238.230; 3.CD.238.231; 3.CD.238.236; 3.CD.238.237; 3.CD.238.238; 3.CD.238.239; 3.CD.238.154; 3.CD.238.157; 3.CD.238.166; 3.CD.238.169; 3.CD.238.172; 3.CD.238.175; 3.CD.238.240; 3.CD.238.244; 3.CD.239.228; 3.CD.239.229; 3.CD.239.230; 3.CD.239.231; 3.CD.239.236; 3.CD.239.237; 3.CD.239.238; 3.CD.239.239; 3.CD.239.154; 3.CD.239.157; 3.CD.239.166; 3.CD.239.169; 3.CD.239.172; 3.CD.239.175; 3.CD.239.240; 3.CD.239.244; 3.CD.154.228; 3.CD.154.229; 3.CD.154.230; 3.CD.154.231; 3.CD.154.236; 3.CD.154.237; 3.CD.154.238; 3.CD.154.239; 3.CD.154.154; 3.CD.154.157; 3.CD.154.166; 3.CD.154.169; 3.CD.154.172; 3.CD.154.175; 3.CD.154.240; 3.CD.154.244; 3.CD.157.228; 3.CD.157.229; 3.CD.157.230; 3.CD.157.231; 3.CD.157.236; 3.CD.157.237; 3.CD.157.238; 3.CD.157.239; 3.CD.157.154; 3.CD.157.157; 3.CD.157.166; 3.CD.157.169; 3.CD.157.172; 3.CD.157.175; 3.CD.157.240; 3.CD.157.244; 3.CD.166.228; 3.CD.166.229; 3.CD.166.230; 3.CD.166.231; 3.CD.166.236; 3.CD.166.237; 3.CD.166.238; 3.CD.166.239; 3.CD.166.154; 3.CD.166.157; 3.CD.166.166; 3.CD.166.169; 3.CD.166.172; 3.CD.166.175; 3.CD.166.240; 3.CD.166.244; 3.CD.169.228; 3.CD.169.229; 3.CD.169.230; 3.CD.169.231; 3.CD.169.236; 3.CD.169.237; 3.CD.169.238; 3.CD.169.239; 3.CD.169.154; 3.CD.169.157; 3.CD.169.166; 3.CD.169.169; 3.CD.169.172; 3.CD.169.175; 3.CD.169.240; 3.CD.169.244; 3.CD.172.228; 3.CD.172.229; 3.CD.172.230; 3.CD.172.231; 3.CD.172.236; 3.CD.172.237; 3.CD.172.238; 3.CD.172.239; 3.CD.172.154; 3.CD.172.157; 3.CD.172.166; 3.CD.172.169; 3.CD.172.172; 3.CD.172.175; 3.CD.172.240; 3.CD.172.244; 3.CD.175.228; 3.CD.175.229; 3.CD.175.230; 3.CD.175.231; 3.CD.175.236; 3.CD.175.237; 3.CD.175.238; 3.CD.175.239; 3.CD.175.154; 3.CD.175.157; 3.CD.175.166; 3.CD.175.169; 3.CD.175.172; 3.CD.175.175; 3.CD.175.240; 3.CD.175.244; 3.CD.240.228; 3.CD.240.229; 3.CD.240.230; 3.CD.240.231; 3.CD.240.236; 3.CD.240.237; 3.CD.240.238; 3.CD.240.239; 3.CD.240.154; 3.CD.240.157; 3.CD.240.166; 3.CD.240.169; 3.CD.240.172; 3.CD.240.175; 3.CD.240.240; 3.CD.240.244; 3.CD.244.228; 3.CD.244.229; 3.CD.244.230; 3.CD.244.231; 3.CD.244.236; 3.CD.244.237; 3.CD.244.238; 3.CD.244.239; 3.CD.244.154; 3.CD.244.157; 3.CD.244.166; 3.CD.244.169; 3.CD.244.172; 3.CD.244.175; 3.CD.244.240; 3.CD.244.244;

Prodrugs of 3.EB

3.EB.228.228; 3.EB.228.229; 3.EB.228.230; 3.EB.228.231; 3.EB.228.236; 3.EB.228.237; 3.EB.228.238; 3.EB.228.239; 3.EB.228.154; 3.EB.228.157; 3.EB.228.166; 3.EB.228.169; 3.EB.228.172; 3.EB.228.175; 3.EB.228.240; 3.EB.228.244; 3.EB.229.228; 3.EB.229.229; 3.EB.229.230; 3.EB.229.231; 3.EB.229.236; 3.EB.229.237; 3.EB.229.238; 3.EB.229.239; 3.EB.229.154; 3.EB.229.157; 3.EB.229.166; 3.EB.229.169; 3.EB.229.172; 3.EB.229.175; 3.EB.229.240; 3.EB.229.244; 3.EB.230.228; 3.EB.230.229; 3.EB.230.230; 3.EB.230.231; 3.EB.230.236; 3.EB.230.237; 3.EB.230.238; 3.EB.230.239; 3.EB.230.154; 3.EB.230.157; 3.EB.230.166; 3.EB.230.169; 3.EB.230.172; 3.EB.230.175; 3.EB.230.240; 3.EB.230.244; 3.EB.231.228; 3.EB.231.229; 3.EB.231.230; 3.EB.231.231; 3.EB.231.236; 3.EB.231.237; 3.EB.231.238; 3.EB.231.239; 3.EB.231.154; 3.EB.231.157; 3.EB.231.166;

3.EB.231.169; 3.EB.231.172; 3.EB.231.175; 3.EB.231.240; 3.EB.231.244; 3.EB.236.228; 3.EB.236.229; 3.EB.236.230; 3.EB.236.231; 3.EB.236.236; 3.EB.236.237; 3.EB.236.238; 3.EB.236.239; 3.EB.236.154; 3.EB.236.157; 3.EB.236.166; 3.EB.236.169; 3.EB.236.172; 3.EB.236.175; 3.EB.236.240; 3.EB.236.244; 3.EB.237.228; 3.EB.237.229; 3.EB.237.230; 3.EB.237.231; 3.EB.237.236; 3.EB.237.237; 3.EB.237.238; 3.EB.237.239; 3.EB.237.154; 3.EB.237.157; 3.EB.237.166; 3.EB.237.169; 3.EB.237.172; 3.EB.237.175; 3.EB.237.240; 3.EB.237.244; 3.EB.238.228; 3.EB.238.229; 3.EB.238.230; 3.EB.238.231; 3.EB.238.236; 3.EB.238.237; 3.EB.238.238; 3.EB.238.239; 3.EB.238.154; 3.EB.238.157; 3.EB.238.166; 3.EB.238.169; 3.EB.238.172; 3.EB.238.175; 3.EB.238.240; 3.EB.238.244; 3.EB.239.228; 3.EB.239.229; 3.EB.239.230; 3.EB.239.231; 3.EB.239.236; 3.EB.239.237; 3.EB.239.238; 3.EB.239.239; 3.EB.239.154; 3.EB.239.157; 3.EB.239.166; 3.EB.239.169; 3.EB.239.172; 3.EB.239.175; 3.EB.239.240; 3.EB.239.244; 3.EB.154.228; 3.EB.154.229; 3.EB.154.230; 3.EB.154.231; 3.EB.154.236; 3.EB.154.237; 3.EB.154.238; 3.EB.154.239; 3.EB.154.154; 3.EB.154.157; 3.EB.154.166; 3.EB.154.169; 3.EB.154.172; 3.EB.154.175; 3.EB.154.240; 3.EB.154.244; 3.EB.157.228; 3.EB.157.229; 3.EB.157.230; 3.EB.157.231; 3.EB.157.236; 3.EB.157.237; 3.EB.157.238; 3.EB.157.239; 3.EB.157.154; 3.EB.157.157; 3.EB.157.166; 3.EB.157.169; 3.EB.157.172; 3.EB.157.175; 3.EB.157.240; 3.EB.157.244; 3.EB.166.228; 3.EB.166.229; 3.EB.166.230; 3.EB.166.231; 3.EB.166.236; 3.EB.166.237; 3.EB.166.238; 3.EB.166.239; 3.EB.166.154; 3.EB.166.157; 3.EB.166.166; 3.EB.166.169; 3.EB.166.172; 3.EB.166.175; 3.EB.166.240; 3.EB.166.244; 3.EB.169.228; 3.EB.169.229; 3.EB.169.230; 3.EB.169.231; 3.EB.169.236; 3.EB.169.237; 3.EB.169.238; 3.EB.169.239; 3.EB.169.154; 3.EB.169.157; 3.EB.169.166; 3.EB.169.169; 3.EB.169.172; 3.EB.169.175; 3.EB.169.240; 3.EB.169.244; 3.EB.172.228; 3.EB.172.229; 3.EB.172.230; 3.EB.172.231; 3.EB.172.236; 3.EB.172.237; 3.EB.172.238; 3.EB.172.239; 3.EB.172.154; 3.EB.172.157; 3.EB.172.166; 3.EB.172.169; 3.EB.172.172; 3.EB.172.175; 3.EB.172.240; 3.EB.172.244; 3. EB.175.228; 3.EB.175.229; 3.EB.175.230; 3.EB.175.231; 3.EB.175.236; 3.EB.175.237; 3.EB.175.238; 3.EB.175.239; 3.EB.175.154; 3.EB.175.157; 3.EB.175.166; 3.EB.175.169; 3.EB.175.172; 3.EB.175.175; 3.EB.175.240; 3.EB.175.244; 3.EB.240.228; 3.EB.240.229; 3.EB.240.230; 3.EB.240.231; 3.EB.240.236; 3.EB.240.237; 3.EB.240.238; 3.EB.240.239; 3.EB.240.154; 3.EB.240.157; 3.EB.240.166; 3.EB.240.169; 3.EB.240.172; 3.EB.240.175; 3.EB.240.240; 3.EB.240.244; 3.EB.244.228; 3.EB.244.229; 3.EB.244.230; 3.EB.244.231; 3.EB.244.236; 3.EB.244.237; 3.EB.244.238; 3.EB.244.239; 3.EB.244.154; 3.EB.244.157; 3.EB.244.166; 3.EB.244.169; 3.EB.244.172; 3.EB.244.175; 3.EB.244.240; 3.EB.244.244;

Prodrugs of 4.B

4.B.228.228; 4.B.228.229; 4.B.228.230; 4.B.228.231; 4.B.228.236; 4.B.228.237; 4.B.228.238; 4.B.228.239; 4.B.228.154; 4.B.228.157; 4.B.228.166; 4.B.228.169; 4.B.228.172; 4.B.228.175; 4.B.228.240; 4.B.228.244; 4.B.229.228; 4.B.229.229; 4.B.229.230; 4.B.229.231; 4.B.229.236; 4.B.229.237; 4.B.229.238; 4.B.229.239; 4.B.229.154; 4.B.229.157; 4.B.229.166; 4.B.229.169; 4.B.229.172; 4.B.229.175; 4.B.229.240; 4.B.229.244; 4.B.230.228; 4.B.230.229;.4.B.230.230; 4.B.230.231; 4.B.230.236; 4.B.230.237; 4.B.230.238; 4.B.230.239; 4.B.230.154; 4.B.230.157; 4.B.230.166; 4.B.230.169; 4.B.230.172; 4.B.230.175; 4.B.230.240; 4.B.230.244; 4.B.231.228; 4.B.231.229; 4.B.231.230; 4.B.231.231; 4.B.231.236; 4.B.231.237; 4.B.231.238; 4.B.231.239; 4.B.231.154; 4.B.231.157; 4.B.231.166; 4.B.231.169; 4.B.231.172; 4.B.231.175; 4.B.231.240; 4.B.231.244; 4.B.236.228; 4.B.236.229;

4.B.236.230; 4.B.236.231; 4.B.236.236; 4.B.236.237; 4.B.236.238; 4.B.236.239; 4.B.236.154; 4.B.236.157; 4.B.236.166; 4.B.236.169; 4.B.236.172; 4.B.236.175; 4.B.236.240; 4.B.236.244; 4.B.237.228; 4.B.237.229; 4.B.237.230; 4.B.237.231; 4.B.237.236; 4.B.237.237; 4.B.237.238; 4.B.237.239; 4.B.237.154; 4.B.237.157; 4.B.237.166; 4.B.237.169; 4.B.237.172; 4.B.237.175; 4.B.237.240; 4.B.237.244; 4.B.238.228; 4.B.238.229; 4.B.238.230; 4.B.238.231; 4.B.238.236; 4.B.238.237; 4.B.238.238; 4.B.238.239; 4.B.238.154; 4.B.238.157; 4.B.238.166; 4.B.238.169; 4.B.238.172; 4.B.238.175; 4.B.238.240; 4.B.238.244; 4.B.239.228; 4.B.239.229; 4.B.239.230; 4.B.239.231; 4.B.239.236; 4.B.239.237; 4.B.239.238; 4.B.239.239; 4.B.239.154; 4.B.239.157; 4.B.239.166; 4.B.239.169; 4.B.239.172; 4.B.239.175; 4.B.239.240; 4.B.239.244; 4.B.154.228; 4.B.154.229; 4.B.154.230; 4.B.154.231; 4.B.154.236; 4.B.154.237; 4.B.154.238; 4.B.154.239; 4.B.154.154; 4.B.154.157; 4.B.154.166; 4.B.154.169; 4.B.154.172; 4.B.154.175; 4.B.154.240; 4.B.154.244; 4.B.157.228; 4.B.157.229; 4.B.157.230; 4.B.157.231; 4.B.157.236; 4.B.157.237; 4.B.157.238; 4.B.157.239; 4.B.157.154; 4.B.157.157; 4.B.157.166; 4.B.157.169; 4.B.157.172; 4.B.157.175; 4.B.157.240; 4.B.157.244; 4.B.166.228; 4.B.166.229; 4.B.166.230; 4.B.166.231; 4.B.166.236; 4.B.166.237; 4.B.166.238; 4.B.166.239; 4.B.166.154; 4.B.166.157; 4.B.166.166; 4.B.166.169; 4.B.166.172; 4.B.166.175; 4.B.166.240; 4.B.166.244; 4.B.169.228; 4.B.169.229; 4.B.169.230; 4.B.169.231; 4.B.169.236; 4.B.169.237; 4.B.169.238; 4.B.169.239; 4.B.169.154; 4.B.169.157; 4.B.169.166; 4.B.169.169; 4.B.169.172; 4.B.169.175; 4.B.169.240; 4.B.169.244; 4.B.172.228; 4.B.172.229; 4.B.172.230; 4.B.172.231; 4.B.172.236; 4.B.172.237; 4.B.172.238; 4.B.172.239; 4.B.172.154; 4.B.172.157; 4.B.172.166; 4.B.172.169; 4.B.172.172; 4.B.172.175; 4.B.172.240; 4.B.172.244; 4.B.175.228; 4.B.175.229; 4.B.175.230; 4.B.175.231; 4.B.175.236; 4.B.175.237; 4.B.175.238; 4.B.175.239; 4.B.175.154; 4.B.175.157; 4.B.175.166; 4.B.175.169; 4.B.175.172; 4.B.175.175; 4.B.175.240; 4.B.175.244; 4.B.240.228; 4.B.240.229; 4.B.240.230; 4.B.240.231; 4.B.240.236; 4.B.240.237; 4.B.240.238; 4.B.240.239; 4.B.240.154; 4.B.240.157; 4.B.240.166; 4.B.240.169; 4.B.240.172; 4.B.240.175; 4.B.240.240; 4.B.240.244; 4.B.244.228; 4.B.244.229; 4.B.244.230; 4.B.244.231; 4.B.244.236; 4.B.244.237; 4.B.244.238; 4.B.244.239; 4.B.244.154; 4.B.244.157; 4.B.244.166; 4.B.244.169; 4.B.244.172; 4.B.244.175; 4.B.244.240; 4.B.244.244;

Prodrugs of 4.D

4.D.228.228; 4.D.228.229; 4.D.228.230; 4.D.228.231; 4.D.228.236; 4.D.228.237; 4.D.228.238; 4.D.228.239; 4.D.228.154; 4.D.228.157; 4.D.228.166; 4.D.228.169; 4.D.228.172; 4.D.228.175; 4.D.228.240; 4.D.228.244; 4.D.229.228; 4.D.229.229; 4.D.229.230; 4.D.229.231; 4.D.229.236; 4.D.229.237; 4.D.229.238; 4.D.229.239; 4.D.229.154; 4.D.229.157; 4.D.229.166; 4.D.229.169; 4.D.229.172; 4.D.229.175; 4.D.229.240; 4.D.229.244; 4.D.230.228; 4.D.230.229; 4.D.230.230; 4.D.230.231; 4.D.230.236; 4.D.230.237; 4.D.230.238; 4.D.230.239; 4.D.230.154; 4.D.230.157; 4.D.230.166; 4.D.230.169; 4.D.230.172; 4.D.230.175; 4.D.230.240; 4.D.230.244; 4.D.231.228; 4.D.231.229; 4.D.231.230; 4.D.231.231; 4.D.231.236; 4.D.231.237; 4.D.231.238; 4.D.231.239; 4.D.231.154; 4.D.231.157; 4.D.231.166; 4.D.231.169; 4.D.231.172; 4.D.231.175; 4.D.231.240; 4.D.231.244; 4.D.236.228; 4.D.236.229; 4.D.236.230; 4.D.236.231; 4.D.236.236; 4.D.236.237; 4.D.236.238; 4.D.236.239;

4.D.236.154; 4.D.236.157; 4.D.236.166; 4.D.236.169; 4.D.236.172; 4.D.236.175; 4.D.236.240; 4.D.236.244; 4.D.237.228; 4.D.237.229; 4.D.237.230; 4.D.237.231; 4.D.237.236; 4.D.237.237; 4.D.237.238; 4.D.237.239; 4.D.237.154; 4.D.237.157; 4.D.237.166; 4.D.237.169; 4.D.237.172; 4.D.237.175; 4.D.237.240; 4.D.237.244; 4.D.238.228; 4.D.238.229; 4.D.238.230; 4.D.238.231; 4.D.238.236; 4.D.238.237; 4.D.238.238; 4.D.238.239; 4.D.238.154; 4.D.238.157; 4.D.238.166; 4.D.238.169; 4.D.238.172; 4.D.238.175; 4.D.238.240; 4.D.238.244; 4.D.239.228; 4.D.239.229; 4.D.239.230; 4.D.239.231; 4.D.239.236; 4.D.239.237; 4.D.239.238; 4.D.239.239; 4.D.239.154; 4.D.239.157; 4.D.239.166; 4.D.239.169; 4.D.239.172; 4.D.239.175; 4.D.239.240; 4.D.239.244; 4.D.154.228; 4.D.154.229; 4.D.154.230; 4.D.154.231; 4.D.154.236; 4.D.154.237; 4.D.154.238; 4.D.154.239; 4.D.154.154; 4.D.154.157; 4.D.154.166; 4.D.154.169; 4.D.154.172; 4.D.154.175; 4.D.154.240; 4.D.154.244; 4.D.157.228; 4.D.157.229; 4.D.157.230; 4.D.157.231; 4.D.157.236; 4.D.157.237; 4.D.157.238; 4.D.157.239; 4.D.157.154; 4.D.157.157; 4.D.157.166; 4.D.157.169; 4.D.157.172; 4.D.157.175; 4.D.157.240; 4.D.157.244; 4.D.166.228; 4.D.166.229; 4.D.166.230; 4.D.166.231; 4.D.166.236; 4.D.166.237; 4.D.166.238; 4.D.166.239; 4.D.166.154; 4.D.166.157; 4.D.166.166; 4.D.166.169; 4.D.166.172; 4.D.166.175; 4.D.166.240; 4.D.166.244; 4.D.169.228; 4.D.169.229; 4.D.169.230; 4.D.169.231; 4.D.169.236; 4.D.169.237; 4.D.169.238; 4.D.169.239; 4.D.169.154; 4.D.169.157; 4.D.169.166; 4.D.169.169; 4.D.169.172; 4.D.169.175; 4.D.169.240; 4.D.169.244; 4.D.172.228; 4.D.172.229; 4.D.172.230; 4.D.172.231; 4.D.172.236; 4.D.172.237; 4.D.172.238; 4.D.172.239; 4.D.172.154; 4.D.172.157; 4.D.172.166; 4.D.172.169; 4.D.172.172; 4.D.172.175; 4.D.172.240; 4.D.172.244; 4.D.175.228; 4.D.175.229; 4.D.175.230; 4.D.175.231; 4.D.175.236; 4.D.175.237; 4.D.175.238; 4.D.175.239; 4.D.175.154; 4.D.175.157; 4.D.175.166; 4.D.175.169; 4.D.175.172; 4.D.175.175; 4.D.175.240; 4.D.175.244; 4.D.240.228; 4.D.240.229; 4.D.240.230; 4.D.240.231; 4.D.240.236; 4.D.240.237; 4.D.240.238; 4.D.240.239; 4.D.240.154; 4.D.240.157; 4.D.240.166; 4.D.240.169; 4.D.240.172; 4.D.240.175; 4.D.240.240; 4.D.240.244; 4.D.244.228; 4.D.244.229; 4.D.244.230; 4.D.244.231; 4.D.244.236; 4.D.244.237; 4.D.244.238; 4.D.244.239; 4.D.244.154; 4.D.244.157; 4.D.244.166; 4.D.244.169; 4.D.244.172; 4.D.244.175; 4.D.244.240; 4.D.244.244;

Prodrugs of 4.AB

4.AB.228.228; 4.AB.228.229; 4.AB.228.230; 4.AB.228.231; 4.AB.228.236; 4.AB.228.237; 4.AB.228.238; 4.AB.228.239; 4.AB.228.154; 4.AB.228.157; 4.AB.228.166; 4.AB.228.169; 4.AB.228.172; 4.AB.228.175; 4.AB.228.240; 4.AB.228.244; 4.AB.229.228; 4.AB.229.229; 4.AB.229.230; 4.AB.229.231; 4.AB.229.236; 4.AB.229.237; 4.AB.229.238; 4.AB.229.239; 4.AB.229.154; 4.AB.229.157; 4.AB.229.166; 4.AB.229.169; 4.AB.229.172; 4.AB.229.175; 4.AB.229.240; 4.AB.229.244; 4.AB.230.228; 4.AB.230.229; 4.AB.230.230; 4.AB.230.231; 4.AB.230.236; 4.AB.230.237; 4.AB.230.238; 4.AB.230.239; 4.AB.230.154; 4.AB.230.157; 4.AB.230.166; 4.AB.230.169; 4.AB.230.172; 4.AB.230.175; 4.AB.230.240; 4.AB.230.244; 4.AB.231.228; 4.AB.231.229; 4.AB.231.230; 4.AB.231.231; 4.AB.231.236; 4.AB.231.237; 4.AB.231.238; 4.AB.231.239; 4.AB.231.154; 4.AB.231.157; 4.AB.231.166; 4.AB.231.169; 4.AB.231.172; 4.AB.231.175; 4.AB.231.240; 4.AB.231.244; 4.AB.236.228;

4.AB.236.229; 4.AB.236.230; 4.AB.236.231; 4.AB.236.236; 4.AB.236.237; 4.AB.236.238; 4.AB.236.239; 4.AB.236.154; 4.AB.236.157; 4.AB.236.166; 4.AB.236.169; 4.AB.236.172; 4.AB.236.175; 4.AB.236.240; 4.AB.236.244; 4.AB.237.228; 4.AB.237.229; 4.AB.237.230; 4.AB.237.231; 4.AB.237.236; 4.AB.237.237; 4.AB.237.238; 4.AB.237.239; 4.AB.237.154; 4.AB.237.157; 4.AB.237.166; 4.AB.237.169; 4.AB.237.172; 4.AB.237.175; 4.AB.237.240; 4.AB.237.244; 4.AB.238.228; 4.AB.238.229; 4.AB.238.230; 4.AB.238.231; 4.AB.238.236; 4.AB.238.237; 4.AB.238.238; 4.AB.238.239; 4.AB.238.154; 4.AB.238.157; 4.AB.238.166; 4.AB.238.169; 4.AB.238.172; 4.AB.238.175; 4.AB.238.240; 4.AB.238.244; 4.AB.239.228; 4.AB.239.229; 4.AB.239.230; 4.AB.239.231; 4.AB.239.236; 4.AB.239.237; 4.AB.239.238; 4.AB.239.239; 4.AB.239.154; 4.AB.239.157; 4.AB.239.166; 4.AB.239.169; 4.AB.239.172; 4.AB.239.175; 4.AB.239.240; 4.AB.239.244; 4.AB.154.228; 4.AB.154.229; 4.AB.154.230; 4.AB.154.231; 4.AB.154.236; 4.AB.154.237; 4.AB.154.238; 4.AB.154.239; 4.AB.154.154; 4.AB.154.157; 4.AB.154.166; 4.AB.154.169; 4.AB.154.172; 4.AB.154.175; 4.AB.154.240; 4.AB.154.244; 4.AB.157.228; 4.AB.157.229; 4.AB.157.230; 4.AB.157.231; 4.AB.157.236; 4.AB.157.237; 4.AB.157.238; 4.AB.157.239; 4.AB.157.154; 4.AB.157.157; 4.AB.157.166; 4.AB.157.169; 4.AB.157.172; 4.AB.157.175; 4.AB.157.240; 4.AB.157.244; 4.AB.166.228; 4.AB.166.229; 4.AB.166.230; 4.AB.166.231; 4.AB.166.236; 4.AB.166.237; 4.AB.166.238; 4.AB.166.239; 4.AB.166.154; 4.AB.166.157; 4.AB.166.166; 4.AB.166.169; 4.AB.166.172; 4.AB.166.175; 4.AB.166.240; 4.AB.166.244; 4.AB.169.228; 4.AB.169.229; 4.AB.169.230; 4.AB.169.231; 4.AB.169.236; 4.AB.169.237; 4.AB.169.238; 4.AB.169.239; 4.AB.169.154; 4.AB.169.157; 4.AB.169.166; 4.AB.169.169; 4.AB.169.172; 4.AB.169.175; 4.AB.169.240; 4.AB.169.244; 4.AB.172.228; 4.AB.172.229; 4.AB.172.230; 4.AB.172.231; 4.AB.172.236; 4.AB.172.237; 4.AB.172.238; 4.AB.172.239; 4.AB.172.154; 4.AB.172.157; 4.AB.172.166; 4.AB.172.169; 4.AB.172.172; 4.AB.172.175; 4.AB.172.240; 4.AB.172.244; 4.AB.175.228; 4.AB.175.229; 4.AB.175.230; 4.AB.175.231; 4.AB.175.236; 4.AB.175.237; 4.AB.175.238; 4.AB.175.239; 4.AB.175.154; 4.AB.175.157; 4.AB.175.166; 4.AB.175.169; 4.AB.175.172; 4.AB.175.175; 4.AB.175.240; 4.AB.175.244; 4.AB.240.228; 4.AB.240.229; 4.AB.240.230; 4.AB.240.231; 4.AB.240.236; 4.AB.240.237; 4.AB.240.238; 4.AB.240.239; 4.AB.240.154; 4.AB.240.157; 4.AB.240.166; 4.AB.240.169; 4.AB.240.172; 4.AB.240.175; 4.AB.240.240; 4.AB.240.244; 4.AB.244.228; 4.AB.244.229; 4.AB.244.230; 4.AB.244.231; 4.AB.244.236; 4.AB.244.237; 4.AB.244.238; 4.AB.244.239; 4.AB.244.154; 4.AB.244.157; 4.AB.244.166; 4.AB.244.169; 4.AB.244.172; 4.AB.244.175; 4.AB.244.240; 4.AB.244.244;

Prodrugs of 4.BI

4.BI.228.228; 4.BI.228.229; 4.BI.228.230; 4.BI.228.231; 4.BI.228.236; 4.BI.228.237; 4.BI.228.238; 4.BI.228.239; 4.BI.228.154; 4.BI.228.157; 4.BI.228.166; 4.BI.228.169; 4.BI.228.172; 4.BI.228.175; 4.BI.228.240; 4.BI.228.244; 4.BI.229.228; 4.BI.229.229; 4.BI.229.230; 4.BI.229.231; 4.BI.229.236; 4.BI.229.237; 4.BI.229.238; 4.BI.229.239; 4.BI.229.154; 4.BI.229.157; 4.BI.229.166; 4.BI.229.169; 4.BI.229.172; 4.BI.229.175;

4.BI.229.240; 4.BI.229.244; 4.BI.230.228; 4.BI.230.229; 4.BI.230.230; 4.BI.230.231; 4.BI.230.236; 4.BI.230.237; 4.BI.230.238; 4.BI.230.239; 4.BI.230.154; 4.BI.230.157; 4.BI.230.166; 4.BI.230.169; 4.BI.230.172; 4.BI.230.175; 4.BI.230.240; 4.BI.230.244; 4.BI.231.228; 4.BI.231.229; 4.BI.231.230; 4.BI.231.231; 4.BI.231.236; 4.BI.231.237; 4.BI.231.238; 4.BI.231.239; 4.BI.231.154; 4.BI.231.157; 4.BI.231.166; 4.BI.231.169; 4.BI.231.172; 4.BI.231.175; 4.BI.231.240; 4.BI.231.244; 4.BI.236.228; 4.BI.236.229; 4.BI.236.230; 4.BI.236.231; 4.BI.236.236; 4.BI.236.237; 4.BI.236.238; 4.BI.236.239; 4.BI.236.154; 4.BI.236.157; 4.BI.236.166; 4.BI.236.169; 4.BI.236.172; 4.BI.236.175; 4.BI.236.240; 4.BI.236.244; 4.BI.237.228; 4.BI.237.229; 4.BI.237.230; 4.BI.237.231; 4.BI.237.236; 4.BI.237.237; 4.BI.237.238; 4.BI.237.239; 4.BI.237.154; 4.BI.237.157; 4.BI.237.166; 4.BI.237.169; 4.BI.237.172; 4.BI.237.175; 4.BI.237.240; 4.BL237.244; 4.BI.238.228; 4.BI.238.229; 4.BI.238.230; 4.BI.238.231; 4.BI.238.236; 4.BI.238.237; 4.BI.238.238; 4.BI.238.239; 4.BI.238.154; 4.BI.238.157; 4.BI.238.166; 4.BI.238.169; 4.BI.238.172; 4.BI.238.175; 4.BI.238.240; 4.BI.238.244; 4.BI.239.228; 4.BI.239.229; 4.BI.239.230; 4.BI.239.231; 4.BI.239.236; 4.BI.239.237; 4.BI.239.238; 4.BI.239.239; 4.BI.239.154; 4.BI.239.157; 4.BI.239.166; 4.BI.239.169; 4.BI.239.172; 4.BI.239.175; 4.BI.239.240; 4.BI.239.244; 4.BI.154.228; 4.BI.154.229; 4.BI.154.230; 4.BI.154.231; 4.BI.154.236; 4.BI.154.237; 4.BI.154.238; 4.BI.154.239; 4.BI.154.154; 4.BI.154.157; 4.BI.154.166; 4.BI.154.169; 4.BI.154.172; 4.BI.154.175; 4.BI.154.240; 4.BI.154.244; 4.BI.157.228; 4.BI.157.229; 4.BI.157.230; 4.BI.157.231; 4.BI.157.236; 4.BI.157.237; 4.BI.157.238; 4.BI.157.239; 4.BI.157.154; 4.BI.157.157; 4.BI.157.166; 4.BI.157.169; 4.BI.157.172; 4.BI.157.175; 4.BI.157.240; 4.BI.157.244; 4.BI.166.228; 4.BI.166.229; 4.BI.166.230; 4.BI.166.231; 4.BI.166.236; 4.BI.166.237; 4.BI.166.238; 4.BI.166.239; 4.BI.166.154; 4.BI.166.157; 4.BI.166.166; 4.BI.166.169; 4.BI.166.172; 4.BI.166.175; 4.BI.166.240; 4.BI.166.244; 4.BI.169.228; 4.BI.169.229; 4.BI.169.230; 4.BI.169.231; 4.BI.169.236; 4.BI.169.237; 4.BI.169.238; 4.BI.169.239; 4.BI.169.154; 4.BI.169.157; 4.BI.169.166; 4.BI.169.169; 4.BI.169.172; 4.BI.169.175; 4.BI.169.240; 4.BI.169.244; 4.BI.172.228; 4.BI.172.229; 4.BI.172.230; 4.BI.172.231; 4.BI.172.236; 4.BI.172.237; 4.BI.172.238; 4.BI.172.239; 4.BI.172.154; 4.BI.172.157; 4.BI.172.166; 4.BI.172.169; 4.BI.172.172; 4.BI.172.175; 4.BI.172.240; 4.BI.172.244; 4.BI.175.228; 4.BI.175.229; 4.BI.175.230; 4.BI.175.231; 4.BI.175.236; 4.BI.175.237; 4.BI.175.238; 4.BI.175.239; 4.BI.175.154; 4.BI.175.157; 4.BI.175.166; 4.BI.175.169; 4.BI.175.172; 4.BI.175.175; 4.BI.175.240; 4.BI.175.244; 4.BI.240.228; 4.BI.240.229; 4.BI.240.230; 4.BI.240.231; 4.BI.240.236; 4.BI.240.237; 4.BI.240.238; 4.BI.240.239; 4.BI.240.154; 4.BI.240.157; 4.BI.240.166; 4.BI.240.169; 4.BI.240.172; 4.BI.240.175; 4.BI.240.240; 4.BI.240.244; 4.BI.244.228; 4.BI.244.229; 4.BI.244.230; 4.BI.244.231; 4.BI.244.236; 4.BI.244.237; 4.BI.244.238; 4.BI.244.239; 4.BI.244.154; 4.BI.244.157; 4.BI.244.166; 4.BI.244.169; 4.BI.244.172; 4.BI.244.175; 4.BI.244.240; 4.BI.244.244;

Prodrugs of 4.1

4.1.228.228; 4.1.228.229; 4.1.228.230; 4.1.228.231; 4.1.228.236; 4.1.228.237; 4.1.228.238; 4.1.228.239; 4.1.228.154; 4.1.228.157; 4.1.228.166; 4.1.228.169; 4.1.228.172; 4.1.228.175; 4.1.228.240; 4.1.228.244; 4.1.229.228; 4.1.229.229; 4.1.229.230; 4.1.229.231; 4.1.229.236; 4.1.229.237; 4.1.229.238; 4.1.229.239; 4.1.229.154; 4.1.229.157; 4.1.229.166; 4.1.229.169; 4.1.229.172; 4.1.229.175; 4.1.229.240; 4.1.229.244; 4.1.230.228; 4.1.230.229; 4.1.230.230; 4.1.230.231; 4.1.230.236; 4.1.230.237; 4.1.230.238; 4.1.230.239; 4.1.230.154;

4.1.230.157; 4.1.230.166; 4.1.230.169; 4.1.230.172; 4.1.230.175; 4.1.230.240; 4.1.230.244; 4.1.231.228; 4.1.231.229; 4.1.231.230; 4.1.231.231; 4.1.231.236; 4.1.231.237; 4.1.231.238; 4.1.231.239; 4.1.231.154; 4.1.231.157; 4.1.231.166; 4.1.231.169; 4.1.231.172; 4.1.231.175; 4.1.231.240; 4.1.231.244; 4.1.236.228; 4.1.236.229; 4.1.236.230; 4.1.236.231; 4.1.236.236; 4.1.236.237; 4.1.236.238; 4.1.236.239; 4.1.236.154; 4.1.236.157; 4.1.236.166; 4.1.236.169; 4.1.236.172; 4.1.236.175; 4.1.236.240; 4.1.236.244; 4.1.237.228; 4.1.237.229; 4.1.237.230; 4.1.237.231; 4.1.237.236; 4.1.237.237; 4.1.237.238; 4.1.237.239; 4.1.237.154; 4.1.237.157; 4.1.237.166; 4.1.237.169; 4.1.237.172; 4.1.237.175; 4.1.237.240; 4.1.237.244; 4.1.238.228; 4.1.238.229; 4.1.238.230; 4.1.238.231; 4.1.238.236; 4.1.238.237; 4.1.238.238; 4.1.238.239; 4.1.238.154; 4.1.238.157; 4.1.238.166; 4.1.238.169; 4.1.238.172; 4.1.238.175; 4.1.238.240; 4.1.238.244; 4.1.239.228; 4.1.239.229; 4.1.239.230; 4.1.239.231; 4.1.239.236; 4.1.239.237; 4.1.239.238; 4.1.239.239; 4.1.239.154; 4.1.239.157; 4.1.239.166; 4.1.239.169; 4.1.239.172; 4.1.239.175; 4.1.239.240; 4.1.239.244; 4.1.154.228; 4.1.154.229; 4.1.154.230; 4.1.154.231; 4.1.154.236; 4.1.154.237; 4.1.154.238; 4.1.154.239; 4.1.154.154; 4.1.154.157; 4.1.154.166; 4.1.154.169; 4.1.154.172; 4.1.154.175; 4.1.154.240; 4.1.154.244; 4.1.157.228; 4.1.157.229; 4.1.157.230; 4.1.157.231; 4.1.157.236; 4.1.157.237; 4.1.157.238; 4.1.157.239; 4.1.157.154; 4.1.157.157; 4.1.157.166; 4.1.157.169; 4.1.157.172; 4.1.157.175; 4.1.157.240; 4.1.157.244; 4.1.166.228; 4.1.166.229; 4.1.166.230; 4.1.166.231; 4.1.166.236; 4.1.166.237; 4.1.166.238; 4.1.166.239; 4.1.166.154; 4.1.166.157; 4.1.166.166; 4.1.166.169; 4.1.166.172; 4.1.166.175; 4.1.166.240; 4.1.166.244; 4.1.169.228; 4.1.169.229; 4.1.169.230; 4.1.169.231; 4.1.169.236; 4.1.169.237; 4.1.169.238; 4.1.169.239; 4.1.169.154; 4.1.169.157; 4.1.169.166; 4.1.169.169; 4.1.169.172; 4.1.169.175; 4.1.169.240; 4.1.169.244; 4gl.172.228; 4.1.172.229; 4.1.172.230; 4.1.172.231; 4.1.172.236; 4.1.172.237; 4.1.172.238; 4:1.172.239; 4.1.172.154; 4.1.172.157; 4.1.172.166; 4.1.172.169; 4.1.172.172; 4.1.172.175; 4.1.172.240; 4.1.172.244; 4.1.175.228; 4.1.175.229; 4.1.175.230; 4.1.175.231; 4.1.175.236; 4.1.175.237; 4.1.175.238; 4.1.175.239; 4.1.175.154; 4.1.175.157; 4.1.175.166; 4.1.175.169; 4.1.175.172; 4.1.175.175; 4.1.175.240; 4.1.175.244; 4.1.240.228; 4.1.240.229; 4.1.240.230; 4.1.240.231; 4.1.240.236; 4.1.240.237; 4.1.240.238; 4.1.240.239; 4.1.240.154; 4.1.240.157; 4.1.240.166; 4.1.240.169; 4.1.240.172; 4.1.240.175; 4.1.240.240; 4.1.240.244; 4.1.244.228; 4.1.244.229; 4.1.244.230; 4.1.244.231; 4.1.244.236; 4.1.244.237; 4.1.244.238; 4.1.244.239; 4.1.244.154; 4.1.244.157; 4.1.244.166; 4.1.244.169; 4.1.244.172; 4.1.244.175; 4.1.244.240; 4.1.244.244;

Prodrugs of 4.T

4.J.228.228; 4.J.228.229; 4.J.228.230; 4.J.228.231; 4.J.228.236; 4J.228.237; 4.J.228.238; 4.J.228.239; 4J.228.154; 4J.228.157; 4.J.228.166; 4J.228.169; 4J.228.172; 4J.228.175; 4J.228.240; 4J.228.244; 4 J.229.228; 4 J.229.229; 4J.229.230; 4J.229.231; 4J.229.236; 4J.229.237; 4J.229.238; 4J.229.239; 4J.229.154; 4 J.229.157; 4 J.229.166; 4J.229.169; 4J.229.172; 4J.229.175; 4J.229.240; 4J.229.244; 4.J.230.228; 4J.230.229; 4J.230.230; 4J.230.231; 4J.230.236; 4 J.230.237; 4J.230.238; 4J.230.239; 4J.230.154; 4J.230.157; 4 J.230.166; 4.J.230.169; 4J.230.172; 4J.230.175; 4J.230.240; 4J.230.244; 4J.231.228; 4J.231.229; 4J.231.230; 4J.231.231; 4J.231.236; 4J.231.237; 4J.231.238; 4J.231.239; 4J.231.154; 4J.231.157; 4J.231.166; 4J.231.169; 4J.231.172; 4J.231.175; 4J.231.240; 4J.231.244; 4.J.236.228; 4J.236.229; 4J.236.230; 4J.236.231; 4J.236.236; 4J.236.237; 4.J.236.238; 4J.236.239; 4J.236.154; 4.J.236.157; 4J.236.166; 4J.236.169; 4J.236.172; 4J.236.175; 4J.236.240; 4J.236.244; 4J.237.228; 4J.237.229; 4.J.237.230; 4J.237.231; 4 J.237.236; 4.J.237.237; 4J.237.238; 4J.237.239; 4.J.237.154; 4J.237.157;

4J.237.166; 4.J.237.169; 4.J.237.172; 4.J.237.175; 4.J.237.240; 4.J.237.244; 4.J.238.228; 4.J.238.229; 4.J.238.230; 4.J.238.231; 4.J.238.236; 4.J.238.237; 4.J.238.238; 4.J.238.239; 4.J.238.154; 4.J.238.157; 4.J.238.166; 4.J.238.169; 4.J.238.172; 4.J.238.175; 4.J.238.240; 4.J.238.244; 4.J.239.228; 4.J.239.229; 4.J.239.230; 4.J.239.231; 4.J.239.236; 4J.239.237; 4J.239.238; 4J.239.239; 4J.239.154; 4 J.239.157; 4.J.239.166; 4J.239.169; 4J.239.172; 4J.239.175; 4J.239.240; 4J.239.244; 4.J.154.228; 4J.154.229; 4J.154.230; 4J.154.231; 4J.154.236; 4 J.154.237; 4J.154.238; 4J.154.239; 4J.154.154; 4J.154.157; 4J.154.166; 4J.154.169; 4J.154.172; 4J.154.175; 4 J.154.240; 4J.154.244; 4J.157.228; 4.J.157.229; 4J.157.230; 4J.157.231; 4J.157.236; 4J.157.237; 4J.157.238; 4J.157.239; 4J.157.154; 4J.157.157; 4J.157.166; 4 J.157.169; 4J.157.172; 4J.157.175; 4 J.157.240; 4J.157.244; 4 J.166.228; 4J.166.229; 4J.166.230; 4J.166.231; 4J.166.236; 4J.166.237; 4J.166.238; 4J.166.239; 4J.166.154; 4J.166.157; 4J.166.166; 4 J.166.169; 4 J.166.172; 4 J.166.175; 4J.166.240; 4J.166.244; 4J.169.228; 4J.169.229; 4J.169.230; 4J.169.231; 4J.169.236; 4J.169.237; 4 J.169.238; 4J.169.239; 4J.169.154; 4J.169.157; 4J.169.166; 4 J.169.169; 4J.169.172; 4J.169.175; 4J.169.240; 4J.169.244; 4J.172.228; 4J.172.229; 4J.172.230; 4J.172.231; 4 J.172.236; 4J.172.237; 4J.172.238; 4J.172.239; 4J.172.154; 4J.172.157; 4J.172.166; 4J.172.169; 4J.172.172; 4.J.172.175; 4J.172.240; 4 J.172.244; 4J.175.228; 4J.175.229; 4J.175.230; 4J.175.231; 4J.175.236; 4J.175.237; 4J.175.238; 4J.175.239; 4J.175.154; 4 J.175.157; 4J.175.166; 4J.175.169; 4J.175.172; 4J.175.175; 4 J.175.240; 4 J.175.244; 4J.240.228; 4 J.240.229; 4 J.240.230; 4 J.240.231; 4 J.240.236; 4J.240.237; 4 J.240.238; 4J.240.239; 4J.240.154; 4J.240.157; 4J.240.166; 4J.240.169; 4 J.240.172; 4 J.240.175; 4J.240.240; 4J.240.244; 4 J.244.228; 4J.244.229; 4J.244.230; 4J.244.231; 4 J.244.236; 4J.244.237; 4 J.244.238; 4J.244.239; 4J.244.154; 4J.244.157; 4 J.244.166; 4J.244.169; 4J.244.172; 4 J.244.175; 4J.244.240; 4J.244.244;

Prodrugs of 4.L

4.L.228.228; 4.L.228.229; 4.L.228.230; 4.L.228.231; 4.L.228.236; 4.L.228.237; 4.L.228.238; 4.L.228.239; 4.L.228.154; 4.L.228.157; 4.L.228.166; 4.L.228.169; 4.L.228.172; 4.L.228.175; 4.L.228.240; 4.L.228.244; 4.L.229.228; 4.L.229.229; 4.L.229.230; 4.L.229.231; 4.L.229.236; 4.L.229.237; 4.L.229.238; 4.L.229.239; 4.L.229.154; 4.L.229.157; 4.L.229.166; 4.L.229.169; 4.L.229.172; 4.L.229.175; 4.L.229.240; 4.L.229.244; 4.L.230.228; 4.L.230.229; 4.L.230.230; 4.L.230.231; 4.L.230.236; 4.L.230.237; 4.L.230.238; 4.L.230.239; 4.L.230.154; 4.L.230.157; 4.L.230.166; 4.L.230.169; 4.L.230.172; 4.L.230.175; 4.L.230.240; 4.L.230.244; 4.L.231.228; 4.L.231.229; 4.L.231.230; 4.L.231.231; 4.L.231.236; 4.L.231.237; 4.L.231.238; 4.L.231.239; 4.L.231.154; 4.L.231.157; 4.L.231.166; 4.L.231.169; 4.L.231.172; 4.L.231.175; 4.L.231.240; 4.L.231.244; 4.L.236.228; 4.L.236.229; 4.L.236.230; 4.L.236.231; 4.L.236.236; 4.L.236.237; 4.L.236.238; 4.L.236.239; 4.L.236.154; 4.L.236.157; 4.L.236.166; 4.L.236.169; 4.L.236.172; 4.L.236.175; 4.L.236.240; 4.L.236.244; 4.L.237.228; 4.L.237.229; 4.L.237.230; 4.L.237.231; 4.L.237.236; 4.L.237.237; 4.L.237.238; 4.L.237.239; 4.L.237.154; 4.L.237.157; 4.L.237.166; 4.L.237.169; 4.L.237.172; 4.L.237.175; 4.L.237.240; 4.L.237.244; 4.L.238.228; 4.L.238.229; 4.L.238.230; 4.L.238.231; 4.L.238.236; 4.L.238.237; 4.L.238.238; 4.L.238.239; 4.L.238.154; 4.L.238.157; 4.L.238.166; 4.L.238.169; 4.L.238.172; 4.L.238.175; 4.L.238.240; 4.L.238.244; 4.L.239.228; 4.L.239.229; 4.L.239.230; 4.L.239.231; 4.L.239.236; 4.L.239.237; 4.L.239.238; 4.L.239.239;

4.L.239.154; 4.L.239.157; 4.L.239.166; 4.L.239.169; 4.L.239.172; 4.L.239.175; 4.L.239.240; 4.L.239.244; 4.L.154.228; 4.L.154.229; 4.L.154.230; 4.L.154.231; 4.L.154.236; 4.L.154.237; 4.L.154.238; 4.L.154.239; 4.L.154.154; 4.L.154.157; 4.L.154.166; 4.L.154.169; 4.L.154.172; 4.L.154.175; 4.L.154.240; 4.L.154.244; 4.L.157.228; 4.L.157.229; 4.L.157.230; 4.L.157.231; 4.L.157.236; 4.L.157.237; 4.L.157.238; 4.L.157.239; 4.L.157.154; 4.L.157.157; 4.L.157.166; 4.L.157.169; 4.L.157.172; 4.L.157.175; 4.L.157.240; 4.L.157.244; 4.L.166.228; 4.L.166.229; 4.L.166.230; 4.L.166.231; 4.L.166.236; 4.L.166.237; 4.L.166.238; 4.L.166.239; 4.L.166.154; 4.L.166.157; 4.L.166.166; 4.L.166.169; 4.L.166.172; 4.L.166.175; 4.L.166.240; 4.L.166.244; 4.L.169.228; 4.L.169.229; 4.L.169.230; 4.L.169.231; 4.L.169.236; 4.L.169.237; 4.L.169.238; 4.L.169.239; 4.L.169.154; 4.L.169.157; 4.L.169.166; 4.L.169.169; 4.L.169.172; 4.L.169.175; 4.L.169.240; 4.L.169.244; 4.L.172.228; 4.L.172.229; 4.L.172.230; 4.L.172.231; 4.L.172.236; 4.L.172.237; 4.L.172.238; 4.L.172.239; 4.L.172.154; 4.L.172.157; 4.L.172.166; 4.L.172.169; 4.L.172.172; 4.L.172.175; 4.L.172.240; 4.L.172.244; 4.L.175.228; 4.L.175.229; 4.L.175.230; 4.L.175.231; 4.L.175.236; 4.L.175.237; 4.L.175.238; 4.L.175.239; 4.L.175.154; 4.L.175.157; 4.L.175.166; 4.L.175.169; 4.L.175.172; 4.L.175.175; 4.L.175.240; 4.L.175.244; 4.L.240.228; 4.L.240.229; 4.L.240.230; 4.L.240.231; 4.L.240.236; 4.L.240.237; 4.L.240.238; 4.L.240.239; 4.L.240.154; 4.L.240.157; 4.L.240.166; 4.L.240.169; 4.L.240.172; 4.L.240.175; 4.L.240.240; 4.L.240.244; 4.L.244.228; 4.L.244.229; 4.L.244.230; 4.L.244.231; 4.L.244.236; 4.L.244.237; 4.L.244.238; 4.L.244.239; 4.L.244.154; 4.L.244.157; 4.L.244.166; 4.L.244.169; 4.L.244.172; 4.L.244.175; 4.L.244.240; 4.L.244.244;

Prodrugs of 4.O

4.O.228.228; 4.O.228.229; 4.O.228.230; 4.O.228.231; 4.O.228.236; 4.O.228.237; 4.O.228.238; 4.O.228.239; 4.O.228.154; 4.O.228.157; 4.O.228.166; 4.O.228.169; 4.O.228.172; 4.O.228.175; 4.O.228.240; 4.O.228.244; 4.O.229.228; 4.O.229.229; 4.O.229.230; 4.O.229.231; 4.O.229.236; 4.O.229.237; 4.O.229.238; 4.O.229.239; 4.O.229.154; 4.O.229.157; 4.O.229.166; 4.O.229.169; 4.O.229.172; 4.O.229.175; 4.O.229.240; 4.O.229.244; 4.O.230.228; 4.O.230.229; 4.O.230.230; 4.O.230.231; 4.O.230.236; 4.O.230.237; 4.O.230.238; 4.O.230.239; 4.O.230.154; 4.O.230.157; 4.O.230.166; 4.O.230.169; 4.O.230.172; 4.O.230.175; 4.O.230.240; 4.O.230.244; 4.O.231.228; 4.O.231.229; 4.O.231.230; 4.O.231.231; 4.O.231.236; 4.O.231.237; 4.O.231.238; 4.O.231.239; 4.O.231.154; 4.O.231.157; 4.O.231.166; 4.O.231.169; 4.O.231.172; 4.O.231.175; 4.O.231.240; 4.O.231.244; 4.O.236.228; 4.O.236.229; 4.O.236.230; 4.O.236.231; 4.O.236.236; 4.O.236.237; 4.O.236.238; 4.O.236.239; 4.O.236.154; 4.O.236.157; 4.O.236.166; 4.O.236.169; 4.O.236.172; 4.O.236.175; 4.O.236.240; 4.O.236.244; 4.O.237.228; 4.O.237.229; 4.O.237.230; 4.O.237.231; 4.O.237.236; 4.O.237.237; 4.O.237.238; 4.O.237.239; 4.O.237.154; 4.O.237.157; 4.O.237.166; 4.O.237.169; 4.O.237.172; 4.O.237.175; 4.O.237.240; 4.O.237.244; 4.O.238.228; 4.O.238.229; 4.O.238.230; 4.O.238.231; 4.O.238.236; 4.O.238.237; 4.O.238.238; 4.O.238.239; 4.O.238.154; 4.O.238.157; 4.O.238.166; 4.O.238.169; 4.O.238.172; 4.O.238.175; 4.O.238.240; 4.O.238.244; 4.O.239.228; 4.O.239.229; 4.O.239.230; 4.O.239.231; 4.O.239.236; 4.O.239.237; 4.O.239.238; 4.O.239.239; 4.O.239.154; 4.O.239.157; 4.O.239.166; 4.O.239.169; 4.O.239.172; 4.O.239.175;

4.O.239.240; 4.O.239.244; 4.O.154.228; 4.O.154.229; 4.O.154.230; 4.O.154.231; 4.O.154.236; 4.O.154.237; 4.O.154.238; 4.O.154.239; 4.O.154.154; 4.O.154.157; 4.O.154.166; 4.O.154.169; 4.O.154.172; 4.O.154.175; 4.O.154.240; 4.O.154.244; 4.O.157.228; 4.O.157.229; 4.O.157.230; 4.O.157.231; 4.O.157.236; 4.O.157.237; 4.O.157.238; 4.O.157.239; 4.O.157.154; 4.O.157.157; 4.O.157.166; 4.O.157.169; 4.O.157.172; 4.O.157.175; 4.O.157.240; 4.O.157.244; 4.O.166.228; 4.O.166.229; 4.O.166.230; 4.O.166.231; 4.O.166.236; 4.O.166.237; 4.O.166.238; 4.O.166.239; 4.O.166.154; 4.O.166.157; 4.O.166.166; 4.O.166.169; 4.O.166.172; 4.O.166.175; 4.O.166.240; 4.O.166.244; 4.O.169.228; 4.O.169.229; 4.O.169.230; 4.O.169.231; 4.O.169.236; 4.O.169.237; 4.O.169.238; 4.O.169.239; 4.O.169.154; 4.O.169.157; 4.O.169.166; 4.O.169.169; 4.O.169.172; 4.O.169.175; 4.O.169.240; 4.O.169.244; 4.O.172.228; 4.O.172.229; 4.O.172.230; 4.O.172.231; 4.O.172.236; 4.O.172.237; 4.O.172.238; 4.O.172.239; 4.O.172.154; 4.O.172.157; 4.O.172.166; 4.O.172.169; 4.O.172.172; 4.O.172.175; 4.O.172.240; 4.O.172.244; 4.O.175.228; 4.O.175.229; 4.O.175.230; 4.O.175.231; 4.O.175.236; 4.O.175.237; 4.O.175.238; 4.O.175.239; 4.O.175.154; 4.O.175.157; 4.O.175.166; 4.O.175.169; 4.O.175.172; 4.O.175.175; 4.O.175.240; 4.O.175.244; 4.O.240.228; 4.O.240.229; 4.O.240.230; 4.O.240.231; 4.O.240.236; 4.O.240.237; 4.O.240.238; 4.O.240.239; 4.O.240.154; 4.O.240.157; 4.O.240.166; 4.O.240.169; 4.O.240.172; 4.O.240.175; 4.O.240.240; 4.O.240.244; 4.O.244.228; 4.O.244.229; 4.O.244.230; 4.O.244.231; 4.O.244.236; 4.O.244.237; 4.O.244.238; 4.O.244.239; 4.O.244.154; 4.O.244.157; 4.O.244.166; 4.O.244.169; 4.O.244.172; 4.O.244.175; 4.O.244.240; 4.O.244.244;

Prodrugs of 4.P

4.P.228.228; 4.P.228.229; 4.P.228.230; 4.P.228.231; 4.P.228.236; 4.P.228.237; 4.P.228.238; 4.P.228.239; 4.P.228.154; 4.P.228.157; 4.P.228.166; 4.P.228.169; 4.P.228.172; 4.P.228.175; 4.P.228.240; 4.P.228.244; 4.P.229.228; 4.P.229.229; 4.P.229.230; 4.P.229.231; 4.P. ,229.236; 4.P.229.237; 4.P.229.238; 4.P.229.239; 4.P.229.154; 4.P.229.157; 4.P.229.166; 4.P.229.169; 4.P.229.172; 4.P.229.175; 4.P.229.240; 4.P.229.244; 4.P.230.228; 4.P.230.229; 4.P.230.230; 4.P.230.231; 4.P.230.236; 4.P.230.237; 4.P.230.238; 4.P.230.239; 4.P.230.154; 4.P.230.157; 4.P.230.166; 4.P.230.169; 4.P.230.172; 4.P.230.175; 4.P.230.240; 4.P.230.244; 4.P.231.228; 4.P.231.229; 4.P.231.230; 4.P.231.231; 4.P.231.236; 4.P.231.237; 4.P.231.238; 4.P.231.239; 4.P.231.154; 4.P.231.157; 4.P.231.166; 4.P.231.169; 4.P.231.172; 4.P.231.175; 4.P.231.240; 4.P.231.244; 4.P.236.228; 4.P.236.229; 4.P.236.230; 4.P.236.231; 4.P.236.236; 4.P.236.237; 4.P.236.238; 4.P.236.239; 4.P.236.154; 4.P.236.157; 4.P.236.166; 4.P.236.169; 4.P.236.172; 4.P.236.175; 4.P.236.240; 4.P.236.244; 4.P.237.228; 4.P.237.229; 4.P.237.230; 4.P.237.231; 4.P.237.236; 4.P.237.237; 4.P.237.238; 4.P.237.239; 4.P.237.154; 4.P.237.157; 4.P.237.166; 4.P.237.169; 4.P.237.172; 4.P.237.175; 4.P.237.240; 4.P.237.244; 4.P.238.228; 4.P.238.229; 4.P.238.230; 4.P.238.231; 4.P.238.236; 4.P.238.237; 4.P.238.238; 4.P.238.239; 4.P.238.154; 4.P.238.157; 4.P.238.166; 4.P.238.169; 4.P.238.172; 4.P.238.175; 4.P.238.240; 4.P.238.244; 4.P.239.228; 4.P.239.229; 4.P.239.230; 4.P.239.231; 4.P.239.236; 4.P.239.237; 4.P.239.238; 4.P.239.239; 4.P.239.154; 4.P.239.157; 4.P.239.166; 4.P.239.169; 4.P.239.172; 4.P.239.175; 4.P.239.240; 4.P.239.244; 4.P.154.228; 4.P.154.229; 4.P.154.230; 4.P.154.231;

4.P.154.236; 4.P.154.237; 4.P.154.238; 4.P.154.239; 4.P.154.154; 4.P.154.157; 4.P.154.166; 4.P.154.169; 4.P.154.172; 4.P.154.175; 4.P.154.240; 4.P.154.244; 4.P.157.228; 4.P.157.229; 4.P.157.230; 4.P.157.231; 4.P.157.236; 4.P.157.237; 4.P.157.238; 4.P.157.239; 4.P.157.154; 4.P.157.157; 4.P.157.166; 4.P.157.169; 4.P.157.172; 4.P.157.175; 4.P.157.240; 4.P.157.244; 4.P.166.228; 4.P.166.229; 4.P.166.230; 4.P.166.231; 4.P.166.236; 4.P.166.237; 4.P.166.238; 4.P.166.239; 4.P.166.154; 4.P.166.157; 4.P.166.166; 4.P.166.169; 4.P.166.172; 4.P.166.175; 4.P.166.240; 4.P.166.244; 4.P.169.228; 4.P.169.229; 4.P.169.230; 4.P.169.231; 4.P.169.236; 4.P.169.237; 4.P.169.238; 4.P.169.239; 4.P.169.154; 4.P.169.157; 4.P.169.166; 4.P.169.169; 4.P '.169 '.172; 4.P.169.175; 4.P.169.240; 4.P.169.244; 4.P.172.228; 4.P.172.229; 4.P.172.230; 4.P.172.231; 4.P.172.236; 4.P.172.237; 4.P.172.238; 4.P.172.239; 4.P.172.154; 4.P.172.157; 4.P.172.166; 4.P.172.169; 4.P.172.172; 4.P.172.175; 4.P.172.240; 4.P.172.244; 4.P.175.228; 4.P.175.229; 4.P.175.230; 4.P.175.231; 4.P.175.236; 4.P.175.237; 4.P.175.238; 4.P.175.239; 4.P.175.154; 4.P.175.157; 4.P.175.166; 4.P.175.169; 4.P.175.172; 4.P.175.175; 4.P.175.240; 4.P.175.244; 4.P.240.228; 4.P.240.229; 4.P.240.230; 4.P.240.231; 4.P.240.236; 4.P.240.237; 4.P.240.238; 4.P.240.239; 4.P.240.154; 4.P.240.157; 4.P.240.166; 4.P.240.169; 4.P.240.172; 4.P.240.175; 4.P.240.240; 4.P.240.244; 4.P.244.228; 4.P.244.229; 4.P.244.230; 4.P.244.231; 4.P.244.236; 4.P.244.237; 4.P.244.238; 4.P.244.239; 4.P.244.154; 4.P.244.157; 4.P.244.166; 4.P.244.169; 4.P.244.172; 4.P.244.175; 4.P.244.240; 4.P.244.244;

Prodrugs of 4.U

4.U.228.228; 4.U.228.229; 4.U.228.230; 4.U.228.231; 4.U.228.236; 4.U.228.237; 4.U.228.238; 4.U.228.239; 4.U.228.154; 4.U.228.157; 4.U.228.166; 4.U.228.169; 4.U.228.172; 4.U.228.175; 4.U.228.240; 4.U.228.244; 4.U.229.228; 4.U.229.229; 4.U.229.230; 4.U.229.231; 4.U.229.236; 4.U.229.237; 4.U.229.238; 4.U.229.239; 4.U.229.154; 4.U.229.157; 4.U.229.166; 4.U.229.169; 4.U.229.172; 4.U.229.175; 4.U.229.240; 4.U.229.244; 4.U.230.228; 4.U.230.229; 4.U.230.230; 4.U.230.231; 4.U.230.236; 4.U.230.237; 4.U.230.238; 4.U.230.239; 4.U.230.154; 4.U.230.157; 4.U.230.166; 4.U.230.169; 4.U.230.172; 4.U.230.175; 4.U.230.240; 4.U.230.244; 4.U.231.228; 4.U.231.229; 4.U.231.230; 4.U.231.231; 4.U.231.236; 4.U.231.237; 4.U.231.238; 4.U.231.239; 4.U.231.154; 4.U.231.157; 4.U.231.166; 4.U.231.169; 4.U.231.172; 4.U.231.175; 4.U.231.240; 4.U.231.244; 4.U.236.228; 4.U.236.229; 4.U.236.230; 4.U.236.231; 4.U.236.236; 4.U.236.237; 4.U.236.238; 4.U.236.239; 4.U.236.154; 4.U.236.157; 4.U.236.166; 4.U.236.169; 4.U .236.172; 4.U.236.175; 4.U.236.240; 4.U.236.244; 4.U.237.228; 4.U.237.229; 4.U.237.230; 4.U.237.231; 4.U.237.236; 4.U.237.237; 4.U.237.238; 4.U.237.239; 4.U.237.154; 4.U.237.157; 4.U.237.166; 4.U.237.169; 4.U.237.172; 4.U.237.175; 4.U.237.240; 4.U.237.244; 4.U.238.228; 4.U.238.229; 4.U.238.230; 4.U.238.231; 4.U.238.236; 4.U.238.237; 4.U.238.238; 4.U.238.239; 4.U.238.154; 4.U.238.157; 4.U.238.166; 4.U.238.169; 4.U.238.172; 4.U.238.175; 4.U.238.240; 4.U.238.244; 4.U.239.228; 4.U.239.229; 4.U.239.230; 4.U.239.231; 4.U.239.236; 4.U.239.237; 4.U.239.238; 4.U.239.239; 4.U.239.154; 4.U.239.157; 4.U.239.166; 4.U.239.169; 4.U.239.172; 4.U.239.175; 4.U.239.240; 4.U.239.244; 4.U.154.228; 4.U.154.229; 4.U.154.230; 4.U.154.231; 4.U.154.236; 4.U.154.237; 4.U.154.238; 4.U.154.239; 4.U.154.154; 4.U.154.157;

4.U.154.166; 4.U.154.169; 4.U.154.172; 4.U.154.175; 4.U.154.240; 4.U.154.244; 4.U.157.228; 4.U.157.229; 4.U.157.230; 4.U.157.231; 4.U.157.236; 4.U.157.237; 4.U.157.238; 4.U.157.239; 4.U.157.154; 4.U.157.157; 4.U.157.166; 4.U.157.169; 4.U.157.172; 4.U.157.175; 4.U.157.240; 4.U.157.244; 4.U.166.228; 4.U.166.229; 4.U.166.230; 4.U.166.231; 4.U.166.236; 4.U.166.237; 4.U.166.238; 4.U.166.239; 4.U.166.154; 4.U.166.157; 4.U.166.166; 4.U.166.169; 4.U.166.172; 4.U.166.175; 4.U.166.240; 4.U.166.244; 4.U.169.228; 4.U.169.229; 4.U.169.230; 4.U.169.231; 4.U.169.236; 4.U.169.237; 4.U.169.238; 4.U.169.239; 4.U.169.154; 4.U.169.157; 4.U.169.166; 4.U.169.169; 4.U.169.172; 4.U.169.175; 4.U.169.240; 4.U.169.244; 4.U.172.228; 4.U.172.229; 4.U.172.230; 4.U.172.231; 4.U.172.236; 4.U.172.237; 4.U.172.238; 4.U.172.239; 4.U.172.154; 4.U.172.157; 4.U.172.166; 4.U.172.169; 4.U.172.172; 4.U.172.175; 4.U.172.240; 4.U.172.244; 4.U.175.228; 4.U.175.229; 4.U.175.230; 4.U.175.231; 4.U.175.236; 4.U.175.237; 4.U.175.238; 4.U.175.239; 4.U.175.154; 4.U.175.157; 4.U.175.166; 4.U.175.169; 4.U.175.172; 4.U.175.175; 4.U.175.240; 4.U.175.244; 4.U.240.228; 4.U.240.229; 4.U.240.230; 4.U.240.231; 4.U.240.236; 4.U.240.237; 4.U.240.238; 4.U.240.239; 4.U.240.154; 4.U.240.157; 4.U.240.166; 4.U.240.169; 4.U.240.172; 4.U.240.175; 4.U.240.240; 4.U.240.244; 4.U.244.228; 4.U.244.229; 4.U.244.230; 4.U.244.231; 4.U.244.236; 4.U.244.237; 4.U.244.238; 4.U.244.239; 4.U.244.154; 4.U.244.157; 4.U.244.166; 4.U.244.169; 4.U.244.172; 4.U.244.175; 4.U.244.240; 4.U.244.244;

Prodrugs of 4.CD

4.CD.228.228; 4.CD.228.229; 4.CD.228.230; 4.CD.228.231; 4.CD.228.236; 4.CD.228.237; 4.CD.228.238; 4.CD.228.239; 4.CD.228.154; 4.CD.228.157; 4.CD.228.166; 4.CD.228.169; 4.CD.228.172; 4.CD.228.175; 4.CD.228.240; 4.CD.228.244; 4.CD.229.228; 4.CD.229.229; 4.CD.229.230; 4.CD.229.231; 4.CD.229.236; 4.CD.229.237; 4.CD.229.238; 4.CD.229.239; 4.CD.229.154; 4.CD.229.157; 4.CD.229.166; 4.CD.229.169; 4.CD.229.172; 4.CD.229.175; 4.CD.229.240; 4.CD.229.244; 4.CD.230.228; 4.CD.230.229; 4.CD.230.230; 4.CD.230.231; 4.CD.230.236; 4.CD.230.237; 4.CD.230.238; 4.CD.230.239; 4.CD.230.154; 4.CD.230.157; 4.CD.230.166; 4.CD.230.169; 4.CD.230.172; 4.CD.230.175; 4.CD.230.240; 4.CD.230.244; 4.CD.231.228; 4.CD.231.229; 4.CD.231.230; 4.CD.231.231; 4.CD.231.236; 4.CD.231.237; 4.CD.231.238; 4.CD.231.239; 4.CD.231.154; 4.CD.231.157; 4.CD.231.166; 4.CD.231.169; 4.CD.231.172; 4.CD.231.175; 4.CD.231.240; 4.CD.231.244; 4.CD.236.228; 4.CD.236.229; 4.CD.236.230; 4.CD.236.231; 4.CD.236.236; 4.CD.236.237; 4.CD.236.238; 4.CD.236.239; 4.CD.236.154; 4.CD.236.157; 4.CD.236.166; 4.CD.236.169; 4.CD.236.172; 4.CD.236.175; 4.CD.236.240; 4.CD.236.244; 4.CD.237.228; 4.CD.237.229; 4.CD.237.230; 4.CD.237.231; 4.CD.237.236; 4.CD.237.237; 4.CD.237.238; 4.CD.237.239; 4.CD.237.154; 4.CD.237.157; 4.CD.237.166; 4.CD.237.169; 4.CD.237.172; 4.CD.237.175; 4.CD.237.240; 4.CD.237.244; 4.CD.238.228; 4.CD.238.229; 4.CD.238.230; 4.CD.238.231; 4.CD.238.236; 4.CD.238.237; 4.CD.238.238; 4.CD.238.239; 4.CD.238.154; 4.CD.238.157; 4.CD.238.166; 4.CD.238.169; 4.CD.238.172; 4.CD.238.175; 4.CD.238.240; 4.CD.238.244; 4.CD.239.228; 4.CD.239.229; 4.CD.239.230; 4.CD.239.231; 4.CD.239.236; 4.CD.239.237; 4.CD.239.238; 4.CD.239.239;

4.CD.239.154; 4.CD.239.157; 4.CD.239.166; 4.CD.239.169; 4.CD.239.172; 4.CD.239.175; 4.CD.239.240; 4.CD.239.244; 4.CD.154.228; 4.CD.154.229; 4.CD.154.230; 4.CD.154.231; 4.CD.154.236; 4.CD.154.237; 4.CD.154.238; 4.CD.154.239; 4.CD.154.154; 4.CD.154.157; 4.CD.154.166; 4.CD.154.169; 4.CD.154.172; 4.CD.154.175; 4.CD.154.240; 4.CD.154.244; 4.CD.157.228; 4.CD.157.229; 4.CD.157.230; 4.CD.157.231; 4.CD.157.236; 4.CD.157.237; 4.CD.157.238; 4.CD.157.239; 4.CD.157.154; 4.CD.157.157; 4.CD.157.166; 4.CD.157.169; 4.CD.157.172; 4.CD.157.175; 4.CD.157.240; 4.CD.157.244; 4.CD.166.228; 4.CD.166.229; 4.CD.166.230; 4.CD.166.231; 4.CD.166.236; 4.CD.166.237; 4.CD.166.238; 4.CD.166.239; 4.CD.166.154; 4.CD.166.157; 4.CD.166.166; 4.CD.166.169; 4.CD.166.172; 4.CD.166.175; 4.CD.166.240; 4.CD.166.244; 4.CD.169.228; 4.CD.169.229; 4.CD.169.230; 4.CD.169.231; 4.CD.169.236; 4.CD.169.237; 4.CD.169.238; 4.CD.169.239; 4.CD.169.154; 4.CD.169.157; 4.CD.169.166; 4.CD.169.169; 4.CD.169.172; 4.CD.169.175; 4.CD.169.240; 4.CD.169.244; 4.CD.172.228; 4.CD.172.229; 4.CD.172.230; 4.CD.172.231; 4.CD.172.236; 4.CD.172.237; 4.CD.172.238; 4.CD.172.239; 4.CD.172.154; 4.CD.172.157; 4.CD.172.166; 4.CD.172.169; 4.CD.172.172; 4.CD.172.175; 4.CD.172.240; 4.CD.172.244; 4.CD.175.228; 4.CD.175.229; 4.CD.175.230; 4.CD.175.231; 4.CD.175.236; 4.CD.175.237; 4.CD.175.238; 4.CD.175.239; 4.CD.175.154; 4.CD.175.157; 4.CD.175.166; 4.CD.175.169; 4.CD.175.172; 4.CD.175.175; 4.CD.175.240; 4.CD.175.244; 4.CD.240.228; 4.CD.240.229; 4.CD.240.230; 4.CD.240.231; 4.CD.240.236; 4.CD.240.237; 4.CD.240.238; 4.CD.240.239; 4.CD.240.154; 4.CD.240.157; 4.CD.240.166; 4.CD.240.169; 4.CD.240.172; 4.CD.240.175; 4.CD.240.240; 4.CD.240.244; 4.CD.244.228; 4.CD.244.229; 4.CD.244.230; 4.CD.244.231; 4.CD.244.236; 4.CD.244.237; 4.CD.244.238; 4.CD.244.239; 4.CD.244.154; 4.CD.244.157; 4.CD.244.166; 4.CD.244.169; 4.CD.244.172; 4.CD.244.175; 4.CD.244.240; 4.CD.244.244;

Prodrugs of 4.EB

4.EB.228.228; 4.EB.228.229; 4.EB.228.230; 4.EB.228.231; 4.EB.228.236; 4.EB.228.237; 4.EB.228.238; 4.EB.228.239; 4.EB.228.154; 4.EB.228.157; 4.EB.228.166; 4.EB.228.169; 4.EB.228.172; 4.EB.228.175; 4.EB.228.240; 4.EB.228.244; 4.EB.229.228; 4.EB.229.229; 4.EB.229.230; 4.EB.229.231; 4.EB.229.236; 4.EB.229.237; 4.EB.229.238; 4.EB.229.239; 4.EB.229.154; 4.EB.229.157; 4.EB.229.166; 4.EB.229.169; 4.EB.229.172; 4.EB.229.175; 4.EB.229.240; 4.EB.229.244; 4.EB.230.228; 4.EB.230.229; 4.EB.230.230; 4.EB.230.231; 4.EB.230.236; 4.EB.230.237; 4.EB.230.238; 4.EB.230.239; 4.EB.230.154; 4.EB.230.157; 4.EB.230.166; 4.EB.230.169; 4.EB.230.172; 4.EB.230.175; 4.EB.230.240; 4.EB.230.244; 4.EB.231.228; 4.EB.231.229; 4.EB.231.230; 4.EB.231.231; 4.EB.231.236; 4.EB.231.237; 4.EB.231.238; 4.EB.231.239; 4.EB.231.154; 4.EB.231.157; 4.EB.231.166; 4.EB.231.169; 4.EB.231.172; 4.EB.231.175; 4.EB.231.240; 4.EB.231.244; 4.EB.236.228; 4.EB.236.229; 4.EB.236.230; 4.EB.236.231; 4.EB.236.236; 4.EB.236.237; 4.EB.236.238; 4.EB.236.239; 4.EB.236.154; 4.EB.236.157; 4.EB.236.166; 4.EB.236.169; 4.EB.236.172; 4.EB.236.175; 4.EB.236.240; 4.EB.236.244; 4.EB.237.228; 4.EB.237.229; 4.EB.237.230; 4.EB.237.231; 4.EB.237.236; 4.EB.237.237; 4.EB.237.238; 4.EB.237.239; 4.EB.237.154; 4.EB.237.157; 4.EB.237.166; 4.EB.237.169; A.εB.237.172; 4.EB.237.175; 4.EB.237.240;

4.EB.237.244; 4.EB.238.228; 4.EB.238.229; 4.EB.238.230; 4.EB.238.231; 4.EB.238.236; 4.EB.238.237; 4.EB.238.238; 4.EB.238.239; 4.EB.238.154; 4.EB.238.157; 4.EB.238.166; 4.EB.238.169; 4.EB.238.172; 4.EB.238.175; 4.EB.238.240; 4.EB.238.244; 4.EB.239.228; 4.EB.239.229; 4.EB.239.230; 4.EB.239.231; 4.EB.239.236; 4.EB.239.237; 4.EB.239.238; 4.EB.239.239; 4.EB.239.154; 4.EB.239.157; 4.EB.239.166; 4.EB.239.169; 4.EB.239.172; 4.EB.239.175; 4.EB.239.240; 4.EB.239.244; 4.EB.154.228; 4.EB.154.229; 4.EB.154.230; 4.EB.154.231; 4.EB.154.236; 4.EB.154.237; 4.EB.154.238; 4.EB.154.239; 4.EB.154.154; 4.EB.154.157; 4.EB.154.166; 4.EB.154.169; 4.EB.154.172; 4.EB.154.175; 4.EB.154.240; 4.EB.154.244; 4.EB.157.228; 4.EB.157.229; 4.EB.157.230; 4.EB.157.231; 4.EB.157.236; 4.EB.157.237; 4.EB.157.238; 4.EB.157.239; 4.EB.157.154; 4.EB.157.157; 4.EB.157.166; 4.EB.157.169; 4.EB.157.172; 4.EB.157.175; 4.EB.157.240; 4.EB.157.244; 4.EB.166.228; 4.EB.166.229; 4.EB.166.230; 4.EB.166.231; 4.EB.166.236; 4.EB.166.237; 4.EB.166.238; 4.EB.166.239; 4.EB.166.154; 4.EB.166.157; 4.EB.166.166; 4.EB.166.169; 4.EB.166.172; 4.EB.166.175; 4.EB.166.240; 4.EB.166.244; 4.EB.169.228; 4.EB.169.229; 4.EB.169.230; 4.EB.169.231; 4.EB.169.236; 4.EB.169.237; 4.EB.169.238; 4.EB.169.239; 4.EB.169.154; 4.EB.169.157; 4.EB.169.166; 4.EB.169.169; 4.EB.169.172; 4.EB.169.175; 4.EB.169.240; 4.EB.169.244; 4.EB.172.228; 4.EB.172.229; 4.EB.172.230; 4.EB.172.231; 4.EB.172.236; 4.EB.172.237; 4.EB.172.238; 4.EB.172.239; 4.EB.172.154; 4.EB.172.157; 4.EB.172.166; 4.EB.172.169; 4.EB.172.172; 4.EB.172.175; 4.EB.172.240; 4.EB.172.244; 4.EB.175.228; 4.EB.175.229; 4.EB.175.230; 4.EB.175.231; 4.EB.175.236; 4.EB.175.237; 4.EB.175.238; 4.EB.175.239; 4.EB.175.154; 4.EB.175.157; 4.EB.175.166; 4.EB.175.169; 4.EB.175.172; 4.EB.175.175; 4.EB.175.240; 4.EB.175.244; 4.EB.240.228; 4.EB.240.229; 4.EB.240.230; 4.EB.240.231; 4.EB.240.236; 4.EB.240.237; 4.EB.240.238; 4.EB.240.239; 4.EB.240.154; 4.EB.240.157; 4.EB.240.166; 4.EB.240.169; 4.EB.240.172; 4.EB.240.175; 4.EB.240.240; 4.EB.240.244; 4.EB.244.228; 4.EB.244.229; 4.EB.244.230; 4.EB.244.231; 4.EB.244.236; 4.EB.244.237; 4.EB.244.238; 4.EB.244.239; 4.EB.244.154; 4.EB.244.157; 4.EB.244.166; 4.EB.244.169; 4.EB.244.172; 4.EB.244.175; 4.EB.244.240; 4.EB.244.244;

Prodrugs of 5.B

5.B.228.228; 5.B.228.229; 5.B.228.230; 5.B.228.231; 5.B.228.236; 5.B.228.237; 5.B.228.238; 5.B.228.239; 5.B.228.154; 5.B.228.157; 5.B.228.166; 5.B.228.169; 5.B.228.172; 5.B.228.175; 5.B.228.240; 5.B.228.244; 5.B.229.228; 5.B.229.229; 5.B.229.230; 5.B.229.231; 5.B.229.236; 5.B.229.237; 5.B.229.238; 5.B.229.239; 5.B.229.154; 5.B.229.157; 5.B.229.166; 5.B.229.169; 5.B.229.172; 5.B.229.175; 5.B.229.240; 5.B.229.244; 5.B.230.228; 5.B.230.229; 5.B.230.230; 5.B.230.231; 5.B.230.236; 5.B.230.237; 5.B.230.238; 5.B.230.239; 5.B.230.154; 5.B.230.157; 5.B.230.166; 5.B.230.169; 5.B.230.172; 5.B.230.175; 5.B.230.240; 5.B.230.244; 5.B.231.228; 5.B.231.229; 5.B.231.230; 5.B.231.231; 5.B.231.236; 5.B.231.237; 5.B.231.238; 5.B.231.239; 5.B.231.154; 5.B.231.157; 5.B.231.166; 5.B.231.169; 5.B.231.172; 5.B.231.175; 5.B.231.240; 5.B.231.244; 5.B.236.228; 5.B.236.229; 5.B.236.230; 5.B.236.231; 5.B.236.236; 5.B.236.237; 5.B.236.238; 5.B.236.239; 5.B.236.154; 5.B.236.157; 5.B.236.166; 5.B.236.169; 5.B.236.172; 5.B.236.175; 5.B.236.240; 5.B.236.244; 5.B.237.228; 5.B.237.229; 5.B.237.230; 5.B.237.231; 5.B.237.236; 5.B.237.237; 5.B.237.238; 5.B.237.239; 5.B.237.154; 5.B.237.157; 5.B.237.166; 5.B.237.169; 5.B.237.172; 5.B.237.175; 5.B.237.240; 5.B.237.244; 5.B.238.228; 5.B.238.229; 5.B.238.230; 5.B.238.231; 5.B.238.236; 5.B.238.237;

5.B.238.238; 5.B.238.239; 5.B.238.154; 5.B.238.157; 5.B.238.166; 5.B.238.169; 5.B.238.172; 5.B.238.175; 5.B.238.240; 5.B.238.244; 5.B.239.228; 5.B.239.229; 5.B.239.230; 5.B.239.231; 5.B.239.236; 5.B.239.237; 5.B.239.238; 5.B.239.239; 5.B.239.154; 5.B.239.157; 5.B.239.166; 5.B.239.169; 5.B.239.172; 5.B.239.175; 5.B.239.240; 5.B.239.244; 5.B.154.228; 5.B.154.229; 5.B.154.230; 5.B.154.231; 5.B.154.236; 5.B.154.237; 5.B.154.238; 5.B.154.239; 5.B.154.154; 5.B.154.157; 5.B.154.166; 5.B.154.169; 5.B.154.172; 5.B.154.175; 5.B.154.240; 5.B.154.244; 5.B.157.228; 5.B.157.229; 5.B.157.230; 5.B.157.231; 5.B.157.236; 5.B.157.237; 5.B.157.238; 5.B.157.239; 5.B.157.154; 5.B.157.157; 5.B.157.166; 5.B.157.169; 5.B.157.172; 5.B.157.175; 5.B.157.240; 5.B.157.244; 5.B.166.228; 5.B.166.229; 5.B.166.230; 5.B.166.231; 5.B.166.236; 5.B.166.237; 5.B.166.238; 5.B.166.239; 5.B.166.154; 5.B.166.157; 5.B.166.166; 5.B.166.169; 5.B.166.172; 5.B.166.175; 5.B.166.240; 5.B.166.244; 5.B.169.228; 5.B.169.229; 5.B.169.230; 5.B.169.231; 5.B.169.236; 5.B.169.237; 5.B.169.238; 5.B.169.239; 5.B.169.154; 5.B.169.157; 5.B.169.166; 5.B.169.169; 5.B.169.172; 5.B.169.175; 5.B.169.240; 5.B.169.244; 5.B.172.228; 5.B.172.229; 5.B.172.230; 5.B.172.231; 5.B.172.236; 5.B.172.237; 5.B.172.238; 5.B.172.239; 5.B.172.154; 5.B.172.157; 5.B.172.166; 5.B.172.169; 5.B.172.172; 5.B.172.175; 5.B.172.240; 5.B.172.244; 5.B.175.228; 5.B.175.229; 5.B.175.230; 5.B.175.231; 5.B.175.236; 5.B.175.237; 5.B.175.238; 5.B.175.239; 5.B.175.154; 5.B.175.157; 5.B.175.166; 5.B.175.169; 5.B.175.172; 5.B.175.175; 5.B.175.240; 5.B.175.244; 5.B.240.228; 5.B.240.229; 5.B.240.230; 5.B.240.231; 5.B.240.236; 5.B.240.237; 5.B.240.238; 5.B.240.239; 5.B.240.154; 5.B.240.157; 5.B.240.166; 5.B.240.169; 5.B.240.172; 5.B.240.175; 5.B.240.240; 5.B.240.244; 5.B.244.228; 5.B.244.229; 5.B.244.230; 5.B.244.231; 5.B.244.236; 5.B.244.237; 5.B.244.238; 5.B.244.239; 5.B.244.154; 5.B.244.157; 5.B.244.166; 5.B.244.169; 5.B.244.172; 5.B.244.175; 5.B.244.240; 5.B.244.244;

Prodrugs of 5.D

5.D.228.228; 5.D.228.229; 5.D.228.230; 5.D.228.231; 5.D.228.236; 5.D.228.237; 5.D.228.238; 5.D.228.239; 5.D.228.154; 5.D.228.157; 5.D.228.166; 5.D.228.169; 5.D.228.172; 5.D.228.175; 5.D.228.240; 5.D.228.244; 5.D.229.228; 5.D.229.229; 5.D.229.230; 5.D.229.231; 5.D.229.236; 5.D.229.237; 5.D.229.238; 5.D.229.239; 5.D.229.154; 5.D.229.157; 5.D.229.166; 5.D.229.169; 5.D.229.172; 5.D.229.175; 5.D.229.240; 5.D.229.244; 5.D.230.228; 5.D.230.229; 5.D.230.230; 5.D.230.231; 5.D.230.236; 5.D.230.237; 5.D.230.238; 5.D.230.239; 5.D.230.154; 5.D.230.157; 5.D.230.166; 5.D.230.169; 5.D.230.172; 5.D.230.175; 5.D.230.240; 5.D.230.244; 5.D.231.228; 5.D.231.229; 5.D.231.230; 5.D.231.231; 5.D.231.236; 5.D.231.237; 5.D.231.238; 5.D.231.239; 5.D.231.154; 5.D.231.157; 5.D.231.166; 5.D.231.169; 5.D.231.172; 5.D.231.175; 5.D.231.240; 5.D.231.244; 5.D.236.228; 5.D.236.229; 5.D.236.230; 5.D.236.231; 5.D.236.236; 5.D.236.237; 5.D.236.238; 5.D.236.239; 5.D.236.154; 5.D.236.157; 5.D.236.166; 5.D.236.169; 5.D.236.172; 5.D.236.175; 5.D.236.240; 5.D.236.244; 5.D.237.228; 5.D.237.229; 5.D.237.230; 5.D.237.231; 5.D.237.236; 5.D.237.237; 5.D.237.238; 5.D.237.239; 5.D.237.154; 5.D.237.157; 5.D.237.166; 5.D.237.169; 5.D.237.172; 5.D.237.175; 5.D.237.240; 5.D.237.244; 5.D.238.228; 5.D.238.229; 5.D.238.230; 5.D.238.231; 5.D.238.236; 5.D.238.237; 5.D.238.238; 5.D.238.239; 5.D.238.154; 5.D.238.157; 5.D.238.166; 5.D.238.169;

5.D.238.172; 5.D.238.175; 5.D.238.240; 5.D.238.244; 5.D.239.228; 5.D.239.229; 5.D.239.230; 5.D.239.231; 5.D.239.236; 5.D.239.237; 5.D.239.238; 5.D.239.239; 5.D.239.154; 5.D.239.157; 5.D.239.166; 5.D.239.169; 5.D.239.172; 5.D.239.175; 5.D.239.240; 5.D.239.244; 5.D.154.228; 5.D.154.229; 5.D.154.230; 5.D.154.231; 5.D.154.236; 5.D.154.237; 5.D.154.238; 5.D.154.239; 5.D.154.154; 5.D.154.157; 5.D.154.166; 5.D.154.169; 5.D.154.172; 5.D.154.175; 5.D.154.240; 5.D.154.244; 5.D.157.228; 5.D.157.229; 5.D.157.230; 5.D.157.231; 5.D.157.236; 5.D.157.237; 5.D.157.238; 5.D.157.239; 5.D.157.154; 5.D.157.157; 5.D.157.166; 5.D.157.169; 5.D.157.172; 5.D.157.175; 5.D.157.240; 5.D.157.244; 5.D.166.228; 5.D.166.229; 5.D.166.230; 5.D.166.231; 5.D.166.236; 5.D.166.237; 5.D.166.238; 5.D.166.239; 5.D.166.154; 5.D.166.157; 5.D.166.166; 5.D.166.169; 5.D.166.172; 5.D.166.175; 5.D.166.240; 5.D.166.244; 5.D.169.228; 5.D.169.229; 5.D.169.230; 5.D.169.231; 5.D.169.236; 5.D.169.237; 5.D.169.238; 5.D.169.239; 5.D.169.154; 5.D.169.157; 5.D.169.166; 5.D.169.169; 5.D.169.172; 5.D.169.175; 5.D.169.240; 5.D.169.244; 5.D.172.228; 5.D.172.229; 5.D.172.230; 5.D.172.231; 5.D.172.236; 5.D.172.237; 5.D.172.238; 5.D.172.239; 5.D.172.154; 5.D.172.157; 5.D.172.166; 5.D.172.169; 5.D.172.172; 5.D.172.175; 5.D.172.240; 5.D.172.244; 5.D.175.228; 5.D.175.229; 5.D.175.230; 5.D.175.231; 5.D.175.236; 5.D.175.237; 5.D.175.238; 5.D.175.239; 5.D.175.154; 5.D.175.157; 5.D.175.166; 5.D.175.169; 5.D.175.172; 5.D.175.175; 5.D.175.240; 5.D.175.244; 5.D.240.228; 5.D.240.229; 5.D.240.230; 5.D.240.231; 5.D.240.236; 5.D.240.237; 5.D.240.238; 5.D.240.239; 5.D.240.154; 5.D.240.157; 5.D.240.166; 5.D.240.169; 5.D.240.172; 5.D.240.175; 5.D.240.240; 5.D.240.244; 5.D.244.228; 5.D.244.229; 5.D.244.230; 5.D.244.231; 5.D.244.236; 5.D.244.237; 5.D.244.238; 5.D.244.239; 5.D.244.154; 5.D.244.157; 5.D.244.166; 5.D.244.169; 5.D.244.172; 5.D.244.175; 5.D.244.240; 5.D.244.244;

Prodrugs of 5.AB

5.AB.228.228; 5.AB.228.229; 5.AB.228.230; 5.AB.228.231; 5.AB.228.236; 5.AB.228.237; 5.AB.228.238; 5.AB.228.239; 5.AB.228.154; 5.AB.228.157; 5.AB.228.166; 5.AB.228.169; 5.AB.228.172; 5.AB.228.175; 5.AB.228.240; 5.AB.228.244; 5.AB.229.228; 5.AB.229.229; 5.AB.229.230; 5.AB.229.231; 5.AB.229.236; 5.AB.229.237; 5.AB.229.238; 5.AB.229.239; 5.AB.229.154; 5.AB.229.157; 5.AB.229.166; 5.AB.229.169; 5.AB.229.172; 5.AB.229.175; 5.AB.229.240; 5.AB.229.244; 5.AB.230.228; 5.AB.230.229; 5.AB.230.230; 5.AB.230.231; 5.AB.230.236; 5.AB.230.237; 5.AB.230.238; 5.AB.230.239; 5.AB.230.154; 5.AB.230.157; 5.AB.230.166; 5.AB.230.169; 5.AB.230.172; 5.AB.230.175; 5.AB.230.240; 5.AB.230.244; 5.AB.231.228; 5.AB.231.229; 5.AB.231.230; 5.AB.231.231; 5.AB.231.236; 5.AB.231.237; 5.AB.231.238; 5.AB.231.239; 5.AB.231.154; 5.AB.231.157; 5.AB.231.166; 5.AB.231.169; 5.AB.231.172; 5.AB.231.175; 5.AB.231.240; 5.AB.231.244; 5.AB.236.228; 5.AB.236.229; 5.AB.236.230; 5.AB.236.231; 5.AB.236.236; 5.AB.236.237; 5.AB.236.238; 5.AB.236.239; 5.AB.236.154; 5.AB.236.157; 5.AB.236.166; 5.AB.236.169; 5.AB.236.172; 5.AB.236.175; 5.AB.236.240; 5.AB.236.244; 5.AB.237.228; 5.AB.237.229; 5.AB.237.230; 5.AB.237.231; 5.AB.237.236; 5.AB.237.237; 5.AB.237.238; 5.AB.237.239; 5.AB.237.154; 5.AB.237.157; 5.AB.237.166; 5.AB.237.169; 5.AB.237.172; 5.AB.237.175; 5.AB.237.240;

5.AB.237.244; 5.AB.238.228; 5.AB.238.229; 5.AB.238.230; 5.AB.238.231; 5.AB.238.236; 5.AB.238.237; 5.AB.238.238; 5.AB.238.239; 5.AB.238.154; 5.AB.238.157; 5.AB.238.166; 5.AB.238.169; 5.AB.238.172; 5.AB.238.175; 5.AB.238.240; 5.AB.238.244; 5.AB.239.228; 5.AB.239.229; 5.AB.239.230; 5.AB.239.231; 5.AB.239.236; 5.AB.239.237; 5.AB.239.238; 5.AB.239.239; 5.AB.239.154; 5.AB.239.157; 5.AB.239.166; 5.AB.239.169; 5.AB.239.172; 5.AB.239.175; 5.AB.239.240; 5.AB.239.244; 5.AB.154.228; 5.AB.154.229; 5.AB.154.230; 5.AB.154.231; 5.AB.154.236; 5.AB.154.237; 5.AB.154.238; 5.AB.154.239; 5.AB.154.154; 5.AB.154.157; 5.AB.154.166; 5.AB.154.169; 5.AB.154.172; 5.AB.154.175; 5.AB.154.240; 5.AB.154.244; 5.AB.157.228; 5.AB.157.229; 5.AB.157.230; 5.AB.157.231; 5.AB.157.236; 5.AB.157.237; 5.AB.157.238; 5.AB.157.239; 5.AB.157.154; 5.AB.157.157; 5.AB.157.166; 5.AB.157.169; 5.AB.157.172; 5.AB.157.175; 5.AB.157.240; 5.AB.157.244; 5.AB.166.228; 5.AB.166.229; 5.AB.166.230; 5.AB.166.231; 5.AB.166.236; 5.AB.166.237; 5.AB.166.238; 5.AB.166.239; 5.AB.166.154; 5.AB.166.157; 5.AB.166.166; 5.AB.166.169; 5.AB.166.172; 5.AB.166.175; 5.AB.166.240; 5.AB.166.244; 5.AB.169.228; 5.AB.169.229; 5.AB.169.230; 5.AB.169.231; 5.AB.169.236; 5.AB.169.237; 5.AB.169.238; 5.AB.169.239; 5.AB.169.154; 5.AB.169.157; 5.AB.169.166; 5.AB.169.169; 5.AB.169.172; 5.AB.169.175; 5.AB.169.240; 5.AB.169.244; 5.AB.172.228; 5.AB.172.229; 5.AB.172.230; 5.AB.172.231; 5.AB.172.236; 5.AB.172.237; 5.AB.172.238; 5.AB.172.239; 5.AB.172.154; 5.AB.172.157; 5.AB.172.166; 5.AB.172.169; 5.AB.172.172; 5.AB.172.175; 5.AB.172.240; 5.AB.172.244; 5.AB.175.228; 5.AB.175.229; 5.AB.175.230; 5.AB.175.231; 5.AB.175.236; 5.AB.175.237; 5.AB.175.238; 5.AB.175.239; 5.AB.175.154; 5.AB.175.157; 5.AB.175.166; 5.AB.175.169; 5.AB.175.172; 5.AB.175.175; 5.AB.175.240; 5.AB.175.244; 5.AB.240.228; 5.AB.240.229; 5.AB.240.230; 5.AB.240.231; 5.AB.240.236; 5.AB.240.237; 5.AB.240.238; 5.AB.240.239; 5.AB.240.154; 5.AB.240.157; 5.AB.240.166; 5.AB.240.169; 5.AB.240.172; 5.AB.240.175; 5.AB.240.240; 5.AB.240.244; 5.AB.244.228; 5.AB.244.229; 5.AB.244.230; 5.AB.244.231; 5.AB.244.236; 5.AB.244.237; 5.AB.244.238; 5.AB.244.239; 5.AB.244.154; 5.AB.244.157; 5.AB.244.166; 5.AB.244.169; 5.AB.244.172; 5.AB.244.175; 5.AB.244.240; 5.AB.244.244;

Prodrugs of 5.BI

5.BI.228.228; 5.BI.228.229; 5.BI.228.230; 5.BI.228.231; 5.BI.228.236; 5.BI.228.237; 5.BI.228.238; 5.BI.228.239; 5.BI.228.154; 5.BI.228.157; 5.BI.228.166; 5.BI.228.169; 5.BI.228.172; 5.BI.228.175; 5.BI.228.240; 5.BI.228.244; 5.BI.229.228; 5.BI.229.229; 5.BI.229.230; 5.BI.229.231; 5.BI.229.236; 5.BI.229.237; 5.BI.229.238; 5.BI.229.239; 5.BI.229.154; 5.BI.229.157; 5.BI.229.166; 5.BI.229.169; 5.BI.229.172; 5.BI.229.175; 5.BI.229.240; 5.BI.229.244; 5.BI.230.228; 5.BI.230.229; 5.BI.230.230; 5.BI.230.231; 5.BI.230.236; 5.BI.230.237; 5.BI.230.238; 5.BI.230.239; 5.BI.230.154; 5.BI.230.157; 5.BI.230.166; 5.BI.230.169; 5.BI.230.172; 5.BI.230.175; 5.BI.230.240; 5.BI.230.244; 5.BI.231.228; 5.BI.231.229; 5.BI.231.230; 5.BI.231.231; 5.BI.231.236; 5.BI.231.237; 5.BI.231.238; 5.BI.231.239; 5.BI.231.154; 5.BI.231.157; 5.BI.231.166; 5.BI.231.169; 5.BI.231.172; 5.BI.231.175; 5.BI.231.240; 5.BI.231.244; 5.BI.236.228; 5.BI.236.229;

5.BI.236.230; 5.BI.236.231; 5.BI.236.236; 5.BI.236.237; 5.BI.236.238; 5.BI.236.239; 5.BI.236.154; 5.BI.236.157; 5.BI.236.166; 5.BI.236.169; 5.BI.236.172; 5.BI.236.175; 5.BI.236.240; 5.BI.236.244; 5.BI.237.228; 5.BI.237.229; 5.BI.237.230; 5.BI.237.231; 5.BI.237.236; 5.BI.237.237; 5.BI.237.238; 5.BI.237.239; 5.BI.237.154; 5.BI.237.157; 5.BI.237.166; 5.BI.237.169; 5.BI.237.172; 5.BI.237.175; 5.BI.237.240; 5.BI.237.244; 5.BI.238.228; 5.BI.238.229; 5.BI.238.230; 5.BI.238.231; 5.BI.238.236; 5.BI.238.237; 5.BI.238.238; 5.BI.238.239; 5.BI.238.154; 5.BI.238.157; 5.BI.238.166; 5.BI.238.169; 5.BI.238.172; 5.BI.238.175; 5.BI.238.240; 5.BI.238.244; 5.BI.239.228; 5.BI.239.229; 5.BI.239.230; 5.BI.239.231; 5.BI.239.236; 5.BI.239.237; 5.BI.239.238; 5.BI.239.239; 5.BI.239.154; 5.BI.239.157; 5.BI.239.166; 5.BI.239.169; 5.BI.239.172; 5.BI.239.175; 5.BI.239.240; 5.BI.239.244; 5.BI.154.228; 5.BI.154.229; 5.BI.154.230; 5.BI.154.231; 5.BI.154.236; 5.BI.154.237; 5.BI.154.238; 5.BI.154.239; 5.BI.154.154; 5.BI.154.157; 5.BI.154.166; 5.BI.154.169; 5.BI.154.172; 5.BI.154.175; 5.BI.154.240; 5.BI.154.244; 5.BI.157.228; 5.BI.157.229; 5.BI.157.230; 5.BI.157.231; 5.BI.157.236; 5.BI.157.237; 5.BI.157.238; 5.BI.157.239; 5.BI.157.154; 5.BI.157.157; 5.BI.157.166; 5.BI.157.169; 5.BI.157.172; 5.BI.157.175; 5.BI.157.240; 5.BI.157.244; 5.BI.166.228; 5.BI.166.229; 5.BI.166.230; 5.BI.166.231; 5.BI.166.236; 5.BI.166.237; 5.BI.166.238; 5.BI.166.239; 5.BI.166.154; 5.BI.166.157; 5.BI.166.166; 5.BI.166.169; 5.BI.166.172; 5.BI.166.175; 5.BI.166.240; 5.BI.166.244; 5.BI.169.228; 5.BI.169.229; 5.BI.169.230; 5.BI.169.231; 5.BI.169.236; 5.BI.169.237; 5.BI.169.238; 5.BI.169.239; 5.BI.169.154; 5.BI.169.157; 5.BI.169.166; 5.BI.169.169; 5.BI.169.172; 5.BI.169.175; 5.BI.169.240; 5.BI.169.244; 5.BI.172.228; 5.BI.172.229; 5.BI.172.230; 5.BI.172.231; 5.BI.172.236; 5.BI.172.237; 5.BI.172.238; 5.BI.172.239; 5.BI.172.154; 5.BI.172.157; 5.BI.172.166; 5.BI.172.169; 5.BI.172.172; 5.BI.172.175; 5.BI.172.240; 5.BI.172.244; 5.BI.175.228; 5.BI.175.229; 5.BI.175.230; 5.BI.175.231; 5.BI.175.236; 5.BI.175.237; 5.BI.175.238; 5.BI.175.239; 5.BI.175.154; 5.BI.175.157; 5.BI.175.166; 5.BI.175.169; 5.BI.175.172; 5.BI.175.175; 5.BI.175.240; 5.BI.175.244; 5.BI.240.228; 5.BI.240.229; 5.BI.240.230; 5.BI.240.231; 5.BI.240.236; 5.BI.240.237; 5.BI.240.238; 5.BI.240.239; 5.BI.240.154; 5.BI.240.157; 5.BI.240.166; 5.BI.240.169; 5.BI.240.172; 5.BI.240.175; 5.BI.240.240; 5.BI.240.244; 5.BI.244.228; 5.BI.244.229; 5.BI.244.230; 5.BI.244.231; 5.BI.244.236; 5.BI.244.237; 5.BI.244.238; 5.BI.244.239; 5.BI.244.154; 5.BI.244.157; 5.BI.244.166; 5.BI.244.169; 5.BI.244.172; 5.BI.244.175; 5.BI.244.240; 5.BI.244.244;

Prodrugs of 5.1

5.1.228.228; 5.1.228.229; 5.1.228.230; 5.1.228.231; 5.1.228.236; 5.1.228.237; 5.1.228.238; 5.1.228.239; 5.1.228.154; 5.1.228.157; 5.1.228.166; 5.1.228.169; 5.1.228.172; 5.1.228.175; 5.1.228.240; 5.1.228.244; 5.1.229.228; 5.1.229.229; 5.1.229.230; 5.1.229.231; 5.1.229.236; 5.1.229.237; 5.1.229.238; 5.1.229.239; 5.1.229.154; 5.1.229.157; 5.1.229.166; 5.1.229.169; 5.1.229.172; 5.1.229.175; 5.1.229.240; 5.1.229.244; 5.1.230.228; 5.1.230.229; 5.1.230.230; 5.1.230.231; 5.1.230.236; 5.1.230.237; 5.1.230.238; 5.1.230.239; 5.1.230.154; 5.1.230.157; 5.1.230.166; 5.1.230.169; 5.1.230.172; 5.1.230.175; 5.1.230.240; 5.1.230.244; 5.1.231.228; 5.1.231.229; 5.1.231.230; 5.1.231.231; 5.1.231.236; 5.1.231.237; 5.1.231.238; 5.1.231.239; 5.1.231.154; 5.1.231.157; 5.1.231.166; 5.1.231.169; 5.1.231.172; 5.1.231.175; 5.1.231.240; 5.1.231.244; 5.1.236.228; 5.1.236.229; 5.1.236.230; 5.1.236.231; 5.1.236.236; 5.1.236.237; 5.1.236.238; 5.1.236.239; 5.1.236.154; 5.1.236.157; 5.1.236.166; 5.1.236.169; 5.1.236.172; 5.1.236.175; 5.1.236.240; 5.1.236.244; 5.1.237.228; 5.1.237.229; 5.1.237.230;

5.1.237.231; 5.1.237.236; 5.1.237.237; 5.1.237.238; 5.1.237.239; 5.1.237.154; 5.1.237.157; 5.1.237.166; 5.1.237.169; 5.1.237.172; 5.1.237.175; 5.1.237.240; 5.1.237.244; 5.1.238.228; 5.1.238.229; 5.1.238.230; 5.1.238.231; 5.1.238.236; 5.1.238.237; 5.1.238.238; 5.1.238.239; 5.1.238.154; 5.1.238.157; 5.1.238.166; 5.1.238.169; 5.1.238.172; 5.1.238.175; 5.1.238.240; 5.1.238.244; 5.1.239.228; 5.1.239.229; 5.1.239.230; 5.1.239.231; 5.1.239.236; 5.1.239.237; 5.1.239.238; 5.1.239.239; 5.1.239.154; 5.1.239.157; 5.1.239.166; 5.1.239.169; 5.1.239.172; 5.1.239.175; 5.1.239.240; 5.1.239.244; 5.1.154.228; 5.1.154.229; 5.1.154.230; 5.1.154.231; 5.1.154.236; 5.1.154.237; 5.1.154.238; 5.1.154.239; 5.1.154.154; 5.1.154.157; 5.1.154.166; 5.1.154.169; 5.1.154.172; 5.1.154.175; 5.1.154.240; 5.1.154.244; 5.1.157.228; 5.1.157.229; 5.1.157.230; 5.1.157.231; 5.1.157.236; 5.1.157.237; 5.1.157.238; 5.1.157.239; 5.1.157.154; 5.1.157.157; 5.1.157.166; 5.1.157.169; 5.1.157.172; 5.1.157.175; 5.1.157.240; 5.1.157.244; 5.1.166.228; 5.1.166.229; 5.1.166.230; 5.1.166.231; 5.1.166.236; 5.1.166.237; 5.1.166.238; 5.1.166.239; 5.1.166.154; 5.1.166.157; 5.1.166.166; 5.1.166.169; 5.1.166.172; 5.1.166.175; 5.1.166.240; 5.1.166.244; 5.1.169.228; 5.1.169.229; 5.1.169.230; 5.1.169.231; 5.1.169.236; 5.1.169.237; 5.1.169.238; 5.1.169.239; 5.1.169.154; 5.1.169.157; 5.1.169.166; 5.1.169.169; 5.1.169.172; 5.1.169.175; 5.1.169.240; 5.1.169.244; 5.1.172.228; 5.1.172.229; 5.1.172.230; 5.1.172.231; 5.1.172.236; 5.1.172.237; 5.1.172.238; 5.1.172.239; 5.1.172.154; 5.1.172.157; 5.1.172.166; 5.1.172.169; 5.1.172.172; 5.1.172.175; 5.1.172.240; 5.1.172.244; 5.1.175.228; 5.1.175.229; 5.1.175.230; 5.1.175.231; 5.1.175.236; 5.1.175.237; 5.1.175.238; 5.1.175.239; 5.1.175.154; 5.1.175.157; 5.1.175.166; 5.1.175.169; 5.1.175.172; 5.1.175.175; 5.1.175.240; 5.1.175.244; 5.1.240.228; 5.1.240.229; 5.1.240.230; 5.1.240.231; 5.1.240.236; 5.1.240.237; 5.1.240.238; 5.1.240.239; 5.1.240.154; 5.L240.157; 5.I?240.166; 5.1.240.169; 5.1.240.172; 5.1.240.175; 5.1.240.240; 5.1.240.244; 5.1.244.228; 5.1.244.229; 5.1.244.230; 5.1.244.231; 5.1.244.236; 5.1.244.237; 5.1.244.238; 5.1.244.239; 5.1.244.154; 5.1.244.157; 5.1.244.166; 5.1.244.169; 5.1.244.172; 5.1.244.175; 5.1.244.240; 5.1.244.244;

Prodrugs of 5.T

5.J.228.228; 5.J.228.229; 5.J.228.230; 5.J.228.231; 5.J.228.236; 5.J.228.237; 5.J.228.238; 5.J.228.239; 5.J.228.154; 5.J.228.157; 5.J.228.166; 5.J.228.169; 5.J.228.172; 5.J.228.175; 5.J.228.240; 5.J.228.244; 5.J.229.228; 5.J.229.229; 5.J.229.230; 5.J.229.231; 5.J.229.236; 5.J.229.237; 5.J.229.238; 5.J.229.239; 5.J.229.154; 5.J.229.157; 5J.229.166; 5.J.229.169; 5.J.229.172; 5.J.229.175; 5.J.229.240; 5.J.229.244; 5.J.230.228; 5.J.230.229; 5.J.230.230; 5.J.230.231; 5.J.230.236; 5.J.230.237; 5.J.230.238; 5.J.230.239; 5.J.230.154; 5.J.230.157; 5.J.230.166; 5.J.230.169; 5.J.230.172; 5.J.230.175; 5.J.230.240; 5.J.230.244; 5.J.231.228; 5.J.231.229; 5.J.231.230; 5.J.231.231; 5.J.231.236; 5.J.231.237; 5J.231.238; 5J.231.239; 5J.231.154; 5J.231.157; 5J.231.166; 5.J.231.169; 5J.231.172; 5J.231.175; 5J.231.240; 5J.231.244; 5J.236.228; 5J.236.229; 5J.236.230; 5J.236.231; 5J.236.236; 5J.236.237; 5 J.236.238; 5 J.236.239; 5 J.236.154; 5 J.236.157; 5 J.236.166; 5J.236.169; 5J.236.172; 5J.236.175; 5J.236.240; 5J.236.244; 5J.237.228; 5J.237.229; 5J.237.230; 5J.237.231; 5J.237.236; 5J.237.237; 5J.237.238; 5J.237.239; 5J.237.154; 5.J.237.157; 5J.237.166; 5 J.237.169; 5J.237.172; 5.J.237.175; 5J.237.240; 5J.237.244; 5 J.238.228; 5J.238.229; 5 J.238.230; 5J.238.231; 5 J.238.236; 5J.238.237; 5 J.238.238; 5J.238.239; 5 J.238.154; 5J.238.157; 5 J.238.166; 5J.238.169; 5J.238.172; 5 J.238.175; 5 J.238.240; 5J.238.244; 5 J.239.228; 5 J.239.229; 5J.239.230; 5J.239.231; 5J.239.236; 5J.239.237; 5J.239.238; 5J.239.239; 5J.239.154; 5J.239.157; 5J.239.166; 5J.239.169; 5J.239.172; 5J.239.175; 5 J.239.240; 5J.239.244; 5 J.154.228; 5 J.154.229; 5J.154.230; 5J.154.231;

5.J.154.236; 5.J.154.237; 5.J.154.238; 5.J.154.239; 5.J.154.154; 5.J.154.157; 5J.154.166; 5 J.154.169; 5J.154.172; 5 J.154.175; 5 J.154.240; 5 J.154.244; 5 J.157.228; 5 J.157.229; 5 J.157.230; 5 J.157.231; 5J.157.236; 5J.157.237; 5J.157.238; 5 J.157.239; 5 J.157.154; 5 J.157.157; 5 J.157.166; 5J.157.169; 5J.157.172; 5J.157.175; 5.J.157.240; 5.J.157.244; 5.J.166.228; 5J.166.229; 5J.166.230; 5J.166.231; 5J.166.236; 5J.166.237; 5.J.166.238; 5.J.166.239; 5 J.166.154; 5J.166.157; 5J.166.166; 5J.166.169; 5J.166.172; 5.J.166.175; 5 J.166.240; 5J.166.244; 5J.169.228; 5J.169.229; 5.J.169.230; 5J.169.231; 5.J.169.236; 5.J.169.237; 5J.169.238; 5J.169.239; 5J.169.154; 5J.169.157; 5J.169.166; 5.J.169.169; 5 J.169.172; 5J.169.175; 5J.169.240; 5J.169.244; 5J.172.228; 5.J.172.229; 5J.172.230; 5J.172.231; 5J.172.236; 5J.172.237; 5J.172.238; 5J.172.239; 5J.172.154; 5.J.172.157; 5J.172.166; 5J.172.169; 5J.172.172; 5J.172.175; 5J.172.240; 5J.172.244; 5.J.175.228; 5J.175.229; 5J.175.230; 5J.175.231; 5J.175.236; 5 J.175.237; 5.J.175.238; 5J.175.239; 5J.175.154; 5 J.175.157; 5.J.175.166; 5J.175.169; 5 J.175.172; 5.J.175.175; 5J.175.240; 5J.175.244; 5J.240.228; 5J.240.229; 5 J.240.230; 5.J.240.231; 5.J.240.236; 5J.240.237; 5 J.240.238; 5.J.240.239; 5.J.240.154; 5J.240.157; 5.J.240.166; 5 J.240.169; 5 J.240.172; 5 J.240.175; 5.J.240.240; 5.J.240.244; 5J.244.228; 5J.244.229; 5.J.244.230; 5J.244.231; 5J.244.236; 5J.244.237; 5.J.244.238; 5J.244.239; 5J.244.154; 5.J.244.157; 5.J.244.166; 5J.244.169; 5.J.244.172; 5.J.244.175; 5.J.244.240; 5.J.244.244;

Prodrugs of 5.L

5.L.228.228; 5.L.228.229; 5.L.228.230; 5.L.228.231; 5.L.228.236; 5.L.228.237; 5.L.228.238; 5.L.228.239; 5.L.228.154; 5.L.228.157; 5.L.228.166; 5.L.228.169; 5.L.228.172; 5.L.228.175; 5.L.228.240; 5.L.228.244; 5.L.229.228; 5.L.229.229; 5.L.229.230; 5.L.229.231; 5.L.229.236; 5.L.229.237; 5.L.229.238; 5.L.229.239; 5.L.229.154; 5.L.229.157; 5.L.229.166; 5.L.229.169; 5.L.229.172; 5.L.229.175; 5.L.229.240; 5.L.229.244; 5.L.230.228; 5.L.230.229; 5.L.230.230; 5.L.230.231; 5.L.230.236; 5.L.230.237; 5.L.230.238; 5.L.230.239; 5.L.230.154; 5.L.230.157; 5.L.230.166; 5.L.230.169; 5.L.230.172; 5.L.230.175; 5.L.230.240; 5.L.230.244; 5.L.231.228; 5.L.231.229; 5.L.231.230; 5.L.231.231; 5.L.231.236; 5.L.231.237; 5.L.231.238; 5.L.231.239; 5.L.231.154; 5.L.231.157; 5.L.231.166; 5.L.231.169; 5.L.231.172; 5.L.231.175; 5.L.231.240; 5.L.231.244; 5.L.236.228; 5.L.236.229; 5.L.236.230; 5.L.236.231; 5.L.236.236; 5.L.236.237; 5.L.236.238; 5.L.236.239; 5.L.236.154; 5.L.236.157; 5.L.236.166; 5.L.236.169; 5.L.236.172; 5.L.236.175; 5.L.236.240; 5.L.236.244; 5.L.237.228; 5.L.237.229; 5.L.237.230; 5.L.237.231; 5.L.237.236; 5.L.237.237; 5.L.237.238; 5.L.237.239; 5.L.237.154; 5.L.237.157; 5.L.237.166; 5.L.237.169; 5.L.237.172; 5.L.237.175; 5.L.237.240; 5.L.237.244; 5.L.238.228; 5.L.238.229; 5.L.238.230; 5.L.238.231; 5.L.238.236; 5.L.238.237; 5.L.238.238; 5.L.238.239; 5.L.238.154; 5.L.238.157; 5.L.238.166; 5.L.238.169; 5.L.238.172; 5.L.238.175; 5.L.238.240; 5.L.238.244; 5.L.239.228; 5.L.239.229; 5.L.239.230; 5.L.239.231; 5.L.239.236; 5.L.239.237; 5.L.239.238; 5.L.239.239; 5.L.239.154; 5.L.239.157; 5.L.239.166; 5.L.239.169; 5.L.239.172; 5.L.239.175; 5.L.239.240; 5.L.239.244; 5.L.154.228; 5.L.154.229; 5.L.154.230; 5.L.154.231; 5.L.154.236; 5.L.154.237; 5.L.154.238; 5.L.154.239; 5.L.154.154; 5.L.154.157; 5.L.154.166; 5.L.154.169; 5.L.154.172; 5.L.154.175; 5.L.154.240; 5.L.154.244; 5.L.157.228; 5.L.157.229; 5.L.157.230; 5.L.157.231; 5.L.157.236; 5.L.157.237; 5.L.157.238; 5.L.157.239; 5.L.157.154; 5.L.157.157; 5.L.157.166; 5.L.157.169;

5.L.157.172; 5.L.157.175; 5.L.157.240; 5.L.157.244; 5.L.166.228; 5.L.166.229; 5.L.166.230; 5.L.166.231; 5.L.166.236; 5.L.166.237; 5.L.166.238; 5.L.166.239; 5.L.166.154; 5.L.166.157; 5.L.166.166; 5.L.166.169; 5.L.166.172; 5.L.166.175; 5.L.166.240; 5.L.166.244; 5.L.169.228; 5.L.169.229; 5.L.169.230; 5.L.169.231; 5.L.169.236; 5.L.169.237; 5.L.169.238; 5.L.169.239; 5.L.169.154; 5.L.169.157; 5.L.169.166; 5.L.169.169; 5.L.169.172; 5.L.169.175; 5.L.169.240; 5.L.169.244; 5.L.172.228; 5.L.172.229; 5.L.172.230; 5.L.172.231; 5.L.172.236; 5.L.172.237; 5.L.172.238; 5.L.172.239; 5.L.172.154; 5.L.172.157; 5.L.172.166; 5.L.172.169; 5.L.172.172; 5.L.172.175; 5.L.172.240; 5.L.172.244; 5.L.175.228; 5.L.175.229; 5.L.175.230; 5.L.175.231; 5.L.175.236; 5.L.175.237; 5.L.175.238; 5.L.175.239; 5.L.175.154; 5.L.175.157; 5.L.175.166; 5.L.175.169; 5.L.175.172; 5.L.175.175; 5.L.175.240; 5.L.175.244; 5.L.240.228; 5.L.240.229; 5.L.240.230; 5.L.240.231; 5.L.240.236; 5.L.240.237; 5.L.240.238; 5.L.240.239; 5.L.240.154; 5.L.240.157; 5.L.240.166; 5.L.240.169; 5.L.240.172; 5.L.240.175; 5.L.240.240; 5.L.240.244; 5.L.244.228; 5.L.244.229; 5.L.244.230; 5.L.244.231; 5.L.244.236; 5.L.244.237; 5.L.244.238; 5.L.244.239; 5.L.244.154; 5.L.244.157; 5.L.244.166; 5.L.244.169; 5.L.244.172; 5.L.244.175; 5.L.244.240; 5.L.244.244;

Prodrugs of 5.O

5.O.228.228; 5.O.228.229; 5.O.228.230; 5.O.228.231; 5.O.228.236; 5.O.228.237; 5.O.228.238; 5.O.228.239; 5.O.228.154; 5.O.228.157; 5.O.228.166; 5.O.228.169; 5.O.228.172; 5.O.228.175; 5.O.228.240; 5.O.228.244; 5.O.229.228; 5.O.229.229; 5.O.229.230; 5.O.229.231; 5.O.229.236; 5.O.229.237; 5.O.229.238; 5.O.229.239; 5.O.229.154; 5.O.229.157; 5.O.229.166; 5.O.229.169; 5.O.229.172; 5.O.229.175; 5.O.229.240; 5.O.229.244; 5.O.230.228; 5.O.230.229; 5.O.230.230; 5.O.230.231; 5.O.230.236; 5.O.230.237; 5.O.230.238; 5.O.230.239; 5.O.230.154; 5.O.230.157; 5.O.230.166; 5.O.230.169; 5.O.230.172; 5.O.230.175; 5.O.230.240; 5.O.230.244; 5.O.231.228; 5.O.231.229; 5.O.231.230; 5.O.231.231; 5.O.231.236; 5.O.231.237; 5.O.231.238; 5.O.231.239; 5.O.231.154; 5.O.231.157; 5.O.231.166; 5.O.231.169; 5.O.231.172; 5.O.231.175; 5.O.231.240; 5.O.231.244; 5.O.236.228; 5.O.236.229; 5.O.236.230; 5.O.236.231; 5.O.236.236; 5.O.236.237; 5.O.236.238; 5.O.236.239; 5.O.236.154; 5.O.236.157; 5.O.236.166; 5.O.236.169; 5.O.236.172; 5.O.236.175; 5.O.236.240; 5.O.236.244; 5.O.237.228; 5.O.237.229; 5.O.237.230; 5.O.237.231; 5.O.237.236; 5.O.237.237; 5.O.237.238; 5.O.237.239; 5.O.237.154; 5.O.237.157; 5.O.237.166; 5.O.237.169; 5.O.237.172; 5.O.237.175; 5.O.237.240; 5.O.237.244; 5.O.238.228; 5.O.238.229; 5.O.238.230; 5.O.238.231; 5.O.238.236; 5.O.238.237; 5.O.238.238; 5.O.238.239; 5.O.238.154; 5.O.238.157; 5.O.238.166; 5.O.238.169; 5.O.238.172; 5.O.238.175; 5.O.238.240; 5.O.238.244; 5.O.239.228; 5.O.239.229; 5.O.239.230; 5.O.239.231; 5.O.239.236; 5.O.239.237; 5.O.239.238; 5.O.239.239; 5.O.239.154; 5.O.239.157; 5.O.239.166; 5.O.239.169; 5.O.239.172; 5.O.239.175; 5.O.239.240; 5.O.239.244; 5.O.154.228; 5.O.154.229; 5.O.154.230; 5.O.154.231; 5.O.154.236; 5.O.154.237; 5.O.154.238; 5.O.154.239; 5.O.154.154; 5.O.154.157; 5.O.154.166; 5.O.154.169; 5.O.154.172; 5.O.154.175; 5.O.154.240; 5.O.154.244; 5.O.157.228; 5.O.157.229; 5.O.157.230; 5.O.157.231; 5.O.157.236; 5.O.157.237; 5.O.157.238; 5.O.157.239; 5.O.157.154; 5.O.157.157; 5.O.157.166; 5.O.157.169; 5.O.157.172; 5.O.157.175; 5.O.157.240; 5.O.157.244; 5.O.166.228; 5.O.166.229;

5.O.166.230; 5.O.166.231; 5.O.166.236; 5.O.166.237; 5.O.166.238; 5.O.166.239; 5.O.166.154; 5.O.166.157; 5.O.166.166; 5.O.166.169; 5.O.166.172; 5.O.166.175; 5.O.166.240; 5.O.166.244; 5.O.169.228; 5.O.169.229; 5.O.169.230; 5.O.169.231; 5.O.169.236; 5.O.169.237; 5.O.169.238; 5.O.169.239; 5.O.169.154; 5.O.169.157; 5.O.169.166; 5.O.169.169; 5.O.169.172; 5.O.169.175; 5.O.169.240; 5.O.169.244; 5.O.172.228; 5.O.172.229; 5.O.172.230; 5.O.172.231; 5.O.172.236; 5.O.172.237; 5.O.172.238; 5.O.172.239; 5.O.172.154; 5.O.172.157; 5.O.172.166; 5.O.172.169; 5.O.172.172; 5.O.172.175; 5.O.172.240; 5.O.172.244; 5.O.175.228; 5.O.175.229; 5.O.175.230; 5.O.175.231; 5.O.175.236; 5.O.175.237; 5.O.175.238; 5.O.175.239; 5.O.175.154; 5.O.175.157; 5.O.175.166; 5.O.175.169; 5.O.175.172; 5.O.175.175; 5.O.175.240; 5.O.175.244; 5.O.240.228; 5.O.240.229; 5.O.240.230; 5.O.240.231; 5.O.240.236; 5.O.240.237; 5.O.240.238; 5.O.240.239; 5.O.240.154; 5.O.240.157; 5.O.240.166; 5.O.240.169; 5.O.240.172; 5.O.240.175; 5.O.240.240; 5.O.240.244; 5.O.244.228; 5.O.244.229; 5.O.244.230; 5.O.244.231; 5.O.244.236; 5.O.244.237; 5.O.244.238; 5.O.244.239; 5.O.244.154; 5.O.244.157; 5.O.244.166; 5.O.244.169; 5.O.244.172; 5.O.244.175; 5.O.244.240; 5.O.244.244;

Prodrugs of 5.P

5.P.228.228; 5.P.228.229; 5.P.228.230; 5.P.228.231; 5.P.228.236; 5.P.228.237; 5.P.228.238; 5.P.228.239; 5.P.228.154; 5.P.228.157; 5.P.228.166; 5.P.228.169; 5.P.228.172; 5.P.228.175; 5.P.228.240; 5.P.228.244; 5.P.229.228; 5.P.229.229; 5.P.229.230; 5.P.229.231; 5.P.229.236; 5.P.229.237; 5.P.229.238; 5.P.229.239; 5.P.229.154; 5.P.229.157; 5.P.229.166; 5.P.229.169; 5.P.229.172; 5.P.229.175; 5.P.229.240; 5.P.229.244; 5.P.230.228; 5.P.230.229; 5.P.230.230; 5.P.230.231; 5.P.230.236; 5.P.230.237; 5.P.230.238; 5.P.230.239; 5.P.230.154; 5.P.230.157; 5.P.230.166; 5.P.230.169; 5.P.230.172; 5.P.230.175; 5.P.230.240; 5.P.230.244; 5.P.231.228; 5.P.231.229; 5.P.231.230; 5.P.231.231; 5.P.231.236; 5.P.231.237; 5.P.231.238; 5.P.231.239; 5.P.231.154; 5.P.231.157; 5.P.231.166; 5.P.231.169; 5.P.231.172; 5.P.231.175; 5.P.231.240; 5.P.231.244; 5.P.236.228; 5.P.236.229; 5.P.236.230; 5.P.236.231; 5.P.236.236; 5.P.236.237; 5.P.236.238; 5.P.236.239; 5.P.236.154; 5.P.236.157; 5.P.236.166; 5.P.236.169; 5.P.236.172; 5.P.236.175; 5.P.236.240; 5.P.236.244; 5.P.237.228; 5.P.237.229; 5.P.237.230; 5.P.237.231; 5.P.237.236; 5.P.237.237; 5.P.237.238; 5.P.237.239; 5.P.237.154; 5.P.237.157; 5.P.237.166; 5.P.237.169; 5.P.237.172; 5.P.237.175; 5.P.237.240; 5.P.237.244; 5.P.238.228; 5.P.238.229; 5.P.238.230; 5.P.238.231; 5.P.238.236; 5.P.238.237; 5.P.238.238; 5.P.238.239; 5.P.238.154; 5.P.238.157; 5.P.238.166; 5.P.238.169; 5.P.238.172; 5.P.238.175; 5.P.238.240; 5.P.238.244; 5.P.239.228; 5.P.239.229; 5.P.239.230; 5.P.239.231; 5.P.239.236; 5.P.239.237; 5.P.239.238; 5.P.239.239; 5.P.239.154; 5.P.239.157; 5.P.239.166; 5.P.239.169; 5.P.239.172; 5.P.239.175; 5.P.239.240; 5.P.239.244; 5.P.154.228; 5.P.154.229; 5.P.154.230; 5.P.154.231; 5.P.154.236; 5.P.154.237; 5.P.154.238; 5.P.154.239; 5.P.154.154; 5.P.154.157; 5.P.154.166; 5.P.154.169; 5.P.154.172; 5.P.154.175; 5.P.154.240; 5.P.154.244; 5.P.157.228; 5.P.157.229; 5.P.157.230; 5.P.157.231; 5.P.157.236; 5.P.157.237; 5.P.157.238; 5.P.157.239; 5.P.157.154; 5.P.157.157; 5.P.157.166; 5.P.157.169; 5.P.157.172; 5.P.157.175; 5.P.157.240; 5.P.157.244; 5.P.166.228; 5.P.166.229; 5.P.166.230; 5.P.166.231; 5.P.166.236; 5.P.166.237; 5.P.166.238; 5.P.166.239;

5.P.166.154; 5.P.166.157; 5.P.166.166; 5.P.166.169; 5.P.166.172; 5.P.166.175; 5.P.166.240; 5.P.166.244; 5.P.169.228; 5.P.169.229; 5.P.169.230; 5.P.169.231; 5.P.169.236; 5.P.169.237; 5.P.169.238; 5.P.169.239; 5.P.169.154; 5.P.169.157; 5.P.169.166; 5.P.169.169; 5.P.169.172; 5.P.169.175; 5.P.169.240; 5.P.169.244; 5.P.172.228; 5.P.172.229; 5.P.172.230; 5.P.172.231; 5.P.172.236; 5.P.172.237; 5.P.172.238; 5.P.172.239; 5.P.172.154; 5.P.172.157; 5.P.172.166; 5.P.172.169; 5.P.172.172; 5.P.172.175; 5.P.172.240; 5.P.172.244; 5.P.175.228; 5.P.175.229; 5.P.175.230; 5.P.175.231; 5.P.175.236; 5.P.175.237; 5.P.175.238; 5.P.175.239; 5.P.175.154; 5.P.175.157; 5.P.175.166; 5.P.175.169; 5.P.175.172; 5.P.175.175; 5.P.175.240; 5.P.175.244; 5.P.240.228; 5.P.240.229; 5.P.240.230; 5.P.240.231; 5.P.240.236; 5.P.240.237; 5.P.240.238; 5.P.240.239; 5.P.240.154; 5.P.240.157; 5.P.240.166; 5.P.240.169; 5.P.240.172; 5.P.240.175; 5.P.240.240; 5.P.240.244; 5.P.244.228; 5.P.244.229; 5.P.244.230; 5.P.244.231; 5.P.244.236; 5.P.244.237; 5.P.244.238; 5.P.244.239; 5.P.244.154; 5.P.244.157; 5.P.244.166; 5.P.244.169; 5.P.244.172; 5.P.244.175; 5.P.244.240; 5.P.244.244;

Prodrugs of 5.U

5.U.228.228; 5.U.228.229; 5.U.228.230; 5.U.228.231; 5.U.228.236; 5.U.228.237; 5.U.228.238; 5.U.228.239; 5.U.228.154; 5.U.228.157; 5.U.228.166; 5.U.228.169; 5.U.228.172; 5.U.228.175; 5.U.228.240; 5.U.228.244; 5.U.229.228; 5.U.229.229; 5.U.229.230; 5.U.229.231; 5.U.229.236; 5.U.229.237; 5.U.229.238; 5.U.229.239; 5.U.229.154; 5.U.229.157; 5.U.229.166; 5.U.229.169; 5.U.229.172; 5.U.229.175; 5.U.229.240; 5.U.229.244; 5.U.230.228; 5.U.230.229; 5.U.230.230; 5.U.230.231; 5.U.230.236; 5.U.230.237; 5.U.230.238; 5.U.230.239; 5.U.230.154; 5.U.230.157; 5.U.230.166; 5.U.230.169; 5.U.230.172; 5.U.230.175; 5.U.230.240; 5.U.230.244; 5.U.231.228; 5.U.231.229; 5.U.231.230; 5.U.231.231; 5.U.231.236; 5.U.231.237; 5.U.231.238; 5.U.231.239; 5.U.231.154; 5.U.231.157; 5.U.231.166; 5.U.231.169; 5.U.231.172; 5.U.231.175; 5.U.231.240; 5.U.231.244; 5.U.236.228; 5.U.236.229; 5.U.236.230; 5.U.236.231; 5.U.236.236; 5.U.236.237; 5.U.236.238; 5.U.236.239; 5.U.236.154; 5.U.236.157; 5.U.236.166; 5.U.236.169; 5.U.236.172; 5.U.236.175; 5.U.236.240; 5.U.236.244; 5.U.237.228; 5.U.237.229; 5.U.237.230; 5.U.237.231; 5.U.237.236; 5.U.237.237; 5.U.237.238; 5.U.237.239; 5.U.237.154; 5.U.237.157; 5.U.237.166; 5.U.237.169; 5.U.237.172; 5.U.237.175; 5.U.237.240; 5.U.237.244; 5.U.238.228; 5.U.238.229; 5.U.238.230; 5.U.238.231; 5.U.238.236; 5.U.238.237; 5.U.238.238; 5.U.238.239; 5.U.238.154; 5.U.238.157; 5.U.238.166; 5.U.238.169; 5.U.238.172; 5.U.238.175; 5.U.238.240; 5.U.238.244; 5.U.239.228; 5.U.239.229; 5.U.239.230; 5.U.239.231; 5.U.239.236; 5.U.239.237; 5.U.239.238; 5.U.239.239; 5.U.239.154; 5.U.239.157; 5.U.239.166; 5.U.239.169; 5.U.239.172; 5.U.239.175; 5.U.239.240; 5.U.239.244; 5.U.154.228; 5.U.154.229; 5.U.154.230; 5.U.154.231; 5.U.154.236; 5.U.154.237; 5.U.154.238; 5.U.154.239; 5.U.154.154; 5.U.154.157; 5.U.154.166; 5.U.154.169; 5.U.154.172; 5.U.154.175; 5.U.154.240; 5.U.154.244; 5.U.157.228; 5.U.157.229; 5.U.157.230; 5.U.157.231; 5.U.157.236; 5.U.157.237; 5.U.157.238; 5.U.157.239; 5.U.157.154; 5.U.157.157; 5.U.157.166; 5.U.157.169; 5.U.157.172; 5.U.157.175; 5.U.157.240; 5.U.157.244; 5.U.166.228; 5.U.166.229; 5.U.166.230; 5.U.166.231; 5.U.166.236; 5.U.166.237; 5.U.166.238; 5.U.166.239; 5.U.166.154; 5.U.166.157; 5.U.166.166; 5.U.166.169; 5.U.166.172; 5.U.166.175;

5.U.166.240; 5.U.166.244; 5.U.169.228; 5.U.169.229; 5.U.169.230; 5.U.169.231; 5.U.169.236; 5.U.169.237; 5.U.169.238; 5.U.169.239; 5.U.169.154; 5.U.169.157; 5.U.169.166; 5.U.169.169; 5.U.169.172; 5.U.169.175; 5.U.169.240; 5.U.169.244; 5.U.172.228; 5.U.172.229; 5.U.172.230; 5.U.172.231; 5.U.172.236; 5.U.172.237; 5.U.172.238; 5.U.172.239; 5.U.172.154; 5.U.172.157; 5.U.172.166; 5.U.172.169; 5.U.172.172; 5.U.172.175; 5.U.172.240; 5.U.172.244; 5.U.175.228; 5.U.175.229; 5.U.175.230; 5.U.175.231; 5.U.175.236; 5.U.175.237; 5.U.175.238; 5.U.175.239; 5.U.175.154; 5.U.175.157; 5.U.175.166; 5.U.175.169; 5.U.175.172; 5.U.175.175; 5.U.175.240; 5.U.175.244; 5.U.240.228; 5.U.240.229; 5.U.240.230; 5.U.240.231; 5.U.240.236; 5.U.240.237; 5.U.240.238; 5.U.240.239; 5.U.240.154; 5.U.240.157; 5.U.240.166; 5.U.240.169; 5.U.240.172; 5.U.240.175; 5.U.240.240; 5.U.240.244; 5.U.244.228; 5.U.244.229; 5.U.244.230; 5.U.244.231; 5.U.244.236; 5.U.244.237; 5.U.244.238; 5.U.244.239; 5.U.244.154; 5.U.244.157; 5.U.244.166; 5.U.244.169; 5.U.244.172; 5.U.244.175; 5.U.244.240; 5.U.244.244;

Prodrugs of 5.CD

5.CD.228.228; 5.CD.228.229; 5.CD.228.230; 5.CD.228.231; 5.CD.228.236; 5.CD.228.237; 5.CD.228.238; 5.CD.228.239; 5.CD.228.154; 5.CD.228.157; 5.CD.228.166; 5.CD.228.169; 5.CD.228.172; 5.CD.228.175; 5.CD.228.240; 5.CD.228.244; 5.CD.229.228; 5.CD.229.229; 5.CD.229.230; 5.CD.229.231; 5.CD.229.236; 5.CD.229.237; 5.CD.229.238; 5.CD.229.239; 5.CD.229.154; 5.CD.229.157; 5.CD.229.166; 5.CD.229.169; 5.CD.229.172; 5.CD.229.175; 5.CD.229.240; 5.CD.229.244; 5.CD.230.228; 5.CD.230.229; 5.CD.230.230; 5.CD.230.231; 5.CD.230.236; 5.CD.230.237; 5.CD.230.238; 5.CD.230.239; 5.CD.230.154; 5.CD.230.157; 5.CD.230.166; 5.CD.230.169; 5.CD.230.172; 5.CD.230.175; 5.CD.230.240; 5.CD.230.244; 5.CD.231.228; 5.CD.231.229; 5.CD.231.230; 5.CD.231.231; 5.CD.231.236; 5.CD.231.237; 5.CD.231.238; 5.CD.231.239; 5.CD.231.154; 5.CD.231.157; 5.CD.231.166; 5.CD.231.169; 5.CD.231.172; 5.CD.231.175; 5.CD.231.240; 5.CD.231.244; 5.CD.236.228; 5.CD.236.229; 5.CD.236.230; 5.CD.236.231; 5.CD.236.236; 5.CD.236.237; 5.CD.236.238; 5.CD.236.239; 5.CD.236.154; 5.CD.236.157; 5.CD.236.166; 5.CD.236.169; 5.CD.236.172; 5.CD.236.175; 5.CD.236.240; 5.CD.236.244; 5.CD.237.228; 5.CD.237.229; 5.CD.237.230; 5.CD.237.231; 5.CD.237.236; 5.CD.237.237; 5.CD.237.238; 5.CD.237.239; 5.CD.237.154; 5.CD.237.157; 5.CD.237.166; 5.CD.237.169; 5.CD.237.172; 5.CD.237.175; 5.CD.237.240; 5.CD.237.244; 5.CD.238.228; 5.CD.238.229; 5.CD.238.230; 5.CD.238.231; 5.CD.238.236; 5.CD.238.237; 5.CD.238.238; 5.CD.238.239; 5.CD.238.154; 5.CD.238.157; 5.CD.238.166; 5.CD.238.169; 5.CD.238.172; 5.CD.238.175; 5.CD.238.240; 5.CD.238.244; 5.CD.239.228; 5.CD.239.229; 5.CD.239.230; 5.CD.239.231; 5.CD.239.236; 5.CD.239.237; 5.CD.239.238; 5.CD.239.239; 5.CD.239.154; 5.CD.239.157; 5.CD.239.166; 5.CD.239.169; 5.CD.239.172; 5.CD.239.175; 5.CD.239.240; 5.CD.239.244; 5.CD.154.228; 5.CD.154.229; 5.CD.154.230; 5.CD.154.231; 5.CD.154.236; 5.CD.154.237; 5.CD.154.238; 5.CD.154.239; 5.CD.154.154; 5.CD.154.157; 5.CD.154.166; 5.CD.154.169; 5.CD.154.172; 5.CD.154.175; 5.CD.154.240; 5.CD.154.244; 5.CD.157.228; 5.CD.157.229; 5.CD.157.230; 5.CD.157.231; 5.CD.157.236; 5.CD.157.237;

5.CD.157.238; 5.CD.157.239; 5.CD.157.154; 5.CD.157.157; 5.CD.157.166; 5.CD.157.169; 5.CD.157.172; 5.CD.157.175; 5.CD.157.240; 5.CD.157.244; 5.CD.166.228; 5.CD.166.229; 5.CD.166.230; 5.CD.166.231; 5.CD.166.236; 5.CD.166.237; 5.CD.166.238; 5.CD.166.239; 5.CD.166.154; 5.CD.166.157; 5.CD.166.166; 5.CD.166.169; 5.CD.166.172; 5.CD.166.175; 5.CD.166.240; 5.CD.166.244; 5.CD.169.228; 5.CD.169.229; 5.CD.169.230; 5.CD.169.231; 5.CD.169.236; 5.CD.169.237; 5.CD.169.238; 5.CD.169.239; 5.CD.169.154; 5.CD.169.157; 5.CD.169.166; 5.CD.169.169; 5.CD.169.172; 5.CD.169.175; 5.CD.169.240; 5.CD.169.244; 5.CD.172.228; 5. CD.172.229; 5.CD.172.230; 5.CD.172.231; 5.CD.172.236; 5.CD.172.237; 5.CD.172.238; 5.CD.172.239; 5.CD.172.154; 5.CD.172.157; 5.CD.172.166; 5.CD.172.169; 5.CD.172.172; 5.CD.172.175; 5.CD.172.240; 5.CD.172.244; 5.CD.175.228; 5.CD.175.229; 5.CD.175.230; 5.CD.175.231; 5.CD.175.236; 5.CD.175.237; 5.CD.175.238; 5.CD.175.239; 5.CD.175.154; 5.CD.175.157; 5.CD.175.166; 5.CD.175.169; 5.CD.175.172; 5.CD.175.175; 5.CD.175.240; 5.CD.175.244; 5.CD.240.228; 5.CD.240.229; 5.CD.240.230; 5.CD.240.231; 5.CD.240.236; 5.CD.240.237; 5.CD.240.238; 5.CD.240.239; 5.CD.240.154; 5.CD.240.157; 5.CD.240.166; 5.CD.240.169; 5.CD.240.172; 5.CD.240.175; 5.CD.240.240; 5.CD.240.244; 5.CD.244.228; 5.CD.244.229; 5.CD.244.230; 5.CD.244.231; 5.CD.244.236; 5.CD.244.237; 5.CD.244.238; 5.CD.244.239; 5.CD.244.154; 5.CD.244.157; 5.CD.244.166; 5.CD.244.169; 5.CD.244.172; 5.CD.244.175; 5.CD.244.240; 5.CD.244.244;

Prodrugs of 5.EB

5.EB.228.228; 5.EB.228.229; 5.EB.228.230; 5.EB.228.231; 5.EB.228.236; 5.EB.228.237; 5.EB.228.238; 5.EB.228.239; 5.EB.228.154; 5.EB.228.157; 5.EB.228.166; 5.EB.228.169; 5.EB.228.172; 5.EB.228.175; 5.EB.228.240; 5.EB.228.244; 5.EB.229.228; 5.EB.229.229; 5.EB.229.230; 5.EB.229.231; 5.EB.229.236; 5.EB.229.237; 5.EB.229.238; 5.EB.229.239; 5.EB.229.154; 5.EB.229.157; 5.EB.229.166; 5.EB.229.169; 5.EB.229.172; 5.EB.229.175; 5.EB.229.240; 5.EB.229.244; 5.EB.230.228; 5.EB.230.229; 5.EB.230.230; 5.EB.230.231; 5.EB.230.236; 5.EB.230.237; 5.EB.230.238; 5.EB.230.239; 5.EB.230.154; 5.EB.230.157; 5.EB.230.166; 5.EB.230.169; 5.EB.230.172; 5.EB.230.175; 5.EB.230.240; 5.EB.230.244; 5.EB.231.228; 5.EB.231.229; 5.EB.231.230; 5.EB.231.231; 5.EB.231.236; 5.EB.231.237; 5.EB.231.238; 5.EB.231.239; 5.EB.231.154; 5.EB.231.157; 5.EB.231.166; 5.EB.231.169; 5.EB.231.172; 5.EB.231.175; 5.EB.231.240; 5.EB.231.244; 5.EB.236.228; 5.EB.236.229; 5.EB.236.230; 5.EB.236.231; 5.EB.236.236; 5.EB.236.237; 5.EB.236.238; 5.EB.236.239; 5.EB.236.154; 5.EB.236.157; 5.EB.236.166; 5.EB.236.169; 5.EB.236.172; 5.EB.236.175; 5.EB.236.240; 5.EB.236.244; 5.EB.237.228; 5.EB.237.229; 5.EB.237.230; 5.EB.237.231; 5.EB.237.236; 5.EB.237.237; 5.EB.237.238; 5.EB.237.239; 5.EB.237.154; 5.EB.237.157; 5.EB.237.166; 5.EB.237.169; 5.EB.237.172; 5.EB.237.175; 5.EB.237.240; 5.EB.237.244; 5.EB.238.228; 5.EB.238.229; 5.EB.238.230; 5.EB.238.231; 5.EB.238.236; 5.EB.238.237; 5.EB.238.238; 5.EB.238.239; 5.EB.238.154; 5.EB.238.157; 5.EB.238.166; 5.EB.238.169; 5.EB.238.172; 5.EB.238.175; 5.EB.238.240; 5.EB.238.244; 5.EB.239.228; 5.EB.239.229; 5.EB.239.230; 5.EB.239.231; 5.EB.239.236; 5.EB.239.237; 5.EB.239.238; 5.EB.239.239; 5.EB.239.154; 5.EB.239.157; 5.EB.239.166; 5.EB.239.169; 5.EB.239.172; 5.EB.239.175; 5.EB.239.240; 5.EB.239.244; 5.EB.154.228; 5.EB.154.229; 5.EB.154.230;

5.EB.154.231; 5.EB.154.236; 5.EB.154.237; 5.EB.154.238; 5.EB.154.239; 5.EB.154.154; 5.EB.154.157; 5.EB.154.166; 5.EB.154.169; 5.EB.154.172; 5.EB.154.175; 5.EB.154.240; 5.EB.154.244; 5.EB.157.228; 5.EB.157.229; 5.EB.157.230; 5.EB.157.231; 5.EB.157.236; 5.EB.157.237; 5.EB.157.238; 5.EB.157.239; 5.EB.157.154; 5.EB.157.157; 5.EB.157.166; 5.EB.157.169; 5.EB.157.172; 5.EB.157.175; 5.EB.157.240; 5.EB.157.244; 5.EB.166.228; 5.EB.166.229; 5.EB.166.230; 5.EB.166.231; 5.EB.166.236; 5.EB.166.237; 5.EB.166.238; 5.EB.166.239; 5.EB.166.154; 5.EB.166.157; 5.EB.166.166; 5.EB.166.169; 5.EB.166.172; 5.EB.166.175; 5.EB.166.240; 5.EB.166.244; 5.EB.169.228; 5.EB.169.229; 5.EB.169.230; 5.EB.169.231; 5.EB.169.236; 5.EB.169.237; 5.EB.169.238; 5.EB.169.239; 5.EB.169.154; 5.EB.169.157; 5.EB.169.166; 5.EB.169.169; 5.EB.169.172; 5.EB.169.175; 5.EB.169.240; 5.EB.169.244; 5.EB.172.228; 5.EB.172.229; 5.EB.172.230; 5.EB.172.231; 5.EB.172.236; 5.EB.172.237; 5.EB.172.238; 5.EB.172.239; 5.EB.172.154; 5.EB.172.157; 5.EB.172.166; 5.EB.172.169; 5.EB.172.172; 5.EB.172.175; 5.EB.172.240; 5.EB.172.244; 5.EB.175.228; 5.EB.175.229; 5.EB.175.230; 5.EB.175.231; 5.EB.175.236; 5.EB.175.237; 5.EB.175.238; 5.EB.175.239; 5.EB.175.154; 5.EB.175.157; 5.EB.175.166; 5.EB.175.169; 5.EB.175.172; 5.EB.175.175; 5.EB.175.240; 5.EB.175.244; 5.EB.240.228; 5.EB.240.229; 5.EB.240.230; 5.EB.240.231; 5.EB.240.236; 5.EB.240.237; 5.EB.240.238; 5.EB.240.239; 5.EB.240.154; 5.EB.240.157; 5.EB.240.166; 5.EB.240.169; 5.EB.240.172; 5.EB.240.175; 5.EB.240.240; 5.EB.240.244; 5.EB.244.228; 5.EB.244.229; 5.EB.244.230; 5.EB.244.231; 5.EB.244.236; 5.EB.244.237; 5.EB.244.238; 5.EB.244.239; 5.EB.244.154; 5.EB.244.157; 5.EB.244.166; 5.EB.244.169; 5.EB.244.172; 5.EB.244.175; 5.EB.244.240; 5.EB.244.244;

Prodrugs of 6.B

6.B.228.228; 6.B.228.229; 6.B.228.230; 6.B.228.231; 6.B.228.236; 6.B.228.237; 6.B.228.238; 6.B.228.239; 6.B.228.154; 6.B.228.157; 6.B.228.166; 6.B.228.169; 6.B.228.172; 6.B.228.175; 6.B.228.240; 6.B.228.244; 6.B.229.228; 6.B.229.229; 6.B.229.230; 6.B.229.231; 6.B.229.236; 6.B.229.237; 6.B.229.238; 6.B.229.239; 6.B.229.154; 6.B.229.157; 6.B.229.166; 6.B.229.169; 6.B.229.172; 6.B.229.175; 6.B.229.240; 6.B.229.244; 6.B.230.228; 6.B.230.229; 6.B.230.230; 6.B.230.231; 6.B.230.236; 6.B.230.237; 6.B.230.238; 6.B.230.239; 6.B.230.154; 6.B.230.157; 6.B.230.166; 6.B.230.169; 6.B.230.172; 6.B.230.175; 6.B.230.240; 6.B.230.244; 6.B.231.228; 6.B.231.229; 6.B.231.230; 6.B.231.231; 6.B.231.236; 6.B.231.237; 6.B.231.238; 6.B.231.239; 6.B.231.154; 6.B.231.157; 6.B.231.166; 6.B.231.169; 6.B.231.172; 6.B.231.175; 6.B.231.240; 6.B.231.244; 6.B.236.228; 6.B.236.229; 6.B.236.230; 6.B.236.231; 6.B.236.236; 6.B.236.237; 6.B.236.238; 6.B.236.239; 6.B.236.154; 6.B.236.157; 6.B.236.166; 6.B.236.169; 6.B.236.172; 6.B.236.175; 6.B.236.240; 6.B.236.244; 6.B.237.228; 6.B.237.229; 6.B.237.230; 6.B.237.231; 6.B.237.236; 6.B.237.237; 6.B.237.238; 6.B.237.239; 6.B.237.154; 6.B.237.157; 6.B.237.166; 6.B.237.169; 6.B.237.172; 6.B.237.175; 6.B.237.240; 6.B.237.244; 6.B.238.228; 6.B.238.229; 6.B.238.230; 6.B.238.231; 6.B.238.236; 6.B.238.237; 6.B.238.238; 6.B.238.239; 6.B.238.154; 6.B.238.157; 6.B.238.166; 6.B.238.169; 6.B.238.172; 6.B.238.175; 6.B.238.240; 6.B.238.244; 6.B.239.228; 6.B.239.229; 6.B.239.230; 6.B.239.231; 6.B.239.236; 6.B.239.237; 6.B.239.238; 6.B.239.239; 6.B.239.154; 6.B.239.157; 6.B.239.166; 6.B.239.169; 6.B.239.172; 6.B.239.175; 6.B.239.240; 6.B.239.244; 6.B.154.228; 6.B.154.229; 6.B.154.230; 6.B.154.231; 6.B.154.236; 6.B.154.237; 6.B.154.238; 6.B.154.239; 6.B.154.154; 6.B.154.157;

6.B.154.166; 6.B.154.169; 6.B.154.172; 6.B.154.175; 6.B.154.240; 6.B.154.244; 6.B.157.228; 6.B.157.229; 6.B.157.230; 6.B.157.231; 6.B.157.236; 6.B.157.237; 6.B.157.238; 6.B.157.239; 6.B.157.154; 6.B.157.157; 6.B.157.166; 6.B.157.169; 6.B.157.172; 6.B.157.175; 6.B.157.240; 6.B.157.244; 6.B.166.228; 6.B.166.229; 6.B.166.230; 6.B.166.231; 6.B.166.236; 6.B.166.237; 6.B.166.238; 6.B.166.239; 6.B.166.154; 6.B.166.157; 6.B.166.166; 6.B.166.169; 6.B.166.172; 6.B.166.175; 6.B.166.240; 6.B.166.244; 6.B.169.228; 6.B.169.229; 6.B.169.230; 6.B.169.231; 6.B.169.236; 6.B.169.237; 6.B.169.238; 6.B.169.239; 6.B.169.154; 6.B.169.157; 6.B.169.166; 6.B.169.169; 6.B.169.172; 6.B.169.175; 6.B.169.240; 6.B.169.244; 6.B.172.228; 6.B.172.229; 6.B.172.230; 6.B.172.231; 6.B.172.236; 6.B.172.237; 6.B.172.238; 6.B.172.239; 6.B.172.154; 6.B.172.157; 6.B.172.166; 6. B.172.169; 6.B.172.172; 6.B.172.175; 6.B.172.240; 6.B.172.244; 6.B.175.228; 6.B.175.229; 6.B.175.230; 6.B.175.231; 6.B.175.236; 6.B.175.237; 6.B.175.238; 6.B.175.239; 6.B.175.154; 6.B.175.157; 6.B.175.166; 6.B.175.169; 6.B.175.172; 6.B.175.175; 6.B.175.240; 6.B.175.244; 6.B.240.228; 6.B.240.229; 6.B.240.230; 6.B.240.231; 6.B.240.236; 6.B.240.237; 6.B.240.238; 6.B.240.239; 6.B.240.154; 6.B.240.157; 6.B.240.166; 6.B.240.169; 6.B.240.172; 6.B.240.175; 6.B.240.240; 6.B.240.244; 6.B.244.228; 6.B.244.229; 6.B.244.230; 6.B.244.231; 6.B.244.236; 6.B.244.237; 6.B.244.238; 6.B.244.239; 6.B.244.154; 6.B.244.157; 6.B.244.166; 6.B.244.169; 6.B.244.172; 6.B.244.175; 6.B.244.240; 6.B.244.244;

Prodrugs of 6.D

6.D.228.228; 6.D.228.229; 6.D.228.230; 6.D.228.231; 6.D.228.236; 6.D.228.237; 6.D.228.238; 6.D.228.239; 6.D.228.154; 6.D.228.157; 6.D.228.166; 6.D.228.169; 6.D.228.172; 6.D.228.175; 6.D.228.240; 6.D.228.244; 6.D.229.228; 6.D.229.229; 6.D.229.230; 6.D.229.231; 6.D.229.236; 6.D.229.237; 6.D.229.238; 6.D.229.239; 6.D.229.154; 6.D.229.157; 6.D.229.166; 6.D.229.169; 6.D.229.172; 6.D.229.175; 6.D.229.240; 6.D.229.244; 6.D.230.228; 6.D.230.229; 6.D.230.230; 6.D.230.231; 6.D.230.236; 6.D.230.237; 6.D.230.238; 6.D.230.239; 6.D.230.154; 6.D.230.157; 6.D.230.166; 6.D.230.169; 6.D.230.172; 6.D.230.175; 6.D.230.240; 6.D.230.244; 6.D.231.228; 6.D.231.229; 6.D.231.230; 6.D.231.231; 6.D.231.236; 6.D.231.237; 6.D.231.238; 6.D.231.239; 6.D.231.154; 6.D.231.157; 6.D.231.166; 6.D.231.169; 6.D.231.172; 6.D.231.175; 6.D.231.240; 6.D.231.244; 6.D.236.228; 6.D.236.229; 6.D.236.230; 6.D.236.231; 6.D.236.236; 6.D.236.237; 6.D.236.238; 6.D.236.239; 6.D.236.154; 6.D.236.157; 6.D.236.166; 6.D.236.169; 6.D.236.172; 6.D.236.175; 6.D.236.240; 6.D.236.244; 6.D.237.228; 6.D.237.229; 6.D.237.230; 6.D.237.231; 6.D.237.236; 6.D.237.237; 6.D.237.238; 6.D.237.239; 6.D.237.154; 6.D.237.157; 6.D.237.166; 6.D.237.169; 6.D.237.172; 6.D.237.175; 6.D.237.240; 6.D.237.244; 6.D.238.228; 6.D.238.229; 6.D.238.230; 6.D.238.231; 6.D.238.236; 6.D.238.237; 6.D.238.238; 6.D.238.239; 6.D.238.154; 6.D.238.157; 6.D.238.166; 6.D.238.169; 6.D.238.172; 6.D.238.175; 6.D.238.240; 6.D.238.244; 6.D.239.228; 6.D.239.229; 6.D.239.230; 6.D.239.231; 6.D.239.236; 6.D.239.237; 6.D.239.238; 6.D.239.239; 6.D.239.154; 6.D.239.157; 6.D.239.166; 6.D.239.169; 6.D.239.172; 6.D.239.175; 6.D.239.240; 6.D.239.244; 6.D.154.228; 6.D.154.229; 6.D.154.230; 6.D.154.231; 6.D.154.236; 6.D.154.237; 6.D.154.238; 6.D.154.239; 6.D.154.154; 6.D.154.157; 6.D.154.166; 6.D.154.169; 6.D.154.172; 6.D.154.175; 6.D.154.240; 6.D.154.244;

6.D.157.228; 6.D.157.229; 6.D.157.230; 6.D.157.231; 6.D.157.236; 6.D.157.237; 6.D.157.238; 6.D.157.239; 6.D.157.154; 6.D.157.157; 6.D.157.166; 6.D.157.169; 6.D.157.172; 6.D.157.175; 6.D.157.240; 6.D.157.244; 6.D.166.228; 6.D.166.229; 6.D.166.230; 6.D.166.231; 6.D.166.236; 6.D.166.237; 6.D.166.238; 6.D.166.239; 6.D.166.154; 6.D.166.157; 6.D.166.166; 6.D.166.169; 6.D.166.172; 6.D.166.175; 6.D.166.240; 6.D.166.244; 6.D.169.228; 6.D.169.229; 6.D.169.230; 6.D.169.231; 6.D.169.236; 6.D.169.237; 6.D.169.238; 6.D.169.239; 6.D.169.154; 6.D.169.157; 6.D.169.166; 6.D.169.169; 6.D.169.172; 6.D.169.175; 6.D.169.240; 6.D.169.244; 6.D.172.228; 6.D.172.229; 6.D.172.230; 6.D.172.231; 6.D.172.236; 6.D.172.237; 6.D.172.238; 6.D.172.239; 6.D.172.154; 6.D.172.157; 6.D.172.166; 6.D.172.169; 6.D.172.172; 6.D.172.175; 6.D.172.240; 6.D.172.244; 6.D.175.228; 6.D.175.229; 6.D.175.230; 6.D.175.231; 6.D.175.236; 6.D.175.237; 6.D.175.238; 6.D.175.239; 6.D.175.154; 6.D.175.157; 6.D.175.166; 6.D.175.169; 6.D.175.172; 6.D.175.175; 6.D.175.240; 6.D.175.244; 6.D.240.228; 6.D.240.229; 6.D.240.230; 6.D.240.231; 6.D.240.236; 6.D.240.237; 6.D.240.238; 6.D.240.239; 6.D.240.154; 6.D.240.157; 6.D.240.166; 6.D.240.169; 6.D.240.172; 6.D.240.175; 6.D.240.240; 6.D.240.244; 6.D.244.228; 6.D.244.229; 6.D.244.230; 6.D.244.231; 6.D.244.236; 6.D.244.237; 6.D.244.238; 6.D.244.239; 6.D.244.154; 6.D.244.157; 6.D.244.166; 6.D.244.169; 6.D.244.172; 6.D.244.175; 6.D.244.240; 6.D.244.244;

Prodrugs of 6.AB

6.AB.228.228; 6.AB.228.229; 6.AB.228.230; 6.AB.228.231; 6.AB.228.236; 6.AB.228.237; 6.AB.228.238; 6.AB.228.239; 6.AB.228.154; 6.AB.228.157; 6.AB.228.166; 6.AB.228.169; 6.AB.228.172; 6.AB.228.175; 6.AB.228.240; 6.AB.228.244; 6.AB.229.228; 6.AB.229.229; 6.AB.229.230; 6.AB.229.231; 6.AB.229.236; 6.AB.229.237; 6.AB.229.238; 6.AB.229.239; 6.AB.229.154; 6.AB.229.157; 6.AB.229.166; 6.AB.229.169; 6.AB.229.172; 6.AB.229.175; 6.AB.229.240; 6.AB.229.244; 6.AB.230.228; 6.AB.230.229; 6.AB.230.230; 6.AB.230.231; 6.AB.230.236; 6.AB.230.237; 6.AB.230.238; 6.AB.230.239; 6.AB.230.154; 6.AB.230.157; 6.AB.230.166; 6.AB.230.169; 6.AB.230.172; 6.AB.230.175; 6.AB.230.240; 6.AB.230.244; 6.AB.231.228; 6.AB.231.229; 6.AB.231.230; 6.AB.231.231; 6.AB.231.236; 6.AB.231.237; 6.AB.231.238; 6.AB.231.239; 6.AB.231.154; 6.AB.231.157; 6.AB.231.166; 6.AB.231.169; 6.AB.231.172; 6.AB.231.175; 6.AB.231.240; 6.AB.231.244; 6.AB.236.228; 6.AB.236.229; 6.AB.236.230; 6.AB.236.231; 6.AB.236.236; 6.AB.236.237; 6.AB.236.238; 6.AB.236.239; 6.AB.236.154; 6.AB.236.157; 6.AB.236.166; 6.AB.236.169; 6.AB.236.172; 6.AB.236.175; 6.AB.236.240; 6.AB.236.244; 6.AB.237.228; 6.AB.237.229; 6.AB.237.230; 6.AB.237.231; 6.AB.237.236; 6.AB.237.237; 6.AB.237.238; 6.AB.237.239; 6.AB.237.154; 6.AB.237.157; 6.AB.237.166; 6.AB.237.169; 6.AB.237.172; 6.AB.237.175; 6.AB.237.240; 6.AB.237.244; 6.AB.238.228; 6.AB.238.229; 6.AB.238.230; 6.AB.238.231; 6.AB.238.236; 6.AB.238.237; 6.AB.238.238; 6.AB.238.239; 6.AB.238.154; 6.AB.238.157; 6.AB.238.166; 6.AB.238.169; 6.AB.238.172; 6.AB.238.175; 6.AB.238.240; 6.AB.238.244; 6.AB.239.228; 6.AB.239.229; 6.AB.239.230; 6.AB.239.231; 6.AB.239.236; 6.AB.239.237; 6.AB.239.238; 6.AB.239.239; 6.AB.239.154; 6.AB.239.157; 6.AB.239.166; 6.AB.239.169; 6.AB.239.172;

6.AB.239.175; 6.AB.239.240; 6.AB.239.244; 6.AB.154.228; 6.AB.154.229; 6.AB.154.230; 6.AB.154.231; 6.AB.154.236; 6.AB.154.237; 6.AB.154.238; 6.AB.154.239; 6.AB.154.154; 6.AB.154.157; 6.AB.154.166; 6.AB.154.169; 6.AB.154.172; 6.AB.154.175; 6.AB.154.240; 6.AB.154.244; 6.AB.157.228; 6.AB.157.229; 6.AB.157.230; 6.AB.157.231; 6.AB.157.236; 6.AB.157.237; 6.AB.157.238; 6.AB.157.239; 6.AB.157.154; 6.AB.157.157; 6.AB.157.166; 6.AB.157.169; 6.AB.157.172; 6.AB.157.175; 6.AB.157.240; 6.AB.157.244; 6.AB.166.228; 6.AB.166.229; 6.AB.166.230; 6.AB.166.231; 6.AB.166.236; 6.AB.166.237; 6.AB.166.238; 6.AB.166.239; 6.AB.166.154; 6.AB.166.157; 6.AB.166.166; 6.AB.166.169; 6.AB.166.172; 6.AB.166.175; 6.AB.166.240; 6.AB.166.244; 6.AB.169.228; 6.AB.169.229; 6.AB.169.230; 6.AB.169.231; 6.AB.169.236; 6.AB.169.237; 6.AB.169.238; 6.AB.169.239; 6.AB.169.154; 6.AB.169.157; 6.AB.169.166; 6.AB.169.169; 6.AB.169.172; 6.AB.169.175; 6.AB.169.240; 6.AB.169.244; 6.AB.172.228; 6.AB.172.229; 6.AB.172.230; 6.AB.172.231; 6.AB.172.236; 6.AB.172.237; 6.AB.172.238; 6.AB.172.239; 6.AB.172.154; 6.AB.172.157; 6.AB.172.166; 6.AB.172.169; 6.AB.172.172; 6.AB.172.175; 6.AB.172.240; 6.AB.172.244; 6.AB.175.228; 6.AB.175.229; 6.AB.175.230; 6.AB.175.231; 6.AB.175.236; 6.AB.175.237; 6.AB.175.238; 6.AB.175.239; 6.AB.175.154; 6.AB.175.157; 6.AB.175.166; 6.AB.175.169; 6.AB.175.172; 6.AB.175.175; 6.AB.175.240; 6.AB.175.244; 6.AB.240.228; 6.AB.240.229; 6.AB.240.230; 6.AB.240.231; 6.AB.240.236; 6.AB.240.237; 6.AB.240.238; 6.AB.240.239; 6.AB.240.154; 6.AB.240.157; 6.AB.240.166; 6.AB.240.169; 6.AB.240.172; 6.AB.240.175; 6.AB.240.240; 6.AB.240.244; 6.AB.244.228; 6.AB.244.229; 6.AB.244.230; 6.AB.244.231; 6.AB.244.236; 6.AB.244.237; 6.AB.244.238; 6.AB.244.239; 6.AB.244.154; 6.AB.244.157; 6.AB.244.166; 6.AB.244.169; 6.AB.244.172; 6.AB.244.175; 6.AB.244.240; 6.AB.244.244;

Prodrugs of 6.BI

6.BI.228.228; 6.BI.228.229; 6.BL228.230; 6.BI.228.231; 6.BI.228.236; 6.BI.228.237; 6.BI.228.238; 6.BI.228.239; 6.BI.228.154; 6.BI.228.157; 6.BI.228.166; 6.BI.228.169; 6.BI.228.172; 6.BI.228.175; 6.BI.228.240; 6.BI.228.244; 6.BI.229.228; 6.BI.229.229; 6.BI.229.230; 6.BI.229.231; 6.BI.229.236; 6.BI.229.237; 6.BI.229.238; 6.BI.229.239; 6.BI.229.154; 6.BI.229.157; 6.BI.229.166; 6.BI.229.169; 6.BI.229.172; 6.BI.229.175; 6.BI.229.240; 6.BI.229.244; 6.BI.230.228; 6.BI.230.229; 6.BI.230.230; 6.BI.230.231; 6.BI.230.236; 6.BI.230.237; 6.BI.230.238; 6.BI.230.239; 6.BI.230.154; 6.BI.230.157; 6.BI.230.166; 6.BI.230.169; 6.BI.230.172; 6.BI.230.175; 6.BI.230.240; 6.BI.230.244; 6.BI.231.228; 6.BI.231.229; 6.BI.231.230; 6.BI.231.231; 6.BI.231.236; 6.BI.231.237; 6.BI.231.238; 6.BI.231.239; 6.BI.231.154; 6.BI.231.157; 6.BI.231.166; 6.BI.231.169; 6.BI.231.172; 6.BI.231.175; 6.BI.231.240; 6.BI.231.244; 6.BI.236.228; 6.BI.236.229; 6.BI.236.230; 6.BI.236.231; 6.BI.236.236; 6.BI.236.237; 6.BI.236.238; 6.BI.236.239; 6.BI.236.154; 6.BI.236.157; 6.BI.236.166; 6.BI.236.169; 6.BI.236.172; 6.BI.236.175; 6.BI.236.240; 6.BI.236.244; 6.BI.237.228; 6.BI.237.229; 6.BI.237.230; 6.BI.237.231; 6.BI.237.236; 6.BI.237.237; 6.BI.237.238; 6.BI.237.239; 6.BI.237.154; 6.BI.237.157; 6.BI.237.166; 6.BI.237.169; 6.BI.237.172; 6.BI.237.175; 6.BI.237.240; 6.BI.237.244; 6.BI.238.228; 6.BI.238.229; 6.BI.238.230; 6.BI.238.231; 6.BI.238.236; 6.BI.238.237;

6.BI.238.238; 6.BI.238.239; 6.BI.238.154; 6.BI.238.157; 6.BI.238.166; 6.BI.238.169; 6.BI.238.172; 6.BI.238.175; 6.BI.238.240; 6.BI.238.244; 6.BI.239.228; 6.BI.239.229; 6.BI.239.230; 6.BI.239.231; 6.BI.239.236; 6.BI.239.237; 6.BI.239.238; 6.BI.239.239; 6.BI.239.154; 6.BI.239.157; 6.BI.239.166; 6.BI.239.169; 6.BI.239.172; 6.BI.239.175; 6.BI.239.240; 6.BI.239.244; 6.BI.154.228; 6.BI.154.229; 6.BI.154.230; 6.BI.154.231; 6.BI.154.236; 6.BI.154.237; 6.BI.154.238; 6.BI.154.239; 6.BI.154.154; 6.BI.154.157; 6.BI.154.166; 6.BI.154.169; 6.BI.154.172; 6.BI.154.175; 6.BI.154.240; 6.BI.154.244; 6.BI.157.228; 6.BI.157.229; 6.BI.157.230; 6.BI.157.231; 6.BI.157.236; 6.BI.157.237; 6.BI.157.238; 6.BI.157.239; 6.BI.157.154; 6.BI.157.157; 6.BI.157.166; 6.BI.157.169; 6.BI.157.172; 6.BI.157.175; 6.BI.157.240; 6.BI.157.244; 6.BI.166.228; 6.BI.166.229; 6.BI.166.230; 6.BI.166.231; 6.BI.166.236; 6.BI.166.237; 6.BI.166.238; 6.BI.166.239; 6.BI.166.154; 6.BI.166.157; 6.BI.166.166; 6.BI.166.169; 6.BI.166.172; 6.BI.166.175; 6.BI.166.240; 6.BI.166.244; 6.BI.169.228; 6.BI.169.229; 6.BI.169.230; 6.BI.169.231; 6.BI.169.236; 6.BI.169.237; 6.BI.169.238; 6.BI.169.239; 6.BI.169.154; 6.BI.169.157; 6.BI.169.166; 6.BI.169.169; 6.BI.169.172; 6.BI.169.175; 6.BI.169.240; 6.BI.169.244; 6.BI.172.228; 6.BI.172.229; 6.BI.172.230; 6.BI.172.231; 6.BI.172.236; 6.BI.172.237; 6.BI.172.238; 6.BI.172.239; 6.BI.172.154; 6.BI.172.157; 6.BI.172.166; 6.BI.172.169; 6.BI.172.172; 6.BI.172.175; 6.BI.172.240; 6.BI.172.244; 6.BI.175.228; 6.BI.175.229; 6.BI.175.230; 6.BI.175.231; 6.BI.175.236; 6.BI.175.237; 6.BI.175.238; 6.BI.175.239; 6.BI.175.154; 6.BI.175.157; 6.BI.175.166; 6.BI.175.169; 6.BI.175.172; 6.BI.175.175; 6.BI.175.240; 6.BI.175.244; 6.BI.240.228; 6.BI.240.229; 6.BI.240.230; 6.BI.240.231; 6.BI.240.236; 6.BI.240.237; 6.BI.240.238; 6.BI.240.239; 6.BI.240.154; 6.BI.240.157; 6.BI.240.166; 6.BI.240.169; 6.BI.240.172; 6.BI.240.175; 6.BI.240.240; 6.BI.240.244; 6.BI.244.228; 6.BI.244.229; 6.BI.244.230; 6.BI.244.231; 6.BI.244.236; 6.BI.244.237; 6.BI.244.238; 6.BI.244.239; 6.BI.244.154; 6.BI.244.157; 6.BI.244.166; 6.BI.244.169; 6.BI.244.172; 6.BI.244.175; 6.BI.244.240; 6.BI.244.244;

Prodrugs of 6.1

6.1.228.228; 6.1.228.229; 6.1.228.230; 6.1.228.231; 6.1.228.236; 6.1.228.237; 6.1.228.238; 6.1.228.239; 6.1.228.154; 6.1.228.157; 6.1.228.166; 6.1.228.169; 6.1.228.172; 6.1.228.175; 6.1.228.240; 6.1.228.244; 6.1.229.228; 6.1.229.229; 6.1.229.230; 6.1.229.231; 6.1.229.236; 6.1.229.237; 6.1.229.238; 6.1.229.239; 6.1.229.154; 6.1.229.157; 6.1.229.166; 6.1.229.169; 6.1.229.172; 6.1.229.175; 6.1.229.240; 6.1.229.244; 6.1.230.228; 6.1.230.229; 6.1.230.230; 6.1.230.231; 6.1.230.236; 6.1.230.237; 6.1.230.238; 6.1.230.239; 6.1.230.154; 6.1.230.157; 6.1.230.166; 6.1.230.169; 6.1.230.172; 6.1.230.175; 6.1.230.240; 6.1.230.244; 6.1.231.228; 6.1.231.229; 6.1.231.230; 6.1.231.231; 6.1.231.236; 6.1.231.237; 6.1.231.238; 6.1.231.239; 6.1.231.154; 6.1.231.157; 6.1.231.166; 6.1.231.169; 6.1.231.172; 6.1.231.175; 6.1.231.240; 6.1.231.244; 6.1.236.228; 6.1.236.229; 6.1.236.230; 6.1.236.231; 6.1.236.236; 6.1.236.237; 6.1.236.238; 6.1.236.239; 6.1.236.154; 6.1.236.157; 6.1.236.166; 6.1.236.169; 6.1.236.172; 6.1.236.175; 6.1.236.240; 6.1.236.244; 6.1.237.228; 6.1.237.229; 6.1.237.230; 6.1.237.231; 6.1.237.236; 6.1.237.237; 6.1.237.238; 6.1.237.239; 6.1.237.154; 6.1.237.157; 6.1.237.166; 6.1.237.169; 6.1.237.172; 6.1.237.175; 6.1.237.240; 6.1.237.244; 6.1.238.228; 6.1.238.229; 6.1.238.230; 6.1.238.231; 6.1.238.236; 6.1.238.237; 6.1.238.238; 6.1.238.239; 6.1.238.154; 6.1.238.157; 6.1.238.166; 6.1.238.169; 6.1.238.172; 6.1.238.175; 6.1.238.240; 6.1.238.244; 6.1.239.228; 6.1.239.229; 6.1.239.230; 6.1.239.231; 6.1.239.236; 6.1.239.237; 6.1.239.238; 6.1.239.239; 6.1.239.154; 6.1.239.157; 6.1.239.166; 6.1.239.169; 6.1.239.172;

6.1.239.175; 6.1.239.240; 6.1.239.244; 6.1.154.228; 6.1.154.229; 6.1.154.230; 6.1.154.231; 6.1.154.236; 6.1.154.237; 6.1.154.238; 6.1.154.239; 6.1.154.154; 6.1.154.157; 6.1.154.166; 6.1.154.169; 6.1.154.172; 6.1.154.175; 6.1.154.240; 6.1.154.244; 6.1.157.228; 6.1.157.229; 6.1.157.230; 6.1.157.231; 6.1.157.236; 6.1.157.237; 6.1.157.238; 6.1.157.239; 6.1.157.154; 6.1.157.157; 6.1.157.166; 6.1.157.169; 6.1.157.172; 6.1.157.175; 6.1.157.240; 6.1.157.244; 6.1.166.228; 6.1.166.229; 6.1.166.230; 6.1.166.231; 6.1.166.236; 6.1.166.237; 6.1.166.238; 6.1.166.239; 6.1.166.154; 6.1.166.157; 6.1.166.166; 6.1.166.169; 6.1.166.172; 6.1.166.175; 6.1.166.240; 6.1.166.244; 6.1.169.228; 6.1.169.229; 6.1.169.230; 6.1.169.231; 6.1.169.236; 6.1.169.237; 6.1.169.238; 6.1.169.239; 6.1.169.154; 6.1.169.157; 6.1.169.166; 6.1.169.169; 6.1.169.172; 6.1.169.175; 6.1.169.240; 6.1.169.244; 6.1.172.228; 6.1.172.229; 6.1.172.230; 6.1.172.231; 6.1.172.236; 6.1.172.237; 6.1.172.238; 6.1.172.239; 6.1.172.154; 6.1.172.157; 6.1.172.166; 6.1.172.169; 6.1.172.172; 6.1.172.175; 6.1.172.240; 6.1.172.244; 6.1.175.228; 6.1.175.229; 6.1.175.230; 6.1.175.231; 6.1.175.236; 6.1.175.237; 6.1.175.238; 6.1.175.239; 6.1.175.154; 6.1.175.157; 6.1.175.166; 6.1.175.169; 6.1.175.172; 6.1.175.175; 6.1.175.240; 6.1.175.244; 6.1.240.228; 6.1.240.229; 6.1.240.230; 6.1.240.231; 6.1.240.236; 6.1.240.237; 6.1.240.238; 6.1.240.239; 6.1.240.154; 6.1.240.157; 6.1.240.166; 6.1.240.169; 6.1.240.172; 6.1.240.175; 6.1.240.240; 6.1.240.244; 6.1.244.228; 6.1.244.229; 6.1.244.230; 6.1.244.231; 6.1.244.236; 6.1.244.237; 6.1.244.238; 6.1.244.239; 6.1.244.154; 6.1.244.157; 6.1.244.166; 6.1.244.169; 6.1.244.172; 6.1.244.175; 6.1.244.240; 6.1.244.244;

Prodrugs of 6.T

6.J.228.228; 6.J.228.229; 6.J.228.230; 6.J.228.231; 6.J.228.236; 6.J.228.237; 6.J.228.238; 6.J.228.239; 6.J.228.154; 6.J.228.157; 6.J.228.166; 6.J.228.169; 6.J.228.172; 6.J.228.175; 6.J.228.240; 6.J.228.244; 6.J.229.228; 6.J.229.229; 6J.229.230; 6.J.229.231; 6J.229.236; 6J.229.237; 6.J.229.238; 6.J.229.239; 6J.229.154; 6J.229.157; 6.J.229.166; 6J.229.169; 6J.229.172; 6J.229.175; 6 J.229.240; 6 J.229.244; 6J.230.228; 6J.230.229; 6J.230.230; 6J.230.231; 6J.230.236; 6J.230.237; 6.J.230.238; 6J.230.239; 6J.230.154; 6J.230.157; 6J.230.166; 6J.230.169; 6J.230.172; 6.J.230.175; 6J.230.240; 6J.230.244; 6J.231.228; 6J.231.229; 6J.231.230; 6J.231.231; 6J.231.236; 6J.231.237; 6J.231.238; 6.J.231.239; 6J.231.154; 6J.231.157; 6J.231.166; 6J.231.169; 6.J.231.172; 6J.231.175; 6.J.231.240; 6J.231.244; 6J.236.228; 6J.236.229; 6J.236.230; 6J.236.231; 6J.236.236; 6 J.236.237; 6 J.236.238; 6J.236.239; 6.J.236.154; 6J.236.157; 6J.236.166; 6J.236.169; 6J.236.172; 6J.236.175; 6J.236.240; 6.J.236.244; 6J.237.228; 6J.237.229; 6J.237.230; 6J.237.231; 6J.237.236; 6J.237.237; 6.J.237.238; 6J.237.239; 6J.237.154; 6J.237.157; 6J.237.166; 6J.237.169; 6J.237.172; 6J.237.175; 6.J.237.240; 6J.237.244; 6J.238.228; 6.J.238.229; 6J.238.230; 6J.238.231; 6J.238.236; 6.J.238.237; 6J.238.238; 6J.238.239; 6J.238.154; 6.J.238.157; 6J.238.166; 6J.238.169; 6 J.238.172; 6J.238.175; 6J.238.240; 6 J.238.244; 6.J.239.228; 6J.239.229; 6J.239.230; 6 J.239.231; 6 J.239.236; 6 J.239.237; 6J.239.238; 6J.239.239; 6.J.239.154; 6J.239.157; 6J.239.166; 6.J.239.169; 6 J.239.172; 6J.239.175; 6J.239.240; 6J.239.244; 6.J.154.228; 6J.154.229; 6J.154.230; 6J.154.231; 6J.154.236; 6J.154.237; 6J.154.238; 6J.154.239; 6J.154.154; 6J.154.157; 6.J.154.166; 6J.154.169; 6J.154.172; 6J.154.175; 6J.154.240; 6J.154.244; 6J.157.228; 6J.157.229; 6J.157.230; 6J.157.231; 6 J.157.236; 6J.157.237; 6J.157.238; 6J.157.239; 6J.157.154; 6J.157.157; 6J.157.166; 6 J.157.169; 6.J.157.172; 6J.157.175; 6J.157.240; 6J.157.244; 6J.166.228; 6 J.166.229; 6J.166.230; 6.J.166.231; 6 J.166.236; 6J.166.237; 6J.166.238; 6J.166.239; 6J.166.154; 6J.166.157; 6J.166.166; 6.J.166.169; 6J.166.172; 6 J.166.175;

6.J.166.240; 6.J.166.244; 6.J.169.228; 6.J.169.229; 6.J.169.230; 6.J.169.231; 6J.169.236; 6.J.169.237; 6.J.169.238; 6.J.169.239; 6.J.169.154; 6J.169.157; 6.J.169.166; 6.J.169.169; 6.J.169.172; 6J.169.175; 6J.169.240; 6J.169.244; 6J.172.228; 6 J.172.229; 6J.172.230; 6J.172.231; 6.J.172.236; 6J.172.237; 6J.172.238; 6J.172.239; 6.J.172.154; 6J.172.157; 6J.172.166; 6J.172.169; 6J.172.172; 6J.172.175; 6 J.172.240; 6J.172.244; 6J.175.228; 6J.175.229; 6J.175.230; 6J.175.231; 6J.175.236; 6J.175.237; 6J.175.238; 6 J.175.239; 6J.175.154; 6J.175.157; 6J.175.166; 6J.175.169; 6.J.175.172; 6J.175.175; 6J.175.240; 6J.175.244; 6J.240.228; 6J.240.229; 6J.240.230; 6J.240.231; 6J.240.236; 6 J.240.237; 6J.240.238; 6J.240.239; 6J.240.154; 6J.240.157; 6J.240.166; 6J.240.169; 6J.240.172; 6J.240.175; 6J.240.240; 6J.240.244; 6J.244.228; 6J.244.229; 6.J.244.230; 6 J.244.231; 6J.244.236; 6J.244.237; 6J.244.238; 6J.244.239; 6J.244.154; 6.J.244.157; 6J.244.166; 6J.244.169; 6J.244.172; 6J.244.175; 6J.244.240; 6J.244.244;

Prodrugs of 6.L

6.L.228.228; 6.L.228.229; 6.L.228.230; 6.L.228.231; 6.L.228.236; 6.L.228.237; 6.L.228.238; 6.L.228.239; 6.L.228.154; 6.L.228.157; 6.L.228.166; 6.L.228.169; 6.L.228.172; 6.L.228.175; 6.L.228.240; 6.L.228.244; 6.L.229.228; 6.L.229.229; 6.L.229.230; 6.L.229.231; 6.L.229.236; 6.L.229.237; 6.L.229.238; 6.L.229.239; 6.L.229.154; 6.L.229.157; 6.L.229.166; 6.L.229.169; 6.L.229.172; 6.L.229.175; 6.L.229.240; 6.L.229.244; 6.L.230.228; 6.L.230.229; 6.L.230.230; 6.L.230.231; 6.L.230.236; 6.L.230.237; 6.L.230.238; 6.L.230.239; 6.L.230.154; 6.L.230.157; 6.L.230.166; 6.L.230.169; 6.L.230.172; 6.L.230.175; 6.L.230.240; 6.L.230.244; 6.L.231.228; 6.L.231.229; 6.L.231.230; 6.L.231.231; 6.L.231.236; 6.L.231.237; 6.L.231.238; 6.L.231.239; 6.L.231.154; 6.L.231.157; 6.L.231.166; 6.L.231.169; 6.L.231.172; 6.L.231.175; 6.L.231.240; 6.L.231.244; 6.L.236.228; 6.L.236.229; 6.L.236.230; 6.L.236.231; 6.L.236.236; 6.L.236.237; 6.L.236.238; 6.L.236.239; 6.L.236.154; 6.L.236.157; 6.L.236.166; 6.L.236.169; 6.L.236.172; 6.L.236.175; 6.L.236.240; 6.L.236.244; 6.L.237.228; 6.L.237.229; 6.L.237.230; 6.L.237.231; 6.L.237.236; 6.L.237.237; 6.L.237.238; 6.L.237.239; 6.L.237.154; 6.L.237.157; 6.L.237.166; 6.L.237.169; 6.L.237.172; 6.L.237.175; 6.L.237.240; 6.L.237.244; 6.L.238.228; 6.L.238.229; 6.L.238.230; 6.L.238.231; 6.L.238.236; 6.L.238.237; 6.L.238.238; 6.L.238.239; 6.L.238.154; 6.L.238.157; 6.L.238.166; 6.L.238.169; 6.L.238.172; 6.L.238.175; 6.L.238.240; 6.L.238.244; 6.L.239.228; 6.L.239.229; 6.L.239.230; 6.L.239.231; 6.L.239.236; 6.L.239.237; 6.L.239.238; 6.L.239.239; 6.L.239.154; 6.L.239.157; 6.L.239.166; 6.L.239.169; 6.L.239.172; 6.L.239.175; 6.L.239.240; 6.L.239.244; 6.L.154.228; 6.L.154.229; 6.L.154.230; 6.L.154.231; 6.L.154.236; 6.L.154.237; 6.L.154.238; 6.L.154.239; 6.L.154.154; 6.L.154.157; 6.L.154.166; 6.L.154.169; 6.L.154.172; 6.L.154.175; 6.L.154.240; 6.L.154.244; 6.L.157.228; 6.L.157.229; 6.L.157.230; 6.L.157.231; 6.L.157.236; 6.L.157.237; 6.L.157.238; 6.L.157.239; 6.L.157.154; 6.L.157.157; 6.L.157.166; 6.L.157.169; 6.L.157.172; 6.L.157.175; 6.L.157.240; 6.L.157.244; 6.L.166.228; 6.L.166.229; 6.L.166.230; 6.L.166.231; 6.L.166.236; 6.L.166.237; 6.L.166.238; 6.L.166.239; 6.L.166.154; 6. ^~ L.l(>b.\57; 6.L.166.166; 6.L.166.169; 6.L.166.172; 6.L.166.175; 6.L.166.240; 6.L.166.244; 6.L.169.228; 6.L.169.229; 6.L.169.230; 6.L.169.231; 6.L.169.236; 6.L.169.237; 6.L.169.238; 6.L.169.239; 6.L.169.154; 6.L.169.157; 6.L.169.166; 6.L.169.169; 6.L.169.172; 6.L.169.175; 6.L.169.240; 6.L.169.244;

6.L.172.228; 6.L.172.229; 6.L.172.230; 6.L.172.231; 6.L.172.236; 6.L.172.237; 6.L.172.238; 6.L.172.239; 6.L.172.154; 6.L.172.157; 6.L.172.166; 6.L.172.169; 6.L.172.172; 6.L.172.175; 6.L.172.240; 6.L.172.244; 6.L.175.228; 6.L.175.229; 6.L.175.230; 6.L.175.231; 6.L.175.236; 6.L.175.237; 6.L.175.238; 6.L.175.239; 6.L.175.154; 6.L.175.157; 6.L.175.166; 6.L.175.169; 6.L.175.172; 6.L.175.175; 6.L.175.240; 6.L.175.244; 6.L.240.228; 6.L.240.229; 6.L.240.230; 6.L.240.231; 6.L.240.236; 6.L.240.237; 6.L.240.238; 6.L.240.239; 6.L.240.154; 6.L.240.157; 6.L.240.166; 6.L.240.169; 6.L.240.172; 6.L.240.175; 6.L.240.240; 6.L.240.244; 6.L.244.228; 6.L.244.229; 6.L.244.230; 6.L.244.231; 6.L.244.236; 6.L.244.237; 6.L.244.238; 6.L.244.239; 6.L.244.154; 6.L.244.157; 6.L.244.166; 6.L.244.169; 6.L.244.172; 6.L.244.175; 6.L.244.240; 6.L.244.244;

Prodrugs of 6.O

6.O.228.228; 6.O.228.229; 6.O.228.230; 6.O.228.231; 6.O.228.236; 6.O.228.237; 6.O.228.238; 6.O.228.239; 6.O.228.154; 6.O.228.157; 6.O.228.166; 6.O.228.169; 6.O.228.172; 6.O.228.175; 6.O.228.240; 6.O.228.244; 6.O.229.228; 6.O.229.229; 6.O.229.230; 6.O.229.231; 6.O.229.236; 6.O.229.237; 6.O.229.238; 6.O.229.239; 6.O.229.154; 6.O.229.157; 6.O.229.166; 6.O.229.169; 6.O.229.172; 6.O.229.175; 6.O.229.240; 6.O.229.244; 6.O.230.228; 6.O.230.229; 6.O.230.230; 6.O.230.231; 6.O.230.236; 6.O.230.237; 6.O.230.238; 6.O.230.239; 6.O.230.154; 6.O.230.157; 6.O.230.166; 6.O.230.169; 6.O.230.172; 6.O.230.175; 6.O.230.240; 6.O.230.244; 6.O.231.228; 6.O.231.229; 6.O.231.230; 6.O.231.231; 6.O.231.236; 6.O.231.237; 6.O.231.238; 6.O.231.239; 6.O.231.154; 6.O.231.157; 6.O.231.166; 6.O.231.169; 6.O.231.172; 6.O.231.175; 6.O.231.240; 6.O.231.244; 6.O.236.228; 6.O.236.229; 6.O.236.230; 6.O.236.231; 6.O.236.236; 6.O.236.237; 6.O.236.238; 6.O.236.239; 6.O.236.154; 6.O.236.157; 6.O.236.166; 6.O.236.169; 6.O.236.172; 6.O.236.175; 6.O.236.240; 6.O.236.244; 6.O.237.228; 6.O.237.229; 6.O.237.230; 6.O.237.231; 6.O.237.236; 6.O.237.237; 6.O.237.238; 6.O.237.239; 6.O.237.154; 6.O.237.157; 6.O.237.166; 6.O.237.169; 6.O.237.172; 6.O.237.175; 6.O.237.240; 6.O.237.244; 6.O.238.228; 6.O.238.229; 6.O.238.230; 6.O.238.231; 6.O.238.236; 6.O.238.237; 6.O.238.238; 6.O.238.239; 6.O.238.154; 6.O.238.157; 6.O.238.166; 6.O.238.169; 6.O.238.172; 6.O.238.175; 6.O.238.240; 6.O.238.244; 6.O.239.228; 6.O.239.229; 6.O.239.230; 6.O.239.231; 6.O.239.236; 6.O.239.237; 6.O.239.238; 6.O.239.239; 6.O.239.154; 6.O.239.157; 6.O.239.166; 6.O.239.169; 6.O.239.172; 6.O.239.175; 6.O.239.240; 6.O.239.244; 6.O.154.228; 6.O.154.229; 6.O.154.230; 6.O.154.231; 6.O.154.236; 6.O.154.237; 6.O.154.238; 6.O.154.239; 6.O.154.154; 6.O.154.157; 6.O.154.166; 6.O.154.169; 6.O.154.172; 6.O.154.175; 6.O.154.240; 6.O.154.244; 6.O.157.228; 6.O.157.229; 6.O.157.230; 6.O.157.231; 6.O.157.236; 6.O.157.237; 6.O.157.238; 6.O.157.239; 6.O.157.154; 6.O.157.157; 6.O.157.166; 6.O.157.169; 6.O.157.172; 6.O.157.175; 6.O.157.240; 6.O.157.244; 6.O.166.228; 6.O.166.229; 6.O.166.230; 6.O.166.231; 6.O.166.236; 6.O.166.237; 6.O.166.238; 6.O.166.239; 6.O.166.154; 6.O.166.157; 6.O.166.166; 6.O.166.169; 6.O.166.172; 6.O.166.175; 6.O.166.240; 6.O.166.244; 6.O.169.228; 6.O.169.229; 6.O.169.230; 6.O.169.231; 6.O.169.236; 6.O.169.237; 6.O.169.238; 6.O.169.239; 6.O.169.154; 6.O.169.157; 6.O.169.166; 6.O.169.169; 6.O.169.172; 6.O.169.175; 6.O.169.240; 6.O.169.244; 6.O.172.228; 6.O.172.229; 6.O.172.230; 6.O.172.231; 6.O.172.236; 6.O.172.237;

6.O.172.238; 6.O.172.239; 6.O.172.154; 6.O.172.157; 6.O.172.166; 6.O.172.169; 6.O.172.172; 6.O.172.175; 6.O.172.240; 6.O.172.244; 6.O.175.228; 6.O.175.229; 6.O.175.230; 6.O.175.231; 6.O.175.236; 6.O.175.237; 6.O.175.238; 6.O.175.239; 6.O.175.154; 6.O.175.157; 6.O.175.166; 6.O.175.169; 6.O.175.172; 6.O.175.175; 6.O.175.240; 6.O.175.244; 6.O.240.228; 6.O.240.229; 6.O.240.230; 6.O.240.231; 6.O.240.236; 6.O.240.237; 6.O.240.238; 6.O.240.239; 6.O.240.154; 6.O.240.157; 6.O.240.166; 6.O.240.169; 6.O.240.172; 6.O.240.175; 6.O.240.240; 6.O.240.244; 6.O.244.228; 6.O.244.229; 6.O.244.230; 6.O.244.231; 6.O.244.236; 6.O.244.237; 6.O.244.238; 6.O.244.239; 6.O.244.154; 6.O.244.157; 6.O.244.166; 6.O.244.169; 6.O.244.172; 6.O.244.175; 6.O.244.240; 6.O.244.244;

Prodrugs of 6.P

6.P.228.228; 6.P.228.229; 6.P.228.230; 6.P.228.231; 6.P.228.236; 6.P.228.237; 6.P.228.238; 6.P.228.239; 6.P.228.154; 6.P.228.157; 6.P.228.166; 6.P.228.169; 6.P.228.172; 6.P.228.175; 6.P.228.240; 6.P.228.244; 6.P.229.228; 6.P.229.229; 6.P.229.230; 6.P.229.231; 6.P.229.236; 6.P.229.237; 6.P.229.238; 6.P.229.239; 6.P.229.154; 6.P.229.157; 6.P.229.166; 6.P.229.169; 6.P.229.172; 6.P.229.175; 6.P.229.240; 6.P.229.244; 6.P.230.228; 6.P.230.229; 6.P.230.230; 6.P.230.231; 6.P.230.236; 6.P.230.237; 6.P.230.238; 6.P.230.239; 6.P.230.154; 6.P.230.157; 6.P.230.166; 6.P.230.169; 6.P.230.172; 6.P.230.175; 6.P.230.240; 6.P.230.244; 6.P.231.228; 6.P.231.229; 6.P.231.230; 6.P.231.231; 6.P.231.236; 6.P.231.237; 6.P.231.238; 6.P.231.239; 6.P.231.154; 6.P.231.157; 6.P.231.166; 6.P.231.169; 6.P.231.172; 6.P.231.175; 6.P.231.240; 6.P.231.244; 6.P.236.228; 6.P.236.229; 6.P.236.230; 6.P.236.231; 6.P.236.236; 6.P.236.237; 6.P.236.238; 6.P.236.239; 6.P.236.154; 6.P.236.157; 6.P.236.166; 6.P.236.169; 6.P.236.172; 6.P.236.175; 6.P.236.240; 6.P.236.244; 6.P.237.228; 6.P.237.229; 6.P.237.230; 6.P.237.231; 6.P.237.236; 6.P.237.237; 6.P.237.238; 6.P.237.239; 6.P.237.154; 6.P.237.157; 6.P.237.166; 6.P.237.169; 6.P.237.172; 6.P.237.175; 6.P.237.240; 6.P.237.244; 6.P.238.228; 6.P.238.229; 6.P.238.230; 6.P.238.231; 6.P.238.236; 6.P.238.237; 6.P.238.238; 6.P.238.239; 6.P.238.154; 6.P.238.157; 6.P.238.166; 6.P.238.169; 6.P.238.172; 6.P.238.175; 6.P.238.240; 6.P.238.244; 6.P.239.228; 6.P.239.229; 6.P.239.230; 6.P.239.231; 6.P.239.236; 6.P.239.237; 6.P.239.238; 6.P.239.239; 6.P.239.154; 6.P.239.157; 6.P.239.166; 6.P.239.169; 6.P.239.172; 6.P.239.175; 6.P.239.240; 6.P.239.244; 6.P.154.228; 6.P.154.229; 6.P.154.230; 6.P.154.231; 6.P.154.236; 6.P.154.237; 6.P.154.238; 6.P.154.239; 6.P.154.154; 6.P.154.157; 6.P.154.166; 6.P.154.169; 6.P.154.172; 6.P.154.175; 6.P.154.240; 6.P.154.244; 6.P.157.228; 6.P.157.229; 6.P.157.230; 6.P.157.231; 6.P.157.236; 6.P.157.237; 6.P.157.238; 6.P.157.239; 6.P.157.154; 6.P.157.157; 6.P.157.166; 6.P.157.169; 6.P.157.172; 6.P.157.175; 6.P.157.240; 6.P.157.244; 6.P.166.228; 6.P.166.229; 6.P.166.230; 6.P.166.231; 6.P.166.236; 6.P.166.237; 6.P.166.238; 6.P.166.239; 6.P.166.154; 6.P.166.157; 6.P.166.166; 6.P.166.169; 6.P.166.172; 6.P.166.175; 6.P.166.240; 6.P.166.244; 6.P.169.228; 6.P.169.229; 6.P.169.230; 6.P.169.231; 6.P.169.236; 6.P.169.237; 6.P.169.238; 6.P.169.239; 6.P.169.154; 6.P.169.157; 6.P.169.166; 6.P.169.169; 6.P.169.172; 6.P.169.175; 6.P.169.240; 6.P.169.244; 6.P.172.228; 6.P.172.229; 6.P.172.230; 6.P.172.231; 6.P.172.236; 6.P.172.237; 6.P.172.238; 6.P.172.239; 6.P.172.154; 6.P.172.157; 6.P.172.166; 6.P.172.169;

6.P.172.172; 6, .P.172.175; 6.P.172.240; 6.P.172.244; 6.P.175.228; 6.P.175.229; 6.P.175.230; 6.P.175.231; 6.P.175.236; 6.P.175.237; 6.P.175.238; 6.P.175.239; 6.P.175.154; 6.P.175.157; 6.P.175.166; 6.P.175.169; 6.?.175.172; 6.P.175.175; 6.P.175.240; 6.P.175.244; 6.P.240.228; 6.P.240.229; 6.P.240.230; 6.P.240.231; 6.P.240.236; 6.P.240.237; 6.P.240.238; 6.P.240.239; 6.P.240.154; 6.P.240.157; 6.P.240.166; 6.P.240.169; 6.P.240.172; 6.P.240.175; 6.P.240.240; 6.P.240.244; 6.P.244.228; 6.P.244.229; 6.P.244.230; 6.P.244.231; 6.P.244.236; 6.P.244.237; 6.P.244.238; 6.P.244.239; 6.P.244.154; 6.P.244.157; 6.P.244.166; 6.P.244.169; 6.P.244.172; 6.P.244.175; 6.P.244.240; 6.P.244.244;

Prodrugs of 6.U

6.U.228.228; 6.U.228.229; 6.U.228.230; 6.U.228.231; 6.U.228.236; 6.U.228.237; 6.U.228.238; 6.U.228.239; 6.U.228.154; 6.U.228.157; 6.U.228.166; 6.U.228.169; 6.U.228.172; 6.U.228.175; 6.U.228.240; 6.U.228.244; 6.U.229.228; 6.U.229.229; 6.U.229.230; 6.U.229.231; 6.U.229.236; 6.U.229.237; 6.U.229.238; 6.U.229.239; 6.U.229.154; 6.U.229.157; 6.U.229.166; 6.U.229.169; 6.U.229.172; 6.U.229.175; 6.U.229.240; 6.U.229.244; 6.U.230.228; 6.U.230.229; 6.U.230.230; 6.U.230.231; 6.U.230.236; 6.U.230.237; 6.U.230.238; 6.U.230.239; 6.U.230.154; 6.U.230.157; 6.U.230.166; 6.U.230.169; 6.U.230.172; 6.U.230.175; 6.U.230.240; 6.U.230.244; 6.U.231.228; 6.U.231.229; 6.U.231.230; 6.U.231.231; 6.U.231.236; 6.U.231.237; 6.U.231.238; 6.U.231.239; 6.U.231.154; 6.U.231.157; 6.U.231.166; 6.U.231.169; 6.U.231.172; 6.U.231.175; 6.U.231.240; 6.U.231.244; 6.U.236.228; 6.U.236.229; 6.U.236.230; 6.U.236.231; 6.U.236.236; 6.U.236.237; 6.U.236.238; 6.U.236.239; 6.U.236.154; 6.U.236.157; 6.U.236.166; 6.U.236.169; 6.U.236.172; 6.U.236.175; 6.U.236.240; 6.U.236.244; 6.U.237.228; 6.U.237.229; 6.U.237.230; 6.U.237.231; 6.U.237.236; 6.U.237.237; 6.U.237.238; 6.U.237.239; 6.U.237.154; 6.U.237.157; 6.U.237.166; 6.U.237.169; 6.U.237.172; 6.U.237.175; 6.U.237.240; 6.U.237.244; 6.U.238.228; 6.U.238.229; 6.U.238.230; 6.U.238.231; 6.U.238.236; 6.U.238.237; 6.U.238.238; 6.U.238.239; 6.U.238.154; 6.U.238.157; 6.U.238.166; 6.U.238.169; 6.U.238.172; 6.U.238.175; 6.U.238.240; 6.U.238.244; 6.U.239.228; 6.U.239.229; 6.U.239.230; 6.U.239.231; 6.U.239.236; 6.U.239.237; 6.U.239.238; 6.U.239.239; 6.U.239.154; 6.U.239.157; 6.U.239.166; 6.U.239.169; 6.U.239.172; 6.U.239.175; 6.U.239.240; 6.U.239.244; 6.U.154.228; 6.U.154.229; 6.U.154.230; 6.U.154.231; 6.U.154.236; 6.U.154.237; 6.U.154.238; 6.U.154.239; 6.U.154.154; 6.U.154.157; 6.U.154.166; 6.U.154.169; 6.U.154.172; 6.U.154.175; 6.U.154.240; 6.U.154.244; 6.U.157.228; 6.U.157.229; 6.U.157.230; 6.U.157.231; 6.U.157.236; 6.U.157.237; 6.U.157.238; 6.U.157.239; 6.U.157.154; 6.U.157.157; 6.U.157.166; 6.U.157.169; 6.U.157.172; 6.U.157.175; 6.U.157.240; 6.U.157.244; 6.U.166.228; 6.U.166.229; 6.U.166.230; 6.U.166.231; 6.U.166.236; 6.U.166.237; 6.U.166.238; 6.U.166.239; 6.U.166.154; 6.U.166.157; 6.U.166.166; 6.U.166.169; 6.U .166.172; 6.U.166.175; 6.U.166.240; 6.U.166.244; 6.U.169.228; 6.U.169.229; 6.U.169.230; 6.U.169.231; 6.U.169.236; 6.U.169.237; 6.U.169.238; 6.U.169.239; 6.U.169.154; 6.U.169.157; 6.U.169.166; 6.U.169.169; 6.U.169.172; 6.U.169.175; 6.U.169.240; 6.U.169.244; 6.U.172.228; 6.U.172.229; 6.U.172.230; 6.U.172.231; 6. \J .172.236; 6.U.172.237; 6.U.172.238; 6.U.172.239; 6.U.172.154; 6.U.172.157; 6.U.172.166; 6.U.172.169; 6.U.172.172; 6.U.172.175; 6.U.172.240; 6.U.172.244; 6.U.175.228; 6.U.175.229;

6.U.175.230; 6.U.175.231; 6.U.175.236; 6.U.175.237; 6.U.175.238; 6.U.175.239; 6.U.175.154; 6.U.175.157; 6.U.175.166; 6.U.175.169; 6.U.175.172; 6.U.175.175; 6.U.175.240; 6.U.175.244; 6.U.240.228; 6.U.240.229; 6.U.240.230; 6.U.240.231; 6.U.240.236; 6.U.240.237; 6.U.240.238; 6.U.24Q.239; 6.U.240.154; 6.U.240.157; 6.U.240.166; 6.U.240.169; 6.U.240.172; 6.U.240.175; 6.U.240.240; 6.U.240.244; 6.U.244.228; 6.U.244.229; 6.U.244.230; 6.U.244.231; 6.U.244.236; 6.U.244.237; 6.U.244.238; 6.U.244.239; 6.U.244.154; 6.U.244.157; 6.U.244.166; 6.U.244.169; 6.U.244.172; 6.U.244.175; 6.U.244.240; 6.U.244.244;

Prodrugs of 6.CD

6.CD.228.228; 6.CD.228.229; 6.CD.228.230; 6.CD.228.231; 6.CD.228.236; 6.CD.228.237; 6.CD.228.238; 6.CD.228.239; 6.CD.228.154; 6.CD.228.157; 6.CD.228.166; 6.CD.228.169; 6.CD.228.172; 6.CD.228.175; 6.CD.228.240; 6.CD.228.244; 6.CD.229.228; 6.CD.229.229; 6.CD.229.230; 6.CD.229.231; 6.CD.229.236; 6.CD.229.237; 6.CD.229.238; 6.CD.229.239; 6.CD.229.154; 6.CD.229.157; 6.CD.229.166; 6.CD.229.169; 6.CD.229.172; 6.CD.229.175; 6.CD.229.240; 6.CD.229.244; 6.CD.230.228; 6.CD.230.229; 6.CD.230.230; 6.CD.230.231; 6.CD.230.236; 6.CD.230.237; 6.CD.230.238; 6.CD.230.239; 6.CD.230.154; 6.CD.230.157; 6.CD.230.166; 6.CD.230.169; 6.CD.230.172; 6.CD.230.175; 6.CD.230.240; 6.CD.230.244; 6.CD.231.228; 6.CD.231.229; 6.CD.231.230; 6.CD.231.231; 6.CD.231.236; 6.CD.231.237; 6.CD.231.238; 6.CD.231.239; 6.CD.231.154; 6.CD.231.157; 6.CD.231.166; 6.CD.231.169; 6.CD.231.172; 6.CD.231.175; 6.CD.231.240; 6.CD.231.244; 6.CD.236.228; 6.CD.236.229; 6.CD.236.230; 6.CD.236.231; 6.CD.236.236; 6.CD.236.237; 6.CD.236.238; 6.CD.236.239; 6.CD.236.154; 6.CD.236.157; 6.CD.236.166; 6.CD.236.169; 6.CD.236.172; 6.CD.236.175; 6.CD.236.24Q; 6.CD.236.244; 6.CD.237.228; 6.CD.237.229; 6.CD.237.230; 6.CD.237.231; 6.CD.237.236; 6.CD.237.237; 6.CD.237.238; 6.CD.237.239; 6.CD.237.154; 6.CD.237.157; 6.CD.237.166; 6.CD.237.169; 6.CD.237.172; 6.CD.237.175; 6.CD.237.240; 6.CD.237.244; 6.CD.238.228; 6.CD.238.229; 6.CD.238.230; 6.CD.238.231; 6.CD.238.236; 6.CD.238.237; 6.CD.238.238; 6.CD.238.239; 6.CD.238.154; 6.CD.238.157; 6.CD.238.166; 6.CD.238.169; 6.CD.238.172; 6.CD.238.175; 6.CD.238.240; 6.CD.238.244; 6.CD.239.228; 6.CD.239.229; 6.CD.239.230; 6.CD.239.231; 6.CD.239.236; 6.CD.239.237; 6.CD.239.238; 6.CD.239.239; 6.CD.239.154; 6.CD.239.157; 6.CD.239.166; 6.CD.239.169; 6.CD.239.172; 6.CD.239.175; 6.CD.239.240; 6.CD.239.244; 6.CD.154.228; 6.CD.154.229; 6.CD.154.230; 6.CD.154.231; 6.CD.154.236; 6.CD.154.237; 6.CD.154.238; 6.CD.154.239; 6.CD.154.154; 6.CD.154.157; 6.CD.154.166; 6.CD.154.169; 6.CD.154.172; 6.CD.154.175; 6.CD.154.240; 6.CD.154.244; 6.CD.157.228; 6.CD.157.229; 6.CD.157.230; 6.CD.157.231; 6.CD.157.236; 6.CD.157.237; 6.CD.157.238; 6.CD.157.239; 6.CD.157.154; 6.CD.157.157; 6.CD.157.166; 6.CD.157.169; 6.CD.157.172; 6.CD.157.175; 6.CD.157.240; 6.CD.157.244; 6.CD.166.228; 6.CD.166.229; 6.CD.166.230; 6.CD.166.231; 6.CD.166.236; 6.CD.166.237; 6.CD.166.238; 6.CD.166.239; 6.CD.166.154; 6.CD.166.157; 6.CD.166.166; 6.CD.166.169; 6.CD.166.172; 6.CD.166.175; 6.CD.166.240; 6.CD.166.244; 6.CD.169.228; 6.CD.169.229; 6.CD.169.230; 6.CD.169.231;

6.CD.169.236; 6.CD.169.237; 6.CD.169.238; 6.CD.169.239; 6.CD.169.154; 6.CD.169.157; 6.CD.169.166; 6.CD.169.169; 6.CD.169.172; 6.CD.169.175; 6.CD.169.240; 6.CD.169.244; 6.CD.172.228; 6.CD.172.229; 6.CD.172.230; 6.CD.172.231; 6.CD.172.236; 6.CD.172.237; 6.CD.172.238; 6.CD.172.239; 6.CD.172.154; 6.CD.172.157; 6.CD.172.166; 6.CD.172.169; 6.CD.172.172; 6.CD.172.175; 6.CD.172.240; 6.CD.172.244; 6.CD.175.228; 6.CD.175.229; 6.CD.175.230; 6.CD.175.231; 6.CD.175.236; 6.CD.175.237; 6.CD.175.238; 6.CD.175.239; 6.CD.175.154; 6.CD.175.157; 6.CD.175.166; 6.CD.175.169; 6.CD.175.172; 6.CD.175.175; 6.CD.175.240; 6.CD.175.244; 6.CD.240.228; 6.CD.240.229; 6.CD.240.230; 6.CD.240.231; 6.CD.240.236; 6.CD.240.237; 6.CD.240.238; 6.CD.240.239; 6.CD.240.154; 6.CD.240.157; 6.CD.240.166; 6.CD.240.169; 6.CD.240.172; 6.CD.240.175; 6.CD.240.240; 6.CD.240.244; 6.CD.244.228; 6.CD.244.229; 6.CD.244.230; 6.CD.244.231; 6.CD.244.236; 6.CD.244.237; 6.CD.244.238; 6.CD.244.239; 6.CD.244.154; 6.CD.244.157; 6.CD.244.166; 6.CD.244.169; 6.CD.244.172; 6.CD.244.175; 6.CD.244.240; 6.CD.244.244;

Prodrugs of 6.EB

6.EB.228.228; 6.EB.228.229; 6.EB.228.230; 6.EB.228.231; 6.EB.228.236; 6.EB.228.237; 6.EB.228.238; 6.EB.228.239; 6.EB.228.154; 6.EB.228.157; 6.EB.228.166; 6.EB.228.169; 6.EB.228.172; 6.EB.228.175; 6.EB.228.240; 6.EB.228.244; 6.EB.229.228; 6.EB.229.229; 6.EB.229.230; 6.EB.229.231; 6.EB.229.236; 6.EB.229.237; 6.EB.229.238; 6.EB.229.239; 6.EB.229.154; 6.EB.229.157; 6.EB.229.166; 6.EB.229.169; 6.EB.229.172; 6.EB.229.175; 6.EB.229.240; 6.EB.229.244; 6.EB.230.228; 6.EB.230.229; 6.EB.230.230; 6.EB.230.231; 6.EB.230.236; 6.EB.230.237; 6.EB.230.238; 6.EB.230.239; 6.EB.230.154; 6.EB.230.157; 6.EB.230.166; 6.EB.230.169; 6.EB.230.172; 6.EB.230.175; 6.EB.230.240; 6.EB.230.244; 6.EB.231.228; 6.EB.231.229; 6.EB.231.230; 6.EB.231.231; 6.EB.231.236; 6.EB.231.237; 6.EB.231.238; 6.EB.231.239; 6.EB.231.154; 6.EB.231.157; 6.EB.231.166; 6.EB.231.169; 6.EB.231.172; 6.EB.231.175; 6.EB.231.240; 6.EB.231.244; 6.EB.236.228; 6.EB.236.229; 6.EB.236.230; 6.EB.236.231; 6.EB.236.236; 6.EB.236.237; 6.EB.236.238; 6.EB.236.239; 6.EB.236.154; 6.EB.236.157; 6.EB.236.166; 6.EB.236.169; 6.EB.236.172; 6.EB.236.175; 6.EB.236.240; 6.EB.236.244; 6.EB.237.228; 6.EB.237.229; 6.EB.237.230; 6.EB.237.231; 6.EB.237.236; 6.EB.237.237; 6.EB.237.238; 6.EB.237.239; 6.EB.237.154; 6.EB.237.157; 6.EB.237.166; 6.EB.237.169; 6.EB.237.172; 6.EB.237.175; 6.EB.237.240; 6.EB.237.244; 6.EB.238.228; 6.EB.238.229; 6.EB.238.230; 6.EB.238.231; 6.EB.238.236; 6.EB.238.237; 6.EB.238.238; 6.EB.238.239; 6.EB.238.154; 6.EB.238.157; 6.EB.238.166; 6.EB.238.169; 6.EB.238.172; 6.EB.238.175; 6.EB.238.240; 6.EB.238.244; 6.EB.239.228; 6.EB.239.229; 6.EB.239.230; 6.EB.239.231; 6.EB.239.236; 6.EB.239.237; 6.EB.239.238; 6.EB.239.239; 6.EB.239.154; 6.EB.239.157; 6.EB.239.166; 6.EB.239.169; 6.EB.239.172; 6.EB.239.175; 6.EB.239.240; 6.EB.239.244; 6.EB.154.228; 6.EB.154.229; 6.EB.154.230; 6.EB.154.231; 6.EB.154.236; 6.EB.154.237; 6.EB.154.238; 6.EB.154.239; 6.EB.154.154; 6.EB.154.157; 6.EB.154.166; 6.EB.154.169; 6.EB.154.172; 6.EB.154.175; 6.EB.154.240; 6.EB.154.244; 6.EB.157.228; 6.EB.157.229; 6.EB.157.230; 6.EB.157.231; 6.EB.157.236; 6.EB.157.237;

6.EB .157.238; 6.EB .157.239; 6.EB .157.154; 6.EB .157.157; 6.EB .157.166;

6.EB .157.169; 6.EB .157.172; 6.EB .157.175; 6.EB .157.240; 6.EB .157.244; 6.EB .166.228; 6.EB .166.229; 6.EB .166.230; 6.EB .166.231; 6.EB .166.236; 6.EB .166.237; 6.EB .166.238; 6.EB .166.239; 6.EB .166.154; 6.EB .166.157; 6.EB .166.166; 6.EB .166.169; 6.EB .166.172; 6.EB .166.175; 6.EB .166.240; 6.EB 166.244; 6.EB..169.228; 6.EB .169.229; 6.EB ,169.230; 6.EB .169.231; 6.EB 169.236; 6.EB.169.237; 6.EB .169.238; 6.EB ,169.239; 6.EB .169.154; 6.EB 169.157; 6.EB.169.166; 6.EB .169.169; 6.EB ,169.172; 6.EB .169.175; 6.EB 169.240; 6.EB, 169.244; 6.EB .172.228; 6.EB ,172.229; 6.EB .172.230; 6.EB.172.231; 6.EB.172.236; 6.EB .172.237; 6.EB.172.238; 6.EB .172.239; 6.EB.172.154; 6.EB.172.157; 6.EB .172.166; 6.EB.172.169; 6.EB .172.172; 6.EB.172.175; 6.EB.172.240; 6.EB .172.244; 6.EB.175.228; 6.EB .175.229; 6.EB.175.230; 6.EB.175.231; 6.EB .175.236; 6.EB.175.237; 6.EB .175.238; 6.EB.175.239; 6.EB.175.154; 6.EB ,175.157; 6.EB.175.166; 6.EB .175.169; 6.EB.175.172; 6.EB.175.175; 6.EB .175.240; 6.EB.175.244; 6.EB .240.228; 6.EB.240.229; 6.EB.240.230; 6.EB .240.231; 6.EB.240.236; 6.EB .240.237; 6.EB.240.238; 6.EB.240.239; 6.EB .240.154; 6.EB.240.157; 6.EB .240.166; 6.EB.240.169; 6.EB.240.172; 6.EB .240.175; 6.EB.240.240; 6.EB .240.244; 6.EB.244.228; 6.EB.244.229; 6.EB 244.230; 6.EB.244.231; 6.EB .244.236; 6.EB.244.237; 6.EB.244.238; 6.EB ,244.239; 6.EB.244.154; 6.EB .244.157; 6.EB.244.166; 6.EB.244.169; 6.EB ,244.172; 6.EB.244.175; 6.EB .244.240; 6.EB.244.244.

[0185] This application specifically excludes compounds disclosed in WO 2005/042556 and WO 2005/044835.

General Synthetic Methods

[0186] The compounds of this embodiments can be prepared from readily available starting materials using the following general methods and procedures. [0187] Many such techniques are well known in the art, such as those elaborated in "Compendium of Organic Synthetic Methods" (John Wiley & Sons, New York), Vol. 1, Ian T. Harrison and Shuyen Harrison, 1971; Vol. 2, Ian T. Harrison and Shuyen Harrison, 1974; Vol. 3, Louis S. Hegedus and Leroy Wade, 1977; Vol. 4, Leroy G. Wade, jr., 1980; Vol. 5, Leroy G. Wade, Jr., 1984; and Vol. 6, Michael B. Smith; as well as March, J., "Advanced Organic Chemistry, Third Edition", (John Wiley & Sons, New York, 1985), "Comprehensive Organic Synthesis. Selectivity, Strategy & Efficiency in Modern Organic Chemistry. In 9 Volumes", Barry M. Trost, Editor-in-Chief (Pergamon Press, New York, 1993 printing). It will be appreciated that where typical or preferred process conditions (i.e., reaction temperatures, times, mole ratios of reactants, solvents, pressures, etc.) are given, other process conditions can also be used

unless otherwise stated. Optimum reaction conditions may vary with the particular reactants or solvent used, but such conditions can be determined by one skilled in the art by routine optimization procedures.

[0188] Additionally, as will be apparent to those skilled in the art, conventional protecting groups may be necessary to prevent certain functional groups from undergoing undesired reactions. Suitable protecting groups for various functional groups as well as suitable conditions for protecting and deprotecting particular functional groups are well known in the art. For example, numerous protecting groups are described in T. W. Greene and G. M. Wuts, Protecting Groups in Organic Synthesis, Third Edition, Wiley, New York, 1999, and references cited therein.

[0189] Furthermore, the compounds of this embodiments contain one or more chiral centers. Accordingly, if desired, such compounds can be prepared or isolated as pure stereoisomers, i.e., as individual enantiomers or diastereomers, or as stereoisomer-enriched mixtures. All such stereoisomers (and enriched mixtures) are included within the scope of the embodiments, unless otherwise indicated. Pure stereoisomers (or enriched mixtures) may be prepared using, for example, optically active starting materials or stereoselective reagents well- known in the art. Alternatively, racemic mixtures of such compounds can be separated using, for example, chiral column chromatography, chiral resolving agents and the like.

[0190] The starting materials for the following reactions are generally known compounds or can be prepared by known procedures or obvious modifications thereof. For example, many of the starting materials are available from commercial suppliers such as Aldrich Chemical Co. (Milwaukee, Wisconsin, USA), Bachem (Torrance, California, USA), Emka-Chemce or Sigma (St. Louis, Missouri, USA). Others may be prepared by procedures, or obvious modifications thereof, described in standard reference texts such as Fieser and Fieser's Reagents for Organic Synthesis, Volumes 1-15 (John Wiley and Sons, 1991), Rodd's Chemistry of Carbon Compounds, Volumes 1-5 and Supplemental (Elsevier Science Publishers, 1989), Organic Reactions, Volumes 1-40 (John Wiley and Sons, 1991), March's Advanced Organic Chemistry, (John Wiley and Sons, 4 ^th Edition), and Larock's Comprehensive Organic Transformations (VCH

Publishers Inc., 1989). Specifically, the compounds of the embodiments may be prepared by various methods known in the art of organic chemistry in general and nucleoside and nucleotide analogue synthesis in particular. General reviews of the preparation of nucleoside and nucleotide analogues include 1) Michelson A.M. "The Chemistry of Nucleosides and Nucleotides " Academic Press, New York, 1963; 2) Goodman L. "Basic Principles in Nucleic Acid Chemistry " Academic Press, New York, 1974, vol. 1, Ch. 2; and 3) "Synthetic Procedures in Nucleic Acid Chemistry," Eds. Zorbach W. & Tipson R., Wiley, New York, 1973, vol. 1 & 2.

[0191] In each of the exemplary Schemes herein, it may be advantageous to separate reaction products from one another and/or from starting materials. The desired products of each step or series of steps is separated and/or purified (hereinafter separated) to the desired degree of homogeneity by the techniques common in the art. Typically such separations involve multiphase extraction, crystallization from a solvent or solvent mixture, distillation, sublimation, or chromatography. Chromatography can involve any number of methods including, for example, size exclusion or ion exchange chromatography, high, medium, or low pressure liquid chromatography, small scale and preparative thin or thick layer chromatography, as well as techniques of small scale thin layer and flash chromatography.

[0192] Another class of separation methods involves treatment of a mixture with a reagent selected to bind to or render otherwise separable a desired product, unreacted starting material, reaction by product, or the like. Such reagents include adsorbents or absorbents such as activated carbon, molecular sieves, ion exchange media, or the like. Alternatively, the reagents can be acids in the case of a basic material, bases in the case of an acidic material, binding reagents such as antibodies, binding proteins, selective chelators such as crown ethers, liquid/liquid ion extraction reagents (LIX), or the like.

[0193] Selection of appropriate methods of separation depends on the nature of the materials involved. For example, boiling point, and molecular weight in distillation and sublimation, presence or absence of polar functional groups in chromatography, stability of materials in acidic and basic media in multiphase

extraction, and the like. One skilled in the art will apply techniques most likely to achieve the desired separation.

[0194] All literature and patent citations above are hereby expressly incorporated by reference at the locations of their citation. Specifically cited sections or pages of the above cited works are incorporated by reference with specificity. The invention has been described in detail sufficient to allow one of ordinary skill in the art to make and use the subject matter of the following Embodiments. It is apparent that certain modifications of the methods and compositions of the following Embodiments can be made within the scope and spirit of the invention.

[0195] Dialkyl phosphonates may be prepared according to the methods of: Quast et al (1974) Synthesis 490; Stowell et al (1990) Tetrahedron Lett. 3261; US Patent No. 5,663,159.

[0196] In general, synthesis of phosphonate esters is achieved by coupling a nucleophile amine or alcohol with the corresponding activated phosphonate electrophilic precursor. For example, chlorophosphonate addition on to 5'- hydroxy of nucleoside is a well known method for preparation of nucleoside phosphate monoesters. The activated precursor can be prepared by several well known methods. Chlorophosphonates useful for synthesis of the prodrugs are prepared from the substituted- 1,3 -propanediol (Wissner, et al, (1992) J Med Chem. 35:1650, herein incorporated by reference in its entirety). Chlorophosphonates are made by oxidation of the corresponding chlorophospholanes (Anderson, et al, (1984) J. Org. Chem. 49:1304), herein incorporated by reference in its entirety, which are obtained by reaction of the substituted diol with phosphorus trichloride. Alternatively, the chlorophosphonate agent is made by treating substituted- 1,3-diols with phosphorusoxychloride (Patois, et al, (199O) J. Chem. Soc. Per kin Trans. I, 1577, herein incorporated by reference in its entirety). Chlorophosphonate species may also be generated in situ from corresponding cyclic phosphites (Silverburg, et al., (1996) Tetrahedron Lett., 37:771-774, herein incorporated by reference in its entirety), which in turn can be either made from chlorophospholane or phosphoramidate intermediate. Phosphorofiouridate intermediate prepared either from pyrophosphate or phosphoric acid may also act as precursor in preparation

of cyclic prodrugs (Watanabe et al., (1988) Tetrahedron Lett., 29:5763-66, herein incorporated by reference in its entirety). Caution: fluorophosphonate compounds may be highly toxic!

[0197] Phosphonate prodrugs of the present invention may also be prepared from the precursor free acid by Mitsunobu reactions (Mitsunobu, (1981) Synthesis, 1; Campbell, (1992) J. Org. Chem., 52:6331), and other acid coupling reagents including, but not limited to, carbodiimides (Alexander, et al, (1994) Collect. Czech. Chem. Commun. 59:1853; Casara, et al, (1992) Bioorg. Med. Chem. Lett., 2:145; Ohashi, et al, (1988) Tetrahedron Lett., 29:1189), and benzotriazolyloxytris-(dimethylamino)phosphonium salts (Campagne, et al, (1993) Tetrahedron Lett., 34:6743).

[0198] Aryl halides undergo Ni ⁺² catalyzed reaction with phosphite derivatives to give aryl phosphonate containing compounds (Balthazar, et al (1980) J Org. Chem. 45:5425). Phosphonates may also be prepared from the chlorophosphonate in the presence of a palladium catalyst using aromatic triflates (Petrakis, et al, (1987) J Am. Chem. 5Oc.109:2831; Lu, et al, (1987) Synthesis, 726). In another method, aryl phosphonate esters are prepared from aryl phosphates under anionic rearrangement conditions (Melvin (1981) Tetrahedron Lett. 22:3375; Casteel, et al, (1991) Synthesis, 691). N-Alkoxy aryl salts with alkali metal derivatives of cyclic alkyl phosphonate provide general synthesis for heteroaryl-2-phosphonate linkers (Redmore (197O) J. Org. Chem. 35:4114). These above mentioned methods can also be extended to compounds where the W ⁵ group is a heterocycle. Cyclic- 1, 3 -propanyl prodrugs of phosphonates are also synthesized from phosphonic diacids and substituted propane- 1, 3 -diols using a coupling reagent such as 1,3-dicyclohexylcarbodiimide (DCC) in presence of a base (e.g., pyridine). Other carbodiimide based coupling agents like 1,3- disopropylcarbodiimide or water soluble reagent, l-(3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride (EDCI) can also be utilized for the synthesis of cyclic phosphonate prodrugs.

[0199] The carbamoyl group may be formed by reaction of a hydroxy group according to the methods known in the art, including the teachings of Ellis, US 2002/0103378 Al and Hajima, US Patent No. 6,018,049.

[0200] Additional detailed descriptions for preparing the phosphate prodrugs of the present embodiments can be found in Arimilli, et al. International Patent Application WO 03/090690, which is incorporated herein by reference in its entirety.

Scheme 1001

27.1 27.3

27.2 27.1

27.3 27.2

27.3 27.1

[0201] Scheme 1001 shows the interconversions of certain phosphonate compounds: acids -P(O)(OH) ₂ ; mono-esters -P(O)(OR ⁵¹ XOH); and diesters - P(O)(OR ^sl ) ₂ in which the R ^sl groups are independently selected, and defined herein before, and the phosphorus is attached through a carbon moiety (link, i.e. linker), which is attached to the rest of the molecule, e.g. drug or drug intermediate (R). The R ^sl groups attached to the phosphonate esters in Scheme 1001 may be changed using established chemical transformations. The interconversions may be carried out in the precursor compounds or the final products using the methods described below. The methods employed for a given

phosphonate transformation depend on the nature of the substituent R ^sl . The preparation and hydrolysis of phosphonate esters is described in Organic Phosphorus Compounds, G. M. Kosolapoff, L. Maeir, eds, Wiley, 1976, p. 9ff. [0202] The conversion of a phosphonate diester 27.1 into the corresponding phosphonate monoester 27.2 (Scheme 1001, Reaction 1) can be accomplished by a number of methods. For example, the ester 27.1 in which R ^sl is an arylalkyl group such as benzyl, can be converted into the monoester compound 27.2 by reaction with a tertiary organic base such as diazabicyclooctane (DABCO) or quinuclidine, as described in J. Org. Chem., 1995, 60:2946. The reaction is performed in an inert hydrocarbon solvent such as toluene or xylene, at about 110°C. The conversion of the diester 27.1 in which R ¹ is an aryl group such as phenyl, or an alkenyl group such as allyl, into the monoester 27.2 can be effected by treatment of the ester 27.1 with a base such as aqueous sodium hydroxide in acetonitrile or lithium hydroxide in aqueous tetrahydrofuran. Phosphonate diesters 27.2 in which one of the groups R ^sl is arylalkyl, such as benzyl, and the other is alkyl, can be converted into the monoesters 27.2 in which R ^s is alkyl, by hydrogenation, for example using a palladium on carbon catalyst. Phosphonate diesters in which both of the groups R ^sl are alkenyl, such as allyl, can be converted into the monoester 27.2 in which R ^sl is alkenyl, by treatment with chlorotris(triphenylphosphine)rhodium (Wilkinson's catalyst) in aqueous ethanol at reflux, optionally in the presence of diazabicyclooctane, for example by using the procedure described in J Org. Chem., 38:3224 1973 for the cleavage of allyl carboxylates.

[0203] The conversion of a phosphonate diester 27.1 or a phosphonate monoester 27.2 into the corresponding phosphonic acid 27.3 (Scheme 1001, Reactions 2 and 3) can be effected by reaction of the diester or the monoester with trimethylsilyl bromide, as described in J Chem. Soc, Chem. Comm., 739, 1979. The reaction is conducted in an inert solvent such as, for example, dichloromethane, optionally in the presence of a silylating agent such as bis(trimethylsilyl)trifluoroacetamide, at ambient temperature. A phosphonate monoester 27.2 in which R ^sl is arylalkyl such as benzyl, can be converted into the corresponding phosphonic acid 27.3 by hydrogenation over a palladium catalyst, or by treatment with hydrogen chloride in an ethereal solvent such as dioxane. A

phosphonate monoester 27.2 in which R ^sl is alkenyl such as, for example, allyl, can be converted into the phosphonic acid 27.3 by reaction with Wilkinson's catalyst in an aqueous organic solvent, for example in 15% aqueous acetonitrile, or in aqueous ethanol, for example using the procedure described in HeIv. Chim. Acta., 68:618, 1985. Palladium catalyzed hydrogenolysis of phosphonate esters 27.1 in which R ^sl is benzyl is described in J. Org. Chem., 24:434, 1959. Platinum-catalyzed hydrogenolysis of phosphonate esters 27.1 in which R ^sl is phenyl is described in J Amer. Chem. Soc, 78:2336, 1956. [0204] The conversion of a phosphonate monoester 27.2 into a phosphonate diester 27.1 (Scheme 1001, Reaction 4) in which the newly introduced R ^sl group is alkyl, arylalkyl, or haloalkyl such as chloroethyl, can be effected by a number of reactions in which the substrate 27.2 is reacted with a hydroxy compound R ^sl OH, in the presence of a coupling agent. Suitable coupling agents are those employed for the preparation of carboxylate esters, and include a carbodiimide such as dicyclohexylcarbodiimide, in which case the reaction is preferably conducted in a basic organic solvent such as pyridine, or (benzotriazol-1- yloxy)tripyrrolidinophosphonium hexafiuorophosphate (PYBOP, Sigma), in which case the reaction is performed in a polar solvent such as dimethylformamide, in the presence of a tertiary organic base such as diisopropylethylamine, or Aldrithiol-2 (Aldrich) in which case the reaction is conducted in a basic solvent such as pyridine, in the presence of a triaryl phosphine such as triphenylphosphine. Alternatively, the conversion of the phosphonate monoester 27.1 to the diester 27.1 can be effected by the use of the Mitsunobu reaction. The substrate is reacted with the hydroxy compound R ¹ OH, in the presence of diethyl azodicarboxylate and a triarylphosphine such as triphenyl phosphine. Alternatively, the phosphonate monoester 27.2 can be transformed into the phosphonate diester 27.1, in which the introduced R ^sl group is alkenyl or arylalkyl, by reaction of the monoester with the halide R ^sl Br, in which R ^sl is as alkenyl or arylalkyl. The alkylation reaction is conducted in a polar organic solvent such as dimethylformamide or acetonitrile, in the presence of a base such as cesium carbonate. Alternatively, the phosphonate monoester can be transformed into the phosphonate diester in a two step procedure. In the first step, the phosphonate monoester 27.2 is transformed into the chloro analog -

P(O)(OR ^sI )Cl by reaction with thionyl chloride or oxalyl chloride and the like, as described in Organic Phosphorus Compounds, G. M. Kosolapoff, L. Maeir, eds, Wiley, 1976, p. 17, and the thus-obtained product -P(O)(OR ^sl )Cl is then reacted with the hydroxy compound R ^s OH, in the presence of a base such as triethylamine, to afford the phosphonate diester 27.1.

[0205] A phosphonic acid -P(O)(OH) ₂ can be transformed into a phosphonate monoester -P(O)(OR ^sl )(OH) (Scheme 1001, Reaction 5) by means of the methods described above of for the preparation of the phosphonate diester - P(O)(OR ^sl ) ₂ 27.1, except that only one molar proportion of the component R ^sl OH or R ^sl Br is employed.

[0206] A phosphonic acid -P(O)(OH) ₂ 27.3 can be transformed into a phosphonate diester -P(O)(OR ^sl ) ₂ 27.1 (Scheme 1, Reaction 6) by a coupling reaction with the hydroxy compound R ^sl OH, in the presence of a coupling agent such as Aldrithiol-2 (Aldrich) and triphenylphosphine. The reaction is conducted in a basic solvent such as pyridine. Alternatively, phosphonic acids 27.3 can be transformed into phosphonic esters 27.1 in which R ^sl is aryl, such as phenyl, by means of a coupling reaction employing, for example, phenol and dicyclohexylcarbodiimide in pyridine at about 70°C. Alternatively, phosphonic acids 27.3 can be transformed into phosphonic esters 27.1 in which R ^sl is alkenyl, by means of an alkylation reaction. The phosphonic acid is reacted with the alkenyl bromide R ^sl Br in a polar organic solvent such as acetonitrile solution at reflux temperature, in the presence of a base such as cesium carbonate, to afford the phosphonic ester 27.1..

Carboalkoxy-substituted phosphonate bisamidates, monoamidates, diesters and monoesters:

[0207] A number of methods are available for the conversion of phosphonic acids into amidates and esters. In one group of methods, the phosphonic acid is either converted into an isolated activated intermediate such as a phosphoryl chloride, or the phosphonic acid is activated in situ for reaction with an amine or a hydroxy compound.

[0208] The conversion of phosphonic acids into phosphoryl chlorides is accomplished by reaction with thionyl chloride, for example as described in J.

Gen. Chem. USSR, 1983, 53, 480, Zh. Obschei Khim., 1958, 28, 1063, or J. Org. Chem., 1994, 59, 6144, or by reaction with oxalyl chloride, as described in J. Am. Chem. Soc, 1994, 116, 3251, or J. Org. Chem., 1994, 59, 6144, or by reaction with phosphorus pentachloride, as described in J. Org. Chem., 2001, 66, 329, or in J. Med. Chem., 1995, 38, 1372. The resultant phosphoryl chlorides are then reacted with amines or hydroxy compounds in the presence of a base to afford the amidate or ester products.

[0209] Phosphonic acids are converted into activated imidazolyl derivatives by reaction with carbonyl diimidazole, as described in J. Chem. Soc, Chem. Comm., 1991, 312, or Nucleosides Nucleotides 2000, 19, 1885. Activated sulfonyloxy derivatives are obtained by the reaction of phosphonic acids with trichloromethylsulfonyl chloride, as described in J. Med. Chem. 1995, 38, 4958, or with triisopropylbenzenesulfonyl chloride, as described in Tet. Lett., 1996, 7857, or Bioorg. Med. Chem. Lett., 1998, 8, 663. The activated sulfonyloxy derivatives are then reacted with amines or hydroxy compounds to afford amidates or esters.

[0210] Alternatively, the phosphonic acid and the amine or hydroxy reactant are combined in the presence of a diimide coupling agent. The preparation of phosphonic amidates and esters by means of coupling reactions in the presence of dicyclohexyl carbodiimide is described, for example, in J. Chem. Soc, Chem. Comm., 1991, 312, or J. Med. Chem., 1980, 23, 1299 or Coll. Czech. Chem. Comm., 1987, 52, 2792. The use of ethyl dimethylaminopropyl carbodiimide for activation and coupling of phosphonic acids is described in Tet. Lett., 2001, 42, 8841, or Nucleosides Nucleotides, 2000, 19, 1885.

[0211] A number of additional coupling reagents have been described for the preparation of amidates and esters from phosphonic acids. The agents include Aldrithiol-2, and PYBOP and BOP, as described in J. Org. Chem., 1995, 60, 5214, and J. Med. Chem., 1997, 40, 3842, mesitylene-2-sulfonyl-3-nitro- 1,2,4- triazole (MSNT), as described in J. Med. Chem., 1996, 39, 4958, diphenylphosphoryl azide, as described in J. Org. Chem., 1984, 49, 1158, 1- (2,4,6-triisopropylbenzenesulfonyl-3-nitro-l,2,4-triazole (TPSNT) as described in Bioorg. Med. Chem. Lett., 1998, 8, 1013, bromotris(dimethylamino)phosphonium hexafluorophosphate (BroP), as

described in Tet. Lett., 1996, 37, 3997, 2-chloro-5,5-dimethyl-2-oxo-l,3,2- dioxaphosphinane, as described in Nucleosides Nucleotides 1995, 14, 871, and diphenyl chlorophosphate, as described in J. Med. Chem., 1988, 31, 1305. [0212] Phosphonic acids are converted into amidates and esters by means of the Mitsonobu reaction, in which the phosphonic acid and the amine or hydroxy reactant are combined in the presence of a triaryl phosphine and a dialkyl azodicarboxylate. The procedure is described in Org. Lett., 2001, 3, 643, or J. Med. Chem., 1997, 40, 3842.

[0213] Phosphonic esters are also obtained by the reaction between phosphonic acids and halo compounds, in the presence of a suitable base. The method is described, for example, in Anal. Chem., 1987, 59, 1056, or J. Chem. Soc. Perkin Trans., I, 1993, 19, 2303, or J. Med. Chem., 1995, 38, 1372, or Tet. Lett., 2002, 43, 1161.

[0214] Schemes 1 - 4 illustrate the conversion of phosphonate esters and phosphonic acids into carboalkoxy-substituted phosphorobisamidates (Scheme 1), phosphoroamidates (Scheme 2), phosphonate monoesters (Scheme 3) and phosphonate diesters, (Scheme 4).

[0215] Scheme 1 illustrates various methods for the conversion of phosphonate diesters 1.1 into phosphorobisamidates 1.5. The diester 1.1, prepared as described previously, is hydrolyzed, either to the monoester 1.2 or to the phosphonic acid 1.6. The methods employed for these transformations are described above. The monoester 1.2 is converted into the monoamidate 1.3 by reaction with an aminoester 1.9, in which the group R ^s2 is H or alkyl, the group R ^s4 is an alkylene moiety such as, for example, CHCH ₃ , CHPr ^j , CH(CH ₂ Ph), CH ₂ CH(CH ₃ ) and the like, or a group present in natural or modified aminoacids, and the group R ^s5 is alkyl. The reactants are combined in the presence of a coupling agent such as a carbodiimide, for example dicyclohexyl carbodiimide, as described in J. Am. Chem. Soc, 1957, 79, 3575, optionally in the presence of an activating agent such as hydroxybenztriazole, to yield the amidate product 1.3. The amidate-forming reaction is also effected in the presence of coupling agents such as BOP, as described in J. Org. Chem., 1995, 60, 5214, Aldrithiol, PYBOP and similar coupling agents used for the preparation of amides and esters. Alternatively, the reactants 1.2 and 1.9 are transformed into the monoamidate 1.3

by means of a Mitsonobu reaction. The preparation of amidates by means of the Mitsonobu reaction is described in J. Med. Chem., 1995, 38, 2742. Equimolar amounts of the reactants are combined in an inert solvent such as tetrahydrofuran in the presence of a triaryl phosphine and a dialkyl azodicarboxylate. The thus- obtained monoamidate ester 1.3 is then transformed into amidate phosphonic acid 1.4. The conditions used for the hydrolysis reaction depend on the nature of the R ^sl group, as described previously. The phosphonic acid amidate 1.4 is then reacted with an aminoester 1.9, as described above, to yield the bisamidate product 1.5, in which the amino substituents are the same or different. [0216] An example of this procedure is shown in Scheme 1, Example 1. In this procedure, a dibenzyl phosphonate 1.14 is reacted with diazabicyclooctane (DABCO) in toluene at reflux, as described in J. Org. Chem., 1995, 60, 2946, to afford the monobenzyl phosphonate 1.15. The product is then reacted with equimolar amounts of ethyl alaninate 1.16 and dicyclohexyl carbodiimide in pyridine, to yield the amidate product 1.17. The benzyl group is then removed, for example by hydrogenolysis over a palladium catalyst, to give the monoacid product 1.18. This compound is then reacted in a Mitsonobu reaction with ethyl leucinate 1.19, triphenyl phosphine and diethylazodicarboxylate, as described in J. Med. Chem., 1995, 38, 2742, to produce the bisamidate product 1.20. [0217] Using the above procedures, but employing, in place of ethyl leucinate 1.19 or ethyl alaninate 1.16, different aminoesters 1.9, the corresponding products 1.5 are obtained.

[0218] Alternatively, the phosphonic acid 1.6 is converted into the bisamidate 1.5 by use of the coupling reactions described above. The reaction is performed in one step, in which case the nitrogen-related substituents present in the product 1.5 are the same, or in two steps, in which case the nitrogen-related substituents can be different.

[0219] An example of the method is shown in Scheme 1, Example 2. In this procedure, a phosphonic acid 1.6 is reacted in pyridine solution with excess ethyl phenylalaninate 1.21 and dicyclohexylcarbodiimide, for example as described in J. Chem. Soc, Chem. Comm., 1991, 1063, to give the bisamidate product 1.22.

[0220] Using the above procedures, but employing, in place of ethyl phenylalaninate, different aminoesters 1.9, the corresponding products 1.5 are obtained.

[0221] As a further alternative, the phosphonic acid 1.6 is converted into the mono or bis-activated derivative 1.7, in which Lv is a leaving group such as chloro, imidazolyl, triisopropylbenzenesulfonyloxy etc. The conversion of phosphonic acids into chlorides 1.7 (Lv = Cl) is effected by reaction with thionyl chloride or oxalyl chloride and the like, as described in Organic Phosphorus Compounds, G. M. Kosolapoff, L. Maeir, eds, Wiley, 1976, p. 17. The conversion of phosphonic acids into monoimidazolides 1.7 (Lv = imidazolyl) is described in J. Med. Chem., 2002, 45, 1284 and in J. Chem. Soc. Chem. Comm., 1991, 312. Alternatively, the phosphonic acid is activated by reaction with triisopropylbenzenesulfonyl chloride, as described in Nucleosides and Nucleotides, 2000, 10, 1885. The activated product is then reacted with the aminoester 1.9, in the presence of a base, to give the bisamidate 1.5. The reaction is performed in one step, in which case the nitrogen substituents present in the product 1.5 are the same, or in two steps, via the intermediate 1.11, in which case the nitrogen substituents can be different.

[0222] Examples of these methods are shown in Scheme 1, Examples 3 and 5. In the procedure illustrated in Scheme 1, Example 3, a phosphonic acid 1.6 is reacted with ten molar equivalents of thionyl chloride, as described in Zh. Obschei Khim., 1958, 28, 1063, to give the dichloro compound 1.23. The product is then reacted at reflux temperature in a polar aprotic solvent such as acetonitrile, and in the presence of a base such as triethylamine, with butyl serinate 1.24 to afford the bisamidate product 1.25.

[0223] Using the above procedures, but employing, in place of butyl serinate 1.24, different aminoesters 1.9, the corresponding products 1.5 are obtained. [0224] In the procedure illustrated in Scheme 1, Example 5, the phosphonic acid 1.6 is reacted, as described in J. Chem. Soc. Chem. Comm., 1991, 312, with carbonyl diimidazole to give the imidazolide 1.32. The product is then reacted in acetonitrile solution at ambient temperature, with one molar equivalent of ethyl alaninate 1.33 to yield the monodisplacement product 1.34. The latter compound is then reacted with carbonyl diimidazole to produce the activated intermediate

1.35, and the product is then reacted, under the same conditions, with ethyl N- methylalaninate 1.33a to give the bisamidate product 1.36. [0225] Using the above procedures, but employing, in place of ethyl alaninate 1.33 or ethyl N-methylalaninate 1.33a, different aminoesters 1.9, the corresponding products 1.5 are obtained.

[0226] The intermediate monoamidate 1.3 is also prepared from the monoester 1.2 by first converting the monoester into the activated derivative 1.8 in which Lv is a leaving group such as halo, imidazolyl etc, using the procedures described above. The product 1.8 is then reacted with an aminoester 1.9 in the presence of a base such as pyridine, to give an intermediate monoamidate product 1.3. The latter compound is then converted, by removal of the R ^sl group and coupling of the product with the aminoester 1.9, as described above, into the bisamidate 1.5. [0227] An example of this procedure, in which the phosphonic acid is activated by conversion to the chloro derivative 1.26, is shown in Scheme 1, Example 4. In this procedure, the phosphonic monobenzyl ester 1.15 is reacted, in dichloromethane, with thionyl chloride, as described in Tet. Let., 1994, 35, 4097, to afford the phosphoryl chloride 1.26. The product is then reacted in acetonitrile solution at ambient temperature with one molar equivalent of ethyl 3-amino-2- methylpropionate 1.27 to yield the monoamidate product 1.28. The latter compound is hydrogenated in ethyl acetate over a 5% palladium on carbon catalyst to produce the monoacid product 1.29. The product is subjected to a Mitsonobu coupling procedure, with equimolar amounts of butyl alaninate 1.30, triphenyl phosphine, diethylazodicarboxylate and triethylamine in tetrahydrofuran, to give the bisamidate product 1.31.

[0228] Using the above procedures, but employing, in place of ethyl 3-amino- 2-methylpropionate 1.27 or butyl alaninate 1.30, different aminoesters 1.9, the corresponding products 1.5 are obtained.

[0229] The activated phosphonic acid derivative 1.7 is also converted into the bisamidate 1.5 via the diamino compound 1.10. The conversion of activated phosphonic acid derivatives such as phosphoryl chlorides into the corresponding amino analogs 1.10, by reaction with ammonia, is described in Organic Phosphorus Compounds, G. M. Kosolapoff, L. Maeir, eds, Wiley, 1976. The diamino compound 1.10 is then reacted at elevated temperature with a haloester

1.12, in a polar organic solvent such as dimethylformamide, in the presence of a base such as dimethylaminopyridine or potassium carbonate, to yield the bisamidate 1.5.

[0230] An example of this procedure is shown in Scheme 1, Example 6. In this method, a dichlorophosphonate 1.23 is reacted with ammonia to afford the diamide 1.37. The reaction is performed in aqueous, aqueous alcoholic or alcoholic solution, at reflux temperature. The resulting diamino compound is then reacted with two molar equivalents of ethyl 2-bromo-3-methylbutyrate 1.38, in a polar organic solvent such as N-methylpyrrolidinone at ca. 15O ⁰ C, in the presence of a base such as potassium carbonate, and optionally in the presence of a catalytic amount of potassium iodide, to afford the bisamidate product 1.39. [0231] Using the above procedures, but employing, in place of ethyl 2-bromo- 3-methylbutyrate 1.38, different haloesters 1.12 the corresponding products 1.5 are obtained.

[0232] The procedures shown in Scheme 1 are also applicable to the preparation of bisamidates in which the aminoester moiety incorporates different functional groups. Scheme 1, Example 7 illustrates the preparation of bisamidates derived from tyrosine. In this procedure, the monoimidazolide 1.32 is reacted with propyl tyrosinate 1.40, as described in Example 5, to yield the monoamidate 1.41. The product is reacted with carbonyl diimidazole to give the imidazolide 1.42, and this material is reacted with a further molar equivalent of propyl tyrosinate to produce the bisamidate product 1.43. [0233] Using the above procedures, but employing, in place of propyl tyrosinate 1.40, different aminoesters 1.9, the corresponding products 1.5 are obtained. The aminoesters employed in the two stages of the above procedure can be the same or different, so that bisamidates with the same or different amino substituents are prepared.

[0234] Scheme 2 illustrates methods for the preparation of phosphonate monoamidates. In one procedure, a phosphonate monoester 1.1 is converted, as described in Scheme 1, into the activated derivative 1.8. This compound is then reacted, as described above, with an aminoester 1.9, in the presence of a base, to afford the monoamidate product 2.1.

[0235] The procedure is illustrated in Scheme 2, Example 1. In this method, a monophenyl phosphonate 2.7 is reacted with, for example, thionyl chloride, as described in J. Gen. Chem. USSR., 1983, 32, 367, to give the chloro product 2.8. The product is then reacted, as described in Scheme 1, with ethyl alaninate 2.9, to yield the amidate 2.10.

[0236] Using the above procedures, but employing, in place of ethyl alaninate 2.9, different aminoesters 1.9, the corresponding products 2.1 are obtained. [0237] Alternatively, the phosphonate monoester 1.1 is coupled, as described in Scheme 1, with an aminoester 1.9 to produce the amidate 2.1. If necessary, the R ^sl substituent is then altered, by initial cleavage to afford the phosphonic acid 2.2. The procedures for this transformation depend on the nature of the R ^sl group, and are described above. The phosphonic acid is then transformed into the ester amidate product 2.3, by reaction with the hydroxy compound R ^s3 OH, in which the group R ^s3 is aryl, heteroaryl, alkyl, cycloalkyl, haloalkyl etc, using the same coupling procedures (carbodiimide, Aldrithiol-2, PYBOP, Mitsonobu reaction etc) described in Scheme 1 for the coupling of amines and phosphonic acids.

Scheme 1

1.14 1.15 1.17 1.18

H ₂ N

1.20

Scheme 1 Example 2

1.6 1.22

1.25

Scheme 1 Example 4

CO ₂ Et

Scheme 1 Example 7

[0238] Examples of this method are shown in Scheme 2, Examples and 2 and 3. In the sequence shown in Example 2, a monobenzyl phosphonate 2.11 is transformed by reaction with ethyl alaninate, using one of the methods described above, into the monoamidate 2.12. The benzyl group is then removed by catalytic hydrogenation in ethyl acetate solution over a 5% palladium on carbon catalyst, to afford the phosphonic acid amidate 2.13. The product is then reacted in dichloromethane solution at ambient temperature with equimolar amounts of l-(dimethylaminopropyl)-3-ethylcarbodiimide and trifluoroethanol 2.14, for example as described in Tet. Lett., 2001, 42, 8841, to yield the amidate ester 2.15.

[0239] In the sequence shown in Scheme 2, Example 3, the monoamidate 2.13 is coupled, in tetrahydrofuran solution at ambient temperature, with equimolar amounts of dicyclohexyl carbodiimide and 4-hydroxy-N-methylpiperidine 2.16, to produce the amidate ester product 2.17.

[0240] Using the above procedures, but employing, in place of the ethyl alaninate product 2.12 different monoacids 2.2, and in place of trifluoroethanol 2.14 or 4-hydroxy-N-methylpiperidine 2.16, different hydroxy compounds R ^s3 OH, the corresponding products 2.3 are obtained. [0241] Alternatively, the activated phosphonate ester 1.8 is reacted with ammonia to yield the amidate 2.4. The product is then reacted, as described in Scheme 1, with a haloester 2.5, in the presence of a base, to produce the amidate product 2.6. If appropriate, the nature of the R ^sl group is changed, using the procedures described above, to give the product 2.3. The method is illustrated in Scheme 2, Example 4. In this sequence, the monophenyl phosphoryl chloride 2.18 is reacted, as described in Scheme 1, with ammonia, to yield the amino product 2.19. This material is then reacted in N-methylpyrrolidinone solution at 17O ⁰ C with butyl 2-bromo-3-phenylpropionate 2.20 and potassium carbonate, to afford the amidate product 2.21.

[0242] Using these procedures, but employing, in place of butyl 2-bromo-3- phenylpropionate 2.20, different haloesters 2.5, the corresponding products 2.6 are obtained.

[0243] The monoamidate products 2.3 are also prepared from the doubly activated phosphonate derivatives 1.7. In this procedure, examples of which are

described in Synlett, 1998, 1, 73, the intermediate 1.7 is reacted with a limited amount of the aminoester 1.9 to give the mono-displacement product 1.11. The latter compound is then reacted with the hydroxy compound R ³ OH in a polar organic solvent such as dimethylfbrmamide, in the presence of a base such as diisopropylethylamine, to yield the monoamidate ester 2.3. [0244] The method is illustrated in Scheme 2, Example 5. In this method, the phosphoryl dichloride 2.22 is reacted in dichloromethane solution with one molar equivalent of ethyl N-methyl tyrosinate 2.23 and dimethylaminopyridine, to generate the monoamidate 2.24. The product is then reacted with phenol 2.25 in dimethylformamide containing potassium carbonate, to yield the ester amidate product 2.26.

[0245] Using these procedures, but employing, in place of ethyl N-methyl tyrosinate 2.23 or phenol 2.25, the aminoesters 1.9 and/or the hydroxy compounds R ^s3 OH, the corresponding products 2.3 are obtained.

Scheme 2 Example 4

Scheme 2 Example 5

[0246] Scheme 3 illustrates methods for the preparation of carboalkoxy- substituted phosphonate diesters in which one of the ester groups incorporates a carboalkoxy substituent.

[0247] In one procedure, a phosphonate monoester 1.1, prepared as described above, is coupled, using one of the methods described above, with a hydroxyester 3.1, in which the groups R ^s4 and R ^s5 are as described in Scheme 1. For example, equimolar amounts of the reactants are coupled in the presence of a carbodiimide such as dicyclohexyl carbodiimide, as described in Aust. J. Chem., 1963, 609, optionally in the presence of dimethylaminopyridine, as described in Tet., 1999, 55, 12997. The reaction is conducted in an inert solvent at ambient temperature. [0248] The procedure is illustrated in Scheme 3, Example 1. In this method, a monophenyl phosphonate 3.9 is coupled, in dichloromethane solution in the presence of dicyclohexyl carbodiimide, with ethyl 3-hydroxy-2-methylpropionate 3.10 to yield the phosphonate mixed diester 3.11.

[0249] Using this procedure, but employing, in place of ethyl 3-hydroxy-2- methylpropionate 3.10, different hydroxyesters 3.1, the corresponding products 3.2 are obtained.

[0250] The conversion of a phosphonate monoester 1.1 into a mixed diester 3.2 is also accomplished by means of a Mitsonobu coupling reaction with the

hydroxyester 3.1, as described in Org. Lett., 2001, 643. In this method, the reactants 1.1 and 3.1 are combined in a polar solvent such as tetrahydrofuran, in the presence of a triarylphosphine and a dialkyl azodicarboxylate, to give the mixed diester 3.2. The R ^sl substituent is varied by cleavage, using the methods described previously, to afford the monoacid product 3.3. The product is then coupled, for example using methods described above, with the hydroxy compound R ^s3 OH, to give the diester product 3.4.

[0251] The procedure is illustrated in Scheme 3, Example 2. In this method, a monoallyl phosphonate 3.12 is coupled in tetrahydrofuran solution, in the presence of triphenylphosphine and diethylazodicarboxylate, with ethyl lactate 3.13 to give the mixed diester 3.14. The product is reacted with tris(triphenylphosphine) rhodium chloride (Wilkinson catalyst) in acetonitrile, as described previously, to remove the allyl group and produce the monoacid product 3.15. The latter compound is then coupled, in pyridine solution at ambient temperature, in the presence of dicyclohexyl carbodiimide, with one molar equivalent of 3-hydroxypyridine 3.16 to yield the mixed diester 3.17. [0252] Using the above procedures, but employing, in place of the ethyl lactate 3.13 or 3-hydroxypyridine, a different hydroxyester 3.1 and/or a different hydroxy compound R ^s3 OH, the corresponding products 3.4 are obtained. [0253] The mixed diesters 3.2 are also obtained from the monoesters 1.1 via the intermediacy of the activated monoesters 3.5. In this procedure, the monoester 1.1 is converted into the activated compound 3.5 by reaction with, for example, phosphorus pentachloride, as described in J. Org. Chem., 2001, 66, 329, or with thionyl chloride or oxalyl chloride (Lv = Cl), or with triisopropylbenzenesulfonyl chloride in pyridine, as described in Nucleosides and Nucleotides, 2000, 19, 1885, or with carbonyl diimidazole, as described in J. Med. Chem., 2002, 45, 1284. The resultant activated monoester is then reacted with the hydroxyester 3.1, as described above, to yield the mixed diester 3.2.

[0254] The procedure is illustrated in Scheme 3, Example 3. In this sequence, a monophenyl phosphonate 3.9 is reacted, in acetonitrile solution at 70°C, with ten equivalents of thionyl chloride, so as to produce the phosphoryl chloride 3.19. The product is then reacted with ethyl 4-carbamoyl-2-hydroxybutyrate 3.20 in dichloromethane containing triethylamine, to give the mixed diester 3.21.

[0255] Using the above procedures, but employing, in place of ethyl 4- carbamoyl-2-hydroxybutyrate 3.20, different hydroxyesters 3.1, the corresponding products 3.2 are obtained.

[0256] The mixed phosphonate diesters are also obtained by an alternative route for incorporation of the R ^s3 O group into intermediates 3.3 in which the hydroxyester moiety is already incorporated. In this procedure, the monoacid intermediate 3.3 is converted into the activated derivative 3.6 in which Lv is a leaving group such as chloro, imidazole, and the like, as previously described.

The activated intermediate is then reacted with the hydroxy compound R ^s3 OH, in the presence of a base, to yield the mixed diester product 3.4.

[0257] The method is illustrated in Scheme 3, Example 4. In this sequence, the phosphonate monoacid 3.22 is reacted with trichloromethanesulfonyl chloride in tetrahydrofuran containing collidine, as described in J. Med. Chem., 1995, 38,

4648, to produce the trichloromethanesulfonyloxy product 3.23. This compound is reacted with 3-(morpholinomethyl)phenol 3.24 in dichloromethane containing triethylamine, to yield the mixed diester product 3.25.

[0258] Using the above procedures, but employing, in place of with

3-(morpholinomethyl)phenol 3.24, different carbinols R ^s3 OH, the corresponding products 3.4 are obtained.

[0259] The phosphonate esters 3.4 are also obtained by means of alkylation reactions performed on the monoesters 1.1. The reaction between the monoacid

1.1 and the haloester 3.7 is performed in a polar solvent in the presence of a base such as diisopropylethylamine, as described in Anal. Chem., 1987, 59, 1056, or triethylamine, as described in J. Med. Chem., 1995, 38, 1372, or in a non-polar solvent such as benzene, in the presence of 18-crown-6, as described in Syn.

Comm, 1995, 25, 3565.

[0260] The method is illustrated in Scheme 3, Example 5. In this procedure, the monoacid 3.26 is reacted with ethyl 2-bromo-3-phenylpropionate 3.27 and diisopropylethylamine in dimethylformamide at 80°C to afford the mixed diester product 3.28.

[0261] Using the above procedure, but employing, in place of ethyl 2-bromo-3- phenylpropionate 3.27, different haloesters 3.7, the corresponding products 3.4 are obtained.

Scheme 3

Scheme 3 Example 3

R ^s -lin

Scheme 3 Example 4

3.22 3.23 3.25

Scheme 3 Example 5

3.26 3.28

[0262] Scheme 4 illustrates methods for the preparation of phosphonate diesters in which both the ester substituents incorporate carboalkoxy groups.

[0263] The compounds are prepared directly or indirectly from the phosphonic acids 1.6. In one alternative, the phosphonic acid is coupled with the hydroxyester 4.2, using the conditions described previously in Schemes 1 - 3, such as coupling reactions using dicyclohexyl carbodiimide or similar reagents, or under the conditions of the Mitsonobu reaction, to afford the diester product

4.3 in which the ester substituents are identical.

[0264] This method is illustrated in Scheme 4, Example 1. In this procedure, the phosphonic acid 1.6 is reacted with three molar equivalents of butyl lactate

4.5 in the presence of Aldrithiol-2 and triphenyl phosphine in pyridine at ca.

70 ⁰ C, to afford the diester 4.6.

[0265] Using the above procedure, but employing, in place of butyl lactate 4.5, different hydroxyesters 4.2, the corresponding products 4.3 are obtained.

[0266] Alternatively, the diesters 4.3 are obtained by alkylation of the phosphonic acid 1.6 with a haloester 4.1. The alkylation reaction is performed as described in Scheme 3 for the preparation of the esters 3.4.

[0267] This method is illustrated in Scheme 4, Example 2. In this procedure, the phosphonic acid 1.6 is reacted with excess ethyl 3-bromo-2-methylpropionate

4.7 and diisopropylethylamine in dimethylformamide at ca. 80°C, as described in

Anal. Chem., 1987, 59, 1056, to produce the diester 4.8.

[0268] Using the above procedure, but employing, in place of ethyl 3-bromo-2- methylpropionate 4.7, different haloesters 4.1, the corresponding products 4.3 are obtained.

[0269] The diesters 4.3 are also obtained by displacement reactions of activated derivatives 1.7 of the phosphonic acid with the hydroxyesters 4.2. The displacement reaction is performed in a polar solvent in the presence of a suitable base, as described in Scheme 3. The displacement reaction is performed in the presence of an excess of the hydroxyester, to afford the diester product 4.3 in which the ester substituents are identical, or sequentially with limited amounts of different hydroxyesters, to prepare diesters 4.3 in which the ester substituents are different.

[0270] The methods are illustrated in Scheme 4, Examples 3 and 4. As shown in Example 3, the phosphoryl dichloride 2.22 is reacted with three molar equivalents of ethyl 3-hydroxy-2-(hydroxymethyl)propionate 4.9 in tetrahydrofuran containing potassium carbonate, to obtain the diester product

4.10.

[0271] Using the above procedure, but employing, in place of ethyl 3-hydroxy-

2-(hydroxymethyl)propionate 4.9, different hydroxyesters 4.2, the corresponding products 4.3 are obtained.

[0272] Scheme 4, Example 4 depicts the displacement reaction between equimolar amounts of the phosphoryl dichloride 2.22 and ethyl 2-methyl-3- hydroxypropionate 4.11, to yield the monoester product 4.12. The reaction is conducted in acetonitrile at 70°C in the presence of diisopropylethylamine. The product 4.12 is then reacted, under the same conditions, with one molar equivalent of ethyl lactate 4.13, to give the diester product 4.14.

[0273] Using the above procedures, but employing, in place of ethyl 2-methyl-

3-hydroxypropionate 4.11 and ethyl lactate 4.13, sequential reactions with different hydroxyesters 4.2, the corresponding products 4.3 are obtained.



Scheme 1002

810 811

[0274] Amino alkyl phosphonate compounds 809:

CbZHNy yk CbzHN

Hn ^x OH

811 814

R ^s " H ₂ N- TIOOR ³¹

820

816 ⁸¹⁵ are a generic representative of compounds 811, 813, 814, 816 and 818. Some methods to prepare embodiments of 809 are shown in Scheme 1002. Commercial amino phosphonic acid 810 was protected as carbamate 811. The phosphonic acid 811 was converted to phosphonate 812 upon treatment with ROH in the presence of DCC or other conventional coupling reagents. Coupling of phosphonic acid 811 with esters of amino acid 820 provided bisamidate 817. Conversion of acid 811 to bisphenyl phosphonate followed by hydrolysis gave mono-phosphonic acid 814 (Cbz = C ₆ H ₅ CH ₂ C(O)-), which was then transformed to mono-phosphonic amidate 815. Carbamates 813, 816 and 818 were converted to their corresponding amines upon hydrogenation. Compounds 811, 813, 814, 816 and 818 are useful intermediates to form the phosphonate compounds of the embodiments.

[0275] Following the similar procedures, replacement of amino acid esters 820 with lactates 821 (Scheme 1003) provides mono-phosphonic lactates 823. Lactates 823 are useful intermediates to form the phosphonate compounds of the embodiments.

Scheme 1003

Example 1

[0276] To a solution of 2-aminoethylphosphonic acid (1.26 g, 10.1 mmol) in 2N NaOH (10.1 mL, 20.2 mmol) was added benzyl chloroformate (1.7 niL, 12.1 mmol). After the reaction mixture was stirred for 2 d at room temperature, the mixture was partitioned between Et ₂ O and water. The aqueous phase was acidified with 6N HCl until pH=2. The resulting colorless solid was dissolved in MeOH (75 mL) and treated with Dowex 50WX8-200 (7 g). After the mixture was stirred for 30 minutes, it was filtered and evaporated under reduced pressure to give carbamate 28 (2.37 g, 91%) as a colorless solid (Scheme 1005).

[0277] To a solution of carbamate 28 (2.35 g, 9.1 mmol) in pyridine (40 mL) was added phenol (8.53 g, 90.6 mmol) and l^-dicyclohexylcarbodiimide (7.47 g, 36.2 mmol). After the reaction mixture was warmed to 70 ⁰ C and stirred for 5 h, the mixture was diluted with CH ₃ CN and filtered. The filtrate was concentrated under reduced pressure and diluted with EtOAc. The organic phase was washed with sat. NH ₄ Cl, sat. NaHCO ₃ , and brine, then dried over Na ₂ SO ₄ , filtered, and evaporated under reduced pressure. The crude product was chromatographed on silica gel twice (eluting 40-60% EtOAc/hexane) to give phosphonate 29 (2.13 g, 57%) as a colorless solid.

[0278] To a solution of phosphonate 29 (262 mg, 0.637 mmol) in iPrOH (5 mL) was added TFA (0.05 mL, 0.637 mmol) and 10% Pd/C (26 mg). After the reaction mixture was stirred under H ₂ atmosphere (balloon) for 1 h, the mixture was filtered through Celite. The filtrate was evaporated under reduced pressure to give amine 30 (249 mg, 100%) as a colorless oil (Scheme 1005). [0279] Scheme 1 below illustrates two different methods for preparing 7-(2'- methyl-β-D-ribofuranosyl)-4-amino-5-(ethyn-l-yl)-pyrrolo[2, 3-d]pyrimidine.

SCHEME 1

[0280] Specifically, in Scheme 1, commercially available 4-chloro-pyrrolo[2,3- d]pyrimidine, compound 2, is converted to the 4-chloro-5-iodo-pyrrolo[2,3- d]pyrimidine, compound 3, by contact with a slight excess and preferably from about 1.05 to 2 equivalents of N-iodo-succinimide in a suitable inert diluent such as DMF, acetonitrile, and the like. The reaction is typically conducted at from about 0° to about 4O ⁰ C and preferably at ambient conditions until substantial completion of the reaction. Preferably, the reaction is conducted in darkness (e.g., in a foil covered reaction chamber) and is typically completed within about

6 to 24 hours. The 4-chloro-5-iodo-pyrrolo[2,3-d]pyrimidine, compound 3, can be isolated by conventional methods such as filtration, evaporation and the like. Purification is preferably accomplished by crystallization with the yield of compound 3 being greater than about 90 percent.

[0281] 4-Chloro-5-iodo-pyrrolo[2,3-d]pyrimidine, compound 3, is combined into a suitable inert solvent such as acetonitrile, DMF, and the like at ambient conditions. A slight excess of sodium hydride, typically from about 1.01 to 1.1 and preferably about 1.04 equivalents relative to compound 3, is added portionwise to the solution. The resulting system is maintained with stirring at ambient conditions for a period of from about 0.5 to about 4 hours and preferably for about 2 hours. Upon substantial completion of the reaction, any insoluble particles are removed from the reaction mixture by filtration. The sodium salt of compound 3 (not shown) in this filtrate is used in the next step without further purification.

[0282] Separately, 1 -methoxy-2-methyl-3,5-di-O-(2,4-dichlorobenzyl)-D- ribofuranose, compound 8 (described below), is dissolved in a suitable inert diluent such as chloroform, methylene chloride, tetrahydrofuran and the like and the resulting system cooled to approximately 0° to 10°C. The corresponding 1- bromo-2-methyl-3,5-di-O-(2,4-dichlorobenzyl)-D-ribofuranose (not shown) is prepared in situ by reaction with gaseous hydrogen bromide which is bubbled through the reaction system until substantial completion of the reaction which typically occurs within about 0.1 to 1 hour. The resulting product is obtained by evaporation, preferably at temperatures not exceeding about 20°C and residual traces of hydrogen bromide removed in vacuo (preferably at a pressure less than about 15 torr).

[0283] An excess, typically from about 1.01 to about 2 equivalents, (more preferably 1.5 to 2 eq) of the sodium salt of compound 3 is combined with 1- bromo-2-methyl-3,5-di-O-(2,4-dichlorobenzyl)-D-ribofuranose in a suitable solvent such as acetonitrile, DMF, and the like. Typically, the reaction is maintained at ambient conditions until substantially complete, which typically occurs within from about 6 to about 24 hours. The resulting product, 7-(2'- methyl-3',5'-di-O-(2,4-dichlorobenzyl)-β-D-ribofuranosyl)-4 -chloro-5-iodo- pyrrolo[2,3-d]pyrimidine, compound 4, is isolated by conventional procedures.

Preferably the reaction solution is neutralized and the solvent evaporated. Compound 4 is then triturated with a suitable solvent, for example, toluene, xylenes, and the like. The product can be purified by flash chromatography followed by crystallization.

[0284] Subsequently, the dichlorobenzyl protecting groups are removed by conventional procedures such as contacting 7-(2'-methyl-3',5'-di-O-(2,4- dichlorobenzyl)-β-D-ribofuranosyl)-4-chloro-5-iodo-pyrrolo[ 2,3-d]pyrimidine, compound 4, with BCl ₃ to provide for 7-(2'-methyl-β-D-ribofuranosyl)-4-chloro- 5-iodo-pyrrolo[2,3-d]pyrimidine, compound 5. Preferably, the reaction is conducted in an inert diluent such as chloroform, methylene chloride and the like. The reaction mixture is initially maintained at from about -60° to about -80°C over a period of from about 1 to 4 hours and then allowed to warm toabout -40° to 0°C until the reaction is substantially complete which typically occurs after about an additional 1 to 24 hours. Afterwards the reaction is quenched with methanol and is then neutralized by raising the pH level to about 7, with a base, preferably with ammonium hydroxide. The resulting 7-(2'-methyl-β-D- ¹ ^ ribofuranosyl)-4-chloro-5-iodo-pyrrolo[2,3-d]pyrimidine, compound 5, is isolated by conventional methods such as filtration, evaporation, chromatography, ; precipitation, and the like.

[0285] The 4-chloro group of compound 5 is then aminated by contact with an excess of liquid ammonia. The reaction is preferably conducted neat at a temperature of from about 75° to about 90°C in a pressure reactor typically maintained at from about 100 to about 500 psi. The reaction is continued until substantial completion which typically occurs in about 12 to about 48 hours. The resulting 7-(2'-methyl-β-D-ribofuranosyl)-4-amino-5-iodo-pyrrolo[2,3- d]pyrimidine, compound 6, is isolated by conventional methods such as filtration, evaporation, chromatography, precipitation, and the like. [0286] As shown in Scheme 1, the iodo group of either the 7-(2'-methyl-β-D- ribofuranosyl)-4-chloro-5-iodo-pyrrolo[2,3-d]pyrimidine, compound 5, or the 7- (2'-methyl-β-D-ribofuranosyl)-4-amino-5-iodo-pyrrolo[2,3-d] pyrimidine, compound 6, is converted to the corresponding (trimethyl)silylacetylenyl group. Conversion is accomplished by first dissolving compound 5 or 6 in a suitable inert diluent such as DMF, THF or a mixture of DMF/THF such as 3:7 ratio. A

catalytic amount of both cuprous iodide (CuI) and tetrakis(triphenylphosphine)palladium(0) is then added to the reaction mixture together with an excess, typically 1.1 to 2 equivalents , of

(trimethylsilyl)acetylene. The reaction is preferably conducted in the presence of a base such as triethylamine and preferably is conducted under an inert atmosphere. The reaction is typically conducted at from about 10° to about 30°C and is continued until substantial completion which typically occurs in about 12 to 48 hours.

[0287] The product derived from compound 5, i.e., 7-(2'-methyl-β-D- ribofuranosyl)-4-chloro-5-(trimethylsilylethynyl)pyrrolo[2,3 -d]pyrimidine, compound 10, is isolated by conventional methods such as filtration, evaporation, chromatography, precipitation, and the like.

[0288] The product derived from compound 6, i.e., 7-(2'-methyl-β-D- ribofuranosyl)-4-amino-5 -(trimethylsilyl-ethynyl)pyrrolo [2,3 -d]pyrimidine, compound 7, is isolated by conventional methods such as filtration, evaporation, chromatography, precipitation, and the like.

[0289] Compound 7 can then be converted to the acetylene derivative (-C≡CH) by desilylation which occurs via conventional methods using ammonium hydroxide, pottasium carbonate or fluoride anions. For example, reaction of 7-

(2'-methyl-β-D-ribofuranosyl)-4-amino-5-(trimethylsilyl- ethynyl)pyrrolo[2,3- djpyrimidine, compound 7, with ammonium hydroxide in methanol provides for compound 1.

[0290] Alternatively, desilylation and animation can be employed with compound 10 by reaction with concentrated ammonia to provide for compound 1.

[0291] In an alternative embodiment, compound 3 is first treated with a trimethylsilyl acetylene as described above to form compound 5a. Compound 5a may be coupled to 2'-methyl-3,5-di-O-(2,4-dichlorobenzyl)-D-ribofuranoseas described above to form compound 7a. Finally removing the 2,4-dichlorobenzyl protecting groups from the sugar provides for compound 10.

[0292] Scheme 2 below illustrates synthetic variations in the preparation of 7-

(2'-methyl-β-D-ribofuranosyl)-4-amino-5-(ethyn-l-yl)-pyr rolo[2,3-d]pyrimidine, compound 1.

SCHEME 2

14

[0293] In Scheme 2, 7-(2'-methyl-3',5'-di-O-(2,4-dichlorobenzyl)-β-D- ribofuranosyl)-4-chloro-5-iodo-pyrrolo[2,3-d]pyrimidine, compound 4, is aminated in the methods as described above to provide for 7-(2'-methyl-3',5'-di- O-(2,4-dichlorobenzyl)-β-D-ribofuranosyl)-4-amino-5-iodo-py rrolo[2,3- d]pyrimidine, compound 12. This compound serves as a focal point for a varity of reaction schemes which can be used to prepare 7-(2'-methyl-β-D- ribofuranosyl)-4-amino-5-(ethyn-l-yl)-pyrrolo[2,3-d]pyrimidi ne, compound 1. [0294] In a first embodiment, the hydroxy protecting groups of compound 12 are removed using boron trichloride in the manner described in Scheme 1 above to provide for 7-(2'-methyl-β-D-ribofuranosyl)-4-amino-5-iodo-pyrrolo[2,3- d]pyrimidine, compound 6. Compound 6, in turn, is converted to the

corresponding 7-(2'-methyl-β-D-ribofuranosyl)-4-amino-5- (trimethylsilylethynyl)-pyrrolo[2,3-d]pyrimidine, compound 7 using a catalytic amount of both cuprous iodide (CuI) and tetrakis(triphenyl-phosphine)palladium (0) together with an excess, typically 1.1 to 2 equivalents , of (trimethylsilyl)acetylene in the presence of a base as described above. [0295] In one embodiment, 7-(2'-methyl-β-D-ribofuranosyl)-4-amino-5- (trimethylsilyl-ethynyl)-pyrrolo[2,3-d]pyrimidine, compound 7 is desilylated as described above to provide for compound 1.

[0296] In another embodiment, compound 12 is converted to the corresponding 7-(2'-methyl-3',5'-di-O-(2,4-dichlorobenzyl)-β-D-ribofurano syl)-4-amino-5- (trimethylsilylethynyl)-pyrrolo[2,3-d]pyrimidine, compound 13 using a catalytic amount of both cuprous iodide (CuI) and tetrakis(triphenylphosphine)palladium (0) together with an excess, typically about 1.1 to 2 equivalents, of (trimethylsilyl)acetylene in the presence of a base as described above. [0297] Compound 13 is subject to both desilylation and removal of the hydroxy protecting groups to provide for compound 1. As shown in Scheme 2, the order ύ of these two steps is immaterial and in one embodiment, desilylation proceeds first in the manner described above to provide for 7-(2'-methyl-3',5'-di-O-(2,4- I dichlorobenzyl)-β-D-ribofuranosyl)-4-amino-5-ethynyl-pyrrol o[2,3-d]pyrimidine, compound 14, which is then subject to removal of the hydroxy blocking groups, also as described above, to provide for compound 1. In another embodiment, removal of the hydroxy blocking groups proceeds first to provide for 7-(2'- methyl-β-D-ribofuranosyl)-4-amino-5-(trimethylsilyl-ethynyl )-pyrrolo[2,3- d]pyrimidine, compound 7 which is then subject to desilylation to provide for compound 1.

[0298] Alternatively, compound 7a can be prepared by reacting compound 4 with a trimethylsilyl acetylene as described above. The trimethylsilyl group of compound 7a can be removed as described above to provide for compound 15. Compound 16 is prepared by removal of the benzyl protecting groups from compound 15. Amination of compound 15 using techniques described above provides for compound 14 which can then be converted to compound 1 as previously described.

[0299] In another alternative process, compound 7a or compound 15 can be converted directly to compound 14 by animating with liquid ammonia. [0300] The 2-substituted ribose sugars used in Schemes 1 and 2 above can be prepared from methods well known in the art. For example, one starting material of these compounds is an appropriately substituted sugar with 2'-OH and 2'-H. The sugar can be purchased or can be prepared by any known means including standard epimerization, substitution, oxidation and/or reduction techniques. For example, commercially available 1,3,5- tri-O-benzoyl-α-D-ribofuranose (Pfanstiel Laboratories, Inc.) can be used. The substituted sugar can then be oxidized with the appropriate oxidizing agent in a compatible solvent at a suitable temperature to yield the 2'-modified sugar. Possible oxidizing agents are, for example, Dess-Martin periodine reagent, Ac ₂ O+ DCC in DMSO, Swern oxidation (DMSO, oxalyl chloride, triethylamine), Jones reagent (a mixture of chromic acid and sulfuric acid), Collins' s reagent (dipyridine Cr(VI) oxide, Corey's reagent (pyridinium chlorochromate), pyridinium dichromate, acid dichromate, potassium permanganate, MnO ₂ , ruthenium tetraoxide, phase transfer catalysts such as chromic acid or permanganate supported on a polymer, Cl ₂ - pyridine, H ₂ θ ₂ -ammonium molybdate, NaBrO ₂ -CAN, NaOCl in HOAc, copper chromite, copper oxide, Raney nickel, palladium acetate, Meerwin-Pondorf- Verley reagent (aluminum t-butoxide with another ketone) and N- bromosuccinimide.

[0301] Coupling of an organometallic carbon nucleophile, such as a Grignard reagent, an organolithium, lithium dialkylcopper or CH ₃ -SiMe ₃ in TBAF with the ketone with the appropriate non-protic solvent at a suitable temperature, yields the 2'-methyl sugar. For example, CH ₃ MgBrZTiCl ₄ or CH ₃ MgBr/CeCl ₃ can be used as described in Wolfe et al. 1997. J. Org. Chem. 62: 1754-1759. The methylated sugar can be optionally protected with a suitable protecting group, preferably with an acyl, substituted alkyl or silyl group, by methods well known to those skilled in the art, as taught by Greene et al Protective Groups in Organic Synthesis, John Wiley and Sons, Second Edition, 1991.

[0302] In addition to the above, the 2'-C-substituted sugars used in the synthetic methods described herein are well known in the art and are described, for

example, by Sommadossi, et al. ¹⁰ and by Carrol, et al. ¹¹ ' ¹² all of which are incorporated herein by reference in their entirety.

[0303] Scheme 3 below describes the alternative synthesis of a protected sugar that is useful for coupling to the bases described herein.

SCHEME 3

^f e d where Ph is phenyl and X' is a suitable leaving group such as halo

[0304] Formation of sugar a in Scheme 1 , above, is accomplished as described by Mandal, S. B., et al, Synth. Commun., 1993, 9, page 1239, starting from commercial D-ribose. Protection of the hydroxy groups to form sugar b is described in Witty, D.R., et al, Tet. Lett., 1990, 31, page 4787. Sugar c and d are prepared using the method of Ning, J. et al, Carbohydr. Res., 2001, 330, page 165, and methods described herein. Sugar e is prepared by using a modification of the Grignard reaction with CH ₃ MgBr or other appropriate organometallic as described herein (with no titanium/cerium needed). Finally the halogenated sugar (X' = halo) used in the subsequent coupling reaction is prepared using the same protection method as used to make sugar b above. The halogenation is described in Seela, US Patent No. 6,211,158.

[0305] Subsequently, any of the described nucleosides can be deprotected by methods well known to those skilled in the art, as taught by Greene et al Protective Groups in Organic Synthesis, Jon Wiley and Sons, Second Edition, 1991.

[0306] An alternative approach to making protected sugars useful for coupling to heterocyclic bases is detailed in Scheme 4 below.

SCHEME 4

[0307] In Scheme 4, methylation of the hydroxy group of compound g proceeds via conventional methodology to provide for compound h. The 2, 3 and 5 hydroxy groups of the compound h are each protected with 2,4-dichlorobenzyl groups to provide for compound i. Selective deprotection of the 2-(2',4'- dichlorobenzyl) group on compound i proceeds via contact with stannous chloride in a suitable solvent such as methylene chloride, chloroform, and the like at reduced temperatures, e.g., ~ 0 to 5°C, until reaction completion, e.g., about 24-72 hours provides for compound j. Oxidation of the 2-hydroxy group proceeds as described herein to provide for compound k. Methylation also proceeds as described herein to provide for compound 1. [0308] Preparation of compounds where W, W ¹ or W ² is other than hydrogen, using the compounds prepared as above as the starting materials, can be accomplished using the methods described in the following reviews of prodrug preparation:

1) Cooperwood, J. S. et al, "Nucleoside and Nucleotide prodrugs, " in Ed(s) Chu, C. K. Recent Advances in Nucleosides (2002), 92-147.

2) Zemlicka, J. et al, Biochimica et Biophysica Acta (2002), 158(2-3), 276- 286.

3) Wagner, C. et al. , Medicinal Research Reviews (2002), 20(6), 417-451.

4) Meier, C. et al., Synlett (1998), (3), 233-242.

For example, conversion of the 5'-hydroxyl group of the l-[5-(alkynyl)-4-amino- pyrrolo[2,3-d]pyrimidine]-2'-C-methyl-β-D-ribofuranoside compounds to a phospho, diphospho or triphospho-analog can prepared using the methods describe in D. W. Hutchinson, (Ed. Leroy b. Townsend) "The Synthesis, reaction and Properties of Nucleoside Mono-, Di-, Tri-, and tertaphosphate and Nucleosides with Changes in the Phosphoryl Residue, " Chemistry of Nucleosides and Nucleotides, Plenum Press, (1991) 2.

[0309] The preparation of amino acid esters on the ribofuranoside can be accomplished as shown in Scheme 5 below:

SCHEME 5

[0310] The desired boc-protected amino acid, (preferably an L-amino acid), and N,N'-carbonyldiimidazole are dissolved in an inert solvent such as THF. The reaction mixture is held between about 20 and about 40 °C for about 0.5 to 24

hours. A solution containing an slight excess of the desired nucleoside in an inert solvent such as DMF, is added to the Boc-protected amino acid mixture and is heated at about 40 to about 8O ⁰ C for about 2 to about 24 hours. A mixture of structural isomers is isolated and separated using conventional techniques such as evaporation, precipitation, filtration, crystallization, chromatography and the like. [0311] The desired ester is then acidified using, for example, about 1 : 1 v/v TFA/DCM solution for about 0.1 to about 1 hour about 20 and about 4O ⁰ C and evaporated. The residue is dissolved in water and held at about 0 to about 3O ⁰ C for about 2 to about 24 hours. The mixture can be separated and the desired product isolated by RP-HPLC using standard techniques and conditions. [0312] While the scheme above demonstrates the production of deazapurine prodrugs, this process can be used on any desired nucleoside compound. Likewise, the amino acid may be protected with any protective group appropriate to the reaction conditions. These protective groups are well known in the art. [0313] The preparation of other alkyl esters on the ribofuranoside can be accomplished as shown in Scheme 6 below: £

SCHEME 6

[0314] Compound 1 is dissolved in a dry solvent, such as pyridine, and a silylhalide, such as tert-butylchlorodiphenylsilane, is added to form a protecting

group at the 5 '-position on the sugar. Any protecting group which can be directed to the 5 '-position and can be removed orthongally to the final desired 3'- ester can be used. This reaction is run for about 4 to 24 hours at a temperature of about 10 to 40°C. The desired acyl chloride is added to the protected nucleoside, compound 30, and stirred for about 4 to about 24 hours to form compound 31. Which can be isolated and purified using standard techniques such as isolation, crystallization, extraction, filtration, chromatography and the like. Compound 32 is prepared by removing the protecting group at the 5 '-position. This can be accomplished by reacting compound 30 with a IM solution of tetrabutylammonium fluoride in THF. The final product is isolated and purified using standard techniques such as isolation, crystallization, extraction, filtration, chromatography and the like.

[0315] While the scheme above demonstrates the production of deazapurine prodrugs, this process can be used on any desired nucleoside compound.

UTILITY, TESTING, AND ADMINISTRATION

Utility

[0316] The present embodiments provide novel compounds possessing antiviral activity, including against hepatitis C virus. The compounds of the embodiments inhibit viral replication by inhibiting the enzymes involved in replication, including RNA dependent RNA polymerase. They may also inhibit other enzymes utilized in the activity or proliferation of viruses in the flaviviridae family, such as HCV.

[0317] The compounds of the present embodiments can also be used as prodrug nucleosides. As such they are taken up into the cells and can be intracellularly phosphorylated by kinases to the triphosphate and are then inhibitors of the polymerase (NS5b) and/or act as chain-terminators.

[0318] Compounds of the embodiments may be used alone or in combination with other compounds to treat viruses.

Administration and Pharmaceutical Composition

[0319] In general, the compounds of the embodiments will be administered in a therapeutically effective amount by any of the accepted modes of administration

for agents that serve similar utilities. The actual amount of the compound of the embodiments, i.e., the active ingredient, will depend upon numerous factors such as the severity of the disease to be treated, the age and relative health of the subject, the potency of the compound used, the route and form of administration, and other factors. The drug can be administered more than once a day, preferably once or twice a day.

[0320] Therapeutically effective amounts of compounds of Formulas I and II may range from about 0.05 to about 50 mg per kilogram body weight of the recipient per day; preferably about 0.01-25 mg/kg/day, more preferably from about 0.5 to about 10 mg/kg/day. Thus, for administration to an about 70 kg person, the dosage range would most preferably be about 35-70 mg per day. [0321] In general, compounds of the embodiments will be administered as pharmaceutical compositions by any one of the following routes: oral, systemic (e.g., transdermal, intranasal or by suppository), or parenteral (e.g., intramuscular, intravenous or subcutaneous) administration. The preferred manner of administration is oral using a convenient daily dosage regimen that can be adjusted according to the degree of affliction. Compositions can take the form of tablets, pills, capsules, semisolids, powders, sustained release formulations, solutions, suspensions, elixirs, aerosols, or any other appropriate compositions. Another preferred manner for administering compounds of the embodiments is inhalation.

[0322] The choice of formulation depends on various factors such as the mode of drug administration and bioavailability of the drug substance. For delivery via inhalation the compound can be formulated as liquid solution, suspensions, aerosol propellants or dry powder and loaded into a suitable dispenser for administration. There are several types of pharmaceutical inhalation devices- nebulizer inhalers, metered dose inhalers (MDI) and dry powder inhalers (DPI). Nebulizer devices produce a stream of high velocity air that causes the therapeutic agents (which are formulated in a liquid form) to spray as a mist that is carried into the patient's respiratory tract. MDI's typically are formulation packaged with a compressed gas. Upon actuation, the device discharges a measured amount of therapeutic agent by compressed gas, thus affording a reliable method of administering a set amount of agent. DPI dispenses

therapeutic agents in the form of a free flowing powder that can be dispersed in the patient's inspiratory air-stream during breathing by the device. In order to achieve a free flowing powder, the therapeutic agent is formulated with an excipient such as lactose. A measured amount of the therapeutic agent is stored in a capsule form and is dispensed with each actuation.

[0323] Recently, pharmaceutical formulations have been developed especially for drugs that show poor bioavailability based upon the principle that bioavailability can be increased by increasing the surface area i.e., decreasing particle size. For example, U.S. Pat. No. 4,107,288 describes a pharmaceutical formulation having particles in the size range from about 10 to about 1,000 nm in which the active material is supported on a crosslinked matrix of macromolecules. U.S. Patent No. 5,145,684 describes the production of a pharmaceutical formulation in which the drug substance is pulverized to nanoparticles (average particle size of about 400 nm) in the presence of a surface modifier and then dispersed in a liquid medium to give a pharmaceutical formulation that exhibits remarkably high bioavailability.

[0324] The compositions are comprised of in general, a compound of Formula I or II in combination with at least one pharmaceutically acceptable excipient. Acceptable excipients are non-toxic, aid administration, and do not adversely affect the therapeutic benefit of the compound of Formulas I and II. Such excipient may be any solid, liquid, semi-solid or, in the case of an aerosol composition, gaseous excipient that is generally available to one of skill in the art.

[0325] Solid pharmaceutical excipients include starch, cellulose, talc, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, magnesium stearate, sodium stearate, glycerol monostearate, sodium chloride, dried skim milk and the like. Liquid and semisolid excipients may be selected from glycerol, propylene glycol, water, ethanol and various oils, including those of petroleum, animal, vegetable or synthetic origin, e.g., peanut oil, soybean oil, mineral oil, sesame oil, etc. Preferred liquid carriers, particularly for injectable solutions, include water, saline, aqueous dextrose, and glycols.

[0326] Compressed gases may be used to disperse a compound of the embodiments in aerosol form. Inert gases suitable for this purpose are nitrogen,

carbon dioxide, etc. Other suitable pharmaceutical excipients and their formulations are described in Remington's Pharmaceutical Sciences, edited by E. W. Martin (Mack Publishing Company, 18th ed., 1990).

[0327] The amount of the compound in a formulation can vary within the full range employed by those skilled in the art. Typically, the formulation will contain, on a weight percent (wt%) basis, from about 0.01-99.99 wt% of a compound of Formula I or II based on the total formulation, with the balance being one or more suitable pharmaceutical excipients. Preferably, the compound is present at a level of about 1-80 wt%. Representative pharmaceutical formulations containing a compound of Formula I are described below. [0328] Additionally, the present embodiments are directed to a pharmaceutical composition comprising a therapeutically effective amount of a compound of the present embodiments in combination with a therapeutically effective amount of another active agent against RNA-dependent RNA virus and, in particular, against HCV. Agents active against HCV include, but are not limited to, Ribavirin, levovirin, viramidine, thymosin alpha- 1, an inhibitor of HCV NS3 serine protease, or an inhibitor of inosine monophosphate dehydrognease, interferon-α, pegylated interferon-α (peginterferon-α), a combination of interferon-α and Ribavirin, a combination of peginterferon-α and Ribavirin, a combination of interferon-α and levovirin, and a combination of peginterferon-α and levovirin. Interferon-α includes, but is not limited to, recombinant interferon-α2a (such as ROFERON interferon available from Hoffman-LaRoche, Nutley, NJ), interferon-α2b (such as Intron-A interferon available from Schering Corp., Kenilworth, New Jersey, USA), a consensus interferon, and a purified interferon-α product. For a discussion of Ribavirin and its activity against HCV, see J.O. Saunders and S.A. Raybuck, "Inosine Monophosphate Dehydrogenase: Consideration of Structure, Kinetics and Therapeutic Potential," Ann. Rep. Med. Chem., 35:201-210 (2000).

Biological Examples

Example 1. Anti-Hepatitis C Activity

[0329] Compounds can exhibit anti-hepatitis C activity by inhibiting HCV polymerase, by inhibiting other enzymes needed in the replication cycle, or by

other pathways. A number of assays have been published to assess these activities. A general method that assesses the gross increase of HCV virus in culture is disclosed in U.S. Patent No. 5,738,985 to Miles et al In vitro assays have been reported in Ferrari et al. JnI ofVir., 73:1649-1654, 1999; Ishii et al, Hepatology, 29:1227-1235, 1999; Lohmann et al, JnI of Bio. Chem., 274:10807- 10815, 1999; and Yamashita et al, JnI of Bio. Chem., 273:15479-15486, 1998. [0330] WO 97/12033, filed on September 27, 1996, by Emory University, listing C. Hagedorn and A. Reinoldus as inventors, which claims priority to United States Provisional Patent Application. Serial No. 60/004,383, filed on September 1995, describes an HCV polymerase assay that can be used to evaluate the activity of the compounds described herein. Another HCV polymerase assay has been reported by Bartholomeusz, et al, Hepatitis C Virus (HCV) RNA polymerase assay using cloned HCV non-structural proteins; Antiviral Therapy 1996:l(Supp 4) 18-24.

[0331] Screens that measure reductions in kinase activity from HCV drugs are disclosed in U.S. Patent No. 6,030,785, to Katze et al, U.S. Patent No. 6,228,576, Delvecchio, and U.S. Patent No. 5,759,795 to Jubin et al. Screens that ? measure the protease inhibiting activity of proposed HCV drugs are disclosed in U.S. Patent No. 5,861,267 to Su et al, U.S. Patent No. 5,739,002 to De Francesco et al, and U.S. Patent No. 5,597,691 to Houghton et al

Example 2. Replicon Assay

[0332] A cell line, ET (Huh-lucubineo-ET) is used for screening of compounds of the present embodiments for HCV RNA dependent RNA polymerase. The ET cell line is stably transfected with RNA transcripts harboring a I ₃₈₉ luc-ubi- neo/NS3-3'/ET; replicon with firefly luciferase-ubiquitin-neomycin phosphotransferase fusion protein and EMCV-IRES driven NS3-5B polyprotein containing the cell culture adaptive mutations (E1202G; T 12801; Kl 846T) (Krieger at al, 2001 and unpublished). The ET cells are grown in DMEM, supplemented with 10% fetal calf serum, 2 mM Glutamine, Penicillin (100 IU/mL)/Streptomycin (100 μg/mL), Ix nonessential amino acids, and 250 μg/mL G418 ("Geneticin"). They are all available through Life Technologies (Bethesda, MD). The cells are plated at 0.5-1.0 xlO ⁴ cells/well in the 96 well plates and

incubated for 24 hrs before adding nucleoside analogs. Then the compounds were added to the cells to achieve a final concentration of 5 or 50 μm. Luciferase activity will be measured 48-72 hours later by adding a lysis buffer and the substrate (Catalog number Glo-lysis buffer E2661 and Bright-Glo leuciferase system E2620 Promega, Madison, WI). Cells should not be too confluent during the assay. Percent inhibition of replication will be plotted relative to no compound control. Under the same condition, cytotoxicity of the compounds will be determined using cell proliferation reagent, WST-I (Roche, Germany). The compounds showing antiviral activities, but no significant cytotoxicities will be chosen to determine IC ₅₀ and TC ₅₀ . For these determinations, 6 dilutions of each compound were used. Compounds were typically diluted 3 fold to span a concentration range of 250 fold. IC ₅₀ and TC ₅₀ values were calculated by fitting %inhibition at each concentration to the following equation:

% inhibition = 100%/[(IC50/[l]) ^b +1] where b is Hill's coefficient.

[0333] Data for compounds of the embodiments and for some homologs and analoguesof the compounds of the embodiments are give in Tables II and III below.

Example 3. Cloning and expression of recombinant HCV-NS 5b

[0334] The coding sequence of NS5b protein is cloned by PCR from pFKI ₃₈₉ luc/NS3-3'/ET as described by Lohmann, V., et al. (1999) Science 285,

110-113 using the primers shown on page 266 of WO 2005/012288, , herein incorporated by reference in its entirety.

[0335] The cloned fragment is missing the C terminus 21 amino acid residues.

The cloned fragment is inserted into an IPTG-inducible expression plasmid that provides an epitope tag (His)6 at the carboxy terminus of the protein.

[0336] The recombinant enzyme is expressed in XL-I cells and after induction of expression, the protein is purified using affinity chromatography on a nickel-

NTA column. Storage condition is 10 mM Tris-HCl pH 7.5, 50 mM NaCl, 0.1 mM EDTA, 1 mM DTT, 20% glycerol at -20 °C.

Example 4. HCV-NS5b Enzyme Assay

[0337] The polymerase activity is assayed by measuring incorporation of radiolabeled UTP into a RNA product using a biotinylated, heteropolyeric template, which includes a portion of the HCV genome. Typically, the assay mixture (50 μL) contains 10 mM Tris-HCl (pH 7.5), 5 mM MgCl ₂ , 0.2 mM EDTA, 10 mM KCl, 1 unit/μL RNAsin, 1 mM DTT, 10 μM each of NTP, including [ ³ H]-UTP, and 10 ng/μL heteropolymeric template. Test compounds are initially dissolved in 100% DMSO and further diluted in aqueous buffer containing 5% DMSO. Typically, compounds are tested at concentrations between 1 nM and 100 μM. Reactions are started with addition of enzyme and allowed to continue at 37°C for 2 hours. Reactions are quenched with 8 μL of 100 mM EDTA and reaction mixtures (30 μL) are transferred to streptavidin- coated scintillation proximity microtiter plates (FlashPlates) and incubated at 4° C overnight. Incorporation of radioactivity is determined by scintillation counting.

Formulation Examples

[0338] The following are representative pharmaceutical formulations containing a compound of the present embodiments.

Example 1: Tablet formulation

[0339] The following ingredients are mixed intimately and pressed into single scored tablets.

Quantity per

Ingredient tablet, mg compound of the embodiments 400 cornstarch 50 croscarmellose sodium 25 lactose 120 magnesium stearate 5

Example 2: Capsule formulation

[0340] The following ingredients are mixed intimately and loaded into a hard-shell gelatin capsule.

Quantity per

Ingredient capsule, mg compound of the embodiments 200 lactose, spray-dried 148 magnesium stearate 2

Example 3: Suspension formulation

[0341] The following ingredients are mixed to form a suspension for oral administration.

Ingredient Amount compound of the embodiments 1.0 g fumaric acid 0.5 g sodium chloride 2.O g methyl paraben 0.15 g propyl paraben 0.05 g granulated sugar 25.O g sorbitol (70% solution) 13.00 g

Veegum K (Vanderbilt Co.) 1.0 g flavoring 0.035 mL colorings 0.5 mg distilled water q.s. to 100 mL

Example 4: Injectable formulation

[0342] The following ingredients are mixed to form an injectable formulation.

Ingredient Amount compound of the embodiments 0.2 mg-20 mg sodium acetate buffer solution, 0.4 M 2.O mL

HCl (lN) or NaOH (lN) q.s. to suitable pH water (distilled, sterile) q.s. to 20 mL

Example 5; Suppository formulation

[0343] A suppository of total weight 2.5 g is prepared by mixing the compound of the embodiments with Witepsol® H- 15 (triglycerides of saturated vegetable fatty acid; Riches-Nelson, Inc., New York), and has the following composition:

Ingredient Amount compound of the embodiments 500 mg

Witepsol® H- 15 balance

[0344] One skilled in the art will recognize that the above Examples are for exemplification only and should in no way limit the scope of the invention. Modifications of the compositions and methods described herein or referred to, herein, will be apparent to one skilled in the art, without departing from the scope of the invention.