601241, 848 filed October 20,2000 and entitled"Inhibitors for Activated Blood Coagulation Factor VIIa (FVIIa)"and S. N. 601281, 735 filed April 6,2001 and entitled"Biaryl Compounds as Serine Protease Inhibitors" Technical Field The present invention relates to the identification, through synthesis and testing, of heretofore unreported compounds which, in appropriate pharmaceutical compositions, exert a therapeutic effect through reversible inhibition of serine proteases.

Background of Invention Serine proteases make up the largest and most extensively studied group of proteolytic enzymes. Their critical roles in physiological processes extend over such diverse areas as blood coagulation, fibrinolysis, complement activation, reproduction, digestion, and the release of physiologically active peptides. Many of these vital processes begin with cleavage of a single peptide bond or a few peptide bonds in precursor protein or peptides. Sequential limited proteolytic reactions or cascades are involved in blood clotting, fibrinolysis, and complement activation. The biological signals to start these cascades can be controlled and amplified as well. Similarly, controlled proteolysis can shut down or inactivate proteins or peptides through single bond cleavages.

While serine proteases are physiologically vital, they also can be hazardous.

Their proteolytic action, if uncontrolled, can destroy cells and tissues through degradation of proteins. As a natural safeguard in normal plasma, 10% of the protein matter is composed of protease inhibitors. The major natural plasma inhibitors are specific for serine proteinases. Diseases (associated protease given in the parentheses) such as pulmonary emphysema (cathepsin G), adult respiratory distress syndrome (chymases), and pancreatitis (trypsin, chymotrypsin, and others) are characterized by uncontrolled serine proteases, Other proteases appear to be involved in tumor invasion (plasmin, plasminogen activator), viral transformation, and inflammation (kallikrein). Thus the design and synthesis of specific inhibitors for this class of proteinases could offer major therapeutic benefits.

Thrombus formation, that is blood coagulation, is normally initiated by tissue injury ; its normal purpose is to slow or prevent blood loss and facilitate wound healing.

There are other conditions, however, not directly connected with tissue injury that may promote the coagulation process and lead instead to harmful consequences ; examples of such conditions are atherosclerosis and inflammation.

The complex pathways of blood coagulation involve a series of enzyme reactions in which plasma coagulation factors, actually enzyme precursors or zymogens, are sequentially activated by limited proteolysis. Blood coagulation, or the coagulation cascade, is viewed mechanistically as two pathways, the extrinsic and the intrinsic (Fig.

1). Each pathway proceeds through a sequence of the Roman-numeral-designated factors until they converge at the activation of factor X after merger of the pathways. Thrombin generation proceeds stepwise through a common pathway. Thrombin then acts on the solution plasma protein, fibrinogen, to convert it to stable insoluble fibrin clots, thus completing the coagulation cascade.

The extrinsic pathway is vital to the initiation phase of blood coagulation while the intrinsic pathway provides necessary factors in the maintenance and growth of fibrin.

The initiation of the coagulation cascade involves the release of tissue factor (TF) from injured vessel endothelial cells and subendothelium. TF then acts upon factor VII to form the TF/FVIIa complex (where VIIa designates the activated factor rather than the zymogen form). This complex initiates coagulation by activating factors IX and X. The resulting factor Xa forms a prothrombinase complex that activates prothrombin to produce the thrombin that converts fibrinogen to insoluble fibrin. In contrast, the intrinsic system is activated in vivo when certain coagulation proteins contact subendothelial connective tissue. In the sequence that follows, contact factors XII and XI are activated. The resulting factor XIa activates factor IX; then factor IXa activates factor X thereby intersecting with the extrinsic pathway.

With time, the TF/FVIIIa complex (of the extrinsic pathway) loses activity due to the action of tissue factor pathway inhibitor (TFPI), a Kunitz-type protease inhibitor protein which, when complexed with factor Xa, can inhibit the proteolytic activity of TF/FVIIa. If the extrinsic system is inhibited, additional factor Xa is produced through the thrombin-mediated action in the intrinsic pathway. Thrombin, therefore, exerts a dual catalytic role in (a) the conversion of fibrinogen to fibrin and (b) mediating its own production. The autocatalytic aspect of thrombin production affords an important safeguard against excessive blood loss, and, assuming presence of a threshold level of prothrombinase, ensures that the blood coagulation process will go to completion.

While the ability to form blood clots is vital to survival, there are disease states wherein the formation of blood clots within the circulatory system can cause death.

When patients are afflicted with such disease states, it is not desirable to completely inhibit the clotting system because life-threatening hemorrhage would follow. Thus, it is highly desirable to develop agents that inhibit coagulation by inhibition of factor VIIa without directly inhibiting thrombin.

Need for the prevention of intravascular blood clots or for anti-coagulant treatment in many clinical situations is well known. Drugs in use today are often not satisfactory. A high percentage of patients who suffer internal injuries or undergo certain surgical procedures develop intravascular blood clots which, if unchecked, cause death.

In total hip replacement surgery, for example, it is reported that 50% of the patients develop deep vein thrombosis (DVT). Current approved therapies involve administration of heparin in various forms, but results are not entirely satisfactory; 10-20% of patients suffer DVT and 5-10% have bleeding complications Along these lines, see International Publication No. WO 00/15658.

Other examples of clinical situations for which better anticoagulants would be of great value are when patients undergo transluminal coronary angioplasty and treatment for myocardial infarction or crescendo angina. The present therapy for these conditions is administration of heparin and aspirin, but this treatment is associated with a 6-8% abrupt vessel closure rate within 24 hours of the procedure. Transfusion therapy due to bleeding complications is required in approximately 7% of cases following the use of heparin. Occurrences of delayed vessel closures are also significant, but administration of heparin after termination of the procedure affords little beneficial effect and can be detrimental.

Heparin and certain derivatives thereof are the most commonly used anti-clotting agents. These substances exert their effects mainly through inactivation of thrombin, which is inactivated 100 times faster than factor Xa. Two other thrombin-specific anticoagulants, hirudin and hirulog, are in clinical trials (as of September 1999).

However, bleeding complications are associated with these agents.

In preclinical studies in baboons and dogs, the targeting of enzymes involved in earlier stages of the coagulation cascade, such as factor VIIa or factor Xa, prevents clot

formation and does not produce bleeding side effects observed with direct thrombin inhibitors.

Several preclinical studies reveal that inhibition of TF/FVIIa offers the widest window of therapeutic effectiveness and safety with respect to bleeding risk of any anticoagulant approach tested including thrombin, platelet, and factor Xa inhibition.

A specific inhibitor of factor VIIa would provide clinicians with a valuable and needed agent that would be safe and effective in situations where the present drugs of choice, heparin and related sulfated polysaccharides, are no better than marginally effective.

There exists a need for a low molecular weight specific serine protease inhibitors specific toward various enzymes, particularly for factor VIIa that does not cause unwanted side effects.

Figure 1. Pathways of Coagulation Extrinsic Pathway Intrinsic Pathway Release of TF Release of Contact Factors XII and XI VIT XIIa----XII i TF/FVIIa xi-xi IXa IX X Common Pathway Prothrombin--------Thrombin ---j-Fibrinogen---- Fibrin

The figure illustrates the extrinsic and intrinsic pathways of blood coagulation.

Summary of Invention An aspect of the present invention relates to compounds represented by the formula: ;pharmaceutically acceptable salts thereof; and prodrugs thereof Each El and L individually is a 5 to 7 membered saturated or unsaturated carbon ring, 5 to 7 membered saturated or unsaturated hetero ring, bicyclic saturated or unsaturated carbon ring, bicyclic saturated or unsaturated hetero ring, or 1-8 hydrocarbon chain which may be substituted with one or more hetero groups selected from N, O, S, S (O), and S (O2) which may be saturated or unsaturated. The bicyclic rings typically contain 7-13 atoms in the ring.

R is-CH=CH-R2,-C_C-R2,-C (R2) =CH2,-C (R2) =C (R3),-CH=NR2,-C (R2)--N-R3, 4-7 membered saturated or unsaturated carbon ring system with or without substitution, 4-7 membered saturated or unsaturated hetero ring system with or without substitution, or chain of 2 to 8 carbon atoms having 1 to 5 double or triple bonds with substitutions selected from R1, R2, or R3.

R1 is H, -R, -NO2, -CN, -halo, -N3, -C1-8 alkyl, -(CH2)nCO2R2, -C2-8alkenyl-CO2R2, -O (CH2)nCO2R2,-C(O)NR2R3,-P(O)(OR2)2, alkyl substituted tetrazol-5-yl, -(CH2)nO(CH2)n aryl, -NR2R3, -(CH2)n OR2, -(CH2)nSR2, -N(R2) C (o) R3, -S(O2)NR2R3, -N (R') S (02) R3, -(CHR2)n NR2R3, -C(O)R3, (CH2)nN(R3)C(O)R3, -N(R2)CR2R3 substituted or unsubstituted (CH2) n-cycloalkyl, substituted or unsubstituted (CH2)n- phenyl, or substituted or unsubstituted (CH2) n-heterocycle which may be saturated or unsaturated. m is 1 except that when EI is a cyclic ring of more than 5 atoms, then m is 1 or higher, depending upon the size of the ring.

W is H,-halo,-alkyl,-haloalkyl,- (CH2),-PhenYl,- (CH2) 1-3-biphenyl,- (CH2) 1-4-Ph- N (SO2-C1-2-alkyl)2, -CO(CHR1)n-OR1, -(CHR1)n-heterocycle, -(CHR1)n-NH-CO-R1, -(CHR1)n-NH-SO2R1, -(CHR1)n-Ph-N(SO2-C1-2-alkyl)2, -(CHR1)n-C(O)(CHR1)-NHR1, - (CHR1)n-C (S) (CHR1)-NHR1, -(CH2)nO(CH2)nCH3,-CF3,-C2-5 acyl, -(CHR1)nOH, -(CHR1)nCO2R1, -(CHR1)n-O-alkyl, -(CHR1)n-O-(CH2)n-O-alkyl, -(CHR1)n-S-alkyl, -(CHR1)n-S(O)-alkyl, -(CHR1)n-S(O2)-alkyl, -(CHR1)n-S(O2)-NHR3, -(CHR3)n-N3, - nNHR4, 2 to 8 carbon atom alkene chain having 1 to 5 double bonds, 2 to 8 carbon atom alkyne chain having 1 to 5 triple bonds, substituted or unsubstituted- (CHR3) n heterocycle, or substituted or unsubstituted-(CHR3) n cycloalkyl which may be saturated or unsaturated.

When n is more than 1, the substitutions Rl and R3 may be same or different.

R3 is H,-OH,-CN, substituted alkyl,-C2-8 alkenyl, substituted or unsubstituted cycloalkyl,-N (R') R2, or 5-6 membered saturated substituted or unsubstituted hetero ring.

-NR2R3 may form a ring system having 4 to 7 atoms or may be bicyclic ring. The ring system may be of carbon or hetero atoms and further it may saturated or unsaturated and also may be substituted or unsubstituted.

W is a direct bond, -CHR2-, -CH=CR2-, -CR2=CH-, -CR2=CR2-, -C=C-, -O-CHR2-, -CHR2-O-, -N(R2)-C(O)-, -C(O)-N(R2)-, -N(R2)-CH-(R3)-, -CH2-N(R2)-, -CH (Ri)-N (R2)-, -S-CHR2-, -CHR2-S-, -S (O2)-N (R2)-, -C (4) N (R2)-(CHR2)n-, -C(R1R2)n-NR2-, -N(R2)-S(O2)-, -R2C(O)NR2-, -R2NC(O)NR2-, -CONR2CO-,- C(=NR2)NR2-, -NR2C(=NR2)NR2, -NR2O-, -N=NCHR2-, or -C(O)NR2SO2-, E2 is 5 to 7 membered saturated or unsaturated carbon ring, 5 to 7 membered saturated or unsaturated hetero ring, bicyclic ring system, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, alkylaryl, aralkyl, aralkenyl, aralkynyl, alkoxy, alkylthio, or alkylamino. each X individually is a direct bond, substituted or unsubstituted Cl-4 methylene chain; O, S, NR2, S (O), S (O2), or N (O) containing one or two C1-4 substituted or unsubstituted methylene chains. X at different places may be same or different.

B is H, -halo, -CN, -NH2, -(CH2)n-C(=NR4)NHR5, -(CH2)n-NHR4,- (CH2)nNHC(=NR4)NR5,-(CH2)n-OR4, C1-8 substituted or unsubstituted alkyl, substituted or unsubstituted ring system having 4 to 7 carbon or hetero atoms which may be saturated or unsaturated.

B1 is selected from B; B1 and B may be same or different.

There may be more than one similar or different Ra groups present on E, when E2 is a cyclic group of more than 5 atoms. In particular, p is 1 except that when E2 is a cyclic ring of more than 5 atoms, p is 1 or higher depending upon the size of the ring. n is 0-4 A is selected from R.

o is 1 except that when L is a cyclic ring of more than 5 atoms, o is 1 or higher depending upon the size of the ring.

Each V and V1 individually is selected from Rl and N-alkyl substituted carboxamidyl (- CONHR) where the alkyl group may be straight, branched, cyclic, or bicyclic; N, N- disubstituted carboxamidyl (-CONR1R2 where R1 and Ra may be substituted or unsubstituted alkyl or aryl and may be the same or different); mono-or disubstituted sulfonamides (SO2NHR or-SO2NR1R2) ; and methylene-or polymethylene chain- extended variants thereof.

Each R4 and W individually is H,-(CH2) nOH,-C (O) OR6,-C (O) SR6,-(CH2) n C (o) NR7R8, -O-C (O)-O-R7, an amino acid or a dipeptide, Each R6 is H, R7, -C(R7)(R8)-(CH2)n-O-C(O)-R9, -(CH2)n-C(R7)(R8)-O-C(O)R9, -(CH2)n- C (R7) (R8)-o-C (O)-O-R9, or-C (R7) (le)- (CH2)n-O-C(O)-O-R9, Each R7, R8 and R9 individually is H, alkyl, substituted alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, heterocycle, substituted heterocycle, alkylaryl, substituted alkylaryl, cycloalkyl, substituted cycloalkyl, or CH2C02alkyl.

The present invention also relates to pharmaceutical compositions containing at least one of the above disclosed compounds and their prodrugs.

A further aspect of the present invention relates to a method for inhibiting trypsin- like serine protease enzymes, such as thrombin, factor Xa, factor VIIa, TF/VIIa, and trypsin in a patient which comprises administering to the patient an effective serine protease inhibiting amount of at least one of the above disclosed compounds.

Still other objects and advantages of the present invention will become readily apparent by those skilled in the art from the following detailed description, wherein it is shown and described preferred embodiments of the invention, simply by way of illustration of the best mode contemplated of carrying out the invention. As will be realized the invention is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, without departing from the invention. Accordingly, the description is to be regarded as illustrative in nature and not as restrictive.

Best and Various Modes for Carrying Out Invention An aspect of the present invention relates to compounds represented by the formula : R R B1 (Ri) E1 W E2 B X p2 ; pharmaceutically acceptable salts thereof; i V1 L V andprodrugsthereof. I (A) 0 Each E'and L individually is a 5 to 7 membered saturated or unsaturated carbon ring, 5 to 7 membered saturated or unsaturated hetero ring, bicyclic saturated or unsaturated carbon ring, bicyclic saturated or unsaturated hetero ring, or 1-8 hydrocarbon chain which may be substituted with one or more hetero groups selected from N, O, S, S (0), and S (O2) which may be saturated or unsaturated.

R is-CH=CH-R2,-C_C-R2,-C (ruz) =CH2,-C (le) =C (R3),-CH=NR2,-C (R2)=N-R3, 4-7 membered saturated or unsaturated carbon ring system with or without substitution, 4-7 membered saturated or unsaturated hetero ring system with or without substitution, or chain of 2 to 8 carbon atoms having 1 to 5 double or triple bonds with substitutions selected from Rl, R2, or R3. Preferably, these R, Rl, R2, or R3 do not include- (C2-4 alkenyl)-CO2-C1-8 alkyl, -(C2-4 alkenyl)-CO2-C1-8 alkyl-phenyl, and- (C2-4 alkenyl)-C02- C1-8 alkyl-O-C1-4 alkyl.

Rl is H,-R,-NO2,-CN,-halo,-N3,-C 1-8 alkyl,- (CH2) nC02R2,-C2-g alkenyl-C02R2, -O (CH2)nCO2R2, -C(O)NR2R3, -P(O)(OR2)2, alkyl substituted tetrazol-5-yl, -(CH2)nO(CH2)n aryl, -NR2R3, -(CH2)n OR2, -(CH2)n SR2,-N(R2) C (O) R3,-S (02) NR2R3, -N(R2)S(O2)R3, -(CHR2)n NR2R3, -C(O)R3, (CH2)n N(R3)C(O)R3, -N(R2)CR2R3 substituted or unsubstituted (CH2) n-cycloalkyl, substituted or unsubstituted (CH2) n- phenyl, or substituted or unsubstituted (CH2)n-heterocycle which may be saturated or unsaturated. m is 1 except that when El is a cyclic ring of more than 5 atoms, then m is 1 or higher, depending upon the size of the ring. For instance if the ring is 6 atoms, m can be 1 or 2.

R is H,-halo,-alkyl,-haloalkyl,- (CH2)n-phenyl, -(CH2)1-3-biphenyl,-(CH2)1-4-Ph- N (SO2-C1-2-alkyl) 2,-CO (CHRI)"-ORI,- (CHR')"heterocycle,- (CHRI) n-NH-CO-Rl, -(CHR1)n-NH-SO2R1, -(CHR1)n-Ph-N(SO2-C1-2-alkyl)2, -(CHR1)n-C(O)(CHR1)-NHR1, -(CHR1)n-C(S)(CHR1)-NHR1, -(CH2)nO(CH2)nCH3,-CF3, -C2-5 acyl, -(CHR1)nOH, -(CHR1)nCO2R1,-(CHR1)n-O-alkyl, -(CHR1)n-O-(CH2)n-O-alkyl, -(CHR1)n-S-alkyl, -(CHR1)n-S(O)-alkyl, -(CHR1)n-S(O2)-alkyl, -(CHR1)n-S(O2)-NHR3, -(CHR3)n-N3, - nNHR4, 2 to 8 carbon atom alkene chain having 1 to 5 double bonds, 2 to 8 carbon atom alkyne chain having 1 to 5 triple bonds, substituted or unsubstituted- (CHR3) n heterocycle, or substituted or unsubstituted-(CHR3) n cycloalkyl which may be saturated or unsaturated.

When n is more than 1, the substitutions R1 and R3 may be same or different.

R3 is H,-OH,-CN, substituted alkyl,-C2-8 alkenyl, substituted or unsubstituted cycloalkyl,-N (R1) R2, or 5-6 membered saturated substituted or unsubstituted hetero ring.

-NR2R3 may form a ring system having 4 to 7 atoms or may be bicyclic ring. The ring system may be of carbon or hetero atoms and further it may saturated or unsaturated and also may be substituted or unsubstituted.

W is a direct bond, -CHR2-, -CH=CR2-, -CR2=CH-, -CR2=CR2-, -C=C-, -O-CHR2-, -CHR2-O-,-N (R2)-C (O)-,-C (O)-N (R2)-, -N (R2)-CH-(R3)-, -CH2-N(R2)-, -CH (Rt)-N (R2)-, -S-CHR2-, -CHR2-S-, -S (02)-N (R2)-,-C (O) N (R2)- (CHR2) n-, -C (R1R2) n-NR2-,-N (R2)-S (02)-,-R2C (O) NR2-, -R2NC (O) NR2-,-CONR2CO-,- C (=NR2)NR2-, -NR2C(=NR2)NR2-, -NR2O-, -N=NCHR2-, or-C (O) NR2SO2-.

E2 is 5 to 7 membered saturated or unsaturated carbon ring, 5 to 7 membered saturated or unsaturated hetero ring, bicyclic ring system, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, alkylaryl, aralkyl, aralkenyl, aralkynyl, alkoxy, alkylthio, or alkylamino. each X individually is a direct bond, substituted or unsubstituted C1-4 methylene chain; O, S, NR2, S (O), S (02), orN (O) containing one or two C1-4 substituted or unsubstituted methylene chains. X at different places may be same or different.

B is H, -halo, -CN, -NH2, -(CH2)n-C(=NR4)NHR5, -(CH2)n-NHR4,- (CH2)nNHC(=NR4)NR5, -(CH2)n-OR4, C1-8 substituted or. unsubstituted alkyl, substituted or unsubstituted ring system having 4 to 7 carbon or hetero atoms which may be saturated or unsaturated.

Bl is selected from B; Bl and B may be same or different.

There may be more than one similar or different R2, groups present on E2, when E2 is a cyclic system of more than 5 atoms. p is 1 or higher if ex is a cyclic ring of more than 5 atoms. For example, if the ring is 6 atoms, p can be 1 or 2. n is 0-4 A is selected from R1. o is 1 except that when L is a cyclic ring of more than 5 atoms, o is 1 or higher depending upon the size of the ring. For instance, if the ring is 6 atoms, o can be 1 or 2.

Each V and V1 individually is selected from R'and N-alkyl substituted carboxamidyl (- CONHR) where the alkyl group may be straight, branched, cyclic, or bicyclic; N, N- disubstituted carboxamidyl (-CONR1R2 where R1 and R2 may be substituted or unsubstituted alkyl or aryl and may be the same or different); mono-or disubstituted sulfonamides (SO2NHR or-SO2NRIR2) ; and methylene-or polymethylene chain- extended variants thereof.

Each R4 and RS individually is H,-(CH2)nOH, -C(O)OR6, -C(O)SR6, -(CH2)n C (O) NR7R8, -O-C (O)-O-W, an amino acid or a dipeptide, Each R6 is H, R7, -C (R7) (R)- (CH2)n-O-C(O)-R9, -(CH2)n-C(R7)(R8)-O-C(O)R9, -(CH2)n- C(R7)(R8)-O-C(O)-O-R9, or -C(R7)(R8)-(CH2)n-O-C(O)-O-R9, Each R7, Ra and R9 individually is H, alkyl, substituted alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, heterocycle, substituted heterocycle, alkylaryl, substituted alkylaryl, cycloalkyl, substituted cycloalkyl, or CH2C02alkyl.

R substituent groups employed pursuant to the present invention contribute to significantly enhanced activity of the compounds of the present invention.

Listed below are definitions of various terms used to describe this invention. These definitions apply to the terms as they are used throughout this specification, unless otherwise limited in specific instances, either individually or as part of a larger group.

The term"alkyl"refers to straight or branched chain unsubstituted hydrocarbon groups of 1 to 20 carbon atoms, preferably 1 to 8 carbon atoms. The expression"lower alkyl"refers to unsubstituted alkyl groups of 1 to 4 carbon atoms.

The terms"alkenyl"and"alkynyl"refer to straight or branched chain unsubstituted hydrocarbon groups typically having 2 to 8 carbon atoms.

The terms"substituted alkyl","substituted alkenyl"or substituted alkynyl"refer to an alkyl, alkenyl or alkynyl group substituted by, for example, one to four substituents, such as halo, trifluoromethyl, trifluoromethoxy, hydroxy, alkoxy, cycloalkyloxy, heterocyclooxy, oxo, alkanoyl, aryloxy, alkanoyloxy, amino, alkylamino, arylamino, aralkylamino, cycloalkylamino, heterocycloamino, disubstituted amines in which the 2 amino substituents are selected from alkyl, aryl or aralkyl, alkanoylamine, aroylamino, aralkanoylamino, substituted alkanolamino, substituted arylamino, substituted aralkanoylamino, thiol, alkylthio, arylthio, aralkylthio, cycloalkylthio, heterocyclothio, alkylthiono, arylthiono, aralkylthiono, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, sulfonamido (e. g. S02N-H2), substituted sulfonamido, nitro, cyano, carboxy, carbamyl (e. g. CONH2), substituted carbamyl (e. g. CONH alkyl, CONH aryl, CONH aralkyl or cases where there are two substituents on the nitrogen selected from alkyl, aryl or aralkyl), alkoxycarbonyl, aryl, substituted aryl, guanidino and heterocyclos, such as indolyl, imidazolyl, furyl, thienyl, thiazolyl, pyrrolidyl, pyridyl, pyrimidyl and the like.

Where noted above where the substituent is further substituted it will be with halogen, alkyl, alkoxy, aryl or aralkyl.

The term"halogen"or"halo"refers to fluorine, chlorine, bromine and iodine.

The term"aryl"refers to monocyclic or bicyclic aromatic hydrocarbon groups having 6 to 12 carbon atoms in the ring portion, such as phenyl, naphthyl, biphenyl and diphenyl groups, each of which may be substituted.

The term"aralkyl"or"alkylaryl"refers to an aryl group bonded directly through an alkyl group, such as benzyl or phenethyl.

The term"substituted aryl"or"substituted alkylaryl"refers to an aryl group or alkylaryl group substituted by, for example, one to four substituents such as alkyl ; substituted alkyl, halo, trifluoromethoxy, trifluoromethyl, hydroxy, alkoxy, azido, cycloalkyloxy, heterocyclooxy, alkanoyl, alkanoyloxy, amino, alkylamino, aralkylamino, hydroxyalkyl, aminoalkyl, azidoalkyl, alkenyl, alkynyl, allenyl, cycloalkylamino, heterocycloamino, dialkylamino, alkanoylamino, thiol, alkylthio, cycloalkylthio, heterocyclothio, ureido, nitro, cyano, carboxy, carboxyalkyl, carbamyl, alkoxycarbonyl, alkylthiono, arylthiono, alkysulfonyl, sulfonamido, aryloxy and the like. The substituent may be further substituted by halo, hydroxy, alkyl, alkoxy, aryl, substituted aryl, substituted alkyl or aralkyl."Substituted benzyl"refers to a benzyl group substituted by, for example, any of the groups listed above for substituted aryl.

The term"cycloalkyl"refers to optionally substituted, saturated cyclic hydrocarbon ring systems, preferably containing 1 to 3 rings and 3 to 7 carbons per ring which may be further fused with an unsaturated C3-C7 carbocyclic ring. Exemplary groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, cyclododecyl and adamantyl. Exemplary substituents include one or more

alkyl groups as described above, or one or more groups described above as alkyl substituents.

The term"cycloalkenyl"refers to optionally substituted, unsaturated cyclic hydrocarbon ring systems, preferably containing 1 to 3 rings and 3-7 carbons per ring.

Exemplary groups include cyclopentenyl and cyclohexenyl.

The terms"heterocycle","heterocyclic"and"heterocyclo"refer to an optionally substituted, fully saturated or unsaturated, aromatic or nonaromatic cyclic group, for example, which is 4 to 7 membered monocyclic, 7 to 11 membered bicyclic, or 10 to 15 membered tricyclic ring system, which has at least one heteroatom in at least one carbon atom-containing ring. Each ring of the heterocyclic group containing a heteroatom may have 1, 2 or 3 heteroatoms selected from nitrogen atoms, oxygen atoms and sulfur atoms, where the nitrogen and sulfur heteroatoms may also optionally be oxidized and the nitrogen heteroatoms may also optionally be quaternized. The heterocyclic group may be attached at any heteroatom or carbon atoms.

Exemplary monocyclic heterocyclic groups include pyrrolidinyl, pyrrolyl, indolyl, pyrazolyl, oxetanyl, pyrazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, oxazolyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolyl, thiadiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, furyl, tetrahydrofuryl, thienyl, thiophenyl, oxadiazolyl, piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxazepinyl, azepinyl, 4-piperidonyl, pyridyl, dihydropyridyl, N-oxo-pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothiopyranyl sulfone, morpholinyl, thiomorpholinyl, thiomorpholinyl sulfoxide, thiomorpholinyl sulfone, 1,3- dixolane and tetrahydro-1, 1-dioxothienyl, dioxanyl, isothiazolidinyl, thietanyl, thiiranyl, triazinyl and triazolyl and the like.

Exemplary bicyclic heterocyclic groups include benzothiazolyl, benzoxazolyl, benzothienyl, quinuclidinyl, quinolinyl, quinolinyl-N-oxide, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, indolizinyl, benzofuryl, chromonyl, cournarinyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolapridyl, furopyridinyl (such as furo [2,3-c] pyridyl, furo [3, 1-b] pyridinyl, or furo [2, 3-b] pyridinyl), dihydroisoindolyl, diyhydroquinazolinyl (such as 3,4-dihydro-4-oxo-quinazolinyl), benzisothiazolyl, benzisoxazolyl, benzodiazinyl, benzofurazanyl, benzothiopyranyl, benzothrasolyl, benzpyrasolyl, dihydrobenzofuryl, dihydrobenzothienyl, dihydrobenzothiopyranyl, dihydrobenzothiopyranyl sulfone, dihydrobenzopyranyl, indolinyl, isochromanyl, isoindolinyl, naphthyridinyl, phthalazinyl, piperonyl, purinyl, pyridopyridyl, quinazolinyl, tetrahydroquinolinyl, theinofuryl, thienopyridyl, thienothienyl, and the like.

Exemplary substituents include one or more alkyl groups as described above or one or more groups described above as alkyl substituents.

Within the above-described definitions, certain embodiments are preferred.

Preferred alkyl groups are lower alkyl groups containing 1 to about 8 carbon, and more preferably 1 to about 5 carbon atoms, and can be straight, branched-chain or cyclic saturated aliphatic hydrocarbon groups.

Examples of suitable alkyl groups include methyl, ethyl and propyl. Examples of branched alkyl groups include isopropyl and t-butyl. An example of a suitable alkylaryl group is phenethyl. Examples of suitable cycloalkyl groups typically contain 3-8 carbon atoms and include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The aromatic or aryl groups are preferably phenyl or alkyl substituted aromatic groups (aralkyl) such as phenyl Cl 3 alkyl such as benzyl.

The N-heterocyclic rings preferably contain 3-7 atoms in the ring and a heteroatom such as N, S or O in the ring. Examples of suitable preferred heterocyclic

groups are pyrrolidino, azetidino, piperidino, 3,4-didehydropiperidino, 2- methylpiperidino and 2-ethylpiperidino. In addition, the above substitutions can include halo such as F, Cl, Br, lower alkyl, lower alkoxy and halo substituted lower alkoxy.

Examples of some preferred B groups include-NHC (NH) NH2,-C (=NH) NH2, NH2, various N-substituted variants, and assorted prodrug derivatives.

Prodrug forms of the compounds bearing various nitrogen functions (amino, hydroxyamino, hydrazino, guanidino, amidino, amide, etc.) may include the following types of derivatives where each R group individually may be hydrogen, substituted or unsubstituted alkyl, aryl, alkenyl, alkynyl, heterocycle, alkylaryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, or cycloalkenyl groups as defined beginning on page 7.

(a) Carboxamides,-NHC (O) R (b) Carbamates,-NHC (O) OR (c) (Acyloxy) alkyl carbamates,-NHC (O) OROC (O) R (d) Enamines,-NHCR (=CHCR02R) or-NHCR (=CHCRONR2) (e) Schiff bases,-N=CR2 (f) Mannich bases (from carboximide compounds), RCONHCH2NR2 Preparations of such prodrug derivatives are discussed in various literature sources (examples are : Alexander et al., J. Med. Chem. 1988,31,318; Aligas-Martin et al., PCT WO pp/41531, p. 30). The nitrogen function converted in preparing these derivatives is one (or more) of the nitrogen atoms of a compound of the invention.

Prodrug forms of carboxyl-bearing compounds of the invention include esters (-CO2R) where the R group corresponds to any alcohol whose release in the body through enzymatic or hydrolytic processes would be at pharmaceutically acceptable levels.

Another prodrug derived from a carboxylic acid form of the invention may be a quaternary salt type of structure described by Boder et al., J. Med. Chem. 1980, 23,469.

Examples of some preferred groups for W are -CH2CH2-, -CH=CH-, -C#C-, - CH2CH2CH2-,-CH2CH=CH-,-CH2C=C-,-CONH,-CH2CONH-,-NHCONH-, -CONHCO-, -CONHCH2-, -C (=NH) NH-,-CH2C (=NH) NH-,-NHC (=NH) NH-,-NHNH-, <BR> <BR> <BR> -NHO-,-CONHSO2-,-S02NH-,-NHS02CH2-,-S02NHCH2-,-CH20-,-CH20CH 2-,<BR> <BR> <BR> <BR> -OCH2CH2-,-CH2NH-,-CH2CH2NH-,-CH2NHCH2-,-CH2S-,-SCH2CH2,-CH2 SCH2-,- CH2SO2CH2-,-CH2SOCH2-,-CH (CO2H) O and-CH (COzH) OCH2.

Examples of some preferred groups for V and Vl are N-alkyl substituted carboxamidyl (-CONHR) where the alkyl group may be straight, branched, cyclic, or bicyclic, and typically containing up to ten carbons; N, N-disubstituted carboxamidyl (- CONRlR2 where R1 and R2 may be substituted or unsubstituted alkyl or aryl and may be the same or different); mono-or disubstituted sulfonamides (SO2NHR or-S02NRIR2) ; methylene-or polymethylene chain-extended variants thereof such as-(CH2) nCONHRIn -(CH2)nCONR1R2, -(CH2)nSO2NHR1, -(CH2)nSO2NR1R2 (where n =1-4),-NHC (O) R, N (R1) C (0) R2, NHSO2R, CH2NHR, CH2NRIR2.

Phannaceutically acceptable salts of the compounds of the present invention include those derived from pharmaceutically acceptable, inorganic and organic acids and bases. Examples of suitable acids include hydrochloric, hydrobromic, sulphuric, nitric, perchloric, fumaric, maleic, phosphoric, glycollic, lactic, salicyclic, succinic, toluene-p- sulphonic, tartaric, acetic, citric, methanesulphonic, formic, benzoic, malonic, naphthalene-2-sulphonic, trifluoroacetic and benzenesulphonic acids.

Salts derived from appropriate bases include alkali such as sodium and ammonia.

It is of course understood that the compounds of the present invention relate to all optical isomers and stereo-isomers at the various possible atoms of the molecule.

The synthetic routes leading to the compounds in formula (I) are described in the following schemes.

Scheme 1 Scheme 2 Scheme 3 Scheme 4 Scheme 5 24,R=(continued)

27, R = (continued) Conversion of The reduction of the formyl group of 24ab, 24ac, 24ae, and 24ad was accomplished with NaBH4 to give corresponding alcohols 24ab-i, 24ac-i, 24ae-i, and 24ad-i, respectively. Later, the MEM group was removed under acidic conditions to give 25ab, 25ac, 25ae, and 25af, respectively.

Conversion of The aldehyde 24ad was oxidized to acid 24ad-i which was protected as benzyl ester to give 24ad-ii. MEM deprotection under acidic conditions produced 25ad.

Conversion of The vinyl compound 24ah was oxidized with Os04 to give diol 24ah-i, followed by acidic hydrolysis of the MEM group to produce 25ah.

L, M, K, N, O, I-1 Conversion of The vinyl compound 24ah on dihydroxylation with Os04 gave diol 24ah-i. Oxidative cleavage of the diol with NaI04 produced aldehyde 24ah-ii. The aldehyde on reduction gave alcohol 24ah-iii, which on further reaction with methane sulfonyl chloride yielded mesylate 24ah-iv. The mesylate on further reaction with sodium azide gave the corresponding azide 24ah-v, which on acidic hydrolysis produced 25ai.

Conversion of Scheme 6

Conversion of Aldehyde 29g was converted to alcohol 29g-i by reduction with NaBH4, followed by the reaction of methanesulfonyl chloride to give mesylate 29g-ii. The mesyl group was displaced with azide to give 29g- iii and finally, the MEM group was removed under acidic conditions to give 30g.

Conversion of The reduction of the formyl group of 29h and 29i was accomplished with NaBH4 to give corresponding alcohols 29h-i and 29i-i, respectively. Later, the MEM group was removed under acidic conditions to give 30h and 30i, respectively.

Compounds of the type 23 and 28, where X =-Sn (Bu) 3, are prepared using the methods AG-1 or AG-2 Scheme 7 CF3so, o CO, H 11 o H3 02c 0 33 NU J NH N NH 0 NH, H E P H /\/\ \ N HCaC /N ' HCOC nu 35 O 34 B (OH) 2 CBz= i''p CH2C6Hs D-2 TIPS 36 TIPS = Tri-isopropylsilyl TIPS NH TIPS NH I I N N 0 INH NH, CBz Nez H G, H 37 38 H CL \ N \ \ N \ g. H /I \/ N N 0 NH2 0 NH 2 I H 11 H 0 0 40 39

Scheme 8A Scheme 8B Scheme 8C

Scheme 8D Scheme 8E

Scheme 9

Scheme 10 0 D-3 &NHBoc 59 + (Bu), Sn 59 + (Bu) 3Sn I/ H3COZC/CO, MEM 66 ll-l NH 0 eNHBoc 1 1 0 X NHBoc , \ H A_4 1 \ H \ /\ H3CO2C NHR H3CO2C4co2H 68 0 67 1-2 NU NU p/, NHBoc I O i NHZ 68 O 67 \ WH S _ \ H w w IR CONHR 69 0 70 0 69 70 68, R= CFi a'b, , CH3 c, _-o d, CH. e, CH3 CH3 CH3 = CH3 CF3 h' . 1> k \CH 1. CH3 /OH CH CFil o CH3 P 4 CH 3 CH3 OH s, u, V, W, x,,,, CH, g . i CH3 3 8 Scheme 11 78b, 79b, R=OSO2CF3 ; R'= Bn; 80b, R = OH 77b, 78c, 79c, R=-O-CH2CO2C2H5 ; R'= Bn; 80c, R =-O-CH2CO2H 77c, 78d, 79d, 80d, R =-O-CH2CONH2 ; R'= Bn 78g, 79g, 80g, R=OCH3, R'= CH3 77i, 78k, 79k, R =OCH2-CH2-OAc ; R'= Bn; 80k, R =-O-CH2-CH2-OH Scheme 12 86a, R=CH (OH) CH2OH 86b, R=CH2OH 86c, R=CO2H Scheme 13 Scheme 14 Scheme 15 Scheme 16 Scheme 16a

Scheme 16b Scheme 17 133,134, R= (continued)

Scheme 17a Scheme 18 Scheme 19

Scheme 19a Scheme 20 Scheme 21 167 Scheme 22 Scheme 23 183 182 Scheme 24 Scheme 25 189a,X = H, Y = OCH3 189b,X=OCH2C6H5, Y=H 189c,X = OH, Y = H 131 AE-3 189d NH2 N NA (Prepared HN NH, by method AJ-1, AJ-2, or AJ-3) Scheme 26 190a, 192a-195a, R = H 190b, 192b-195b, R=CH3 Scheme 27 Scheme 28 Scheme 29 Scheme 30 Scheme 31 Scheme 32 231a, 232a, 233a, 234a, 235a, R = H 231b, R=CO2CH3 232b, 233b, 234b, R = CO2H Scheme 33 Scheme 34 Scheme 35 Scheme 36

General Methods of Preparation The following abbreviations have been used: THF: Tetrahydrofuran ; DMF: Dimethylformamide DME: 1,2-Dimethoxyethane; DMAP: 4- (Dimethylamino) pyridine Boc anhydride: Di-tert-butyl dicarbonate ; TIPS: Triisopropylsilyl MEM: Methoxyethoxymethyl ; Bn: Phenylmethyl or Benzyl The organic extracts were dried over sodium sulfate or magnesium sulfate.

The general methods for the preparation of the compounds of formula (I) are given below: A-1 : Conversion of acid to amide To derivative (1 mmol), was added thionyl chloride (12.6 mmol) and a few drops of DMF. The reaction mixture was refluxed for 2 h and concentrated in vacuo to obtain an oily residue. The residue was dissolved in dichloromethane (3 mL) ; cooled with ice water and amine (5 mmol) was added. The reaction mixture was stirred at room temperature overnight, washed with IN HCI, saturated sodium hydrogen carbonate, water, brine, dried and concentrated in vacuo. The product obtained was purified by crystallization or flash column chromatography to furnish the desired amide.

A-2: Conversion of acid to amide To a solution of acid derivative (1 mmol) in dichloromethane (10 mL) at 0 °C was added triethylamine (3 mmol) and ethyl chloroformate (3 mmol). The reaction mixture was stirred at the same temperature for 30 min and the corresponding amine (6

mmol) was added. The reaction mixture was stirred at room temperature overnight and quenched with IN HCI. The organic layer was separated, washed with water, brine, dried and concentrated in vacuo. The product obtained was purified by crystallization or flash column chromatography to furnish the desired amide.

A-3: Conversion of acid to amide To a solution of acid (1 mmol) in dichloromethane (5 mL) was added 2M oxalyl chloride in dichloromethane (2.5 mmol), followed by a drop of DMF. The reaction mixture was stirred for 2h at room temperature and concentrated in vacuo. The residue was co-evaporated once with dichloromethane (5 mL) and then dried in vacuo. To the residue in dichloromethane (10 mL) were further added triethylamine (3 mmol) and the corresponding amine (1.2 mmol). The reaction mixture was stirred for 16 h and washed with water, brine, dried and concentrated in vacuo. The product obtained was purified by crystallization or flash column chromatography to furnish the desired amide.

A-4: Conversion of acid to amide To a solution of acid (1 mmol) in dichloromethane or THF (10 mL) cooled with an ice bath was added triethylamine (1.2 mmol) and ethyl chloroformate or isobutyl chloroformate (1.2 mmol). The reaction mixture was stirred at 0°C for 30 min and the corresponding amine (2.5 mmol) was added. The reaction mixture was stirred at room temperature overnight and quenched with IN HCI. The organic layer was separated, washed with water, brine, dried and concentrated in vacuo. The product obtained was purified by crystallization or flash column chromatography to furnish the desired amide.

A-5: Conversion of acid to amide A mixture of carboxylic acid (1 mmol), amine (1. 1 mmol), 1- hydroxybenzotriazole (1 mmol) and 1- (3-dimethylaminopropyl)-3-ethylcarbodiimide methiodide (1. 1 mmol) in pyridine (10 mL) was stirred overnight at room temperature and was concentrated in vacuo to dryness. The residue obtained was purified by column chromatography or used as such for the next step.

A-6: Reduction of acid to alcohol To a solution of acid (1 mmol) in dichloromethane or THF (10 mL) at 0 °C was added triethylamine (1.2 mmol) and ethyl chloroformate or isobutyl chloroformate (1.2 mmol). The reaction mixture was stirred at 0 °C for 30 min and sodium borohydride (1.25 mmol) was added. The reaction mixture was stirred at room temperature overnight and quenched with IN HC1. The reaction mixture was extracted with ethyl acetate. The organic layers were combined, washed with water, brine, dried and concentrated in vacuo to furnish the desired alcohol. This can be purified further, if needed, by crystallization or column chromatography.

A-7: Conversion of acid to amide A mixture of carboxylic acid (1 mmol), amine (1 mmol), and 4- dimethylaminopyridie (0.12 mmol) in xylene (10 mL) was stirred at 80 °C for 10 min. Phosphorus trichloride (1 mmol) was added and the reaction mixture was heated with stirring at 150 °C for 2 hr. After cooling, the product was extracted with EtOAc. The organic layers were combined, washed with water, brine, dried and concentrated in vacuo. The product obtained was purified by flash column chromatography to furnish the desired amide.

B-1 : Conversion of phenolic hydroxyl to triflate To a phenol (1 mmol) in dichloromethane (2.5 mL) was added pyridine (5 mmol) under a nitrogen atmosphere and cooled to-10 C. To the cold reaction mixture was added dropwise triflic anhydride (2 mmol) in dichloromethane (2.5 mL) over a period of 10 mins and allowed to warm to room temperature and stirred for 16 h. The reaction mixture was quenched with saturated aqueous sodium hydrogen carbonate solution and the organic layer was separated. The organic layer was washed with IN HC1, saturated sodium hydrogen carbonate, water, brine, dried and concentrated in vacuo. The product obtained was purified by crystallization or flash column chromatography to furnish the desired triflate.

B-2: Conversion of phenolic hydroxyl to triflate To a solution of substituted phenol (1 mmol) in DMF (10 mL) was added N- phenylbis (trifluoromethanesulphonimide) (1.1 mmol), and triethylamine (2 mmol) and stirred at room temperature overnight. The reaction mixture was quenched with ice water and extracted twice with ether. The organic layers were combined, washed with brine, dried and concentrated in vacuo. to furnish the desired triflate.

C: Conversion of acid to MEM ester To a solution of acid derivative (1 mmol) in DMF (10 mL) was added sodium bicarbonate (1.05 mmol), and MEM-CI (1.05 mmol) and was stirred at room temperature for 24 h. The reaction mixture was quenched with ice water and extracted twice with ether. The organic layers were combined, washed with brine, dried and concentrated in vacuo to furnish crude product. Purification by flash column chromatography or crystallization gave the desired MEM ester.

D-1 : Coupling of boronic acid with triflate A mixture of triflate (1 mmol), aryl boronic acid (1.5 mmol), potassium phosphate (3 mmol), potassium bromide (2.4 mmol) and tetrakis (triphenylphosphine) palladium (0.05 mmol) in dioxane (10 mL) was heated at reflux overnight under an argon atmosphere. The reaction mixture was cooled, quenched with water and was extracted with ethyl acetate. The organic layers were combined, dried and concentrated in vacuo.

Purification by flash column chromatography or crystallization gave the coupled product.

D-2: Coupling of boronic acid with triflate A mixture of triflate (1 mmol), aryl boronic acid (2 mmol), sodium hydrogen carbonate (3 mmol) and tetrakis (triphenylphosphine) palladium (0. 05 mmol) or bis (triphenylphosphine) palladium (II) chloride (0.05 mmol) in DME/water (9: 1,10 mL) was heated at reflux overnight. The reaction mixture was cooled, quenched with water and extracted with ethyl acetate. The organic layer was dried and concentrated in vacuo.

Purification by flash column chromatography or crystallization gave the coupled product.

D-3: Coupling of tributyltin derivative with triflate A mixture of triflate (1 mmol), tributyltin derivative (3 mmol), tetraethylammonium chloride (6 mmol), and bis (triphenylphosphine) palladium (II)- chloride (0.05 mmol) in DMF (10 mL) was heated at 70 °C overnight under an argon atmosphere. The reaction mixture was cooled, quenched with water (20 mL) and extracted with ethyl acetate (2 X 10 mL). The organic layers were combined, dried and concentrated in vacuo. Purification by flash column chromatography or crystallization gave the coupled product.

D-4: Coupling of trimethyltin derivative with triflate A mixture of triflate (1 mmol), trimethyltin derivative (3 mmol), and bis (triphenylphosphine) palladium (II) chloride (0.05 mmol) in THF (10 mL) was heated at 70 °C overnight under an argon atmosphere. The reaction mixture was cooled, quenched with water and extracted with ethyl acetate (2 X 10 mL). The organic layers were combined, dried and concentrated in vacuo. Purification by flash column chromatography or crystallization gave the coupled product.

D-5: Coupling of alkyne with triflate A mixture of triflate (1 mmol), triethylamine (4.5 mmol), substituted alkyne (3.5 mmol), and bis (triphenylphosphine) palladium (II) chloride (0.05 mmol) in DMF (10 mL) was heated at 70 °C overnight under an argon atmosphere. The reaction mixture was cooled, quenched with water (20 mL) and extracted with ethyl acetate (2 X 10 mL). The organic layers were combined, dried and concentrated in vacuo. Purification by flash column chromatography or crystallization gave the coupled product.

D-6: Coupling of boronate ester with aryl bromides A mixture of boronate ester (2 mmol),'aryl bromide (1 mmol), potassium phosphate (3 mmol) and bis (diphenylphosphinoferrocene) palladium (II) chloride (0.05 mmol) in DMF (10 mL) was heated at 100'C for overnight under an argon atmosphere.

The reaction mixture was cooled, quenched with water (20 mL) and extracted with ethyl acetate (2 X 10 mL). The organic layers were combined, dried and concentrated in vacuo. Purification by flash column chromatography or crystallization gave the desired product.

D-7: Coupling of boronate ester with aryl bromides A mixture of boronate ester (2 mmol), aryl bromide (1 mmol), sodium hydrogen carbonate (3 mmol) and bis (diphenylphosphinoferrocene) palladium (II) chloride (0.05 mmol) in DME/water (9: 1, 10 mL) was heated at 50-70 °C for overnight under an argon atmosphere. The reaction mixture was cooled, quenched with water (20 mL) and was extracted with ethyl acetate (2 X 10 mL). The organic layers were combined, dried and concentrated in vacuo. Purification by flash column chromatography or crystallization gave the coupled product.

D-8: Coupling of phenol with boronic acid A mixture of phenol (1 mmol), aryl boronic acid (3 mmol), molecular sieves (4A°), pyridine (5 mmol), copper (II) acetate (1 mmol) and bis (triphenylphosphine)- palladium (II) chloride (0. 05 mmol) in dichloromethane (10 mL) was stirred at room temperature overnight under an argon atmosphere. The reaction mixture was cooled, filtered through a pad of Celite and concentrated in vacuo. Purification of the crude by flash column chromatography gave the coupled aryl ether.

D-9: Coupling of trimethyltin derivative with triflate To a solution of triflate (1 mmol), LiCl (4 mmol), PPh3 (0.15 mmol), CuBr (0.2 mmol), and bis (triphenylphosphine) palladium (II) chloride (0.07 g) in DMF (10 mL) under an atmosphere of argon was added trimethylstannyl compound (0.8 mmol) and a crystal of 2, 6-di-t-butyl-4-methylphenol. After the mixture was stirred at 90 °C for 3 h, a second portion of aryl-trimethylstannyl compound (0.5 mmol) was added. The reaction mixture was stirred at 90 °C overnight. Water was added and extracted with ethyl acetate. The organic layer was dried (MgSO4), concentrated and purified by flash column chromatography or crystallization to furnish the desired coupled product.

D-10 : Coupling of amine with triflate A mixture of triflate (0.75 mmol), amine (0.9 mmol), potassium phosphate (1. 1 mmol), 2- (di-t-butylphosphino) biphenyl (0.015 mmol) and tris (dibenzylideneacetone) dipalladium (O) (10 mg) in DME (10 mL) was heated at reflux overnight under an argon atmosphere. The reaction mixture was concentrated in vacuo and the residue was purified by flash column chromatography to furnish the desired coupled product.

D-11 : Conversion of triflate to cyano compound To a solution of triflate (0.84 mmol), zinc cyanide (0.54 rnmol), Palladium acetate (0.016 mmol), 2- (di-tert-butylphosphine) biphenyl (0.016 mmol) and N-methyl pyrrolidine (10 mL) was heated under argon at 160 °C for 48 h. The reaction mixture was cooled to room temperature and quenched with water (50 mL). The reaction mixture was extracted with ethyl acetate (2 X 25 mL). The organic layers were combined, dried, filtered and concentrated in vacuo. The residue obtained was purified by flash column chromatography to furnish the desired cyano compound.

D-12: Coupling of tetravinyltin with triflate or halide To a solution of aryl triflate or bromide (1 mmol) in DMF (5 mL) were added LiCl (5 mmol), tetravinyltin (2 mol), and dichlorbis (triphenylphosphine) palladium (II) (0. 01 mmol). The reaction mixture was stirred at 70 °C under nitrogen for 5 h and then diluted with ethyl acetate and filtered. The organic layer was washed with water and brine and dried (MgS04). After evaporating the solvent in vacuo, the compound was purified by flash-column chromatography to give the desired product.

E: Oxidation of aryl aldehyde to acid A mixture of aldehyde (1 mmol), tert-butanol (5 mL), water (2 mL) and acetonitrile (1 mL, additional amount may be added until the reaction mixture was homogenous) was stirred at room temperature. The solution was cooled in ice-bath and 2-methyl-2-butene (l mL), sodium chlorite (6 mmol) and sodium dihydrogenphosphate (1. 6 mmol) were added. The reaction mixture was stirred at room temperature for 2 h. If the solid separated out, the mixture was filtered to collect the solid, the desired product.

If no solid separated out, then the reaction mixture was concentrated in vacuo to remove acetonitrile, diluted with water (10 mL) and extracted with ethyl acetate (2 X 10 mL).

The organic layers were combined, washed with water, brine, dried and concentrated in vacuo to furnish crude acid. Purification was achieved, if needed, by crystallization or using flash column chromatography to obtain pure acid.

E-2 : Oxidation of vinyl compound to acid To a solution of vinyl compound (1 mmol) in acetone (5 mL) was added KMn04 (4 mmol). The reaction mixture was stirred for 3 h (the reaction is exothennic, and refluxed on its own during the addition of KMnO4). The reaction mixture was diluted with methanol and water and filtered. The organic solvents were evaporated in vacuo and the aqueous layer was acidified to pH 1 and extracted several times with ethyl acetate/DME. The combined organic layers were dried (MgSO4) to furnish the desired acid.

F: Conversion of aromatic acid to MEM ester To a solution of aromatic acid (1 mmol) in THF (10 mL) was added diisopropylethylamine (2 mmol) and 2-methoxyethoxymethylchloride (1.1 mmol). The reaction mixture was stirred a room temperature for 3 h and diluted with ether (25 mL).

The reaction mixture was washed with water (10 mL), brine (10 mL), dried and concentrated in vacuo to obtain product as colorless oil. The product was purified by flash column chromatography to furnish desired product.

G: Conversion of aromatic benzyl ether to aromatic phenol, benzyl ester to acid, benzyl carbamate to amine, alkene to alkane, azide to amine, nitro to amine, and oxime to amine To a solution of appropriate substrate (1 mmol) in ethanol (10 mL) was added 10% palladium on carbon (10-wt%). The reaction mixture was hydrogenated at 50 psi for 2 to 24 h (until all starting material disappeared as confirmed by MS and TLC analysis). The catalyst was removed by filtration through a pad of Celite under nitrogen.

The filtrate was concentrated in vacuo to furnish the product, which was purified by flash column chromatography or crystallization.

H : Conversion of aromatic acid to benzyl ester To a solution of aromatic acid (1 mmol) in DMF (10 mL) was added sodium bicarbonate (1.05 mmol), and benzyl bromide (1.05 mmol) and stirred at room temperature for 24 h. The reaction mixture was quenched with ice water and extracted twice with ethyl acetate. The organic layers were combined, washed with water and brine, dried and concentrated in vacuo to furnish crude product. Purification by crystallization or flash column chromatography gave the desired ester.

1-1 : Hydrolysis of MEM ester to acid < To a solution of MEM ester (I mmol) in DME (8 mL) was added 6 N HC1 (2 mL) and stirred at room temperature overnight. The reaction mixture was neutralized with solid sodium hydrogen carbonate (18 mmol) and concentrated in vacuo. The reaction

mixture was acidified with 0.5 N HC1 (20 mL) and extracted with ethyl acetate (2 X 20 mL). The organic layers were combined, washed with brine (20 mL), dried and concentrated in vacuo to furnish crude product. Purification of the crude by flash column chromatography gave the product. Alternatively the crude reaction mixture was diluted with water (10 mL) and concentrated in vacuo to remove DME. The solid obtained was collected by filtration and dried in vacuo to furnish pure acid.

I-2 : Hydrolysis of ester to acid To a solution of ester (1 mmol) in MeOH (10 mL) was added 1 N NaOH (10 mmol). The reaction mixture was stirred at room temperature for 2-3 h, filtered through a plug of cotton, and concentrated in vacuo to remove MeOH. The pH of the aqueous layer was adjusted to below 7. The solid that separated, was collected by filtration, washed with water and dried in vacuo to furnish the desired acid.

J: Coupling of acid with amino compounds To a solution of acid (1 mmol) in DMF (5 mL) was added corresponding amine (1. 1 mmol) and stirred at room temperature until homogenous. Pyridine (5 mL) was added to the reaction mixture followed by 1,3-dicyclohexylcarbodiimide (1.2 mmol) and stirred overnight at room temperature. The mixture was quenched with 6 N HC1 (10 mL), diluted with ice cold water (10 mL) and extracted with chloroform (2 X 10 mL).

The organic layers were combined washed with brine (10 mL), dried and filtered.

Purification of the crude by flash column chromatography gave the product as a solid. If the product was soluble in water, then the reaction mixture was concentrated in vacuo to remove pyridine and DMF and purified by flash column chromatography.

K: Reduction of aldehyde to alcohol To a solution of aldehyde (1 mmol) in THF (10 mL) was added sodium borohydride (0.4 mmol). The reaction mixture was stirred for 30 mins and quenched with glacial acetic acid (0.3 mL). The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (2 X 10 mL)., The organic layers were combined and washed with brine (10 mL), dried, filtered and concentrated in vacuo to obtain crude product which was purified by flash column chromatography.

L: Conversion of vinyl group to diol To a solution of vinyl compound (1 mmol) in THF/tert-butanol (1: 1,10 mL) and water (2 mL) was added 4-methylmorpholine N-oxide (2.5 mmol) and osmium tetraoxide (1 mL, 2.5 wt% in tert-butanol, 0.1 mmol). The reaction mixture was stirred at room temperature for 2 h and quenched with saturated aqueous solution of sodium sulfite (5 mL). The reaction was stirred at room temperature for 30 mins and diluted with brine (10 mL) and ethyl acetate (10 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (10 mL). The organic layers were combined and washed with brine (10 mL), dried, filtered and concentrated in vacuo. The crude product was purified by flash column chromatography to furnish the desired diol.

M: Conversion of diol to aldehyde To a solution of diol (1 mmol) in DME/water (9: 1,10 mL) was added sodium metaperiodate (3 mmol) and stirred at room temperature for 30 min. The reaction mixture was quenched with water (10 mL) and extracted with ethyl acetate (2 X 10 mL).

The organic layers were combined and washed with brine (10 mL), dried, filtered and concentrated in vacuo. The crude product was purified by flash column chromatography to furnish the desired aldehyde.

N: Conversion of alcohol to mesylate To a solution of alcohol (1 mmol) in DME (10 mL) was added dimethylaminopyridine (0.1 mmol), methane sulfonyl chloride (3 mmol) and diisopropylethylamine or triethylamine (5 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (2 X 10 mL). The combined organic layers were washed with brine, dried, filtered and concentrated in vacuo. The residue obtained, was purified by column chromatography to furnish the desired mesylate.

0 : Conversion of mesylate to azide To a solution of mesylate (1 mmol) in DMSO (10 mL) was added sodium azide (25 mmol) and heated at 100 °C overnight. The reaction mixture was cooled and diluted with cold water (25 mL). The reaction mixture was extracted with ethyl acetate (2 X 15 mL). The combined organic layers were washed with water (10 mL), brine (10 mL), dried, filtered and concentrated in vacuo The residue obtained was purified by column chromatography to furnish the desired azido compound.

P: Protection of amine as benzyl carbamate A mixture of amino compound (1 mmol), benzyl chloroformate (2 mmol) and triethylamine (10 mL) in pyridine (10 mL) was stirred at room temperature overnight.

The reaction mixture was concentrated in vacuo to remove organic solvents and diluted with 0.1 N HC1 (10 mL). The product was extracted with chloroform (2 X 10 mL), dried, filtered and concentrated in vacuo. The residue obtained was purified by column chromatography to furnish the desired carbamate.

Q: Conversion of silyl protected amine to amine A mixture of silyl protected amine (1 mmol), tetrabutylammonium fluoride (1.0 M in THF, 2 mmol) in THF (10 mL) was stirred at room temperature for 1.5 h. The reaction mixture was concentrated in vacuo and purified by column chromatography to obtain the desired product.

R: Protection of amine as ter-butyl carbamate To a solution of amino compound (1 mmol) in acetonitrile (5 mL) was added triethylamine (2 mmol) and BOC anhydride (1.2 mmol). The reaction mixture was stirred for 2 h and concentrated in vacuo. Water was added to the residue and extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSOa.), and the solvent was evaporated in vacuo to furnish tert-butyl carbamate. If needed, the product was purified by crystallization or column chromatography.

S: Conversion of tert-butyl carbamate to amine To a solution of tert-butyl carbamate (1 mmol) in dichloromethane (10 mL) was added trifluoroacetic acid (2 mL). The solution was stirred at room temperature for 4 h and concentrated in vacuo. The residue was purified by column chromatography or crystallization to give the desired amine.

S-2: Conversion of tert-butyl carbamate to amine To a solution of tert-butyl carbamate (1 mmol) in methanol (13 mL) was added 6 N HCl (8. 75 mL, 52 mmol) and water (4.25 mL). The reaction mixture was stirred at room temperature for 2 days. The pH was adjusted to 7 using conc. ammonium hydroxide and the solid that separated out, was collected by filtration, washed with ether,

dried in vacuo to furnish the desired product. If no solid separated out, the product was isolated by extraction with chloroform and evaporating the organic layer.

T: Protection of aldehyde as acetal To a solution of aldehyde (1 mmol) in ethanol (5 mL) was added triethyl orthoformate (1.4 mmol), ammonium nitrate (0.2 mmol) and stirred at room temperature overnight (if reaction was not complete by TLC and NMR analysis of an aliquot, the reaction mixture was heated at 50 °C until complete). After completion of the reaction, the mixture was quenched with triethylamine (0.2 mmol) and concentrated in vacuo to remove ethanol. The residue was dissolved in ether, filtered to remove any insoluble inorganic impurities, and evaporated to dryness. The product obtained was used as such without further purification.

U-1 : Conversion of bromide to boronic acid To a mixture of bromo compound (1 mmol) in ether (10 mL), cooled to-78 °C, n- butyl lithium (1.2 mmol) was added dropwise and the reaction mixture was stirred for 30 mins after the addition was completed. Tributyl borate (1. 3 mmol) in ether (10 mL) was added to the reaction and stirred at-78 °C for 2 h. The reaction mixture was allowed to warm to 0 °C and quenched with 2 M HCl (10 mL). The reaction mixture was stirred at room temperature for lh and cooled with ice. The aqueous layer was separated and the organic layer was extracted twice with 1N NaOH (2 X 10 mL). The basic extracts were combined and washed with ether (10 mL). The basic layer was acidified to pH 4 using 6 N HC1 and the solid that separated out was collected by filtration, washed with water and hexane and dried in vacuo to furnish boronic acid as a solid. If no solid product is obtained then the basic layer was extracted with ether (2 X 10 mL). The organic layers were combined, dried and concentrated in vacuo to furnish boronic acid.

U-2 : Synthesis of boronic acid by ortho lithiation of aryl aldehyde To a solution of N, N, N'-trimethylethylenediamine (1 mmol) in THF/ether (10 mL, 1: 1) cooled to-20 °C was added dropwise, over a period of 15 mins, n-butyl lithium (1 mmol) and stirred at-20 °C for 15 mins. Aldehyde (1 mmol) at-20 °C was added dropwise over a period of 10 mins to this mixture. The reaction mixture was further stirred for 15 mins at-20 °C followed by the addition of n-butyl lithium (2.8 mmol) dropwise over a period of 15 mins and stirred at 4 °C overnight. The reaction mixture was cooled to-40 °C and tributyl borate (5.6 mmol) in ether (20 mL) was added to the reaction and stirred at 4 °C for 12 h. The reaction mixture was allowed to warm to 0 °C and quenched with 2 M HCl (3 mmol) and heated at reflux for 2 h and added to ice water (25 mL). The aqueous layer was separated and the organic layer extracted twice with IN NaOH (2 X 10 mL). The basic extracts were combined and washed with ether (10 mL).

The basic layer was acidified to pH 3 using 6 N HC1 and the solid that separated out was collected by filtration, washed with water and hexane and dried in vacuo to furnish boronic acid as a solid. If no solid product was obtained, then the basic layer was extracted with ether (2 X 10 mL). The organic layers were combined, dried and concentrated in vacuo to furnish boronic acid.

U-3: Synthesis of boronic acid by ortho lithiation of aryl acetal To a solution of aryl acetal compound (1 mmol) in ether (10 mL) at-78'C, tert- butyl lithium (1. 1 mmol) was added dropwise and the reaction mixture was stirred for 3 h at-20 °C after the addition was completed. Tributyl borate (1.2 mmol) in ether (10 mL) was added to the reaction and stirred at-20 °C for 1 h. The reaction mixture was allowed to warm to 0 °C and quenched with 2 M HCl (10 mL). The reaction mixture was stirred at room temperature for lh. The aqueous layer was separated and the organic layer was extracted twice with IN NaOH (2 X 10 mL). The basic extracts were combined and washed with ether (10 mL). The basic layer was acidified to pH 4 using 6 N HC1 and the

solid that separated out was collected by filtration, washed with water and hexane and dried in vacuo to furnish boronic acid as a solid. If no solid product was obtained then the mixture was extracted with ether (2 X 10 mL). The organic layers were combined, dried and concentrated in vacuo to furnish boronic acid.

V-1 : Demethylation of aryl methyl ether to phenol In a round bottom flask (50 mL), pyridine hydrochloride (lOg) was heated in an oil bath at 180 °C. After the entire solid had melted, the corresponding aryl methyl ether (1 mmol) was added in small portions over a period of 20 min. The reaction mixture was heated at 180 °C for 4 h, cooled and quenched with water (100 mL). The reaction mixture was extracted with ethyl acetate (3 X lOmL). The combined organic layers were washed with brine, dried over MgS04, concentrated to give phenol. This can be further purified if needed by crystallization or column chromatography.

V-2: Demethylation of aryl methyl ether to phenol To a solution of aryl ether (1 mmol) in dichloromethane (10 mL) cooled to-78 °C was added boron tribromide (3 mmol). The reaction mixture was allowed to warm to room temperature overnight and quenched with water (10 mL). The solid obtained was collected by filtration to give the desired product. More product was obtained after evaporation of the organic layer and washing the residue with water. Alternatively, if a homogenous biphasic mixture was obtained on addition of water, the organic layer was separated, washed with brine, dried over MgS04, and concentrated to give the desired phenol. This can be further purified if needed by crystallization or column chromatography.

V-3: Demethylation of aryl methyl ether to phenol To a solution of aryl methyl ether (1 mmol) in dichloromethane (5 mL) was added Aids (8. 5 mmol). The reaction mixture was heated to reflux for 12 h under nitrogen. To this mixture was added 12 mL of 1 N HC1 slowly and the organic layer was separated.

The aqueous layer was re-extracted several times with ethyl acetate/DME. The combined organic layers were washed with brine, dried (MgS04), and evaporated in vacuo to furnish the desired phenol, which was purified by column chromatography.

V-4: Demethylation of aryl methyl ether to phenol To a stirred slurry of NaH (2 mmol) in anhydrous toluene (5 mL) under nitrogen atmosphere was added para-thiocresol (2 mmol) dissolved in toluene (40 mL). The mixture was stirred at room temperature for 30 min and hexamethylphosphoric triamide (2 mmol) in toluene (5 mL) was added dropwise over a period of 30 min. A solution of aryl ether (1 mmol) in toluene (5 mL) was added in one portion. The reaction mixture was stirred at reflux for 9.5 h, cooled to room temperature and diluted with ethyl acetate (40 mL). The organic layer was extracted with 1 N aqueous NaOH solution (2 X 20 mL).

The basic layer was acidified to pH 5 and extracted with ethyl acetate (2 X 20 mL). The organic layers were combined, washed with water, dried (MgS04) and concentrated in vacuo. The residue obtained was purified by flash column chromatography to afford the desired phenol compound.

W: Conversion of acid to methyl ester A mixture of acid (1 mmol), conc. H2S04 or cone H : C1 (0.5 mL) and methanol (10 mL) was heated at reflux for 16 h. The mixture was concentrated to half of its volume and the residue poured into a saturated sodium bicarbonate solution. The precipitate was collected by filtration, washed with water and dried to give the desired ester. If the ester

did not come as solid, it was extracted with ethyl acetate. The organic layer was dried, filtered and concentrated to give the desired ester.

W-2 : Conversion of acid to ester A solution of methanolic HC1 or ethanolic HC1 was prepared by the addition of acetyl chloride (1 mL) to methanol/ethanol (9 mL) at 0 °C and stirred for 30 mins. To the solution of anhydrous methanolic HC1 was added acid (1 mmol) and stirred at room temperature (or reflux if needed) overnight. The reaction mixture was concentrated to dryness in vacuo and the residue was purified by column chromatography or crystallization to furnish the desired ester.

X: Conversion of phenol to alkyl aryl ethers or alkylation of amines To a solution phenol or amine (1 mmol) in DMF (10 mL) was added cesium carbonate (1.25 mmol) and corresponding bromide (1. 1 mmol). The reaction mixture was stirred at room temperature overnight and quenched with water (25 mL). The product was extracted with ether (2 X 25 mL), the organic layers were combined and washed with water (25 mL), brine (25 mL), dried and concentrated in vacuo to furnish crude product. The crude was purified by crystallization or flash column chromatography.

Y: Conversion of nitrile to hydroxycarbamimidoyl To a solution of nitrile compound (1 mmol) in ethyl alcohol (10 mL) was added hydroxylamine (50% aqueous solution, 5 mmol). The mixture was stirred at reflux for 2- 5 h. The reaction mixture was concentrated in vacuo to furnish the desired hydroxycarbamimidoyl compound.

Z: Opening of aromatic methylene dioxy compound with alcohol A solution of potassium tert-butoxide (2.25 mmol) in DMSO (1.25 mL) was heated at 50 °C for 30 min. Methanol (1.25 mL) was added to it and continued heating at 50 °C for 30 min. To the reaction mixture was added 1,2-methylenedioxy aromatic compound (1 mmol) and continued heating at 50 °C for 30 min. The reaction mixture was cooled to room temperature and quenched with water (10 mL) and 1 N sodium hydroxide (16 mL). The reaction m mixture was washed with ether (2 X 10 mL) and acidified to pH 4 using conc HC1. The solid obtained was collected by filtration to furnish the desired product.

Z-l : Opening of aromatic methylene dioxy compound with alcohol To a mixture of methylene dioxy compound (1 mmol) in HMPA (2.5 mL) were added solidum methoxide (2.5 mmol) and heated with stirring at 150°C for 12 min. The mixture was cooled and poured into ice water (20 mL), NaOH (30 mg) and stirred for 10 min. It was then extracted with ether and the aqueous layer was acidified to pH 4 with HC1 and extracted with ether. The later ethereal extracts were combined, dried and concentrated. The residue was purified by crystallization or column chromatography.

AA: Conversion of amine to amide in the presence of a phenol To a solution of amino compound (1 mmol) in pyridine (5 mL) was added, dropwise, acid chloride (2 mmol) at 0 °C under N2. The mixture was stirred for 45 min and was then poured into ice water and acidified with 1 N HC1. The precipitated solid was collected by filtration, washed with IN HC1, hexane, and then dried in vacuo to give crude product. The crude product was added to freshly prepared sodium methoxide solution (0. 1 M, 10 mL) and stirred for 30 min at room temperature. The reaction mixture was quenched with acetic acid (1 mmol) and concentrated in vacuo. The residue

was dissolved in ethyl acetate and washed with water. The water layer was extracted with ethyl acetate, and the combined organic layers were washed with brine, dried (MgS04) and evaporated to yield a solid. The solid was washed with hexane and dried in vacuo to furnish the desired amide.

AB-1 Conversion of amino of amidine to amino carbamate To amidine compound (1 mmol) was added 0. 1N NaOH (10 mL) and stirred at room temperature for 5 min. The reaction mixture was concentrated in vacuo and to the residue was added alkyl or aryl 4-nitrophenyl carbonate (2 mmol) in 20 mL of hexamethylphosphoramide and stirred at 45 °C for 24 h. The reaction was quenched with water (100 mL) and extracted with ethyl acetate (2 X 100 mL). The combined extracts were washed with water (100 mL) and brine (100 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue obtained was purified by flash column chromatography to furnish the desired product.

AB-2: Conversion of amino of amidine to amino carbamate To a solution of amidine compound (1 mmol) in acetonitrile (25 mL) was added triethylamine (5 mL) and arylalkyl chloroformate (2 mmol) or dialkyl/aryl carbonate. The reaction mixture was stirred at room temperature for 16 h and quenched with water (100 mL). The reaction mixture was extracted with ethyl acetate (2 X 100 mL). The combined extracts were washed with brine (100 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue obtained was purified by flash column chromatography to furnish the desired product.

AC: Conversion of aldehyde to oxime To a stirred solution of aldehyde (1 mmol) in ethanol (10 mL) was added pyridine (10 mL) and hydroxylamine hydrochloride (1.25 mmol). The reaction mixture was stirred overnight at room temperature under nitrogen and then concentrated in vacuo to one third of its original volume. Water (10 mL) was added and the precipitated solid was collected by filtration and dried in vacuo. The product was used as such for next step without further purification.

AD: Debenzylation in the presence of aldehyde To a solution of phenyl methoxyaryl aldehyde (1 mmol) in dichloromethane (10 mL) cooled to-78 °C was added dropwise under a nitrogen atmosphere boron tribromide (1M solution in dichloromethane, 1.2 mmol). The reaction mixture was allowed to warm to room temperature and stirred at room temperature overnight. The reaction mixture was quenched with water (10 mL) and the layers were separated. The aqueous layer was extracted with chloroform (10 mL). The organic layers were combined, washed with brine (10 mL), dried, filtered and concentrated in vacuo to furnish crude product.

Purification of the crude by flash column chromatography furnished the desired phenolic aldehyde AE-1 : Reductive amination of aldehyde To a stirred solution of aldehyde (1 mmol) in methanol (40 mL) was added amine (3.3 mmol) followed by the addition of glacial acetic acid (0.3 mL). The reaction mixture was stirred for 30 min under nitrogen at room temperature, and then sodium cyanoborohydride (1.5 mmol) was added. After stirring for 20 min, the solvent was evaporated in vacuo, and the residue was taken in ethyl acetate. The organic layer was washed with water, and the insoluble material was removed from the organic layer by

filtration. The pH of the aqueous phase was adjusted to 7 with 1N NaOH and was extracted twice with ethyl acetate. The combined organic layers were washed with brine and dried (MgS04). The solvent was evaporated in vacuo to furnish crude product. The crude product was purified by crystallization or flash column chromatography.

AE-2: Reductive amination of aldehyde To a mixture of aminoarylamidine (1.2 mmol), 4A° molecular sieves, and sodium hydroxide (1 N solution in anhydrous methanol, 1.2 mL, 1.2 mmol) in methanol (10 mL) was added a solution of aldehyde (1 mmol) in THF (10 mL). The reaction mixture was heated for 15 mins at reflux temperature and was cooled to room temperature. Acetic acid (1 %) and sodium cyanoborohydride (1 M solution in THF, 5 mmol) was added to the reaction mixture and stirred at room temperature overnight. The reaction mixture was quenched with 1 N NaOH (30 mmol) and stirred for additional 2 h and concentrated in vacuo to remove methanol. The mixture was diluted with water (15 mL) and washed with ether (2 x 10 mL). The aqueous layer was acidified to pH 2 using 6 N HC1 and the solid that separated out was collected by filtration, washed with ether, dried in vacuo to furnish product, which was purified by flash column chromatography, if needed.

AE-3 : Reductive amination of aldehyde A mixture of aminoarylamidine (2 mmol), 4A° molecular sieves, pyridine (6 mL) in methanol (9 mL) was heated at 50 °C for one hour. A solution of aldehyde (1 mmol) in methanol (7.5 mL) containing acetic acid (1 %) was added and continued heating for 4 h to 12 h. The reaction mixture was cooled and sodium cyanoborohydride (1 M solution in THF, 5 mmol) was added to the reaction mixture and stirred at room temperature overnight. The reaction mixture was quenched with 5 N NaOH (30 mmol) and stirred for additional 2 h. The reaction mixture was filtered through Celite (to remove molecular sieves) and concentrated to remove methanol. The mixture was diluted with water (15

mL) and washed with ether (2 X 10 mL). The aqueous layer was filtered and solid obtained was kept aside (mainly product). The aqueous layer was acidified to pH 2 using 6 N HCl and the solid that separated out was collected by filtration. The combined solid materials were purified, if needed, by flash column chromatography.

AE-4: Reductive amination of aldehyde To a mixture of aldehyde (1 mmol) and aminoarylamidine (1. 1 mmol) in MeOH at room temperature was added triethyl amine (2.75 mmol), sodium cyanoborohydride (0.83 mmol) and zinc chloride (0.9 mmol). The reaction mixture was stirred at room temperature overnight and concentrated to remove methanol. The reaction mixture was quenched with 1 N NaOH (10 mL), diluted with water (10 mL), and extracted with EtOAc (5 X 20 mL). The combined organic extracts were washed with brine (15 mL), dried (MgS04), filtered through Celite and concentrated to give the product. Purification of the crude by flash column chromatography gave the desired product.

AE-5: Reductive amination of aldehyde To a solution of amine (1.2 mmol) in MeOH (10 mL) was added aldehyde (1 mmol) in THF (10 mL) containing acetic acid (0.1 mL) drop-wise. The mixture was stirred at 50 °C for 4-12 h and then cooled to room temperature. Sodium cyanoborohydride (1. 5 mmol) was added to the reaction mixture and stirred at room temperature overnight. Water was added and pH of the solution was adjusted to 7. The solution was extracted with ethyl acetate. The organic layer was dried (MgS04) and evaporated in vacuo. The residue was purifeid by flash column chromatography to furnish the desired amine.

AF-1 : Synthesis of amidine from nitrile Acetyl chloride (5 mL) was added to methanol (5 mL) at 0 °C drop-wise and stirred at room temperature for 15 mins. To this solution of methanolic HCI was added nitrile compound (1 mmol) and stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and dried. The residue obtained of the resulting methyl imidate was dissolved in methanol (10 mL). Dry ammonia gas was bubbled into the reaction mixture at reflux temperature for 5 h. The reaction mixture was concentrated to furnish the required amidine.

AG: Addition of Grignard reagent to aryl aldehyde To a solution of aryl aldehyde (1 mmol) in THF (15 mL) cooled to-78 °C was added drop wise under a nitrogen atmosphere, vinyl magnesium bromide (1 M solution in THF, 5 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 48 h. The reaction was quenched carefully with saturated aqueous ammonium chloride solution (10 mL) and extracted with ethyl acetate (2 X 10 mL). The organic layers were combined, washed with brine (10 mL), dried and concentrated in vacuo. The residue obtained was purified by flash column chromatography to obtain the desired addition product.

AG-1: Synthesis of tributylvinyltin compounds from vinyl bromide containing hydroxyl To a solution of vinyl bromide with hydroxyl (1 mmol) in dichloromethane (20 mL) was added tert-butyldimethylsilyl chloride (1.5 mmol) and DMAP (1.5 mmol) and stirred at room temperature overnight. The reaction mixture was quenched with water (20 mL) and the aqueous layer separated. The organic layer was washed with 0.1 N aqueous HC1 (10 mL), brine (20 mL), dried and concentrated in vacuo to furnish

corresponding tert-butyldimethylsilyloxy compound as an oil which was used as such for the next step.

To a solution of the above oily residue (1 mmol) in diethyl ether (20 mL) cooled to-78 °C was added dropwise tert-butyllithium (1.7 M in pentane, 2 mmol) over a period of 15 mins. The reaction mixture was stirred at-78 °C for 3 h and quenched at-78 °C with 2 N aqueous sulfuric acid (2 mL) and water (18 mL). The reaction mixture was neutralized using 2 N NaOH and the organic layer was separated. The organic layer was washed with water (20 mL), brine (20 mL), dried and concentrated in vacuo. Purification of the crude residue obtained by flash column chromatography furnished the desired tributyltin compound.

AG-2 : Synthesis of tributylmethyltin compounds from arylmethyl bromides or allyl bromides To lithium clippings (10 mmol) in THF (10 mL) cooled to-40 °C was added dropwise tributyltin chloride (0.27 mL, 1 mmol) in THF (5 mL) over a period of 15 min.

The reaction mixture was allowed to warm to room temperature and stirred for 16 h. The reaction mixture was filtered through glass wool to remove insoluble impurities and cooled to-40 °C. A freshly prepared solution of arylmethyl bromide or allyl bromide (1 mmol) was added dropwise over a period of 10 mins and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous ammonium chloride solution (10 mL) and extracted with ether (2 X 10 mL). The organic layers were combined, washed with brine (10 mL), dried, filtered and concentrated in vacuo to furnish desired tributyltinalkyl and was used as such without further purification.

AG-3 : 4-Bromo-5-formyl-benzot1, 3ldioxole-2-carboxylic acid methyl ester To a mixture of 2-bromo-3,4-dihydroxy-benzaldehyde (2.17 g, 10.0 mmol) and K2C03 (5.56 g, 40.2 mmol) in n-propanol (25 mL) was added dibromoacetic acid (2.18, 10.0 mmol) and the mixture was heated at reflux temperature for 24 h. After cooling to room temperature, another portion of dibromoacetic acid (1.75 g, 8.0 mmol) was added.

The mixture was stirred at reflux for 46 h. n-Propanol was evaporated and water (30 mL) was added. The resulting aqueous solution was acidified to pH 2 by adding 1 N HC1 and extracted with ethyl acetate (3 X 100 mL). The combined organic layers were dried (MgSO4) and evaporated in vacuo to afford crude 4-bromo-5-formyl-benzo [1, 3] dioxole- 2-carboxylic acid (1.34 g) as a brownish solid. This crude product was dissolved in anhydrous methanol (50 mL) and conc. H2SO4 (5 mL) was added drop by drop. The resulting mixture was refluxed overnight and cooled to room temperature. Water (50 mL) was added and the resulting aqueous solution was extracted with ethyl acetate (100 mL X 3). The combined organic layers were dried (MgS04) and evaporated in vacuo.

The residue was purified by flash column chromatography (ethyl acetate : hexane = 5: 95) to furnish 4-bromo-5-formyl-benzo [1, 3] dioxole-2-carboxylic acid methyl ester as a white solid.

AH : Synthesis of tert-butyl ester of phenol To a solution of phenol (1 mmol) in pyridine (10 mL) was added 2,2-dimethyl- propionyl chloride (1.2 mmol) dropwise. The mixture was stirred at room temperature for overnight and diluted with water (100 mL). The reaction mixture was extracted with ethyl acetate (3 X 50 mL). The organic layers were combined and washed with aqueous 0.5 N HCI (100 mL), water, brine, dried (MgSO4) and concentrated in vacuo. The crude residue was purified by flash column chromatography to furnish the desired ester.

AI : Preparation of 2-bromo-5-hydroxy benzaldehyde To a solution 3-hydroxybenzaldehyde (Aldrich, 101.39 g, 805 mmol) in chloroform (1000 mL), was added bromine (45 mL, 845 mmol) in chloroform (200 mL) drop wise over a period of 2 h at room temperature. The reaction mixture was stirred at room temperature overnight and filtered to collect crude 2-bromo-5-hydroxy benzaldehyde (32 g) as a dark brown solid. The filtrate was concentrated to 200 mL, filtered through a pad of Celite and silica gel (40 g) and washed with ether (1000 mL).

The filtrate was concentrated in vacuo to give a second crop of the crude desired aldehyde (60 g) as a dark brown solid. The above solids were combined and dissolved in glacial acetic acid (360 mL) by heating. Water (840 mL) was added and the solution was filtered hot. The solution was allowed to attain room temperature and kept in a refrigerator overnight. The crystals obtained were collected by filtration and washed with water, dried overnight in vacuo to furnish (60 g, 37%) of the desired product as a purplish brown crystalline solid, mp: 135 °C.

AJ-1 : Amidine from nitrile A mixture of nitrile (1 mmol) and hydroxylamine (aqueous 50%, 1.8 mL) in EtOH (15 mL) was refluxed for 3 h and concentrated in vacuo. To the residue obtained was added EtOH (20 mL), acetic acid (2 mL) and a small amount of Raney nickel. The reaction mixture was hydrogenated (50 psi) for 14-24 h, filtered and concentrated in vacuo. The residue obtained, was purified by flash column chromatography to obtain the corresponding amidine.

AJ-2 : Amidine from nitrile A mixture of nitrile (1 mmol) and saturated methanolic HC1 solution (freshly prepared by bubbling HC1 gas or prepared in-situ by premixing methanol and acetyl

chloride at ice cold temperature) was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo to furnish methyl imidate. To the residue of methyl imidate was added MeOH (40 mL) and ammonia gas was bubbled at reflux temperature for 16 h or till the reaction was complete. The reaction mixture was concentrated in vacuo and dried to furnish the desired amidine. Alternatively, the methyl imidate was dissolved in methanol and ammonium acetate (10 mmol) was added. The reaction mixture was concentrated in vacuo and purified by flash column chromatography to obtain the corresponding amidine.

AJ-3: Amidine from nitrile To a solution of nitrile (1 mmol) dissolved in methanol (5 mL) was added N- acetyl cystein (0.1 or 1 mmol) and ammonium acetate (5 mmol) and heated at reflux till the reaction was complete. The reaction mixture was concentrated in vacuo and purified by flash column chromatography to obtain the corresponding amidine AK: Conversion of aryl triflates or halides to boronate ester To dichloro [1, 1'-bis (diphenylphosphino) ferrocene] palladium (II) dichloro- methane adduct (0.75 mmol) under argon in dioxane (100 mL) was added aryl triflate (25 mmol), pinacolborane (31.5 mmol) and triethylamine (75 mmol). The reaction mixture was heated under argon at 100 °C for 3h or until complete as evidenced from TLC analysis. The reaction mixture was concentrated in vacuo. The residue obtained was purified by flash column chromatography to furnish the desired boronate ester.

Alternatively, the following method can be used.

To dichloro [1, 1'-bis (diphenylphosphino) ferrocene] palladium (II) dichloro- methane adduct (0.03 mmol), l, l'-bis (diphenylphosphino) ferrocen (0.03 mmol) under argon in dioxane (100 mL) was added aryl triflate (1 mmol), bis (pinacolata) diboron (1.1

mmol) and potassium acetate (3 mmol). The reaction mixture was heated under argon at 100 °C for 3h or until complete as evidenced from TLC analysis. The reaction mixture was concentrated in vacuo. The residue obtained was purified by flash column chromatography to furnish the desired boronate ester.

The examples of the compounds prepared are given in the following tables. The tables describe the compounds, their method of preparation, the starting material, and the analytical data. In some cases, where analytical data have not been given, those compounds were characterized at the later step in the synthesis. c : pd., Starting Method No.-R-R'From Used No. From Used" CH'I-j NMR (DMSO-d6): 8 10.26 (s, 1 H), 9.84 (s, 1 H 3 H), 8.15 (d, J= 3. 0 Hz, 1 H), 7.64 (dd, J= 2. 0 dz 2a OH wN\>\CH 1 A 1 or A-2 d g9 Hz, 1 H), 6.94 (d, J= 8.9 Hz, 1 H), 3.90 (s, 3 H), 2. 15 (d, J= 6. 9 Hz, 2 H), 2.06 (m, J= 6. 9 Hz, 0 1 H), 0.93 (d, J= 6.9 Hz, 1 H), 0.93 (d, J = 6 Hz, 6H); MS (ES+) : 252.12 H N CH3 2b-OH 1 A-1 or A-2 Characterized in the next step 0 CH3 H N CH 2c-OH 1-CH3 1 A-1 orA-2 MS (ES+) : 294.54 O H N CH3 2d-OH yN 1 A-lorA-2 MS (ES+) : 288.49 (M+Na) + 0

Cpd. Starting Method No. From Used H H H 2e-OH f 1 A-1 or A-2 Characterized in the next step 0 H H 2f 2 ? < I A-lorA-2 pMS (ES+) : 300.40 (M+Na) + 0 H 2g-OH gNo 1 A-1 or A-2 MS (ES+) : 272.48 (M+Na) + ; MS (ES~) : 248.66 0 H N 2h-OH ( 1 A-1 or A-2 MS (ES+) : 286.48 (M+Na) + il H H 2i-OH X \/3 1 A-1 orA-2 MS (ES+) : 224.54 0 CH3 H 2j-OH O CH3 1 A-1 or A-2 Characterized in the next step n Cpd._R _R, Starting Method No. From Used No. From Used- CH3 H 3a-OSO2CF3 NCH 2a B-1 or B-2 MS (ES+) : 384.37 0 H H 3b-OSO2CF3 X \1/2b B-1 or B-2 MS (ES+) : 370.36 0 chez H H N CH 3c-OS02CF3""CCH3 2c B-1 or B-2 MS (ES+) : 426.37 0 H H _ 3d-OS02CF3 f) J 2d B-1 or B-2 Characterized in the next step O 'H NMR (CDC13): 8 8.41 (d, J=2. 3 Hz, 1 H), 8.10 (dd, J = 8. 5,2.4 Hz, 1 H), 7.37 (d, J= 8.5 Hz, 1 H), 3e-OSO2CF3 O tzCH3 2e B-1 or B-2 6.48 (broad, 1 H), 3.98 (s, 3 H), 3.46 (q, J= 7. 2 Hz, 3 2 H), 1.62 (m, 2 H), 1.42 (m, 2H), 0.96 (t, J= 7. 2 Hz, 3 H); MS (ES+) : 384.1 H'H NMR (CDC13) : 8 8.45 (d, J= 2. 4 Hz, 1 H), 8.14 . S F wNCF3 2f B 1 B-2 (dd, J= 8. 7, 2. 4 Hz, 1 H), 7. 42 (d, J= 8. 7 Hz, 1 H), 6. 52 (broad, 1 H), 4.14 (m, 2 H), 4.00 (s, 3 H) ; MS (ES+) : 410.2 Cpd. Starting Method "-R-R'-° . AnaIyttca! Data No. From Used No. | {From Used IHNMR (CDC13) : 8 8.42 (d, J=2. 3 Hz, I H), 8.12 H, z1 (dd, J=8. 5,2. 3 Hz, 1H), 7. 39 (d, J=8. 7Hz, l H), 3g-OSO2CF3 9'I 2g B-lorB-2 6.31 (broad, 1 H), 4.00 (s, 3 H), 3. 34 (dd, J= 7. 2, 5. 5 Hz, 2 H), 1.07 (m, 1 H), 0.59 (m, 2 H), 0.30 (m, 2 H) ; MS (ES+) : 382.2 H 3h-OSO2CF3 NXo 2h B-lorB-2 MS (ES+) : 396.36 ... 'HNMR (DMSO-d6) : 8 8.85 (t, J= 5. 5 Hz, 1 H), 3i-OSO2CF3 XN\"CH3 2i B-lorB-2 8. 49 (d, J-2. 3 Hz, lH), 8.23 (dd, J=8. 7,2. 3Hz, 3i-OS02CF3 N CH3 2i B-1 or B-2 (m, 2H), 1. 14 (t, J= 7. 2 Hz, 3 H) ; MS (ES+) : 356. 1 o 'H NMR (DMSO-d6) : 5 8.81 (t, J= 6. 0 Hz, 1 H), CH3 8.49 (d, J=2. 3 Hz, 1 H), 8.24 (dd, J= 8. 7,2.4 Hz, 3j-OS02CF3 NU -CHO 2j B-1 or B-2 1 H), 7.71 (d, J= 8. 7 Hz, 1 H), 3.92 (s, 3 H), 3.15 (m, 2 H), 1.64 (m, 1H), 1.41 (m, 1H), 1. 12 (m, 1 H), 0.88 (m, 6 H) ; MS (ES+) : 398.2 'H NMR (DMSO-d6): 8 8.52 (d, J= 2. 0 Hz, 1 H), 8. 32 (dd, J=2. 0and8. 9Hz, lH), 7.72 (d, J= 7. 9 5-OSO2CF3-CO2MEM 4 B-2 Hz, 1 H), 5.50 (s, 2 H), 3.88 (s, 3 H), 3.78 (t, J= 4. 9 Hz, 2 H), 3.44 (d, J=4. 9Hz, 2H), 3.17 (s, 3 H) ; MS (ES+) : 439.1 (M+Na) + CH3 1HNMR (CDC13) : 8 8. 29 (d, J =1. 6 Hz, 1 H), 7.96 H (dd, J=7. 5&1. 6Hz, lH), 7.58 (d, J=7. 5Hz, l 6a-Bu N'/CH 3a AK H), 6.24 (bs, 1 H), 3.94 (s, 3 H), 3. 30 (t, J = 6. 5 Hz, 2 H), 1.92 (m, 1 H), 1.43 (s, 12H), 0.99 (d, J=6. 5 Hz, 6H) ; MS (ES+) 362.2 Cpd. Starting Method No. From Used No | X From Used 0 CH3 tH NMR (DMSO-d6) : 8 10.26 (s, 1 H), 9.84 (s, 1 H), 8. 15 (d, J = 3.0 Hz, 1 H), 7.64 (dd, J = 2.0 Hz J= 8.9 Hz, 1 H 3.90 (s, 139-OHN CH3 138 AA and 8. 9 Hz, I H), 6. 94 (d, J= 8. 9 Hz, 1 H), 3. 90 (s, H 3 3 H), 2.15 (d, J= 6. 9 Hz, 2 H), 2.06 (m, J= 6. 9 Hz, 1 H), 0. 93 (d, J= 6.9 Hz, 6 H); MS (ES+) : 252.12 O CH3 lH NMR (DMSO-d6) : 5 10. 38 (s, 1 H), 8.36 (d, J= 2. 8 Hz, 1 H), 7.99 (dd, J= 2. 6 and 8. 9 Hz, 1 H), 140 139 B-2 7.52 (d, J= 9. 0 Hz, 1 H), 3.89 (s, 3 H), 2.23 (d, J 2 3 H 3 7.0 Hz, 2 H), 2.09 (m, J= 6. 6 Hz, 1 H), 0.94 (d, J= 6.6 Hz, 6 H); MS (ES+) : 384.0 'H NMR (CDC13) : 8 8.08 (s, 1 H), 8.00 (d, J= 2. 3 169-oh 168 AC Hz, 1 H), 7.75 (dd, J= 2. 3 and 8.7 Hz, 1 H), 7.01 -OH vNOH (d, J-8. 7 Hz, 1 H), 3.97 (s, 3 H), 3.50 (s, 1 H); MS (ES+) : 196.1 'H NMR (DMSO-d6) : 8 7.79 (d, J= 2.0 Hz, 1 H), 170-OH-CH2NH2 169 G 7. 51 (dd, J= 2. 3 and 8. 5 Hz, 1 H), 6. 95 (d, J= 8. 5 Hz, 1 H), 7. 01 (d, J= 8. 7 Hz, 1 H), 3.90 (s, 3 H), 3. 72 (s, 2 H), 3.50 (bs, 2H); MS (ES+) : 182.12 c 3 H N 171-OH CH3 170 AA MS (ES-) : 250.50 ; MS (ES+) : 274. 50 (M+Na) + 0 P Starting Method No. From Used No. I From I Used CH,'H NMR (CDC13) : 8 7.96 (d, J= 2. 3 Hz, 1 H), 7.55 1 H) 7.26 (d, J= 83 Hz, 1 H l (d, J= 2. 3 and 8.3 Hz, 1 H), 7. 26 (d, J= 8. 3 Hz, 1 172-OS02CF3 171 B-2 H), 5.90 (br s, 1 H), 4.50 (d, J= 4. 1 Hz, 2 H), 3.97 (s, 3 H), 2.44 (sep, J= 7.0 Hz, 1 H), 1.20 (d, J= 7.0 Hz, 6 H) ; MS (ES+) : 384.1 CH'H NMR (DMSO-d6): 5 10.62 (s, 1 H), 8.88 (m, 2 177-OHH), 7. 99 (d, J=2. 3 Hz, 1 H), 7. 70 (dd, J=2. 3 and \N+ 8. 5 Hz, 1 H), 7.06 (d, J= 8. 7 Hz, 1 H), 4.09 (m, 2 CH3 H), 3.91 (s, 3 H), 2.70 (m, 2 H), 1.98 (m, 1 H, J= 6.8 Hz), 0.93 (d, J= 6.8 Hz, 6 H); MS (ES) : 238. 1 'H NMR (CDC13) : 5 8.05 (d, J= 2.3 Hz, 1 H), 7.63 H CH 3 (dd, J= 2. 3 and 8. 3 Hz, 1 H), 7.25 (d, J= 8.3 Hz, 1 178-OSO2CF3 X N X 177 B-2 H), 3.96 (s, 3 H), 3.85 (s, 2 H), 2.43 (d, J= 6. 8 Hz, CH3 2 H), 1.77 (m, J= 6. 6 Hz, 1 H), 0.93 (d, J= 6. 6 Hz, 1 H); MS (ES+) : 370.2 1H NMR (DMSO-d6) : 8 7.93 (m, 1 H), 7.47 (m, 1 Boc l CIH3 H), 7. 26 (m, 1H), 4.48 (m, 2H), 3.96 (s, 3H), 3.03 (m, 2 H), 1.91 (m, 1 H), 1.52 (m, 9 H), 0.89 (d, J= CH3 6.6 Hz, 6 H); MS (ES+) : 492.2 (M+Na) + 3 Cpd. _R R, Starting Method Analytbcal Data "-R-R' ° . AnaIyttcaIData No. From Used 'H NMR (DMSO-d6): S9_78 (s, 1H), 8. 85 (t, J = 5.7 Hz, 1H), 8. 50 (d, J = 2.0 Hz, 1H), 8.20 (dd, J = 8.2,1.9 Hz, 1H), 7.55 (m, 9H), 7-OBn-CHO 6 + 3a D-2 5.35 (s, 2H), 3.69 (s, 3H), 3.23 (t, J = 6.5 Hz, 2H), 1.98 (m, 1H), 1.02 (d, J = 6.8 Hz, 6H); MS (ES+): 446. 3 8-OBn-CO2H 7 E MS (ES+) : 484.33 (M+Na) + -OBn-CO2MEM MS (ES+) : 572.2 (M+Na) + 10-OH-C02MEM 9 G MS (ES+) : 482. 33 [ (M-MEM) + Na] + 'H NMR (DMSO-d6) : 58. 75 (t, J = 5.6 Hz, 1H), 8.44 (d, J = 1. 6 Hz, 1H), 8.11 (dd, J = 8.0,1.9 Hz, 1H), 8.01 (d, J =2. 9 Hz, 1H), 7.84 (dd, J = 8. 4,2.6 Hz, 1H), 7.47 (d, J = 8. 5 Hz, 1H), 7.41 (d, J = 11-OSO2CF3-CO2MEM 10 B-2 8.0 Hz, 1H), 5.23 (q, AB system, 2H), 3.59 (s, 3H), 3.44 (m, 2H), 3.30 (m, 2H), 3.18 (s, 3H), 3.13 (t, J = 6.6 Hz, 2H), 1.88 (m, 1H), 0.91 (d, J = 6. 7 Hz, 6H); MS (ES+): 614.3 (M+Na) + 0 29a A-COzMEM 11 D-3 Characterized in the next step CH3

p Starting Method No. From Used No_ 29b/<\CH3-CO2MEM 11 D-3 MS (ES+) : 520.2 (M+Na) + 29c 2-C02MEM 11 D-3 MS (ES+) : 482. 3 29d S-COZMEM 11 D-3 MS (ES+) : 562. 3 (1\4+Na) + 29e-C02MEM 11 D-3 MS (ES+) : 556.4 (M+Na) + IH NMR (DMSO-d6): 68. 50 (t, J = 5. 6 Hz, 1H), 8.18 (d, J = 1. 9 Hz, 1H), 7.86 (dd, J = 7.9,1.9 Hz, 1H), 7.78 (d, J =1.7 Hz, 1H), 7.56 (dd, J = 8.0,1.8 Hz, 1H), 7.13 (d, J = 8.0 Hz, 1H), 7. 00 (d, J = 7. 9 Hz, 1H), 6.67 (dd, J = 17. 6,11.1 Hz, 1H), 5.76 (d, J = 17. 6 Hz, CHZ 1H), 5.19 (d, J = 11. 1 Hz, 1H), 4.99 (q, AB system, 2H), 3.37 (s, 3H), 3.20 (m, 2H), 3.11 (m, 2H), 2.97 (s, 3H), 2.91 (t, J = 6.7 Hz, 2H), 1.67 (m, 1H), 0.70 (d, J = 6.6 Hz, 6H); MS (ES+): 492.3 (M+Na)+ OHC 29g//-C02MEM 11 D-2 MS (ES+) : 576.2 (M+Na) + ; MS (ES-): 552.2 S Cpd-R Starting Method Analytical Data No. From Used CHO 29h 4-CO2MEM 11 D-2 MS (ES+) : 538.2 O one. 29i -COzMEM 11 D-2 MS (ES+) : 560.4 (M+Na) + o 0 30a-CO2H 29a I-1 MS (ES+) : 398.3; MS (ES-): 396.3 CH3. 30b/ 30b 3-C02H 29b I-1 Characterized in the next step 30c CH2-CO2H 29c I-1 MS (ES-) : 392.1 e 30d 0-CO2H 29d I-1 MS (ES+) : 452.1 \ 30e I-COZH 29e LI MS (ES+) : 446. 2 Cpd.-R-Rt Starting Method Analytical Data "-R-R* ° ,. AnaiyticData No. From Used 30f/% CH2-CO2H 29f I-1 MS (ES-) : 380.1 N3H2C. 30g-C02H 29g K, N, O, MS (ES+) : 515.3 (M+Na) + ; MS (ES-): 491.2 S CHOH 30h X-CO2H 29h K, I-1 MS (ES-) : 450.1 0 HOH2Cx _/ 30i-C02H 29i K, I-1 MS (ES-) : 450.3 o. 33-OSO2CF3-CO2H 11 I-1 Characterized in the next step 41-CO2MEM 10 D-8 MS (ES-) : 534. 30 42-C02H 41 I-1 MS (ES-): 446.30 -48-OCH3-CHO 47 + 3a D-2 MS (ES+) : 392.2 (M+Na) + 49-OCH3-CO2H 48 E MS (ES+) : 386.1 ; 408.1 (M+Na) + Cpd.-R-Rv Starting Method Analytical Data No. From Used - zedin then t step 14-OS02CF3-CHO 13 B-2 Characterized in the next step 15-OSO2CF3-CO2H 14 MS (ES) : 403.58 H CH'HNMR (DMSO-d6) : 6 8.83 (t, J = 6 Hz, 1 H), 8.49 (d, J = 2. 6 N Hz, 1 H), 8.23 (dd, J = 8. 6 Hz, 1 H), 7.72 (d, J = 8. 6 Hz, 1 H), 16-OSOZCF3 N 15 A-3 or A-4 'CH3 7. 49 (m, 2 H), 7.41 (m, 3 H), 5.43 (s, 2 H), 3.1 (t, J = 6. 9 Hz, 2 o H), 2. 29 (m, 1 H), 0.89 (d, J = 6. 9 Hz, 6 H). 0

Cpd. Starting Method -R -R' Analytical Data No. From Used 1HNMR (DMSO-d6)L: # 0.88 (d, J=6.0 Hz, 6 H), 1.85 (m, 1 H), 3.1 (t, J=6.0 Hz, 2 H), 5.02 (q, J=13 and 2.5 Hz, 2 H), 5.18 (s, 2 17 -OBn -CHO 16 + 6 D-2 H), 6.88 (m, 2 H), 7.17 (d, J=8.6 Hz, 1 H), 7.26 (m, 4 H), 7.35 (m, 1 H), 7.40 (m, 4 H), 7.49 (d, J=7.7 Hz, 2 H), 8.07 (dd, J=7.7 and 1.7 Hz, 1 H), 8.38 (d, J=1.7 Hz, 1 H), 8.72 (t, J=6 Hz, 1 H), 9.63 (s, 1 H); MS (ES+):522.89 1HNMR (DMSO-d6): # 0.86 (d, J=6.9 Hz, 6 H), 1.85 (m, 1 H), 3.09 (t, J=6.9 Hz, 2 H), 5.01 (d, J=5.01 Hz, 2 H), 5.14 (s, 2 H), 18 -OBn -CO2H 17 E 7.08 (m, 3 H), 7.14 (dd, J=8.6 and 2.6 Hz, 1 H), 7.27 (m, 4 H), 7.34 (m, 1 H), 7.41 (m, 3 H), 7.48 (m, 2 H), 7.99 (dd, J=6.9 and 1.8 Hz, 1 H), 8.32 (s, 1 H), 8.64 (t, J=6 Hz, 1 H), 12.57 (s, 1 H); MS (ES+):538.86 1HNMR (DMSO-d6):# 0.90 (d, J=6.8 Hz, 6 H), 1.86 (m, 1 H), 3.10 (t, J=6.5 Hz, 2 H), 3.16 (s, 3 H), 3.28 (dd, J=3 and 6 Hz, 2 19 -OBn -CO2MEM 18 F H), 3.36 (dd, J=3 and 6 Hz, 2 H), 5.02 (d, J=3.8 Hz, 2 H), 5.12 d, J=15 Hz, 2 H), 5.64 (s, 2 H), 7.11 (m, 3 H), 7.24 (dd, J=8.25 and 2.75 Hz, 1 H), 7.29 (m, 4 H), 7.35 (m, 1 H), 7.42 (m, 3 H), 7.49 (m, 2 H), 8.02 (dd, J=1.7 and 8.2 Hz, 1 H), 8.36 (d, 1.7 Hz, 1 H), 8.68 (t, J=6 Hz, 1 H); MS (ES+): 626.44

Cpd.-R'Starfing Melhod AnalyticalData No. From Used No. From Used" 1HNMR (DMSO-d6) : 8 0.88 (d, J = 6 Hz, 6 H), 1.85 (m, 1 H) 3.10 (t, J = 6 Hz, 2 H) 3.16 (s, 3 H), 3.28 (m 2 H), 3.35 (m, 2 H), 5.04 21-OH-C02MEM 19 G, H (d, J 3. 5 Hz, 2 H) 5.11 (d, J=14Hz, 2H), 6.98 (m, 2H), 7.11 m, 2 H), 7. 29 (m, 5 H), 8. 03 (dd, J = 8 and 2 Hz, 1 H), 8.32 (d, J= 2 Hz, 1 H), 8.67 (t, J = 6 Hz, 1 H), 9.9 (s, 1 H) ; MS (ES+) 536.30 (100% : M) IHNMR (DMSO-d6) : 8 0. 89 (d, J = 6. 8 Hz, 6 H), 1.86 (m, 1 H), 3.12 (t, J = 6. 5 Hz, 2 H), 3.16 (s, 3 H), 3.29 (m, 2 H), 3.40 (m, 2 M OSnCP CO MEM 21 B2 H), 5.04 (dd, J=18and6Hz, 2H), 7.15 (m, 2H), 7. 31 (m, 3 H), 7. 36 (d, J = 8. 5 Hz, I H), 7.41 (d, J=8. 5Hz, lH), 7.73 (dd, J = 8. 6 and 2. 6 Hz, 1 H), 7.85 (d, J = 2. 6 Hz, 1 H), 8.07 (dd, J = 7. 7and 1. 7 Hz, 1 H), 8.45 (d, J = 1. 7 Hz, 1 H), 8.73 (t, J = 6 Hz, 1 H); MS (ES+) 668.15 'HNMR (DMSO-d6) : 8 0.89 (d, J = 6. 8 Hz, 6 H), 1.87 (m, 1 H), 3.12 (t, J = 6 Hz, 2 H), 3.16 (s, 3 H), 3.29 (m, 2 H), 3.39 (m, 2 H), 5.05 (d, J=2. 6Hz, 2H), 5.16 (d, J = 17 Hz, 2 H), 7.08 (m, 2 H), -COzMEM 22 + 23 D-1 21 (m, 4 H), 7.24 (d, J=7. 7Hz, lH), 7.35 (d, J=7. 7Hz, 1H), 24a 7. 62 (d, J = 3. 5 Hz, 1 H), 7.64 (d, J = 5 Hz, 1 H), 7.86 (d, J=8. 6 Hz, 1 H), 8.06 (m, 2 H), 8.42 (s, 1 H), 8.73 (t, J = 6 Hz, 1 H) ; MS (ES+)602.52 Cpd. _R Starting Method Analytical Data "-R-R' ° . AnaiyticaiData No.From Used 'HNMR (DMSO-d6) : 8 0.89 (d, J = 6. 8 Hz, 6 H), 1.87 (m, 1 H), \ 3. 12 (t, J = 6 and 6. 8 Hz, 2 H), 3.16 (s, 3 H), 3.30 (m, 2 H), 3. 39 (. (dd, J=5. 2al1d3. 4Hz, 2H), 5.04 (d, J=4. 3Hz, 2H), 5.16 (d, J= 24b t 9-CO2MEM 22 + 23 D-1 16 Hz, 2 H), 7.08 (m, 2 H), 7.20 (m, 3 H), 7. 24 (d, J = 8.6 Hz, 1 S H), 7. 35 (d, J = 8.6 Hz, 1 H), 7.61 (d, J = 5 Hz, 1 H), 7.71 (dd, J = 4.8 and 3 Hz, 1 H), 7.91 (dd, J = 1. 7 and 7.7 Hz, 1 H), 8.00 (m, 1 H), 8.06 (dd, J =2 and 8 Hz, 1 H), 8.14 (d, J = 1. 7 Hz, 1 H), 8.41 (d, J = 1.7 Hz, 1 H), 8.68 (t, J = 6 Hz, 1 H); MS (ES+) 602.27 'HNMR (DMSO-d6) : 6 0.89 (d, J = 6.8 Hz, 6 H), 1.87 (m, 1 H), 3. 12 (t, J = 6 and 6. 8 Hz, 2 H), 3.16 (s, 3 H), 3. 30 (m, 2 H), 3.40 (m, 2 H), 5.05 (d, J = 5 Hz, 2 H), 5.17 (d, J = 17 Hz, 2 H), 7.09 (m, 24c WJ-CO2MEM 22 + 23 D-1 2 H), 7.21 (m, 3 H), 7. 30 (d, J = 7. 7 Hz, 1 H), 7. 37 (d, J = 7. 7 Hz, 1 H), 7.44 (m, 1 H), 7.54 (t, J = 7. 7 Hz, 2 H), 7.73 (d, J = 6. 8 Hz, 2 H), 7.88 (dd, J = 1. 7 and 7.7 Hz, 1 H), 8.07 (dd, J = 7.7 and 1. 7 Hz, 1 H), 8.11 (d, J = 1. 7 Hz, 1 H), 8.42 (d, J = 1. 7 Hz, 1 H), 8.72 (t, J = 6 Hz, 1 H); MS (ES+) 596.45 24d l -CO2MEM 22 + 23 D-1 MS (ES+) 616 Hic 24e /\-COzMEM 22+23 D-l MS (ES+) 586.4 o 0 Cd., Starting Method No. From Used No. From Used" 24f-C02MEM 22 + 23 D-1 MS (ES+) : 586. 39 0 H3C 24g-CO2MEM 22 + 23 D-1 MS (ES+) : 616. 63 s 24h-C02MEM 22 + 23 D-1 MS (ES+) : 597.25 Nua 24i X/-CO2MEM 22 + 23 D-1 MS (ES+) : 597.4 N 24j-C02MEM 22 + 23 D-1 MS (ES+) : 597.4 2F4j N c//\\-C02MEM 22+23 D-l MS (ES+) : 644.3 s 0 Cpd. _R _R, Starting Method Analytical Data No.From Used No. From Used" N 0\--3 Characterized at the next step 241 N C02MEM 22 + 23 D 24m N-COzMEM 22+23 D-10 Characterized at the next step N 24n CH2-CO2MEM 22 + 23 D-3 MS (ES+) : 560.74 24O SN-CO2MEM 22 + 23 D-4 MS (ES+) : 603.72 24p/=\CH-CO2MEM 22 + 23 D-5 MS (ES+) : 558. 3 /LH 24q v-CO2MEM 22 + 23 D-5 Characterized in the next step Hic 24r _C02MEM 22 + 23 D-5 MS (ES : 610.4 (M+Na) + Cpd. _R _R, Starting Method Analytical Data No. From Used -CHZ 24s CH-CO2MEM 22 + 23 D-3 Characterized in the next step CH3 CHZ 24t--COZMEM 22 + 23 D-3 Characterized in the next step CH3 24u H-COzMEM 22 + 23 D-3 MS (ES+) : 598.4 (M+Na) + CHZ 24v--\ -COzMEM 22+23 D-3 MS (ES-): 500.4 [(M-MEM)-1]- OH 24w-C02MEM 22 + 23 D-5 Characterized in the next step CH3 24x CH3-C02MEM 22 + 23 D-3 MS (ES+) : 610.5 (M+Na) CH3 24y-C02MEM 22 + 23 D-5 MS (ES+) : 596.4 (M+Na) + chez. 24z OH-C, 02MEM 22 + 23 D-3 MS (ES+) : 576. 3 (M+Na) + OH OH 24aa N-CO2MEM 22 + 23 D-l l Characterized in the next step Cpd. _R _R, Starting Method Analytical Data No. From Used CHO 24ab-C02MEM 22 + 23 D-2 MS (ES+) : 630.55 S 24ac-CO2MEM 22 + 23 D-2 MS (ES+) :630.74 s ho onc i 4ad t S-CO2ME M 22 + 23 D-MS (ESt : 652. 3 su 24ae OHC S-CO2M EM 22 + 23 D-2 Characterized in the next step 24ag N C02MEM 22 + 23 D-1 MS (ES+) : 685.01 Boc 24an-cH2-CO2M E M 22 + 23 D-3 MS (ES+) : 546.49 z Cpd. _R _R, Starting Method Analytical Data No. From Used No. From Used" 'HNMR (DMSO-d6): 5 0. 91 (d, J = 6.9 Hz, 6 H), 1.88 (m, 1 H), 3. 13 (t, J = 6. 9 and 6 Hz, 2 H), 5.07 (d, J = 11. 2 Hz, 2 H), 7.09 (m, 2 H), 722 (m, 5 H), 735 (d, 7.7 Hz, I H), 7.63 (d, 2.6 Hz, 1 H), 25a \ s/CO2H a 7. 65 (d, J = 5. 2 Hz, 1 H), 7.82 (dd, J = 7.7 and 1.7 Hz, 1 H), 8.05 (d, J = 1. 7 Hz, 1 H), 8.07 (s, 1 H), 8.40 (s, 1 H), 8.72 (t, J = 6 Hz, 1 H), 12.77 (brs, 1 H); MS (ES+) 514.19 'HNMR (DMSO-d6) : 8 0.92 (d, J = 6.9 Hz, 6 H), 1.88 (m, 1 H), 3. 12 (t, J=6. 9and6Hz, 2H), 5.07 (d, J = 13 Hz, 2 H), 7.09 (m, 2 H), 7.22 (m, 4 H), 7.35 (d, J = 8.6 Hz, 1 H), 7.63 (d, J = 5.2 Hz, 1 25b 1l \\ CO2H 24b I-1 H), 7.70 (dd, J = 2.6 and 4. 3 Hz, 1 H), 7.88 (dd, J = 7.2 and 1.7 \s/Hz, 1 H), 8.02 (d, J = 1. 7 Hz, 1 H), 8.07 (dd, J = 1. 7 and 7.7 Hz, 1 H), 8.15 (m, 1 H), 8. 39 (d, J = 1. 7 Hz, 1 H), 8.72 (t, J = 6 Hz, 1 H), 12.70 (brs, 1 H); MS (ES+) 514.06 IHNMR (DMSO-d6) : 6 12.73 (bs, 1 H), 8.73 (t, J = 6 Hz, 1 H), 8. 41 (d, J = 1. 7 Hz, 1 H), 8.12 (d, J = 1.7 Hz, 1 H), 8.07 (dd, J = 7. 7 & 1.7 Hz, 1 H), 7.83 (dd, J = 7.7 & 1.7 Hz, 1 H), 7.72 (d, J = 25c/) CO2H 24c I-1 6.9 Hz, 2 H), 7.54 (t, J = 7. 7,2 H), 7.44 (t, J = 7. 7 Hz, 1 H), 7.37 (d, J = 7. 7 Hz, 1 H), 7.28 (d, J = 7.7 Hz, 1 H), 7.21 (m, 3 H), 7.09 (m, 2 H), 5.08 (d, J = 14 Hz, 2 H), 3.13 (t, J = 6. 5 Hz, 2 H), 1.88 (m, 1 H), 0.91 (d, 6.8 Hz, 6 H); MS (ES+) 507.93 'HNMR (DMSO-d6) : 8 12.75 (bs, 1 H), 8.71 (t, J = 6 Hz, 1 H), 8.39 (d, J =1. 7 Hz, 1 H), 8.05 (dd, J = 1. 7 & 7. 7 Hz, 1 H), 8.01 (d, J = 2.5 Hz, 1 H), 7.75 (dd, J = 2.5 & 7.7 Hz, 1 H), 7.42 (d, 3.4 Hz, 25d C02H 24d I H), 7.34 (d, J = 7. 7 Hz,-1 H), 7.22 (m, 3 H), 7.19 (d, J = 8. 6 Hz, H3C g 1 H), 7.09 (m, 2 H), 6.95 (d, J = 3. 4 Hz, 1 H), 5.06 (d, J=llHz, 2 H), 3.12 (t, J = 6. 5 Hz, 2 H), 2.52 (s, 3 H), 1.89 (m, 1 H), 0.81 (d, 6.8 Hz, 6 H); MS (ES+) 528. 51 Cpd. _R _R, Starting Method Analytical Data No.From Used 1HNMR (DMSO-d,) : 8 0.89 (d, J = 6 Hz, 6 H), 1.86 (m, 1 H), 3.12 (t, J = 6. 8 and 6. 0 Hz, 2 H), 5.03 (d, J = 10 Hz, 2 H), 7.02 (s, 1 H), 25e 1l \\ CO2H 24e I-1 7. 06 (m, 2H), 7.16 (d, J=8. 6Hz, lH), 7.21 (m, 3H), 7. 31 (d, J= X/7. 7Hz, lH), 7.75 (dd, J=8. 5andl. 7Hz, lH), 7.78 (t, J=1. 7 Hz, 1 H), 8. 04 (m, 2 H), 8.29 (s, 1 H), 8.36 (d, T = 1. 7 Hz, 1 H), 8.66 (t, J = 6 and 5. 2 Hz, 1 H), 12.58 (bs, 1 H) ; MS (ES+) 498.49 25f C02H 24f I-1 MS (ESt : 498.36 0 H, c'HNMR (DMSO-d6) : 8 12. 72 (bs, 1 H), 8. 69 (t, J = 6 Hz, 1 H), 8. 39 (d, J=1. 7Hz, lH), 8.06 (m, 2 H), 7.79 (dd, J = 1. 7 & 7. 7 25g COZH 24g I-1 Hz, lH), 7.45 (s, 1H), 7.35 (d, J=7. 7Hz, lH), 7.21 (m, 5H), 7. 1 (m, 2 H), 5. 07 (d, J = 8. 6 Hz, 2 H), 3.12 (t, J=6. 5Hz, 2H), 2. 29 (s, 3 H), 1.89 (m, 1 H), 0.91 (d, 6.8 Hz, 6 H) ; MS (ES+) 528. 38 'HNMR (DMSO-d6) : 8 12. 74 (bs, 1 H), 8.73 (m, 2 H), 8.63 (d, J = 1. 7 Hz, 1 H), 8.41 (d, J =1. 7 Hz, 1 H), 8.23 (dd, J = 1. 7 and 7. 7 Hz, 1 H), 8.08 (dd, J = 1. 7 & 7. 7 Hz, 1 H), 8.05 (d, J = 7. 7 Hz, 1 H), 7. 96 (dt, J = 7.96 (dt, J=7. 7 Hz, 1 H), 7.43 (dd, J=6 &7Hz, lH), r" 7. 37 (d, J=7. 7Hz, lH), 7.29 (d, J=8. 6Hz, lH), 7. 18 (m, 3H), 7.08 (m, 2 H), 5.01 (q, J = 10 & 25 Hz, 2 H), 3.13 (t, J = 6. 9 and 6 Hz, 2 H), 1. 89 (m, 1H), 0.92 (d, J = 6. 9 Hz, 6 H) ; MS (ES+) 509.58 Cpd. _R _R, Starting Method Analytical Data "-R-R* ° .. AnaiyttcalData No. From Used 'HNMR (DMSO-d6) : 6 12. 70 (bs, 1 H), 8.91 (d, J = 2.6 Hz, 1 H), 8.68 (t, J = 6 & Hz, 1 H), 8.62 (d, J=2Hz, lH), 8.4 (d, J= 1. 7 Hz, I H), 8.12 (m, 2 H), 8.05 (dd, J = 8. 6 & 1.7 Hz, 1 H), 7.88 (d, 25i l ll CO2H 24i I-1 8.5 & 1.7 Hz, 1 H), 7.53 (dd, J = 8.6 & 5.2 Hz, 1 H), 7.34 (d, J = 7. 7 Hz, 1 H), 7.28 (d, J = 8.6 Hz, 1 H), 7.18 (m, 3 H), 7.08 (m, 2 H), 5.04 (d, J = 12 Hz, 2 H), 3.11 (t, J = 6.5 Hz, 2 H), 1.87 (m, 1 H), 0.9 (d, 6.8 Hz, 6 H); MS (ES+) 509.11 'HNMR (DMSO-d6) : 8 0.90 (d, J = 6.9 Hz, 6 H), 1.88 (m, 1 H), 3. 11 (t, J = 6.9 and 6 Hz, 2 H), 5.03 (s, 2 H), 7.06 (m, 2 H), 7.18 1 H), 730 d, J = 8.4 Hz,,, (m, 3 H), 7.33 (d, 8.4 Hz, I H), 7. 30 (d, J = 8. 4 Hz, 1 H), 7. 75 (d, J 25j COZH 24j I-1 = 6_2 Hz, 2 H), 7.85 (m, 1 H), 8.05 (dd, J = 7.6 and 1. 7 Hz, 1 H), N 8.18 (s, 1 H), 8.40 (d, J = 2 Hz, 1 H), 8.71 (m, 4 H) ; MS (ES+) 509.49 25k H3C ! \ COZH 24K I-1 Characterized in the next step ) ! S 0 O 251 N C02H 241 I-1 MS (ES+) : 511.54 CH3 . 25m \/COzH 24m 1-1 MS (ES+) : 501.66 N Cpd. _R _R, Starting Method Analytical Data "-R-R' ° . AnaIyticaIData No. From Used 25n CH, C02H 24n 1-1 MS (ES+) : 472. 4 /\ 25O SXfN CO2H 24O I-l MS (ES+) : 515.65 25p/=\CH3 CO2H 24p I-1. Characterized in the next step CH CH3 25q oH3 CO2H 24q I-1 MS (ES+) : 536. 3 (M+Na) + Hic 25r OH C02H 24r I-1 MS (ES-): 500.4 -CHZ 25s \ C02H 24s I-1 Characterized in the next step CH3 CH2 25t C02H 24t I-1 Characterized in the next step CH3 oh 25n CO2H 24n I 1 MS (ES) : 486.4 Cpd. _R _R, Starting Method Analytical Data No.From Used Chez CH 25v OH C02H 24v I-1 MS (ES+) : 524. 3 (M+Na) + OH 25w =CH COzH 24w I-1, Q Characterized in the next step CH3 25x/=<CH3 CO2H 24x I-1 MS (ES-): 498. 3 CH 25y H CO2H 24y I-1 MS (ES-) : 484.3 CHZ 25z OH C02H 24z I-1 MS (ES+) : 488.3 OH OH 25aa CO2H 24aa 1-1 Characterized in the next step OH 25ab C02H 24ab K, I-1 MS (ES+) : 544.27 S _ Cpd.-R-RI Starting Method A-nalytical Data No. From Used No. From Used' 25ac < CO2H 24ac K, I-1 MS (ES+) : 544.2 OH BnO2C 25ad C02H 24ad E, H MS (ES+) : 670.3 (M + {a) + s 'HNMR (DMSO-d6) : 8 9.1 (bs, 2 H), 8.8 (bs, 2 H), 8.5 (t, J = 6 dz, 1 H), 8.02 (s, 1 H), 7.68 (s, 1 H), 7.62 (m, 6 H), 7.53 (d, J = 25ae HOH2CSSX CO2H 24ae K, I-1 5.8 Hz, 1 H), 7.15 (d, J = 6 Hz, 1 H),), 7.13 (m, 1 H), 7.01 (s, 1 H), 5.5 (t, J = 5 Hz, 1 H), 4.7 (d, J 5 Hz, 2 H), 3.01 (m, 2 H), 1.8 (m, 1 H), 0.85 (d, J = 6.8 Hz, 6 H) HOHZC 25af 4/CO2H 24ad K, I-1 MS (ES+) : 566.2 (M+Na) + S s 25ag Boc COzH 24ag I-1 MS (ES+) : 597.7 Bouc Boy 25ah t COzH 24ah L, 1-1 MS (ES+) : 492.54- L, M, 25ai/\N3 C°2H 24ai K, N, Characterized in the next step O, I-1 Cpd.-R Starting Method Analytical Data No. From Used No. From Used" 'HNMR (DMSO-d6) : 5 0.88 (d, J = 6.9 Hz, 6 H), 1.84 (m, 1 H), 3.07 (t, J = 6.9 and 6.0 Hz, 2 H), 5.05 (s, 2 H), 7.04 (d, J = 6.9 Hz, 2 H), 7.20 (m, 4 H), 7. 35 n (d, J=7. 7Hz, 1 H), 7.43 (d, J=7. 7Hz, 1 H), 7.66 (d, J = 5. 2 Hz, 1 H), 7.70 26a 25a J (d, J = 4.3 Hz, 1 H), 7.75 (m, 4 H), 7.82 (dd, J = 7.7 and 1.7 Hz, 1 H), 7.94 (d, S J = 1.7 Hz, 1 H), 8.03 (dd, J = 7.7 and 1.7 Hz, 1 H), 8.26 (dd, J = 7.7. and 1.7 Hz, 1 H), 8.69 (t, J = 6 Hz, 1 H), 8.80 (s, 2 H), 9.17 (s, 2 H), 10.76 (s, 1 H); MS (ES+) 631.05 IHIvTMR (DMSO-d6) : 8 0.88 (d, J =-6. 9 Hz, 6 H), 1.84 (m, 1 H), 3.07 (t, J = 6.8 and 6. 0 Hz, 2 H), 5.04 (s, 2 H), 7.02 (d, J = 6. 8 Hz, 2 H), 7. 20 (m, 3 H), 7. 34 26b ll \ 25b J (d, J = 7. 7 Hz, 1 H), 7.43 (d, J = 8. 6 Hz, 1 H), 7.72 (m, 6 H), 7.90 (dd, J = 1. 7 and 7.7 Hz, 1 H), 8.05 (m, 3 H), 8.23 (d, J = 1. 7 Hz, 1 H), 8.68 (t, J = 6 and 5. 2 Hz, 1 H), 8.82 (s, 2 H), 9.17 (s, 2 H), 10.73 (s, 1 H); MS (ES+) 631.82 'HNMR (DMSO-d6) : 8 10.75 (s, 1 H), 9.19 (s, 2 H), 8.89 (s, 2 H), 8.69 (t, J = 6 Hz, 1 H), 8. 29 (d, J =1. 7 Hz, 1 H), 8.07 (dd, J = 7. 7 & 1. 7 Hz, 1 H), 7.99 (d, J 26c 25c = 1. 7 Hz, I H), 7.87 (dd, J = 7. 7 & 1. 7 Hz, 1 H), 7.83 (d, J-7. 7 Hz, 2 H), 7. 77 (m 5 H), 7.54 (t, J=7. 7,2H), 7.43 (m, 3H), 7.19 (m, 3H), 7.03 (d, J= 6. 9 Hz, 2 H); 5.04 (bs, 2 H), 3.09 (t, J = 6.5 Hz, 2 H), 1. 84 (m, 1 H), 0.89 (d, 6.8 Hz, 6 H); MS (ES+) 625.81 1

Cpd. l | Stardng [Methodl Cpd. _R Starting Method Analytical Data -R ° . AnalytcaIData No. From Used IHNMR (DMSO-d6) : 8 10. 7 (s, 1 H), 9.14 (s, 2 H), 8.82 (s, 2 H), 8.64 (t, J = 6 Hz, 1 H), 8 21 (s, 1 H), 7.98 (dd, J = 7. 8 & 2 Hz, 1 H), 7.8 (d, J = 2 Hz, 1 H), 26d 25d 1 7. 7 (m, 4 H), 7. 68 (dd, J = 2 & 7. 8 Hz, 1 H), 7.44 (d, J=3 Hz, lH), 7.37 (d, H C 7. 8 Hz, 1 H), 7.27 (d, J = 7. 7 Hz, 1 H), 7.16 (m, 3 H), 7.0 (s, 1 H), 6.99 (s, 1 7.8 Hz, 3 S H), 6. 86 (d, J = 3 Hz, 1 H), 5.0 (s,. 2 H), 3.03 (t, J = 6. 5 Hz, 2 H), 2.46 (s, 3 H), 1.78 (m, 1 H), 0.83 (d, 6.8 Hz, 6 H); MS (ES+) 645. 77 'HNMR (DMSO-d6) : 8 0. 87 (d, J = 6. 2 Hz, 6 H), 1.73 (m, 1 H), 3.07 (t, J = 6. 7 and 6. 2 Hz, 2 H), 5.05 (s, 2 H), 7.03 (dd, J = 1. 7 and 8 Hz, 2 H), 7.11 (d, J 1. 7 26e 25e i Hz, lH), 7.21 (m, 3 H), 7.31 (d, J=8Hz, lH), 7.42 (d, J=8Hz, lH), 7.78 (m, 5 H), 7.92 (d, J=1. 7Hz, l H), 8.02 (dd, J=8and1. 7Hz, lH), 8.25 (d, J o =1. 9 Hz, 1 H), 8.33 (s, 1 H), 8.63 (t, J = 6 and 5 Hz, 1 H), 8.80 (bs, 2 H), 9.14 (bs, 2 H), 10.67 (s, 1 H) ; MS (ES+) 615.75 'HNMR (DMSO-d6) : 8 0. 87 (d, J = 6. 7 Hz, 6 H), 1.83 (m, 1 H), 3.06 (t, J = 6. 7 and 6. 2 Hz, 2 H), 5.04 (s, 2 H), 6.67 (m, 1 H), 7.03 (m, 2 H), 7.16 (m, 3 H), 26f 25f 1 7. 35 (d, J=8. 6Hz, l H), 7.42 (d, J=8Hz, lH), 7.74 (m, 4H), 7.85 (m, 2 H), 7. 98 (d, J=1. 2Hz, lH), 8.03 (dd, J=1. 7and8Hz, lH), 8.25 (d, J=1. 8Hz, l o H), 8.67 (t, J = 6. 2 and 5. 5 Hz, 1 H), 8.88 (bs, 2 H), 9.12 (bs, 2 H), 10.772 (bs, 1H) ; MS (ES+) 615.75 C.'HNMR (DMSO-d6): 8 10. 67 (s, 1 H), 9.12 (s, 2 H), 8.78 (s, 2 H), 8.61 (t, J = 6 Hz, 1 H), 8.21 (s, 1 H), 7.98 (dd, J = 7. 8 & 2 Hz, 1 H), 7.84 (d, J = 2 Hz, 1 H), 26g'25g 7.7 (m, 5H), 7.46 (s, 1H), 7.39 (d, 7.8Hz, lH), 7.29 (d, J=7. 7Hz, lH), 7.16 s (m, 4H), 7.01 (s, 1 H), 6.99 (s, 1 H), 5.0 (s, 2 H), 3.03 (t, J = 6. 5 Hz, 2 H), 223 (s, 3 H), 1.79 (m, 1 H), 0.83 (d, 6.8 Hz, 6 H); MS (ES+) 645.77 Cpd Starting Method '-R-.". AnaIyticaIData No.From Used IHNMR (DMSO-d6): 8 10.77 (bs, 1 H), 8.95 (bs, 4 H), 8.76 (d, J = 4.3 Hz, 1 H), 8.69 (t, J = 6 Hz, 1 H), 8. 4 (s, 1 H), 8. 29 (m, 2 H), 8.15 (d, J = 7.7 Hz, 1 H), 1 H) 8.4 (s, H) 829 (m, '1 H) 7.76 (m, 4 8. 07 (dd, J =1. 7 and 7.7 Hz, 1 H), 7.99 (dt, J = 1. 7 & 7.7 Hz, 1 H), 7. 76 (m, 4 "N --H), 7. 46 (m, 2H), 7.18 (m, 3H), 7.05 (s, lH), 7.03 (s, 1 H), 5.06 (s, 2H), 3.10 (t, J = 6.9 and 6 Hz, 2 H), 1.86 (m, 1 H), 0.89 (d, J = 6.9 Hz, 6 H); MS (ES+) 626.69 'HNMR (DMSO-d6) : 5 10.73 (bs, 1 H), 9.16 (bs, 2 H), 9.05 (d, J = 1. 9 Hz, 1 H), 8.79 (s, 2 H), 8.69 (t, J = 6 & Hz, 1 H), 8.64 (dd, J = 1. 2 & 5 Hz, I H), 26 ß W 25i J 8. 29 (d, J = 1. 7 Hz, 1 H), 8. 24 (d, J = 8 Hz, 1 H), 8. 05 (m, 2 H), 7. 93 (dd, 8 & % ß 1. 8 Hz, 1 H), 7.76 (m, 5 H), 7.56 (dd, J = 8 & 43 Hz, 1 H), 7.44 (d, J = 7. 4 Hz, N 2H), 7.18 (m, 3 H), 7.0 (m, 2 H), 5.0 (s, 2 H), 3.08 (t, J = 6. 5 Hz, 2 H), 1.82 (m, 1 H), 0.88 (d, 6.8 Hz, 6 H) ; ; MS (ES+) 626.44 'HNMR (DMSO-d6) : 6 0.87 (d, J = 6.9 Hz, 6 H), 1.75 (m, 1 H), 3.08 (t, J = 6.9 and 6.0 Hz, 2 H), 5.03 (s, 2 H), 7.03 (m, 1 H), 7.18 (m, 3 H), 7.45 (t, J = 7.8 26-l l | 25 J and 7 Hz, 2 H), 7.76 (s, 4 H), 7.87 (d, J = 6 Hz, 2 H), 7.94 (dd, J = 8 and 2 Hz, 1 H), 8. 05 (dd, J = 8 and 2 Hz, 1 H), 8.08 (d, J = 2 Hz, 1 H), 8.29 (d, J = 2 Hz, 1 H), 8.70 (m, 3 H), 8.84 (s, 2 H), 9.11 (s, 2 H), 10.76 (s, 1 H); MS (ES+) 626. 76 IHNMR (DMSO-d6) : 6 10. 72 (bs, 1 H), 9.15 (bs, 2 H), 8.81 (bs, 2 H), 8.86 (t, J HNMR (DMSO-db) : 8 10. $20 m, 3 H), 7.91 (d, J = 7. 9 Hz, 1 H), 7.81 (d, J = g3C = 6 Hz, 1 H), 8.28 (s, 1 H), 26k Y \S/25k J 4 Hz, 1 H), 7.74 (s, 4 H), 7.42 (d, J = 7. 9 Hz, 1 H), 7. 38 (d, J = 7. 9 Hz, 1 H), 0 7.18 (m, 3 H), 7.04 (m, 2 H), 5.04 (bs, 2 H), 3.07 (t, J = 6 Hz, 2 H), 2.57 (s, 3 H), 1.83 (m, 1 H), 0.87 (d, J = 6.8 Hz, 6 H); MS (ES+) 673.7 J Cpd.Starting Method No. From Used No. From Used" 'HNMR (DMSO-d6) : 8 10. 66 (s, 1 H), 9.20 (s, 2 H), 8.86 (s, 2 H), 8.66 (t, J = 6 dz, 1 H), 8.24 (d, J = 2 Hz, 1 H), 8.15 (dd, J = 7.8 & 2 Hz, 1 H), 7.69 (m, 4 H), N 251 J 7. 68 (d, J = Hz, 1 H), 7.63 (d, J = 7. 9 Hz, 1 H), 7.43 (d, J = 7.9 Hz, 1 H), 7.37 I (d, J = 7. 9 Hz, 1 H), 7.24 (m, 3 H), 7.09 (m, 2 H), 6.92 (s, 1 H), 6.40 (s, 1 H), CH3 6.17 (t, J = 4 Hz, 1 H), 5.10 (bs, 2 H), 3.74 (s, 3 H), 3.09 (t, J = 6 Hz, 2 H), 1.83 (m, 1 H), 0.88 (d, J = 6.8 Hz, 6 H); MS (ES+) 628.65 26m X 25m J MS (ES+) : 618.91 N 'HNMR (DMSO-d6) : 8 10.56 (s, 1 H), 9.15 (bs, 2 H), 8.84 (bs, 2 H), 8.64 (t, J = 6 Hz, 1 H), 8.19 (d, J = 2 Hz, 1 H), 7.99 (d, J = 7 Hz, 1 H), 7.70 (m, 4 H), 26n CH2 25n 1 7. 46 (s, 1 H), 7. 36 (m, 2 H), 7. 24 (m, 3 H), 7.05 (s, 1 H), 7.00 (s, 1 H), 6.0 (m, n < 2 lH), 5. 18 (d, J=16Hz, lH), 5.10 (d, J=llHz, lH), 5. 0 (s, 2H), 3.47 (d, J = 6 Hz, 1 H), 3.03 (t, J = 6 Hz, 2 H), 1.79 (m, 1 H), 0.83 (d, J = 6.8 Hz, 6 H); MS (ES+) 589.5 'HNMR (DMSO-d6) : 8 10.84 (s, 1 H), 9.16 (s, 2 H), 8.78 (s, 2 H), 8.69 (t, J = 6 /=\ Hz, 1 H), 8.27 (d, J = 2 Hz, 1 H), 8.19 (s, 1 H), 8.09 (dd, J = 2 & 7.7 Hz, 1 H), S N 8. 04 (dd, J = 2 & 7. 7 Hz, 1 H), 8.01 (d, J = 4 Hz, 1 H), 7.89 (d, J = 3 Hz, 1 H), Y 7. 73 (m, 4 H), 7.44 (dd, J = 3 & 7. 8 Hz, 2 H), 7.16 (m, 3 H), 7.30 (s, 1 H), 7.05 (s, I H), 5.03 (bs, 2 H), 3.06 (t, J = 6. 5 Hz, 2 H), 1.82 (m, 1 H), 0.86 (d, 6.8 Hz, 6 H); MS (ES+) 632.4 26p/CH3 25p J MS (ES+) : 609. 3 (M+Na) + 3 Cpd. _R Starting Method Analytical Data No. From Used CH3 E=r. CH, 26q 25q i MS (ES+) 631.5 H3C 'HNMR (DMSO-d6) : 6 10.71 (s, 1 H), 9.16 (s, 2 H), 8.81 (s, 2 H), 8.68 (t, J = 6 Hz, 1 H), 8.25 (s, 1 H), 8.03 (d, J = 7.8 Hz, 1 H), 7.73 (m, 5 H), 7.69 (s, 1 H), 26r \ oH 25r J 7. 55 (d, J = 7. 8 Hz, 1 H), 7.39 (d, J= 8. 9 Hz, 1 H), 7.26 (m, 3 H), 7.03 (m, 2 H), 5.02 (bs, 2 H), 4.95 (t, J=5Hz, lH), 3.62 (q, J = 6 & 12. 8 Hz, 2 H), 3.07 (t, J = 6 Hz, 2 H), 2.62 (t, J = 6 Hz, 2 H), 1.83 (m, 1 H), 0.88 (d, J = 6. 8 Hz, 6 H); MS (ES+) 617.4 'HNMR (DMSO-d6) : 6 0.89 (d, J = 6.8 Hz, 6 H), 1.84 (m, 1 H), 1.99 (s, 3 H), CH 3.09 (t, J = 6 Hz, 2 H), 5.04 (s, 2 H), 5.18 (s, 1 H), 5.28 (s, 1 H), 6.73 (d, J = 16 26s ass J Hz, 1 H), 7.04 (d, J = 6 Hz, 2 H), 7.23 (m, 5 H), 7.42 (d, J = 9 Hz, 1 H), 7.73 CH3 (m, 5 H), 7.85 (s, 1 H), 8.03 (dd, J = 9 and 2 Hz, 1 H), 8.26 (d, J = 2 Hz, 1 H), 8.69 (t, J = 6 Hz, 1 H), 8.87 (bs, 4 H), 10.91 (s, 1 H); MS (ES+) 615.4 IHNMR (DMSO-d6) : 8 10.8 (br s, 1 H), 9.1 and 8.9 (2 br s, 4 H), 8.6 (m, 1 H), 26t CHz 25t J $ 2 s, 1 H), 8. 0 (m, 1 H), 7. 8-7. 6 (m,, l H), 7.3 (m, 4 H), 7.0 (d, 1 H), 5.6 (m, 1 H), 5.2 (m, 1 H), 5.0 (br s, 1 H), 3.1 (t, J = 6. 8 Hz, 2 CH3 H), 2.2 (s, 3 H), 1.8 (m, 1 H), 0.95 (d, 6 H) ; MS (ES+) 589.4, MS (ES-) 587. 5 'HNMR (DMSO-d6) : 8 0.88 (d, J = 6.8 Hz, 6 H), 1.84 (m, 1 H), 3.09 (t, J = 6 Hz, 2 H), 4.33 (t, J = 5. 5 Hz, 2 H), 5.02 (s, 2 H), 5.01 (t, J = 5.5 Hz, 1 H), 5.95 26u ./H 25u J (m, l H), 6.57 (d, J = 11. 5 Hz, 1 H), 7.04 (d, J = 6. 7 Hz, 2 H), 7. 25 (m, 3 H), 7. 31 (d, J = 7.8 Hz, 1 H), 7.43 (m, 2 H), 7.54 (s, 1 H), 7.74 (s, 4 H), 8.05 (dd, J = 7.8 and 2 Hz, 1 H), 8.23 (d, J = 2 Hz, 1 H), 8.69 (t, J = 6 Hz, 1 H), 8.83 (bs, 2 H), 9.18 (bs, 2 H), 10.66 (s, 1 H); MS (ES+) 605.3 Cpd. Starting Method No. From Used No. From Used' 'HNMR (DMSO-d6) : 5 0.88 (d, J = 6.8 Hz, 6 H), 1.84 (m, 1 H), 2.75 (t, J = 7 CHZ Hz, 2 H), 3.09 (t, J = 6 Hz, 2 H), 3.60 (m, 2 H), 4.65 (t, J = 5 Hz, 1 H), 5.05 (s, 26 H H), 7. 05 (d, J = 7 Hz, 2 H), 7.29 (m, 5 H), 7.42 (d, J = 7. 8 Hz, 1 H), 7.66 (dd, "OH-'J=7. 8and2Hz, lH), 7.75 (m, 6 H), 8.03 (dd, J = 7. 8 aIld 2 Hz, 1 H), 8.25 (s, 1 H), 8.68 (t, J = 6 Hz, 1 H), 8.82 (bs, 2 H), 9.18 (bs, 2 H), 10.68 (s, 1 H); MS (ES+)619.4 'HNMR (DMSO-d6) : 8 0.88 (d, J = 6.8 Hz, 6 H), 1.84 (m, 1 H), 3.09 (t, J = 6 Hz, 2 H), 4.41 (s, 1 H), 5.04 (d, J = 11 Hz, 2 H), 7.05 (d, J = 5.5 Hz, 2 H), 7.29 -g (m, 3 H), 734 (d, J = 8 Hz, 1 H), 7.40 (d, J = 8 Hz, 1 H), 7.65 (dd, J = 8 and 2 Hz, 1 H), 7.75 (s, 4 H), 7.79 (s, 1 H), 8. 05 (dd, J = 8 and 2 Hz, 1 H), 8.28 (d, J = 2 Hz, 1 H), 8.71 (t, J = 6 Hz, 1 H), 8.82 (bs, 2 H), 9.17 (bs, 2 H), 10.73 (s, 1 H); MS (ES+) 573.3 IHNMR (DMSO-d6) : 8 0.86 (d, J = 6.8 Hz, 6 H), 1.47 (s, 3 H), 1.74 (s, 3 H), CH 1. 85 (m, 1 H), 3.06 (t, J = 6 Hz, 2 H), 3.43 (d, J = 8 Hz, 1 H), 5.04 (s, 2 H), 26x 25x 1 5.11 (m, 1 H), 7.03 (m, 2 H), 7.23 (m, 5 H), 7.52 (m, 2 H), 7.72 (m, 5 H), 8.02 CH3 (m, 1 H), 8.21 (s, 1 H), 8.66 (t, J = 6 Hz, 1 H), 8.81 (bs, 2 H), 9.23 (bs, 2 H), 10.52 (s, 1 H); MS (ES+) 617.6 'HNMR (DMSO-d6) : b 0.87 (d, J = 6.8 Hz, 6 H), 1.72 (m, 1 H), 3.07 (t, J = 6 Hz, 2H), 4. 36 (d, J = 6 Hz, 2 H), 5.0 (m, 2 H), 5.42 (t, J = 6 Hz, 1 H), 7.03 (d, ===-OH J=7Hz, 2H), 7.25 (m, 3 H), 7.31 (d, J = 8 Hz, 1 H), 7.39 (d, J = 8 Hz, 1 H), 7. 58 (d, J = 8 Hz, 1 H), 7.73 (m, 5 H), 8.02 (dd, J = 10 and 2 Hz, 1 H), 8.23 (s, 1 H), 8.68 (t, J = 6 Hz, 1 H), 8.76 (bs, 2 H), 9.15 (bs, 2 H), 10. 71 (s, 1 H) ; MS (ES+)603.4 Cpd.Starting Method No.From Used No. From Used" CH,' (DMSO-d6) : 6 10.6 (s, 1 H), 9.17 (s, 1 H), 8.85 (s, 1 H), 8.68 (d, J = 5. 9 Hz, 2 H), 8. 25 (d, 1.98 Hz, 1 H), 8.05 (d, J = 1. 96 Hz, 1 H), 8.03 (d, J = 1. 9 26z 25z Hz, 1 H), 7.75 (m, 4 H), 7. 65 (m, 4 H), 7.41 (d, J = 7. 87 Hz, 4 H), 7.25 (m, 1 OH H) 5. 4 (s, I H), 5. 2 (d, J = 5. 9 Hz, 2 H), 4.44 (d, J=5. 9Hz, lH), 3.09 (d, J= 6.89 Hz, 2 H), 1.89 (d, J = 6.89 Hz, 2 H) 0.88 (d, J = 5.9 Hz, 6 H); MS (ES+) 605.69 26aa N 25aa J Characterized in the next step 'HNMR (DMSO-d6): 610. 70 (s, 1 H) 9.15 (bs, 2 H), 8.77 (bs, 2 H), 8.67 (t, J= 6 Hz, 1 H), 8,25 (s, 1 H), 8.04 (d, J = 7 Hz, 1 H), 7.77 (d, J = 2 Hz, 1 H), 7.71 /g\ J (m 4 H), 7.70 (d, J = 2 Hz, 1 H), 7.59 (d, J = 6 Hz, 1 H), 7.46 (d, J = 8 Hz, 1 H), 7.41 (d, J = 8 Hz, 1 H), 7.22 (m, 3 H), 7.05 (s, 1 H), 7.03 (d, J = 2 Hz, 1 S H), 5. 31 (t, J = 6 Hz, 1 H), 5.04 (bs, 2 H), 4.51 (d, J = 6 Hz, 2 H), 3.07 (t, J = 6 Hz, 2 H), 1.82 (m, 1 H), 0.86 (d, J = 6.8 Hz, 6 H); MS (ES+) 661.74 'HNMR (DMSO-d6): 8 0.87 (d, J = 6.8 Hz, 6 H), 1.83 (m, 1 H), 3.07 (t, J = 6 /Hz, 2 H), 4.71 (d, J = 5 Hz, 2 H), 5.04 (bs, 2 H), 5.69 (t, J = 5 Hz, 1 H), 7.03 26 ht 25ac J (d, J = 5. 8 Hz, 2 H), 7.21 (m, 3 H), 7. 35 (d, J = 5 Hz, 1 H), 7.38 (d, J = 8 Hz, 1 ac 9 NOH H), 7.44 (m, d, J=8Hz, 1 H), 7.58 (d, J = 5 Hz, I H), 7.74 (m, 6H), 8.03 (d, J OH = 8 Hz, 1 H), 8,24 (s, 1 H), 8.67 (t, J = 6 Hz, 1 H), 8.79 (bs, 2 H), 9.14 (bs, 2 H), 10.64 (s, 1 H); MS (ES+) 661.74 'HNMR (DMSO-d6) : 8 9.65 (s, 1 H), 8.71 (t, J = 5.15 Hz, 1 H) 8.39 (d, J = 2. 57 Hz, 4 H), 8.09 (d, J = 1. 79 Hz, 4 H), 8.05 (d, J = 1. 79 Hz, 4 H), 7.43 (d, J 26ad < 25ad J = 7. 77 Hz, 2 H), 7.29 (s, 2 H), 7.19 (m, 2 H), 7.08 (m, 2 H), 5. 03 (d, J = 2. 58 Hz, 2 H) 3.29 (m, 2 H), 3.12 (s, 4 H), 2.49 (m, 2 H), 1.87 (m, 2 H), 0.90 (d, J = S 6.87 Hz, 6 H); MS (ES+) 765.4 Cpd. l | Starting {Method i -R , AnaIyticatData No. From Used < IHNDMR (DMSO-d6) : 69. 1 (bs, 2 H), 8.8 (bs, 2 H), 8.5 (t, J = 6 Hz, 1 H), 8.02 7.53 (d, 26ae/\ (s, 1 H), 7. 68 (s9 1 H), 7.62 (m, 6 H), J = 5. 8 Hz, 1 H) 67 15 (d, J=6 2 S Hz, lH),), 7.13 (m, 1H), 7.01 (s, 1H), 5.5 (t, J=5Hz, lH), 4.7 (d, J = 5 Hz, 2 H), 3.01 (m, 2 H), 1. 8 (m, 1 H), 0.85 (d, J = 6. 8 Hz, 6 H) ; MS (ES+) 571.2 'HNMR (DMSO-d6): 5 10. 6 (s, 1 H), 9.17 (s, 1 H), 8. 85 (s, 1 H), 8.68 (d, J = 5. 9 Hz, 2 H), 8. 25 (d, 1.98 Hz, 1 H), 7.75 (m, 4 H), 7.65 (m, 4 H), 7.41 (d, J = 26af/\ 25af J 7. 87Hz, 4H), 7.25 (m, 4H), 5.4 (s, 1H), 5.2 (d, J=5. 9Hz, 2H), 4.44 (d, J= 5. 9 Hz, 1 H), 3.09 (d, J = 6. 89 Hz, 2 H), 1.89 (d, J 6. 89 Hz, 2 H), 0.88 (d, J = S5.9 Hz, 6 H). 'HNMR (DMSO-d,) : 8 0.90 (d, J = 6. 9 Hz, 6 H), 1. 41 (s, 9 H), 1.87 (m, 1 H), 3. 11 (t, J = 6. 9 and 6 Hz, 2 H), 5.07 (s, 2 H), 6.37 (t, J = 3. 4 Hz, 1 H), 6.51 (s, 1 26ag N 25ag J H), 7. 11 (m, 2 H), 7.26 (m, 3 H), 7. 33 (d, 7.7Hz, lH), 7.41 (d, J=8. 6Hz, l l H), 7. 45 (d, J=1. 7 Hz, lH), 7.61 (dd, J=1. 7and7. 7,1 H), 7.74 (m, 5H), Boc 8.05 (dd, J = 8. 6 and 1. 7 Hz, 1 H), 8.26 (d, J =1. 7 Hz, 1 H), 8.66 (t, J = 5 and 6 Hz, 1 H), 8.77 (bs, 2 H), 9.15 (bs, 2 H), 10.58 (s, 1 H) ; MS (ES+) 714.78 OH 26ah t KOH 25ah J MS (ES+) : 609.6 'HNMR (DMSO-d6) : 8 10. 8 (s, 1 H), 6.2 and 8.9 (2 br s, 2 H each, 4H), 8.7 (t, 1 H), 8.2 (s, 1 H), 8.0 (d, J = 6 Hz, 1 H), 7.7 (m, 5 H), 7.6 (d, J = 5 Hz, 1 H), 26ai 25ai J 7.4 (d, J=5. 8Hz, l H), 7.35 (d, J=6. 9Hz, lH), 7.29 (m, 3 H), 7.0 (m, 2H), 3 5. 0 (m, 2 H), 4.6 (s, 2 H), 3.01 (t, J = 6. 8 Hz, 2 H), 1.81 (m, 1 H), 0.95 (d, J = 6. 8 Hz, 6 H) ; MS (ES+) 604. 3 Cpd. _R _R, Starting Method Analytical Data No. From Used No. From Used 'H NMR (DMSO-d6) : 8 14.95 (s, 1 H), 8.97 (s, 4 H), 8.5 (t, J = 6 Hz, 1 H), 7.97 (d, J = 2 Hz, 1 H), 7.80 (d, J = 2 CH3 Hz, 1 H), 7.73 (dd, J = 7. 9 and 2 Hz, 1 H), 7.61 (m, 7 H), 7. 18 (t, J = 3.9 Hz, 1 H), 7.05 (d, J = 7.9 Hz, 1 H), 6.93 CH3 (d, J = 7_9 Hz, 1 I, 3.01 (t, J = 6. 9 and 6. 0 Hz, 2 H), 1.81 (m, 1 H), 0.84 (d, J = 6.9 Hz, 6 H); MS (ES+) : 541.17 lH NMR (DMSO-d6) : 5 13.24 (s, 1 H), 9.05 (s, 2 H), 8.9 (s, 2 H), 8.49 (t, J = 6 and 5. 2 Hz, 1 H), 7.97 (s, 1 H), 7.99 n CH3 26 I-2 (s, 1 H), 7.87 (s, 1H), 7.75 (d, J = 7.7 Hz, 1 H), 7.65 (m, 1 _ H), 7.62 (m, 6 H), 7.05 (d, J = 7. 7 Hz, 1 H), 6.93 (d, J = S /\CH3 7.7 Hz, 1 H), 3.01 (t, J = 6.9 and 6.0 Hz, 2 H), 1.81 (m, 1 H), 0.85 (d, J = 6.9 Hz, 6 H); MS (ES+) : 541. 42 'H NMR (DMSO-d6) : 5 13.28 (s, 1 H), 9.04 (s, 4 H), 8.5 CH3 (t, J = 6 Hz, 1 H), 7.97 (s, 1 H), 7.82 (s, 1 H), 7.74 (m, 3 /H), 7. 62 (m, 5 H), 7.5 (t, J = 7.7 Hz, 2 H), 7.4 (t, J = 7. 7, 27c I CH3 26c I-2 1 H), 7.1 (d, J = 7. 7 Hz, 2 H), 6.97 (d, J = 7. 7. Hz, 1 H), 3. 01 (t, J = 6. 5 Hz, 2 H), 1.8 (m, 1 H), 0.85 (d, 6.8 Hz, 6 H) ; MS (ES+) : 535.48

Cpd. Starting Method No. From Used No. From Used' 1H NMR (DMSO-d6) : 8 9. 03 (s, 2H), 8.89 (s, 2H), 8.49 (t, J = 6 Hz, I H), 7.99 (s, 1 H), 7.65 (m, 8H), 7. 37 (d, J= 27d H3C- 26d I-2 3 Hz, lH), 7.04 (d, J=7. 7Hz, lH), 6.98 (s, 1H), 6.82 CH3 (d, J = 3 Hz, 1 H), 2.98 (t, J = 6. 5 Hz, 2 H), 2.46 (s, 3 H), 1.76 (m, 1 H), 0.81 (d, 6.8 Hz, 6 H); MS (ES+) : 555.61 tH NDMR (DMSO-d6) : 8 14. 10 (s, 1 H), 9.05 (bs, 2 H), cH3 8.79 (bs, 2 H), 8. 47 (t, J = 5. 6 Hz, 1 H), 8.3 (s, 1 H), 7.96 (d, J = 2 Hz, 1 H), 7.78 (m, 1 H), 7.63 (m, 7H), 7.05 (m, 27e o CH3 e lH), 7. 01 (d, J=7. 7Hz, lH), 6.92 (d, J = 7. 7 Hz, 1 H), 3. 02 (t, J=4. 9Hz, 2H), 1.81 (m, 1H), 0.85 (d, J=6. 3 Hz, 6 H) ; MS (ESt : 525.36 'H NMR (DMSO-d6) : 8 9.07 (s, 2 H), 8.86 (s, 2 H), 8.53 CH3 (t, J=5 Hz, l H), 8. 03 (s, 1 H), 7.89 (d, J=1. 4Hz, lH), 7. 78 (m, 2 H), 7.65 (m, 6 H), 7.1 (m, 2 H), 7.08 (d, J=7 ""CH,""'""Hz, lH), 6.64 (dd, J=3. 5and2Hz, lH), 3.03 (t, J=6. 9 and 6. 0 Hz, 2 H), 1.81 (m, 1 H), 0.86 (d, J = 6. 9 Hz, 6 H) ; MS (ES+) : 525.43 H3C CH 1H NMR (DMSO-d6) : 8 13. 81 (s, 1H), 8.74 (bs, 4H), 9\ l 3 8. 43 (t, J=6 Hz, 1 H), 7.92 (d, J=2Hz, lH), 7.69 (d, J= 27g-,-, 2 Hz, lH), 7.62 (dd, J=7. 7 &2Hz, lH), 7.54 (m, 5H), Z7g/\ v'CH3 26g T-2 7. 38 (s, I H), 7.15 (s, 1H), 6. 99 (d, J= 7. 8 Hz, 1H), 6.89 (d, J = 6. 8 Hz, 1 H), 2.97 (t, J = 6. 5 Hz, 2 H), 2.20 (s, 3 H), 1.76 (m, 1 H), 0.8 (d, 6.8 Hz, 6 H) ; MS (ES+) : 555.67 Cpd. Starting Method No. From Used I No. From Used iH NMR (DMSO-d6) : 8 13.95 (bs, 1 H), 8.99 (bs, 2 H), 8.79 (bs, 2 H), 8.65 (d, J = 5 Hz, 1 H), 8.43 (t, J = 6 Hz, 1 CH3 H), 8.25 (s, 1 H), 8.09 (d, J = 7.8 Hz, 1 H), 8.00 (d, J = 26h 1-2 7. 8 Hz, 1 H), 7.94 (s, 1 H), 7.87 (t, J = 7.8 Hz, I H), 7.58 4 \ \/CH3 _ (m, 5 H), 7. 34 (dd, J = 7. 8 & 5 Hz, 1 H), 7.09 (dd, J = 7. 7 Na Hz, 1 H), 6.90 (d, J=7. 8Hz, 1 H), 2.97 (t, J = 5 Hz, 2 H), 1.76 (m, 1 H), 0.81 (d, 6.8 Hz, 6 H); MS (ES+) : 268.64 (m/2) 'H NMR (DMSO-d6) : 5 9.05 (bs, 2 H), 8.95 (d, J = 2. 1 Hz, 1 H), 8.75 (s, 2 H), 8.65 (dd, J = 5 & 1. 4 Hz, 1 H), 8.5 CH3 (t, J = 5. 6 Hz, 1 H), 8.2 (dt, J = 1. 8 & 7. 7 Hz, I H), 7.99 27i 26i 1-2 (d, J 2. 1 Hz, 1 H), 7. 9 (d, J = 2. 1 Hz, 1 H), 7. 85 (dd, J = "-'K CH3 7. 7 &2. 2 Hz, 2 H), 7.65 (m, 5 H), 7.55 (dd, J = 7. 7 & 4. 5 Hz, 1 H), 7.15 (d, J = 7. 7 Hz, 1 H), 6.95 (d, J = 7. 7 Hz, 1 H), 3.08 (t, J = 5 Hz, 2 H), 1.82 (m, 1 H), 0.9 (d, 6.8 Hz, 6 H); MS (ES+) : 268.85 (m/2) 'H NMR (DMSO-d6) : 8 14.19 (s, 1 H), 9.06 (bs, 2 H), l CH 8.67 (bs, 2H), 8.67 (d, J=6Hz, 2H), 8.50 (t, J=6Hz, l H),'7. 97 (m, 2 H), 7.91 (dd, J = 7.7 and 2 Hz, 1 H), 7.80 (6 H) 7.18 (d, J = 7.7 Hz, 1 27j 26j CH3 26j I-2 (d, J = 6 Hz, 2 H), 7. 64 m,, Nv 3 H), 6.95 (d, J = 7. 7 Hz, 1 H), 3.02 (t, J = 5. 0 Hz, 2 H), 1.82 (m, 1 H), 0.80 (d, J = 6.9 Hz, 6 H); MS (ES+) : 536.43 'H NMR (DMSO-d6): 8 9.04 (bs, 2 H), 8.78 (bs, 2 H), H, C CH3 8.55 (t, J = 6 Hz, 1 H), 8.1 (s, 1 H), 7.98 (d, J = 4 Hz, 1 27k < S t 26k I 2 H), 7.95 (s, 1 H), 7.87 (d, J = 7.9 Hz, 1 H), 7.75 (d, J = , 27k S CH3 26k -2 6. 9 Hz, 1 H), 7.66 (m, 4 H), 7. 2 (m, 2 H), 7.09 (s, 1 H), 0 3.03 (t, J = 6 Hz, 2 H), 2.55 (s, 3 H), 1.81 (m, 1 H), 0.85 (d, J = 6.8 Hz, 6 H); MS (ES+) : 583.59 Cpd. |-R |-R'| Starting Method Analytical Data No.From Used 'H NMR (DMSO-d6) : 69. 1 (s, 2 H), 8.84 (s, 2 H), 8.56 (t, CH3 J = 6 Hz, 1 H), 8.08 (bs, 1 H), 7.67 (m, J=7H), 7.58 (d, J \ CH3 2 H) 6.91 (bs,, 261 I-2-9 Hz, 1 H), 7. 11 (m,, 1 I 631 (bs, 1 N 6. 11 (t, J = 3 Hz, 1 F3, 3. 74 (s, 3 H), 3.05 (t, J=6Hz, 2 H), 1.83 (m, 1H), 0.88 (d, J=6. 8Hz, 6H) ; MS (ES+) : CH3538.64 'H NMR (DMSO-d6) : 89. 04 (s, 2 H), 8. 94 (s, 2 H), 8.46 CH3 (t, J=6Hz, l H), 7.96 (s, 1H), 7.63 (m, 6H), 6.94 (s, 1 27m N H), 6.83 (d, J=7. 7Hz, l H), 6.7 (d, J = 2, 1 H), 6.62 (dd, 26m I-2 J-. d 2 Hz, 1 H), 3.28 (m, 4H), 3.02 (t, J=6. 5Hz, 2 H), 1.98 (m, 4 H), 1.82 (m, lH), 0.82 (d, 6.8 Hz, 6 H); MS (ES+) : 528.76 CH3'H NMR (DMSO-d6) : 8 13. 96 (s, 1 H), 9.02 (s, 2 H), 8.85 l (s, 2 H), 8.46 (t, J = 6 Hz, 1 H), 7.91 (s, 1 H), 7.58 (m, 4 XCH2 XCH H), 7.39 (s, 1 H), 7.25 (d, J= 7. 8 Hz, 1H), 6.92 (d, J= 27n 3 26n I-2 7.7,1 H), 6.87 (d, J= 7. 7 Hz, 1H), 6.01 (m, 1H), 5.17 (d, J = 16. 7 Hz, 1 H), 5.08 (d, J = 10 Hz, 1 H), 3.45 (d, J = 6 Hz, 2H), 2.99 (t, J = 6 Hz, 2 H), 1.78 (m, 1 H), 0.83 (d, J = 6. 8 Hz, 6 H) ; MS (ES+) : 499.3 IH NMR (DMSO-d6) : 8 14. 08 (bs, 1 H), 9.06 (s, 2 H), 3 8. 79 (s, 2 H), 8.51 (t, J = 6 Hz, 1 H), 8.11 (d, J = 2 Hz, 1 l H), 8. 01 (m, 3 H), 7. 85 (d, J=3Hz, lH), 7.63 (m, 6H), " Y" CH, i- 7. 17 (d, J = 7. 8 Hz, 1 H), 6.97 (d, J= 7. 8 Hz, 1H), 3.02 (t, J=6. 5Hz, 2H), 1.81 (m, 1 H), 0.86 (d, 6.8 Hz, 6 H); MS (ES+) : 542.2) Cpd. _R _R, Starting Method Analytical Data No. From Used 'H NMR (DMSO-d6): 8 9.1 and 9.2 (2 br s, 4 H, NH proton), 8.6 (m, 1 H), 8.3 (m, 1 H), 8.0-7.6 (m, 8 H, 27p/=\CH3 1 26p I-2 aromatic proton), 7.3 (m, 2 H), 3.1 (t, 2 H), 2.2 (s, 3 H), CH3 1.8 (m, 1 H), 0.9 (2s, 6 H); IR (KBr Pellets) 2957,1676, 1480,1324,844cm''. MS (ES+) : 497 CH3 NMR (DMSO-d6): 6 9.06 (s, 2 H), 8.77 (s, 2 H), 8.53 /< CH3 (t, J = 6 Hz, 1 H), 8.03 (m, 1 H), 7.64 (m, 6 H), 7.46 (d, J C OH _ 26q I-2 = 6. 9 Hz, 1 H), 7.05 (s, 2 H), 6.96 (s, 1 H), 5.52 (s, 1 H), 3 CH3 3.02 (t, J = 6. 8 Hz, 2 H), 1.81 (m, 1 H), 1.48 (s, 6 H), 0.85 (d, J= 6.8 Hz, 6 H); MS (ES) : 539.4 'H NMR (DMSO-d6): 8 9.06 (s, 2 H), 8.78 (s, 2 H), 8.52 OB CH3 (t, J=6Hz, lH), 8.01 (d, J = 6. 8 Hz, 1 H), 7.62 (m, 7 H), 7 ! 7. 46 (d, J=6. 8Hz, lH), 7.0 (m, 2H), 4.94 (t, J=6Hz, 1 2 r /CH3 r H), 3.60 (q, J = 6 & 12. 8 Hz, 2 H), 3.01 (t, J = 6 Hz, 2 H), CH3 2. 58 (t, J = 6 Hz, 2 H), 1.82 (m, 1 H), 0.85 (d, J = 6.8 Hz, 6 H); MS (ES-): 525.4 'H NMR (DMSO-d6): 8 9.01 (s, 2 H), 8.88 (s, 2 H), 8.5 (t, -CH2 CH3 J = 6 Hz, 1 H), 8.07 (m, 1 H), 7.73 (m, 1 H), 7.63 (m, 7 H), 7. 11 (d, J = 17 Hz, 1 H), 7.01 (d, J = 17 Hz, 1 H), 6.97 S CH \/\CH _ (m, l H), 6.69 (d, J = 17 Hz, 1 H), 5.24 (s, 1H), 5.14 (s, 1H), 3.03 (t, J = 6.9 and 6.0 Hz, 2 H), 1.92 (s, 3 H), 1.81 (m, 1 H), 0.84 (d, J = 6.9 Hz, 6 H); MS (ES+) : 525.4 /CH2 CH lH NMR (DMSO-d6): 8 9. 08 (s, 2 H), 8.82 (s, 2 H), 8.53 (t, f = 6 Hz, 1 H), 8.04 (m, I H), 7.67 (m, 7 H), 7. 04 (m, 2 J,= 6.9 and 6.0 Hz, 1 H), 5.20 (s, 1 H), 3.04 (t, Zt \CH 26t I-2 H), 5.55 (s, '32H), 2. 19 (s, 3H), 1. 81 (m, lH), 0. 87 (d, J=6. 9Hz, 6 CH3 2 H), 2. 19 (s, 3 H), 1. 81 (m, 1 H), 0. 87 (d, J = 6. 9 Hz, 6 H); MS (ES+) : 499.4 Cpd.R'Starting Method No. From Used No. From Used 'H NMR (DMSO-d6): 8 9. 11 (s, 2 H), 8.86 (s, 2 H), 8.57 CH3 (t, J = 6 Hz, 1 H), 8.13 (m, 1 H), 7.53 (m, 2 H), 7.74 (m, 6 OH H), 7. 7 (d, J = 7 Hz, 1 H), 7.17 (m, 2 H), 6.54 (d, J = 12 CH 3 Hz, 1 H), 5.91 (m, 1 H), 4.99 (m, 1 H), 4. 31 (m, 2 H), 3. 06 (t, J = 6.9 and 6.0 Hz, 2 H), 1.83 (m, 1 H), 0.87 (d, J = 6. 9 Hz, 6 H); MS (ES+) : 515.4 CH IH NMR (DMSO-d6): 8 9.08 (s, 2 H), 8.82 (s, 2 H), 8.54 8 H) 7.06 (m, 2 CH (t, J = 6 Hz, I H), 8. 05 (m, 8H), 7.06 (m, 2 H), 5. 52 (s, 1 I, 5.2 (s, 1 H), 4. 63 (t, J = S Hz, 1 H), 3.56 OH (m, 2 H), 3.05 (t, J = 6. 9 and 6. 0 Hz, 2 H), 2.71 (t, J = 7 Hz, 2 H), 1.82 (m, 1 H), 0.87 (d, J = 6. 9 Hz, 6 H) ; MS (ES+) : 529.4 'H NMR (DMSO-d6): 8 9.08 (s, 2 H), 8.86 (s, 2 H), 8.54 CH CH3 (t, J = 6 Hz, 1 H), 8.03 (m, 1 H), 7.62 (m, 7 H), 7.08 (d, J 27w 26w 1-2 = 7.5 Hz, 1 H), 6.99 (m, 1 H), 4. 32 (s, I H), 3.03 (t, J = CH3 6.9 and 6. 0 Hz, 2 H), 2.71 (t, J = 7 Hz, 2 H), 1.82 (m, 1 H), 0.87 (d, J = 6.9 Hz, 6 H); MS (ES+) : 483.3 'H NMR (DMSO-d6) : 6 13.8 (s, 1 H), 9.04 (s, 2 H), 8.96 CH3 CH3 (s, 2 H), 8.47 (t, J = 6 Hz, 1 H), 7.93 (s, 1 H), 7.61 (m, 6 27x H), 7.42 (m, 1 H), 6.91 (m, 2 H), 6.07 (dd, J = 17 and 9 CH 3 CH 3 26x I-2 Hz, 1 H), 5. 35 (m, 1 H), 5.09 (dd, J 17 and 11 Hz, 1 H), 3. 38 (d, J = 6. 5 Hz, 1 H), 3.0 (t, J = 7 Hz, 2 H), 1.78 (m, 1 H), 1.72 (s, 3 H), 1.41 (s, 3 H), 0.84 (d, J = 6.9 Hz, 6 H); MS (ES+) : 527.5 Cpd. |-R |-R'| Starting | Method AnalyticalData "-R-R' ° , AnaIyttcaIData No. From Used CH3'H NMR (DMSO-d6) : 8 8. 99 (s, 2 H), 8.86 (s, 2 H), 8.52 OH (t, J=6Hz, lH), 8.03 (m, 1 H), 7.63 (m, 6H), 7.50 (d, J 27y 26y 1-2 = 7 Hz, 1 H), 7.07 (d, J=7Hz, lH), 7.12 (m, 1H), 5.40 27y CH 26y I-2 (t, J = 6 Hz, 1 H), 4.33 (d, J=6. 0Hz, 2H), 3.01 (t, J = 7 Hz, 2 H), 1.80 (m, 1 H), 0.84 (d, J = 6. 9 Hz, 6 H) ; MS (ES+) : 513.4 CH,'H NMR (DMSO-d6) : 5 9. 50 (bs, 1 H), 8.77 (bs, 2 H), CH3 8.49 (t, J = 6 Hz, 1 H), U CH, 8. 49 (t, J=6Hz, lH), 7. 98 (m, lH), 7.63 (m, 6H), 7.55 /\ JX 26 I-2 (d, J=6. 9Hz, lH), 7.01 (d, J=7. 9Hz, lH), 6.99 (m, 1 CH3 H), 5.55 (s, 1H), 5. 38 (s, 1 H), 5.-13 (t, J = 5 Hz, 1 H), 4. 39 (d, J = 5 Hz, 2 H), 3.02 (t, J = 6. 9 and 6. 0 Hz, 2 H), 1.81 (m, 1 H), 0.86 (d, J = 6. 9 Hz, 6 H) ; MS (ES+) : 515.4 CH3 IH NMR (DMSO-d6) : 8 9. 08 (s, 2 H), 8.73 (s, 2 H), 8.53 N (t, J = 6 Hz, 1 H), 8.06 (s, 1 H), 8.02 (bs, 1 H), 7.94 (d, J 27aa < \/CH3 26aa I-2 =7. 8Hz, lH), 7.62 (m, 6H), 7.24 (d, J=7. 8Hz, lH), 6. 95 (d, J = 7. 8 Hz, 1 H), 3.03 (t, J = 6 Hz, 2 H), 1.82 (m, 1 H), 0.87 (d, J = 6. 8 Hz, 6 H); MS (ES+) : 484. 3 1H NMR (DMSO-d6) : 8 9. 05 (bs, 2 H), 8.81 (bs, 2 H), OH CH3 8.49 (t, J = 6 Hz, 1 H), 8.02 (s, 1H), 7.68 (s, 1H), 7.62 (m, 6 H), 7. 53 (d, J = 6 Hz, 1 H), 7.21 (d, J=6Hz, lH), 27ab . 26ab I-2 CH3 7. 13 (d, J = 7 Hz, 1 H), 7.01 (s, 1H), 5.25 (t, J=5Hz, l S H), 4.51 (d, J = 5 Hz, 2 H), 3.01 (t, J = 6 Hz, 2 H), 1.81 (m, 1 H), 0.85 (d, J = 6. 8 Hz, 6 H) ; MS (ES+) : 571.64 p Starting Method No. From Used No. From Used 'H NMR (DMSO-d6): 8 9.05 (bs, 2 H), 8.78 (s, 2 H), 8.52 CH3 (t, J = 6 Hz, 1 H), 8.02 (bs, 1 H), 7.65 (m, 6 H), 7.53 (d, J OH = 5 Hz, 1 H), 7.54 (d, J = 5 Hz, 1 H), 7.26 (d, J = 5 Hz, 1 27ac s 26ac 1-2 H), 7.10 (m, 1 H), 6.99 (m, 1 H), 5.64 (t, J = 5 Hz, 1H), CH3 4.71 (d, J = 5 Hz, 2H), 3. 07 (t, J = 6.9 and 6.0 Hz, 2 H), 1. 73 (m, 1 H), 0.84 (d, J = 6.9 Hz, 6 H); MS (ES+) : 571.56 27ad CH3 26ad I-2 MS (ES+) : 585.4 HOzC -CH3 CH IH NMR (DMSO-d6) : 8 14.11 (bs, 1 H), 9.05 (bs, 2 H), 3 8. 75 (bs, 2 H), 8.5 (m, 1 H), 8.0 (s, 1 H), 7.8-7.6 (m, 8 H), 27ae _ 26ae I-2 7.49 (d, J = 3 Hz, 1 H), 7.1 (d, J = 6. 9 Hz, 1 H), 7.0 (m, 1 HOH2Cs/ \/CH3 H), 5.5 (m, l H), 4.7 (m, 2 H), 3.09 (m, 2 H), 1.74 (m, 1 H) 0.86 (d, J = 6.9 Hz, 6 H); MS (ES+) 571.2 'H NMR (DMSO-d6) : 8 14.11 (bs, 1 H), 9.05 (bs, 2 H), 8. 75 (bs, 2 H), 8.49 (t, J = 6 Hz, 1 H), 7.97 (s, 1 H), 7.67 HOH, C CH3 (d, J = 3 Hz, 1 H), 7.61 (m, 7 H), 7.54 (d, J = 3 Hz, 1 H), 27af 26af I-2 7.06 (d, J = 6.9 Hz, 1 H), 6.89 (d, J = 6.9 Hz, 1 H), 5.23 /1\ CH3 (t, J = 5 Hz, 1 H), 5.42 (d, J = 5 Hz, 2 H), 3.09 (t, J = 6.9 s and 6. 0 Hz, 2 H), 1.74 (m, 1 H) 0.86 (d, J = 6. 9 Hz, 6 H) ; MS (ES+) : 571. 3 Cpd.--. Starting Method Analytical Data "-R-R' ° . AnatyttcaIData No.From Used CH 1H NMR (DMSO-d6) : 8 11.45 (s, 1 H), 9.08 (bs, 2 H), 8. 88 (bs, 2 H), 8.75 (t, J = 6 Hz, 1 H), 8.04 (bs, 1 H), 7.88 27a 26ag 1-2 (m, 1 H), 7.7 (m, 7 H), 7.03 (m, 2 H), 6.9 (m, 1 H), 6.62 'CH 26a I-2 27ag. N 3 g (m, 1 H), 6.17 (m, I H), 3.07 (t, J = 6. 9 and 6. 0 Hz, 2 H), 1.84 (m, 1 H), 0.86 (d, J = 6.9 Hz, 6 H); MS (ES+) : 524.65 OH IH NMR (DMSO-d6) : 8 13.83 (s, 1 H), 8.9 (bs, 4 H), 8.47 (t, J = 6 Hz, 1 H), 7.61 (m, 6 CH3 (t, J = 6 Hz, 1 H), 7. 95 (s, 1 H), 5. 3 (s, 1 H), 7. 61 (m, 6 XOH 7. 4 (m, 1 H), 6.95 (d, J = 7.7 Hz, 1 H), 6.85 (d, J = 7.7 CH 1 H), 6.22 (s, 1 H), 4.6 (t, J = 27ah CH3 26ah I-2 Hz, 1 H), 6.64 (d, J = 9 Hz, 5.1 Hz, 1 H), 3.51 (d, J = 5.6 Hz, 2 H), 3.01 (t, J = 7 Hz, 2 H), 1.8 (m, 1 H), 0.85 (d, J = 6.9 Hz, 6 H) ; MS (ES+) : 519.52 CH 3 27ai ~ CH3 26ai I-2 MS (ES+) 514.25 IH NMR (DMSO-d6) : 8 9.05 (s, 2 H), 8.67 (s, 2 H), 8.47 CH3 (t, J = 6 and 5 Hz, 1 H), 7.95 (m, 1 H), 7.95 (m, 1 H), 7.63 CH3 (m, SH), 7.40 (s, 1 H), 7.38 (d, J = 7.7 Hz, 1 H), 6.92 (m, CH 3 2 H), 3.02 (t, J = 6. 8 Hz, 2 H), 2.64 (m, 2 H), 1.80 (m, 1 H), 1.66 (m, 2 H), 0.96 (t, J = 8 and 6. 5 Hz, 3 H), 0.85 (d, J = 6. 8 Hz, 6 H); MS (ES-) 499. 31 p Starting Method No. From Used No. From Used" CH3'H NMR (DMSO-d6) : 6 14.3 (bs, 1 H), 9.05 (bs, 2 H), 8. 75 (bs, 2 H), 8.5 (m, 1 H), 8.0 (s, 1 H), 7.8-7.6 (m, 8 H), 27ak'CH, 32f G 7.49 (d, J = 3 Hz, 1 H), 7.1 (d, J = 6.9 Hz, 1 H), 7.0 (m, 1 H), 5.5 (m, 1 H), 4.7 (m, 2 H), 3.09 (m, 2 H), 1.74 (m, 1 H), 0.86 (d, J = 6.9 Hz, 6 H); MS (ES+) 487.2 CH3 27a1 26ai G MS (ES+) 488.3 (100%: M+l) CH IH NMR (DMSO-d6) : 8 13.9 (bs, 1 H), 9.05 (2 bs, 4 H), 8. 5 (nn, 1 H), 7.9 (s, 1H), 7.7-7.5 (m, 8H), 7. 3 (d, J=3 1H) 3.5 (m, 2 H), 3.09 (m, 27am/OH \CH 26u G Hz, I H), 6. 9 (m, 2 H), 4. 6 (m, 1H), 3. 5 (m, 2 H), 3. 09 (m, 2 H), 2.6 (m, 2 H), 1.8 (m, 1 H) 0.85 (d, J = 6. 9 Hz, 6 H) ; MS (ES+) 517.3 'H NMR (DMSO-d6): 8 9.84 (bs, 1 H), 9.07 (bs, 2 H), 0 CH3 8.87 (bs, 2 H), 8.51 (t, J = 6 and 5 Hz, 1 H), 8.13 (m, 1 11 l 2 H), 8.03 (m, 2 H), 7.65 (m, 5 H), 7.20 (d, J = 7. 7 Hz, 1 32a ACH oCH 31a I-H), 6.94 (d, J = 7. 7. Hz, 1 H), 3.04 (t, J = 6. 8 Hz, 2 H), 2. 66 (s, 3 H), 1.83 (m, 1 H), 0.86 (d, J = 6. 8 Hz, 6 H) ; MS (ES-) 499.4, (ES+) 501.4 CH3 32b \v~ CH3 1 31b I-2 Characterized in the next step CH3 3 Cpd.Starting Method No. From Used No. From Used" 'H NMR (DMSO-d6) : 8 14. 24 (s, 1 H), 9.29 (bs, 2 H), CH3 9.01 (bs, 2 H), 8.73 (t, J = 6 Hz, 1 H), 8.2 (d, J = 2 Hz, 1 CH2 H), 7.85 (m, 5 H), 7.74 (d, 2 Hz, 1 H), 7.4 (d, J = 8 Hz, 1 32c \/CH 31c I-2 H), 7.22 (d, J=7. 4Hz, lH), 7.13 (d, J = 7. 5,1H), 6.73 (t, J = 6. 8 Hz, 1 H), 5.59 (d, J = 6. 8 Hz, 2 H), 3.25 (t, J = 6.8 Hz, 2 H), 2.04 (m, 1 H), 1.08 (d, J = 6. 8 Hz, 6 H) ; MS (ES-) 495.1, (ES+): 497.2 CH 3 32d S 31d 1-2 MS (ES-): 553.3 "jL t -CH CH 1H NMR (DMSO-d6) : 6 13. 642 (bs, 1 H), 9.06 (s, 2 H), 8. 89 (s, 2 H), 8.50 (t, J = 6 and 5 Hz, 1 H), 7.98 (s, 1 H), 32e f/CH3 31e I-2 7.62 (m, 7 H), 7.43 (s, 1H), 7. 33 (m, 4 H), 6.95 (m, 2 H), 4. 04 (s, 2 H), 3.02 (t, J = 6. 8 Hz, 2 H), 1.80 (m, 1H), 0.86 (d, J = 6. 8 Hz, 6 H) ; MS (ES-) : 547.4 'H NMR (DMSO-d6) : 8 0.85 (d, J = 6. 9 Hz, 6 H), 1.81 (m, 1 H), 3.03 (t, J = 7 Hz, 2 H), 5. 35 (d, J = I I Hz, 1 H), CH 2 31f 1-2 5.94 (d, J=17Hz, lH), 6.84 (dd, J=17andllHz, 2H), 7. 0 (m, 2 H), 7.64 (m, 8H), 8.01 (s, 1 H), 8.54 (t, J=6 CH3 Hz, 1 H), 8.77 (s, 2 H), 9.06 (s, 2 H) ; MS (ES+): 485.57 W\/CH 32g 31g I-2 MS (ES+) 596.. 2 CHZ S Cpd. Starting Method No. From Used CHZOH C H NMR (DMSO-d6) : 8 14. 2 (bs, 1 H), 9.1 (bs, 4 H), 8.6 32h < /\CH3 31h I-2 (m, 1 H), 8.15 (s, 1 H), 7.9-7.6 (m, 8 H), 7.2 (m, 2 H), 6.7 /C (s, I H), 5. 3 (br s, I H), 4.6 (m, 2 H), 3.1 (m, 2 H), 1. 9 (m, 1 H), 0.9 (d, J = 6.7 Hz, 6 H); MS (ES+) 555.1 'H NMR (DMSO-d6) : 8 13.84 (bs, I H), 9.01 (bs, 2 H), 8.80 (bs, 2 H), 8.46 (t, J = 6 and 5 Hz, 1 H), 8.03 (s, 1 H), HOH, C CH3 7.95 (s, 1 H), 7.77 (s, 1 H), 7.67 (m, 2 H), 7. 61 (m, 5 H), 32i 31i 1-2 7.02 (d, J = 7. 7 Hz, 1 H), 6.94 (m, 1 H), 5.13 (t, J = 5 Hz, \/CH 1 H), 4.47 (m, 2 H), 2.97 (t, J = 6. 8 Hz, 2 H), 1.78 (m, 1 H), 0.80 (d, J = 6.8 Hz, 6 H); MS (ES-) 553. 3, (ES+) 555. 3 CH3 40 Y H jL 39 I-2 MS (ES+) 524. 3 CH3 'H NMR (DMSO-d6) : 5 13.82 (s, 1 H), 9. 20 (bs, 1 H), CH 9.10 (bs, 1 H), 8.51 (t, J = 6 Hz, 1 H), 7.97 (s, 1 H), 7.73- 44 O/\) JX 43 I-2 7.45 (m, 5 H), 7.43-7.39 (m, 2 H), 7. 20 (t, J = 8 Hz, 1 H), 7. 10 (m, 6 H), 6.96 (d, J = 8 Hz, 1 H), 3.0 (t, J = 6 Hz, 2 H), 1.80 (m, 1 H), 0.68 (d, J = 6.8 Hz, 6 H); MS (ES+) 551.30 CH3'H NMR (DMSO-d6) : 8 9.21 (2 bs, 2 H each, 4 H), 8.61 46 45 1-2 (m, 1 H), 8.1 (s, 1H), 7.8-7.4 (m, 10 H), 7. 3 (s, 1 H), 7.2 46 v CH3 45 I-2 (d, I = 7 Hz, 1 H), 7.1 (m, 2H), 5.2 (s, 2 H), 3.1 (m, 2H), 1. 8 (m, 1 H), 0.91 (d, J = 6. 8 Hz, 6 H) ; MS (ES+) 565. 27 p Starting Method No. From Used No. From Used 'H NMR (CF3COzD) : 8 8.43 (s, 1 H), 8.01 (d, J = 7. 5 Hz, CH 1 H), 7.67 (q, J = 24 and 8.4 Hz, 4 H), 7.56 (d, J = 7. 7 Hz, 51 OCH3 l 3 50 I-2 1 H), 7. 38 (s, 1 H), 7. 23 (s, 2 H), 3.98 (s, 3 H), 3.43 (d, J = 7 Hz, 2 H), 2.01 (m, 1 H), 1.01 (d, J = 6. 8 Hz, 6 H) ; MS (ES-) 487., (ES+) 489.3 'H NMR (DMSO-d6) : 8 14.00 (bs, 1 H), 8.52 (t, J = 6 and 3 5 Hz, 1 H), 7.98 (s, 1 H), 7.63 (m, 8 H), 7.07 (d, J = 7. 7 53 52 1-2 Hz, 1 H), 6.96 (d, J = 7. 7 Hz, 1 H), 3.83 (s, 2 H), 3.02 (t, J CH3 = 6. 8 Hz, 2 H), 1.81 (m, 1 H), 0.86 (d, J = 6. 8 Hz, 6 H) ; NH2 MS (ES-) 568.1 'H NMR (DMSO-d6) : 8 13.84 (br s, 1 H), 9.05 (s, 2 H), 8.94 (s, 2 H), 8.48 (t, J= 5.7 Hz, 1 H), 7.97 (d, J= 1. 9 CH2 Hz, 1 H), 7.70 (m, 7 H), 7.00 (d, J= 7.9 Hz, 1 H), 6.92 (d, 70a k <CH3 68a I-2, S J= 7.9 Hz, 1 H), 6.84 (dd, J= 10. 9 and 17.7 Hz, 1 H), 5. 93 (d, J= 17. 7 Hz, 1 H), 5.34 (d, J= 10. 9 Hz, 1 H), 3.19 (m, 2 H), 1.46 (qui, J= 7.0 Hz, 2 H), 1.29 (sex, J= 7.0 Hz, 2 H), 0.87 (t, J= 7. 3 Hz, 3 H); MS (ES+) : 485.2 'H NMR (DMSO-d6) : 8 12.71 (br s, 1 H), 9.12 (s, 2 H), 8. 93 (s, 2 H), 8.20 (m, 2 H), 7.86 (m, 1 H), 7.70 (m, 6 H), CH 70b 68b 1-2, S 7. 20 (m, 2 H), 6. 87 (dd, J= 10. 9 and 17. 7 Hz, 1 H), 5. 99 CH3 (d, J= 17. 7 Hz, 1 H), 5.40 (d, J= 10. 9 Hz, 1 H), 3.97 (m, 1 H), 1.50-1.20 (m, 8 H) 0.86 (t, J= 7. 2 Hz, 6 H); MS (ES+) : 527. 3 Cpd. Starting Method No. From Used No. From Used 'H NMR (DMSO-d6) : 6 12 : 84 (br s, 1 H), 9.08 (m, 3 H), cl 8. 36 (d, J= 7. 7 Hz, 1 H), 8.18 (s, 1 H), 7.83 (m, 1 H), 70c 2 68c I-2, S 7. 67 (m, 6 H), 7.15 (m, 3 H), 6.86 (dd, J= 10. 9 and 17.7 -0 Hz, 1 H), 5.98 (d, J= 17.7 Hz, 1 H), 5. 39 (d, J= 10. 9 Hz, 1 H), 3.74 (m, 1 H), 1.84-1.55 (m, 5 H), 1. 38-1. 04 (m, 5 H); MS (ES) : 511. 3 CH NMR (DMSO-d6) : 6 9. 11 (s, 2 H), 8. 89 (s, 2 H), 8. 81 1 H) 8.21 (s,), r H (t, J= 5. 7 Hz, 1 H), 8. 21 (s, 1 H), 7. 85 (m, 1 H), 7. 68 (m, 7 d 9 \/% CH2 68d I 2 S 7 H), 7. 17 (m, 3 H), 6. 87 (dd, J= 10. 9 alld l7. 7 Hz, l H), 5. 99 (d, J= 17. 7 Hz, 1 H), 5.88 (m, 1 H), 5.39 (d, J= 10. 9 Hz, 1 H), 5.12 (m, 2 H), 3.88 (t, J= 5.0 Hz, 1 H); MS (ES+) : 469.2 'H NMR (DMSO-d6) : 5 9. 11 (s, 2 H), 9.01 (s, 2 H), 8.38 CH2 CH3 (d, J= 7. 5 Hz, I H), 8.18 (s, 1 H), 7.83 (m, 1 H), 7.67 (m, CHZ CH3 (d, J= 7.5 Hz,, 70e 68e 1-2, S 6 H), 7.16 (m, 3 H), 6.86 (dd, J= 10. 9 and 17. 7 Hz, 1 H), \ CH3 5. 98 (d, J= 17. 7 Hz, 1 H), 5.39 (d, J= 10. 9 Hz, 1 H), 4.09 (m, 1 H), 1.15 (d, J= 6.6 Hz, 6 H); MS (ES+) : 471.3 'H NMR (DMSO-d6) : 8 9.11 (s, 2 H), 9.05 (s, 2 H), 8.31 CH, CH3 (d, J= 8.1 Hz, 1 H), 8.20 (s, 1 H), 7.85 (d, J= 7.7 Hz, 1 70f V < 68f I 2 S H), 7. 69 (m, 6 H), 7.17 (m, 3 H), 6.86 (dd, J=10. 9 and CH3 Mi 17. 7 Hz, 1 H), 5.98 (d, J= 17. 7 Hz, 1 H), 5. 39 (d, J= 10.9 Hz, 1 H), 3.91 (m, 1 H), 1.50 (m, 2 H), 1.12 (d, J= 6.6 Hz, 3 H). 0.85 (t, J= 7.3 Hz, 3 H); MS (ES : 485.3 Cpd. Starting Method No. From Used- No. From Used" 'H NMR (DMSO-d6) : 8 12. 82 (br s, 1 H), 9.25 (m, 1 H), CH2 9.12 (s, 2 H), 8.91 (s, 2 H), 8.23 (s, 1 H), 7.87 (m, 1 H), 70g V CF3 68g 1-2, S 7.68 (m, 7 H), 7.18 (m, 3 H), 6.87 (dd, J=10. 9aIldl7. 7 Hz, 1 H), 5.99 (d, J= 17. 7 Hz, 1 H), 5.40 (d, J=10. 9Hz, 1 H), 4.07 (m, 2 H) ; MS (ES+) : 511.2 CH NMR (DMSO-d6) : 8 34 (s, 1H), 9.05 (m, 4 H) 8.18 (s, 1 H), 7.71 (m, 11 H), 7. 34 (t, J=7. 8Hz, 2H), 7.09 70h \/68h I-2, S (m, 3 H), 6.86 (dd, J= 10. 9 and 17. 7 Hz, 1 H), 5.98 (d, J = 17. 7 Hz, 1 H), 5.39 (d, J= 10. 9 Hz, 1 H) ; MS (ES+) : 505.3 'H NMR (DMSO-d6) : 8 12. 64 (br s, 1 H), 9.09 (m, 4 H), 1 H), 8.09 (s, 1 H), 7.66 (m, 9 H), 7.08 (m, 3 H), cH2 8_56 (m, 70i 68i I-2, S 6. 86 (dd, J= 10. 9 and 17. 7 Hz, 1 H), 5.96 (d, J= 17. 7 Hz, 1 H), 5.37 (d, J=10. 9Hz, l H), 4.40 (m, 2H) 3. 39 (m, 2 H), 3.22 (m, 2 H), 1.48 (m, 4 H) ; MS (ES+) : 501. 3 (100%: Milz 'H NMR (DMSO-d6) : 8 9.08 (m, 4 H), 8.69 (t, J= 6. 0 Hz, CH 1 H), 8.16 (s, 1H), 7.69 (m, 5 H), 7.13 (d, J=7. 7Hz, 2 CHZ/ H), 7.09 (m, 3 H), 6.86 (dd, J=10. 9 and 17. 7 Hz, 1 H), 70J 9 J-, 5. 97 (d, J= 17. 7 Hz, 1 H), 5.38 (d, J=10. 9Hz, lH), 3.11 (t, J= 6. 0 Hz, 2 H), 1.01 (m, 1 H), 0.41 (m, 2 H), 0.21 (m, 2 H); MS (ES+) : 483.3 CH NMR (DMSO-d6) : 8 9.11 (s, 2 H), 8.97 (s, 2 H), 8.54 CHZ (m, 1 H), 8.12 (s, 1 H), 7.68 (m, 7 H), 7.17 (m, 4 H), 6.86 70k CH 68k 1-2, S (dd, J=10. 9and17. 7Hz, I H), 5.97 (d, J=17. 7Hz, I H), 5. 38 (d,. 7= 10. 9 Hz, 1 H), 2.75 (d, J= 4. 3 Hz, 1 H) ; MS (ES+) : 443.26 p Starting Method No. From Used No _ From Used 'H NMR (DMSO-d6) : 8 9.07 (s, 2 H), 8.92 (s, 2 H), 8.53 CH (t, J= 5. 5 Hz, 1 H), 8.02 (s, 1 H), 7.62 (m, 7 H), 7.01 (m, (J=10. 9 and 17.7 Hz, 1 H), 5.95 (d, J= It 17. 7 Hz, 1 H), 5. 36 (d, J=10. 9 Hz, 1 H), 3.24 (qui, J= 6. 7 Hz, 2 H), 1.08 (t, J= 7.2 Hz, 3 H); MS (ES) : 457.2 IH NMR (DMSO-d6) : 6 12.53 (br s, 1 H), 9.10 (m, 3 H), CH/) S. 38 (d, J= 7.9 Hz, 1 H), 8.11 (s, 1 H), 7.68 (m, 7 H), 70m CI I Z 68m 1-2, S 7.12 (m, 3 H), 6.86 (dd, J=10. 9 and 17. 7 Hz, 1 H), 5.96 (d, J= 17. 7 Hz, 1 H), 5. 37 (d, J=10. 9 Hz, 1 H), 3.94 (m, 1 H), 1.88-1. 33 (m, 12 H); MS (ES+) : 525. 3 'H NMR (DMSO-d6) : 8 9. 09 (m, 4 H), 8.59 (t, J= 5.2 Hz, 1 H), 8.17 (s, 1 H), 7.70 (m, 7 H), 7.16 (m, 4 H), 6.87 68n I-2, S (dd, J=10. 9 and 17.7 Hz, 1 H), 5.98 (d, J= 17. 7 Hz, 1 70n H), 5. 39 (d, J=10. 9 Hz, 1 H), 3.20 (q, J= 6. 7 Hz, 2 H), 1.52 (sex, J= 7.2 Hz, 2 H), 0.87 (t, J= 7.3 Hz, 3 H) ; MS (ES+) : 471. 3 n IH NMR (DMSO-d6) : 8 12.97 (br s, 1 H), 9.08 (s, 2 H), CH2 8. 99 (s, 2 H), 8.53 (t, J= 5. 1 Hz, 1 H), 8.06 (s, 1 H), 7.64 (m, 7 H), 7.06 (m, 2 H), 6.85 (dd, J= 10. 9 and 17.7 Hz, 1 70O \ 68O I-2, S H), 5.96 (d, J= 17. 7 Hz, 1 H), 5. 36 (d, J=10. 9 Hz, 1 H), 3. 20 (q, J= 6.5 Hz, 2 H), 1.49 (qui, J= 6.6 Hz, 2 H), 1.27 (m, 4 H), 0.86 (t, J= 6.6 Hz, 3 H); MS (ES+) : 499.3 /'CH'H NMR (DMSO-d6) : 8 9.10 (s, 2 H), 8.91 (s, 2 H), 8.55 CHZ \\\ CHs (t, J= 5.5 Hz,, 1 H) 8. 13 (s, 1 H), 7.68 (m, 7 H), 7.12 (m, ll CH 2 H), 6. 86 (dd, J = 10. 9 aIld 17. 7 Hz, 1 H), 5. 98 (d, J= ./CH3 68p I-2, S 1 H'Hz $6 a 5 g a J1 9. HH 1 H), 5. 98 (m, J= P 1. 62 (m, 1 H), 1. 39 (m, 1 H), 1. 10 (m, 1 H), 0. 86 (m, 6 1.62 (m, 1 H), 1.39 (m, I H), 1.10 (m, 1 H), 0.86 (m, 6 H) ; MS (ES+)499.3 Cpd. Starting Method No. From Used No. From Used" CH 2'H NMR (DMSO-d6) : 6 9.06 (s, 2 H), 8.82 (s, 2 H), 8. 11 CH (t, J= 7. 9 Hz, 1 H), 8. 00 (s, 1 H), 7. 62 (m, 7 H), 6. 99 (m, CH3 2 H), 6.85 (dd, J= 10. 9 and 17. 7 Hz, 1H), 5.95 (d, J= ---CH 17. 7 Hz, 1 H), 5. 35 (d, J= 10. 9 Hz, 1 H), 3.81 (q, J= 7. 5 Hz, 1 H), 1.45 (m, 4 H), 1. 24 (m, 4 H), 0.82 (m, 6 H); MS (ES+) : 527. 3 1 H) 8. 44 (m, 4 H), CHZ'H NMR (DMSO-d6) : 8 13.81 (s, 1 H), 8. 44 (m, 4 H), 70r < ~ NH2 68r I 2 S 7. 97 (s, 1 H), 7. 61 (m, 3H), 5. 93 (d, J= 17. 7 Hz, 1. H), 5.34 (d, J= 10. 9 Hz, 1 H), 3.22 (m, 5 H), 2.73 (m, 2 H), 1.52 (m, 4 H); MS (ES+) : 500. 3 IH NMR (DMSO-d6) : 8 9.09 (s, 2 H), 8.86 (s, 2 H), 8.42 Cl2 (d, J= 7.5 Hz, 1 H), 8.11 (s, 1 H), 7.68 (m, 8 H), 7.10 (m, 70s 68s 1-2, S 2 H), 6.86 (dd, J= 10. 9 and 17.7 Hz, 1 H), 5.97 (d, J= 17. 7 Hz, 1 H), 5.38 (d, J= 10. 9 Hz, 1 H), 4.20 (q, J= 7.2 Hz, 1 H), 1.93-1.44 (m, 8 H); MS (ES+) : 497.2 'H NMR (DMSO-d6) : 6 13.78 (br s, 1 H), 9.07 (s, 2 H), CH2/\ 8.87 (s, 2 H), 8.25 (d, J= 8.1 Hz, 1 H), 8.00 (s, 1 H), 7.62 "" (m, 7 H), 6.98 (m, 2 H), 6.85 (dd, J= 10. 9 and 17. 7 Hz, I 70t \ \, H), 5.94 (d, J= 17. 7 Hz, 1 H), 5.35 (d, J= 10. 9 Hz, 1 H), 4.55 (d, J= 4.1 Hz, 1 H), 3.68 (m, 1 H), 3.39 (m, 1 H), 1.79 (m, 4 H), 1.28 (m, 4 H); MS (ES) : 527. 2 1 H) 9. 05 (m, 3 H), CH2'H NMR (DMSO-d6) : 6 13. 36 (br s, 1 H), 9. 05 (m, 3 H), 70u 68u I-2, S g49 (s, 1 H), 7. 98 (s, 5. 94 (d, J = 17. 7 Hz, 1 H), 5. 35 (d, J=10. 9 Hz, 1 H), 2.81 (m, 1 H), 0.69-0.48 (m, 4 H); MS (ES+) : 469.3 Cpd., Starting Method "-R-R' °.,. AnatyttcatData No. From Used 'H NMR (DMSO-d6) : 8 9.05 (m, 4 H), 8.75 (d, J= 7.5 Hz, 1 H), 8.15 (s, 1 H), 7.70 (m, 7 H), 7.14 (d, J= 7. 9 Hz, 70v 68v I-2, S 2 H), 6.86 (dd, J= 10. 9 and 17.7 Hz, 1 H), 5.97 (d, J= 17. 7 Hz, 1 H), 5.39 (d, J= 10. 9 Hz, 1 H), 4.40 (q, J = 8.2 Hz, 1 H), 2. 12 (m, 4 H) 1.65 (m, 2 H); MS (ES+) : 483.3 IH NMR (DMSO-d6) : 8 13.17 (br s, 1 H), 9.05 (m, 4 H), 8. 51 (t, J= 5.8 Hz, 1 H), 8.06 (s, 1 H), 7.64 (m, 7 H), 7.03 68w I-2, S m 2 H), 6.85 (dd, J= 10. 9 and 17.7 Hz, 1 H), 5.95 (d, J = 17. 7 Hz, 1 H), 5.36 (d, J= 10. 9 Hz, 1 H), 4. 72 (t, J= 5.4 Hz, 1 H) 3. 47 (q, J= 5.7 Hz, 2 H), 3. 28 (m, 2 H); MS (ES+) : 473.2 CH'H NMR (DMSO-d6)', 8 9.07 (s, 2 H), 8.90 (s, 2 H), 8.50 ? (t, J = 5. 5 Hz, 1 H), 8.04 (s, 1 H), 7.63 (m, 7 H), 7.03 (m, t J = 5.5 Hz, CH 2 H), 6. 85 (dd, J =10. 9 and 17. 7 Hz, 1 H), 5. 96 (d, J= 70x 3 68x I-2, S 17. 7 Hz, 1 H), 5. 36 (d, J= 10. 9 Hz, 1 H), 3.23 (q, J= 6.5 Hz, 2 H), 1.59 (m, J= 7.0 Hz, 1 H), 1. 39 (q, J= 6.8 Hz, 2 H), 0.88 (d, J= 6.6 Hz, 6 H). Cpd.-R Starting Method Analytical Data No, From Used 'HNMR (DMSO-d6): å 10. 85 (s, 1 H), 9.21 (s, 2 H), 8.91 (s, 2 H), 8.71 (t, J = 5.9 o Hz, 1 H), 8.21 (d, J = 1.96 Hz, 1 H), 8.23 (d, J = 1. 96 Hz, 1 H), 8.19 (d, J = 2. 19 31a 30a J Hz, 1 H), 8.17 (d, J = 1. 97 Hz, 1 H), 8.09 (d, J = 1. 91 Hz, 1 H), 7.77 (s, 4 H), nCH3 7. 53 (d, J = 7. 53 Hz, 1 H), 3.57 (s, 3 H), 3.11 (q, J = 6.89 Hz, 1 H), 2.71 (s, 3 H), 1.86 (m, 1 H), 3.88 (d, 6.87 Hz, 6H); MS (ES+) 515.3 31b 30b i MS (ES+) : 527.2 31c 30c i Cliaracterized in the next step 'HNMR (DMSO-d6) : 8 10.59 (bs, 1 H), 9.16 (s, 2 H), 8.85 (s, 2 H), 8.69 (t, J = 6 and 5 Hz, 1 H), 8.21 (s, 1 H), 8.04 (d, J = 1. 5 Hz, 1 H), 7.73 (m, 4 H), 7.58 (s, 1 31d 30d H), 7. 50-7. 38 (m, 3 H), 7.32 (m, 1 H), 7.03 (d, J = 7.5 Hz, 2 H), 4. 31 (s, 2 H), 31d/S/30d J H, 7.50-738 m,, j 3. 55 (s, 2 H), 3.07 (t, J = 6.8 Hz, 2 H), 1.85 (m, 1 H), 0.87 (d, J = 6.8 Hz, 6 H),; MS (ES-) 567.3, (ES+) 569.3 31e/< 30e J MS (ES-) : 561.4 ; MS (ES+) : 563.4 v

Cpd.-R Starting Method A-ualytical Data r-R TT AnatyttcaiData No. From Used 'H NMR (DMSO-d6): 8 10.73 (s, 1H), 9.24 (s, 2H), 9.00 (s, 2H), 8.71 (t, J = 5.7 Hz, 1H), 8.24 (d, J = 1.9 Hz, 1H), 8.05 (dd, J = 8.0,1.9 Hz, 1H), 7. 77 (m, 5H), 31f CH 30f J 7. 71 (dd, J = 7. 9,1.5 Hz, 1H), 7.42 (d, J = 7. 9 Hz, 1H), 7. 31 (d, J = 7. 9 Hz, 1H), 6. 89 (dd, J = 17. 6,11.0 Hz, 1H), 6.04 (d, J =17. 6 Hz, 1H), 5.42 (d, J = 11. 0 Hz, 1H), 3.56 (s, 3H), 3.10 (t, J = 6.4 Hz, 2H), 1.85 (m, 1H), 0.89 (d, J = 6.7 Hz, 6H); MS (ES+): 499. 3 IHNMR (DMSO-d6) : 8 10.73 (s, 1 H), 9. 19 (bs, 2 H), 8.88 (bs, 2 H), 8.71 (t, J = N3H2C/6 Hz, 1 H), 8.27 (d, J = 2 Hz, 1 H), 8.07 (dd, J = 7. 7 and 2 Hz, 1 H), 7.88 (d, 2 Hz, 1 H), 7.8 (d, J = 2 Hz, 1 H), 7.83 (m, 4 H), 7.72 (dd, J = 2 and 7.7 Hz, 1 H), g t g 7. 46 (d, J=7. 7,1 H), 7.41 (d, J = 7. 7 Hz, 1 H), 4.56 (s, 2 H), 3.56 (s, 3 H), 3.11 s (t, J = 6.8 Hz, 2 H), 1.87 (m, 1 H), 0.92 (d, J = 6.8 Hz, 6 H); MS (ES-) 608.2, (ES+)610.3 CH20H 31h/\\ 30h J Characterized at the next step \ 'HNMR (DMSO-d6) : 8 10.68 (s, 1 H), 9.17 (bs, 2 H), 8.82 (bs, 2 H), 8.68 (t, J = HOHzC 6 Hz, 1 H), 8. 25 (d, J = 2 Hz, 1 H), 8.16 (d, J = 2 Hz, 1 H), 8.05 (dd, J = 8 and 2 31-1in 30 J Hz, 1 H), 7.87 (m, 1 H), 7.89 (dd, J = 8 and 2 Hz, 1 H), 7.75 (m, 5 H), 7.44 (d, J t) l =9Hz, 1 H), 7.36 (d, J=8Hz, lH), 5.22 (t, J=5Hz, lH), 4.54 (d, J=SHz, 2 O H), 3.57 (s, 3 H), 3.10 (t, J = 6. 8 Hz, 2 H), 1.84 (m, 1 H), 0.88 (d, J = 6. 8 Hz, 6 H; MS (ES-) 567. 4, (ES+) 569. 4 43 oX 42 J MS (ES) : 563.4 45-Obn 8 J Characterized in the next step 50-OCH3 49 MS (ES+) : 503.1 Cpd.-R | Starting Method | AnalyticalData "-R ° .. AnaIyttcaIData No. From Used s 52 31g G Characterized in the next step NH, Cpd.-R-Rv Starting Method Analytical Data No. From Used No. From Used" 34-OSO2CF3-H 33 J MS (ES+) : 621.2 O 35-OSO2CF3 AOBN 34 P MS (ES+) : 755.2; (ES-) 753. 3 OBn TIPS 0 37 N 35 + 36 D-2 MS (ES+) : 828.5 OBEN TIPS TIPS 38 F I-H 37 G MS (ES+) : 694.4; (ES-) 692.4 W 39 !-H 38 Q Characterized in the next step

Cpd. _R-R'_R, Starting Method Analytical Data No. From Used No. From Used' IH NMR (DMSO-d6) : 8 9.69 (s, 1 H), 8.49 (d, J= 2.0 Hz, 1 H), 8. 22 (d, J= 6.9 Hz, 1 H), 7.53 (m, 4 H), 7.43 (m, 2 H), 7.37 (m, 2 H), 7. 24 (d, 54-OBn-CHO-CO2MEM 5 + 6 D-2 J= 8.9 Hz, 1 H), 5.57 (s, 2 H), 5.26 (s, 2 H), 3.85 (t, J= 4.9 Hz, 2 H), 3.60 (s, 3 H), 3.51 (t, J= 4.9 Hz 2 H), 3. 32 (s, 3 H); MS (ES+) : 501. 02 (M+Na) + lH NMR (DMSO-d6) : â 12.65 (s, 1 H), 8.41 (d, J= 2.0 Hz 1 H), 8.14 (dd, J= 2.0 and 7.9 Hz, 1 H), 7.50 (m, 3 H), 7.38 (m, 4 H), 7.24 (dd, J= 55-OBn-CO2H-CO2MEM 54 E 3.0 and 8.9 Hz, 1 H), 7.11 (d, J= 8.9 Hz, 1 H), 5.54 (s, 2 H), 5.20 (s, 2 H), 3.82 (t, J= 4. 9 Hz, 2 H), 3.57 (s, 3 H), 3.49 (t, J= 4.9 Hz, 2 H), 3.23 (s, 3 H); MS (ES-) : 493.2 'H NMR (DMSO-d6): 8 10.2 (s, 1 H), 9.65 (s, 1 H), 8. 25 (d, J= 2.0 Hz, 1 H), 7.85 (dd, J= 2. 0 and 8.9 Hz, 1 H), 7.51 (d, J= 7.9 Hz, 2 H), 141-OBn-CHO 7. 45 (m, 2 H), 7. 35 n, 3 H), 7.29 (d, J=7. 9 141-OBn-CHO I I 140 + 6 D-2 . Hz, 1 H) 7. 2 (d, J= 7. 9 Hz, 1 H), 5.24 (s, 2 H), H 3. 5 5 (s, 3 H), 2.3 (d, J= 6. 9 Hz, 2 H) 2.1 (m, J = 6. 9 Hz, 1 H), 1.0 (d, J= 6. 9 Hz, 6 H); MS (ES+) : 446. 31

Starting Method No. From Used" 'HNMR (DMSO-d6) : 6 12. 38 (s, 1 H), 10. 01 No. From Used (s, 1 H), 8. 05 (s, 1 H), 7. 68 (d, J= 7. 9 Hz, 1 H), 7.41 (d, J= 7. 9 Hz, 2 H), 7. 35 (m, 5 H), 7. 27 142-OBn-CO. H 141 E (m, lH), 7. 11 (d, J=8. 9Hz, lH), 7. 04 (d, J= O CH3 8. 9 Hz, 1 H), 6. 99 (d, J= 8. 9 Hz, 1 H), 5. 11 (s, 2 H), 2.13 (d, J = 6. 9 Hz, 2 H), 2.02 (m, J = 6. 9 XN \CH3 Hz, 1 H), 0.852 (d, J= 6.9 Hz, 6 H); MS (ES-): 4602 1H NMR (DMSO-d6): 8 10.12 (s, 1 H), 8.16 (d, J= 1. 9 Hz, 1 H), 7.80 (dd, J= 1. 9 and 8.3 O CH3 Hz, 1 H), 7.42 (m, 6 H), 7.26 (dd, J= 2.8 and 0 CHL, Hz, 1 H), 7. 13 (m, 2 H), 5. 21 (s, 2 H), 5. and N CH3(s, 2 H), 3. 54 (s, 3 H), 3. 40 (m, 2 H), 3. 32 (m, 2 "N"-"CH, (s, 2H), 3.54 (s, 3H), 3.40 (m, 2H), 3.32 (m, 2 H H), 2.22 (d, J = 7. 0 Hz, 2 H), 2.10 (m, 4H), 0.95 (d, J= 6.4 Hz, 6H); MS (ES+) : 572. 3 (M+Na) + 'H NMR (DMSO-d6) : å 12.7 (br s, 1 H), 9.09 o CH3 (s, 2 H), 8.91 (s, 2 H), 8.57 (m, 1 H), 8.11 (s, 1 144-OH-CO2MEM NJ\CH 143 G H), 7. 92 (d, J=1. 9 Hz, 1 H), 7.81 (m, 3 H), 7. 67 (m, 5 H), 7. 14 (m, 3 H), 6. 66 (m, 1 H), H 4. 40 (t, J= 5.3 Hz, 1 H), 3. 39 (m, 2 H), 3.22 (m, 2 H), 1.48 (m, 4 H); MS (ES-) : 592.2. OCH3 145-OSO2CF3-CO2MEM 144 B-2 MS (ES+) : 592.2 NCH3 H OCH3 146a 43-CO2MEM X Jt 1 145 D-2 MS (ES+) : 532.5 (M+Na) + N CH3 0 H' Cpd.-R-Rf-R"Starting Method Analytical Data No. From Used No. From Used" 1H NMR (DMSO-d6): 8 10.1 (s, 1 H), 8.21 (d, O CH J= 2. 0 Hz, 1 H), 8.10 (d, J= 2. 0 Hz, 1 H), 7.89 (dd, J= 2. 0 and 7. 9 Hz, 1 H), 7.84 (d, J= 3. 0 and 8. 9 Hz, 1 H), 7.63 (m, 2 H), 7.25 (d, J= 146b-CO MEM \N"CH3 a. nd 8. 9 Hz, g) (2 H) 5.22 (d,. l=14. z 145 D-2 7.9 Hz, 1 H, 7.19 m,, S Hz, 2 H), 3.57 (s, 3 H), 3.43 (t, J=4. 9Hz, 2 H), 3.34 (t, J=4. 9Hz, 2H), 3.20 (s, 3H), 2.23 (d, J= 6. 9 Hz, 2 H), 2.11 (m, J=6. 9Hz, 1 H), 0.96 (d, J= 5.9 Hz, 6 H); MS (ES+) : 526.48 ouCH3 146c-CH=CH2-CO2MEM X < 145 D-3 MS (ES+) : 470.2 (M+Na) + N CH 3 H 147a -COZH , L 146a I-1 MS (ES-) : 420.29 ONH CH3 'H NMR (DMSO-d6) : 8 12.65 (s, 1 H), 10.12 1 H) 8.07 (d J= o CH3 (s, 1 H), 8.18 (d, J=1. 9 Hz,,, 147b <-CO2H X t1 146b I-1 3.0 Hz, 1 H), 7.83 (m, 2 H), 7.61 (m, 2 H), 7.19 \/N CH3 (m, 3 H), 3.56 (s, 3 H), 2.22 (d, J= 6. 9 Hz, 2 H), 2.11 (m, J= 6. 9 Hz, 1 H), 0.96 (d, J= 6. 9 Hz, 6 H); MS (ES+) : 438. 52 OCH3 147c-CH=CH2-CO2H X 91) 146c I-1 MS (ES-) : 380.32 NH CH3 H Cpd.. From Method Analytical Data No. From Used No. From Used" 'H NMR (DMSO-d6) : 8 9.70 (s, 1 H), 8.42 (t, CH3 J= 6.2 Hz, 1 H), 7.90 (dd, J= 1. 1 & 6.6 Hz, 1 N 1 172 + H), 7. 82 (d, J= 1. 9 Hz, 1 H), 7.72-7.50 (m, 3 CH3 130 D-2 H), 7.34 (d, J= 7.7 Hz, 1 H), 7.27 (dd, J= 1. 3 & 6. 2 Hz, 1 H), 438 (d, J= 6. 0 Hz, 2 H), 3.53 (s, 3 H), 2.47 (m, 1 H),, 1.07 (d, J= 7.0 Hz, 6 H); MS (ES+) : 340.05 'H NMR (DMSO-d6): 8 12.35 (br s, 1 H), 8. 31 1 3 (t, J=7. 5Hz, 1 H), 7.80-7.31 (m, 5 H), 7.06 174-H-CO2H N < 173 E (m, 2 H), 4.25 (d, J= 6. 0 Hz, 2 H), 3.41 (s, 3 y CH3 H), 2.37 (m, 1 H), 0.97 (d, J= 7.0 Hz, 6 H) ; o MS (ES-) : 353. 83 IH NMR (DMSO-d6) : 8 9.70 (s, 1 H), 7.87 (m, 2 H), 7.69 (m, 1 H), 7.55 (m, 2 H), 7.35 (d, J= 7. 9 Hz, 1 H), 7. 27 (d, J= 7.5 Hz, 1 H), 4.51 (s, N Jo 130 2H), 3.52 (s, 3H), 3.05 (m, 2H), 1.92 (m, 1 CH3 H), 1.40 (m, 9 H), 0.85 (d, J= 6. 8 Hz, 6 H) ; MS (ES+) : 448. 3 (M+Na) + H NMR (DMSO-d6) : 6 7.81 (m, 2 H), 7.56 (m, oc CH3 1 H), 7.44 (m, 2 H), 7.16 (m, 2 H), 4.47 (s, 2 -CO2H 180 E H), 3.51 (s, 3 H), 3.02 (m, 2 H), 1.92 (m, J= CH3 7. 0 Hz, 1 H), 1.41 (m, 9 H), 0.85 (d, J= 6 Hz, 6 H); MS (ES) : 440.2 'H NMR (DMSO-d6): 59. 78 (s, 1H), 8.85 (t, J CH3 = 5.7 Hz, 1H), 8.50 (d, J = 2.0 Hz, 1H), 8.20 H (dd, J = 8. 2,1.9 Hz, 1H), 7.55 (m, 9H), 5. 35 (s, ß< CH3 2H), 3.69 (s, 3H), 3.23 (t, J = 6.5 Hz, 2H), 1.98 (m, 1H), 1.02 (d, J = 6.8 Hz, 6H); MS (ES+): 446. 3 Cpd.-R-Rv-Rfv Starting Method Analytical Data No.From Used H H N CF3 184b-OBn-CHO n 3f+6 D-2 MS (ES) : 470.2 0 o NCH3 184c-OBn-CHO X 3i + 6 D-2 MS (ES-) : 418. 3 O CH3 H 184d-OBn-CHO Ns z CH 3j + 6 D-2 MS (ES+) : 460.3 o 1HNMR (DMSO-d6) : 8 10. 06 (s, 1 H), 9.63 (s, CH3 1 H), 8. 73 (t, J = 6. 5 Hz, 1 H), 8. 36 (d, J = 2 1 H), 8.73 t, 1 H) 8, Hz, 1 H), 8.09 (dd, J = 2 and 8 Hz, 1 H), 7.45 185a-OH-CHO \ CH3 184a AD (d, J = 8 Hz, 1 H), 7.28 (s, 1 H), 7.11 (s, 2 H), 0 3. 58 (s, 3 H), 3.13 (d, J = 7 Hz, 2 H), 1.87 (m, 1 H), 0.91 (d, J = 6.8 Hz, 6 H); MS (ES-): 354.2 and (ES+) 378.2 (M+Na) +) H NCF3 185b-OH-CHO n 184b AD MS (ES) : 380. 1 0 H'HNMR (DMSO-d6) : 5 10.21 (s, 1 H), 9.78 (s, N CH 3 1 H), 8.87 (t, J = 5.80 Hz, 1 H), 8.51 (s, 1 H), 185c-OH-CHO 184c AD 8.23 (d, J = 7.92 Hz, I H), 7.60 (d, J = 7.9 Hz, o 1 H), 7.43 (s, 1 H), 7.25 (s, 2 H), 3.74 (s, 3 H), 3. 46 (q, J = 5. 65, 2 H), 1. 32 (t, J = 7.8 Hz, 3 H) Cpd.-R-Rf-Rlt Starting Method Analytical Data No. From Used No. From Used 'HNMR (DMSO-d6) : 5 10.06 (s, 1 H), 9.62 (s, CH3 1 H), 8.69 (t, J = 5. 90 Hz, 1 H), 8.36 (s, 1 H), y N CH 3 8.08 (d, J = 7. 92 Hz, 1 H), 7.45 (d, J = 8. 1 Hz, 185d-OH-CHO Y 184d AD 1 H), 7.28 (s, 1 H), 7.10 (s, 2H), 3.58 (s, 3 H), o 3.22 (m, 1 H), 3.11 (m, 1 H), 1.66 (m, 1 H), 1.44 (m, 1 H), 1.18 (m, 1 H), 0.89 (t, J = 6. 4 Hz, 6 H). CH 3 H 186a-OSOZCF3-CHO N \CH 185a B-2 MS (ES+) : 488.24 0 g'HNMR (DMSO-d6) : 8 9.74 (s, 1 H), 9.44 (t, J 186b-OSO. CF,-CHO " lg5b B-2''-'-'Sf' 186b-OSOZCF3-CHO . NCF3 185b B_2-590 Hz, 1 H), 8. 51 (s, 1 H), 8. 11 (d, J = 7. 91 Dz, 1 H), 7.54 (m, 4 H), 4.18 (m, 2 H), 3.59 (s, 0 3 H). IHNMR (DMSO-d6): 8 9.45 (s, 1 H), 8.59 (t, J H = 5. 90 Hz, 1 H), 8.28 (s, 1 H), 7.94 (d, J = 8. 10 N CH Hz,1 H), 7. 79 (d, = 2. 8 Hz,1 H), 7.67 (d, J = 186c-OS02CF3-CHO 3 185c B-2'''''' 7. 9 Hz, 1 H), 7. 32 (d, J = 7. 9 Hz, 2 H), 3. 40 (s, 0 3 H), 3. 12 (q, J = 7. 1 Hz, 2 H), 0.97 (t, J = 7. 16 Hz, 3 H). IHNMR (DMSO-d6) : 8 9.71 (s, 1 H), 8.78 (t, J CH3 = 5.90 Hz, 1 H), 8.49 (s, 1 H), 8.18 (d, J = 7. 92 186d-OSOZCF3-CHO N'/CH3 1 g5d B_2 Hz, 1 H), 8. 00 (s, 1H), 7.88 (d, J = 8. 51 Hz, 1 H), 7. 52 (q, J = 8. 1 Hz, 2 H), 3.67 (s, 3H), 3.22 o (m, 1 H), 3.16 (m, 1 H), 1.68 (m, 1 H), 1.44 (m, 1 H), 1.18 (m, 1 H), 0.89 (t, J = 6. 4 Hz, 6 H). Starting Method No. From Used" IHNMR (DMSO-d6) : 8 9.74 (s, 1 H), 8.76 (t, J = 6.5 Hz, 1 H), 8.42 (d, J = 2 Hz, 1 H), 8.11 CH (dd, J = 2 and 8 Hz, 1 H), 8.00 (d, J = 1. 7 Hz, 1 H H), 7.84 (dd, J = 8 and 2 Hz, 1 H), 7.47 (d, J = \ 8 Hz, 1 H), 7. 27 (d, J = 8 Hz, 1 H), 6. 90 (dd, 3 187a-CH=CHZ-CHO v CH3 I86a D-3 = 11 and 17. 7 Hz, 1 H), 6.01 (d, J = 17. 7 Hz, 1 o H), 5.42 (d, J = I I Hz, 1 H), 3.59 (s, 3 H), 3.14 (d, J = 7 Hz, 2 H), 1.88 (m, 1 H), 0.92 (d, J = 6.8 Hz, 6 H); MS (ES-): 364.2 and (ES+) 388.2 (M+Na)+ H N<CF3 187b-CH=CH2-CHO n"186b D-3 MS (ES) : 390.1 ii H H \/N CH3 187c-CH=CH2-CHO Y"186c D-3 MS (ES-): 336.2 o O CH3 H H j ! 187d-CH=CH2-CHO N CH3 186d D-3 MS (ES) : 378.2 po | | Cpd.-R-Rl-R"Starting Method Analytical Data No. From Used 'H NMR (DMSO-d6) : 8 10. 67 (s, 1 H), 9. 2 (s, 2 H), 8.87 (s, 2 H), 8. 33 (d, J= 2.0 Hz, 1 H), 8.17 (dd, J= 2.0 and 7. 9 Hz, 1 H), 7.77 (s, 4 H), 7.49 (m, 4H), 7. 39 (m, 2 H), 7. 30 (s, 2 H), 5. 54 (s, 2 H), 5. 27 (s, 2 H), 3.83 (t, J= 4. 9 Hz, 2 H) ; 3.57 (s, 3 H), 3.49 (t, J = 4.9 Hz, 2 H), 3.23 (s, 3 H) ; MS (ES+) : 612.4 57-OBn-Boc-CO2MEM 56 R MS (ES+) : 712.4 'H NMR (DMSO-d6) : 8 10.4 (s, 1 H), 10.0 (s, 1 H), 8.9 (s, 1H), 8.28 (d, J= 2.0 Hz, 1 H), 8.12 (dd, J= 2. 1 and 7.7 Hz, 1 H), 7.89 (d, J= 8.4 Hz, 2 H), 7.61 (d, J= 8.4 58-OH-Boc-CO2MEM 57 G Hz, 2H), 7. 45 (d, J=7. 7Hz, lH), 7. 13 (d, J=8. 4Hz, l H), 7.06 (s, 1 H), 6.98 (dd, J= 2.8 and 8.4 Hz, 1 H), 5.52 (s, 2 H), 3.81 (t, J= 4. 9 Hz, 2 H), 3.56 (s, 3 H), 3.46 (t, J = 4.9 Hz, 2 H), 3.20 (s, 3 H), 1.43 (s, 9 H); MS (ES-) : 620.5

S S Cpd. _R-R'_R, Starting Method Analytical Data No. Froni Used Jo. From Used" lH NMR (DMSO-d6) : 5 10.55 (s, 1 H), 8.38 (d, J= 2.0 Hz, 1 H), 8.18 (dd, J= 2.0 and 7.9 Hz, 1 H), 7.86 (m, 4 59-OSO2CF3-Boc-CO2MEM 58 B-2 H), 7. 75 (dd, J= 2. 0 and 8. 9 Hz, 1 H), 7.54 (m, 5 H), 5. 51 (s, 2H), 3. 77 (t, J=4. 9Hz, 2H), 3.55 (s, 3H), 3.46 (t, J= 4.9 Hz, 2 H), 3.18 (s, 3 H) 1.41 (s, 9 H); MS (ES+) : 754.3 'H NMR (DMSO-d6) : 5 10.61 (s, 1 H), 8.94 (s, 1 H), 8.37 (s, 1 H), 8.19 (dd, J= 2.0 and 7.9 Hz, 1 H), 8.02 (s, 1 H), 7.89 (m, 5 H), 7.65 (d, J= 8. 9 Hz, 2 H), 7.54 (d, J 60-Boc-CO2MEM 59 D-2 = 7.9 Hz, 1 H), 7.39 (d, J= 7.9 Hz, 1 H), 7.17 (d, J= 3. 9 0 Hz, 1 H), 6.68 (m, 1 H), 5.54 (s, 2 H), 3.82 (t, J= 4.9 Hz, 2 H), 3.58 (s, 3 H), 3.49 (t, J=4. 9Hz, 2H), 3.22 (s, 3 H), 1.45 (s, 9 H); MS (ES+) : 672.5 'H NMR (DMSO-d6) : 8 10.50 (s, 1 H), 8.96 (s, 1 H), /H\ 8. 32 (s, 1 H), 8.07 (d, J= 7.9 Hz, 1 H), 7.98 (s, 1 H), 61 t 9-Boc-CO2H 60 I-1 7. 87 (m, 5 H), 7. 63 (d, J= 8. 9 Hz, 2 H), 7.38 (m, 2 H), 0 7.15 (d, J= 3.0 Hz, 1 H), 6.67 (m, 1 H), 3.57 (s, 3 H), 1. 45 (s, 9 H) ; MS (ESI) : 582.4 'H NMR (DMSO-d6) : b 10.56 (s, 1 H), 9.02 (br s, 1 H), 8. 35 (d, J= 1. 7 Hz, 1 H), 8.18 (dd, J= 1. 9 and 6.0 Hz, 1 H), 7. 88 (d, J= 9.0 Hz, 2 H), 7.80 (d, J= 1. 3 Hz, 1 H), 7.71 (dd, J= 1. 7 and 6.2 Hz, 1 H), 7.63 (d, J= 8.9 Hz, 2 66-CH=CH2-Boc-CO2MEM 59 D-3 H), 7.50 (d, J= 8.3 Hz, 1 H), 7.32 (d, J= 8. 1 Hz, 1 H), 6.89 (dd, J= 10. 7 and 17.7 Hz, 1 H), 6.04 (d, J= 17. 4 Hz, 1 H), 5.54 (s, 2 H), 5.43 (d, J= 11. 7 Hz, 1 H), 3.82 (t, J=4. 5Hz, 2H), 3.57 (s, 3 H), 3.48 (t, J=4. 5Hz, 2 H), 3.22 (s, 3 H), 1.44 (s, 9 H); MS (ES+) : 632.1 Cpd. Starting Method No. -R -R' -R'' From Used Analytical Data 1H NMR (DMSO-d6): # 10.49 (s, 1 H), 8.99 (br s, 1 H), 8.31 (s, 1 H), 8.07 (d, J = 8.3 Hz, 1 H), 7.87 (d, J = 9.0 Hz, 2 H), 7.77 (m, 2 H), 7.66 (m, 3 H0, 7.38 (d, J = 7.7 67 -CH=CH2 -Boc -CO2H 66 I-1 Hz, 1 H), 7.29 (d, J = 7.7 Hz, 1 H), 6.88 (dd, J = 10.7 and 17.7 Hz, 1 H0, 6.03 (d, J=17.4 Hz, 1 H), 5.41 (d, J= 10.9 YHz, 1 H), 3.56 (s, 3 H0, 1.43 (s 9 H); MS (ES-): 542.1 Cpd. _R-Rl Starting Method Analytical Data No. From Used No. From Used 'H NMR (DMSO-d6) : 8 10. 57 (s, 1 H), 8.92 (s, 1 H), 8.64 (t, J= 5.4 Hz, 1 H), 8.24 (d, J= 2.0 Hz, 1 H), 8.02 (dd, J= 2.0 and 7.9 Hz, 1 H), 7.98 (s, 1 H), 7.88 (m, 3 H) 7.84 (s, 1 H), 7.64 (d, J= 62a-CH3 oCH3 61 A-4 8.9 Hz, 2 H), 7.42 (d, J= 7. 9 Hz, 1 H), 7.36 (d, J= 7. 9 Hz, 1 H), 7.14 (d, J= 3.0 Hz, 1 H), 6.67 (m, 1 H), 3.55 (s, 3 H), 3.26 (m, 2 H), 1.50 (m, J= 7. 4 Hz, 2 H), 1.43 (s, 9 H), 1. 32 (m, J= 7. 4 Hz, 2 H), 0.89 (t, 3 H); MS (ES-) : 639.5 62b-CH3 61 A-4 MS (ES+) : 625.5 62c-CH3 \/% CH2 61 A-4 MS (ES+) : 623.4 62d-CH3 61 A-4 MS (ES+) : 687.4 CH3

Cd., Starting Method No. From Used CH, 62e-CH3 H 61 A-4 MS (ES+) : 625. 4 CH 62f-CH3 CH3 61 A-4 MS (ES+) : 653. 5 CH, CH3 62g-CH3 \ 61 A-4 MS (ES+) : 653.5 CH3 62h-CH3 61 A-4 MS (ES+) : 667. 3 0 CH3 62i-CH3 CH3 61 A-4 MS (ES+) : 681.5 CH3 ß i 61 A-4 MS (ES+) : 637. 3 OH 62k-CH3 61 A-4 MS (: ESt) : 640.3 CH3 621-CH3 61 A-4 MUS (EST : 665.4 Cpd.-,-,, Starting Method Analytical Data No. From Used No. From Used" 62m-CH3 sCH3 61 A-4 MS (ES+) : 597. 3 CH3 62n-CH3 \ 61 A-4 MS (ES+) : 639.4 3 62o-CH3 61 A-4 MS (ES+) : 695.4 (M+Na) + 0 62p-CH3 CF3 61 A-4 MS (ES-): 665.4 62q-CH3 CH3 61 A-4 MS (ES+) : 653.4 62r-CH3 CH3 61 A-4 MS (ES+) : 567.3 CH3 62s-CH3/XSCH3 61 A-4 MS (ES+) : 667.5 CH3 CH3 62t-CH3 pg 61 A-4 MS (ES+) : 641. 3 62u-CH3 OH 61 A-4 MS (ES+) : 655.3 Cpd. _R _R, Starting Method Analytical Data *--R-R'",,, AnaIyttcatData No.From Used 0 62v-CH3 61 A-4 MS (ES+) : 663.1 62w-CH3 61 A-4 MS (ES-) : 577.2 62x-CH3 61 A-4 MS (ES+) : 679.2 61 A-4 MS (ES+) : 621.1 62z-CH3 DCH3 61 A-4 MS (ES+) : 611.1 OH 62aa-CH3 <\°H 61 A-4 MS (ES+) : 657.1 62ab-CH3 61 A-4 MS (ES+) : 659. 1 62ac-CH361 A-4 MS (ES+) : 679. 3 Cpd., Starting Method No From Used OH 62ad-CH3 61 A-4 MS (ES) : 695.3 o 0 62ae-CH3 61 A-4 MS (ES+) : 651. 3 CH3 62af-CH3 NHR'=N~cH3 61 A-4 MS (ES) : 679.4 Cpd. _R _R, Starting Method Analytical Data '-R-R' °, , AnalyttcalData No. From Used 'H NMR (DMSO-d6): 6 12.80 (s, 1 H), 9.09 (s, 2 H), \O CH 8. 91 (s, 2 H), 8.57 (m, 1 H), 8.15 (s, 1 H), 7.91 (s, 1 H), O CHs \//3 I-2 S 7. 80 (m, 3H), 7.67 (m, 4 H), 7.20 (m, 2 H), 7.07 (s, 1 H), 6. 63 (s, 1 H) 3. 21 (m, J= 5. 9 Hz, 2 H), 1.46 (m, J= 7.4Hz, 2H), 1.28 (m, J=7. 4Hz, 2H) 0.86 (t, J=7. 4 Hz, 3 H); MS (ES+) : 525. 3 'H NMR (DMSO-d6) : 8 12. 76 (s, I H), 9.10 (s, 2 H), /o H 8. 82 (s, 2 H), 8. 59 (m, 1 H), 8. 20 (s, 1 H), 7. 95 (s, 1 H), 64b'62b I-2, S 7.83 (m, 3 H), 7.70 (s, 4 H), 7.25 (m, 2 H), 7.10 (s, 1 H), 6. 65 (s, 1 H), 3.20 (q, J = 6. 0 Hz, 2 H), 1.51 (m, J = 7. 4 Hz, 2 H), 0.87 (t, J= 7.4 Hz, 3 H); MS (ES+) : 511. 2 'H NMR (DMSO-d6): 8 12.84 (s, 1 H), 9.11 (s, 2 H), "o 8. 84 (m, 2 H), 8.26 (m, 1 H), 7.94 (m, 2 H), 7.83 (m, 3 64c 2 62c 1-2, S H), 7.71 (s, 4 H), 7.28 (m, 2 H), 7.12 (s, 1 H), 6.65 (s, 1 H), 5. 87 (m, 1 H), 5.15 (d, J=17. 2Hz, 1H), 5.07 (d, J 10.3 Hz, 1 H) 3.88 (t, J= 5.2 Hz, 2 H); MS (ES+) : 509.2

Cpd.-R-R, Starting Method Analytical Data No. From Used No. From Used \ lH NMR (DMSO-d6) : â 12.78 (s, 1 H), 9.11 (m, 2 H), 64d 62d I-2, S 8. 85 (s, 2H), 8.22 (s, 1H), 7.93 (s, 1H), 7.83 (m, 3H), 7. 68 (s, 4 H), 7. 19 (m, 3 H), 7.10 (m, 5 H), 6.65 (s, 1 H), CH3 4.41 (s, 2 H), 2.27 (s, 3 H); MS (ES+) : 573. 3 'H NMR (DMSO-d6) : 8 12.82 (s, 1 H), 9.11 (s, 2 H), zozo 3 8.86 (s, 2 H), 8. 39 (d, J= 7.7 Hz, 1 H), 8.24 (s, 1 H), 64e 62e I-2, S 7.95 (s, 1 H), 7.90 (m, 1 H), 7.84 (m, 2 H), 7.71 (s, 4 H), CH3 7.28 (m, 2 H), 7.11 (m, 1 H), 6.65 (s, 1 H), 4.08 (m, J= 6.9 Hz, 1 H), 1.14 (d, J= 6.9 Hz, 6 H) ; MS (ES+) : 511. 3 CH 3'H NMR (DMSO-d6) : 5 13.28 (br s, 1 H), 9.05 (m, 2 H), 8. 84 (s, 2 H), 8.46 (m, 1 H), 7.99 (s, 1 H), 7.88 (s, 1 H), 64f \/CH3 62f I-2, S 7.77 (m, 2 H), 7.63 (m, 5 H), 7.07 (m, 2 H), 6.96 (m, 1 H), 6.63 (s, 1 H), 3.16-2.96 (m, 2 H), 1.65-1.03 (m, 3 H), 0.85 (m, 6 H) ; MS (ES+) : 539.3 'H NMR (DMSO-d6) : 8 13. 37 (s, 1 H), 9.06 (s, 2 H), CH 3 8. 84 (s, 2 H), 8. 47 (m, 1 H), 8.00 (s, 1 H), 7.88 (s, 1 H), 0 7. 78 (m, 2 H), 7. 70 (m, 5H), 7.08 (m, 2H), 6.97 (s, 1 7.78 (m, 7.70 (m, g >\ CH3 g, H), 6.63 (s, 1 H), 3.22 (m, 2 H), 1.58 (m, J= 6. 0 Hz, 1 H), 1. 38 (m, J= 6.9 Hz, 2 H), 0.87 (d, J= 6.9 Hz, 6 H) ; MS (ES+) : 539. 3 1H NMR (DMSO-d6) : 5 12.71 (br s, 1 H), 9.13 (s, 1 H), gPo 8. 75 (m, 3 H), 8.31 (m, 1 H), 7.97 (m, 2 H), 7.86 (m, 2 \/</H), 7.73 (m, 4H), 7.64 (m, 2H), 7. 33 (m, 2H), 7.13 (m, 64h . %'' '62h I-2, S 1 H), 6. 67 (m, 1 H), 3. 98 (m, 1 H), 3.77 (q, J= 6. 9 Hz, 1 H), 3.62 (q, J=6. 9Hz, 1 H), 3.29 (m, 2 H), 1.86 (m, 3 H), 1.59 (m, 1 H); MS (ES+) : 553.3 Cpd. _R _R, Starting Method Analytical Data No From Used No. From Used" 'HNMR (DMSO-d6): 6 12.81 (br s, 1 H), 9.13 (s, 2 H), 2 H) 7.96 (m, 2 H), 7.86 (m, 2 w CH 3 8. 85 (s, 2 H), 8. 26 (m, 2 H), 7.96 (m, 2 H), 7. 86 (m, 2 64i \/62i I-2, S H), 7.74 (m, 7. 32 (m, CH3 I H), 3. 99 (m, 1 H), 1.5-0.85 (m, 14 H); MS (ES : 567. 3 'H NMR (DMSO-d6) 6 13.74 (br s, 1 H), 9.07 (s, 2 H), 8. 92 (s, 2 H), 8.62 (t, J= 5.6 Hz, 1 H), 8.03 (s, 1 H), 7.89 64j 62j 1-2, S (d, J = 1. 7 Hz, I H), 7.79 (m, 2 H), 7.64 (m, 4 H), 7.10 (m, 3 H), 6.99 (d, J= 8.5 Hz, 1 H), 6.64 (m, 1 H), 3.08 (t, J= 6. 0 Hz, 2 H), 1.00 (m, 1 H), 0.40 (m, 2 H), 0.20 (m, 2 H) ; MS (ES+) : 523.4 OH'H NMR (DMSO-d6): 8 9.12 (s, 2 H), 8.88 (s, 2 H), 8.52 1 H) 7. 92 (m, 2 H), 7.81 (m, 3 H), 64k \=2\ w\CH3 62k S 7. 67 (m, 4 H), 7. 14 (m, 3 H), 6.66 (m, 1 H), 4.75 (d, J= 64k Cg3 62k I-2, S 7.67 (m, 7.14 m, 4. 5 Hz, 1 H), 3.77 (m, 1 H), 3.17 (m, 1 H), 1.04 (d, J= 6.0 Hz, 3 H); MS (ES+) : 527.2 'H NMR (DMSO-d6) : 8 13.91 (br s, 1 H), 9.07 (s, 2 H), 8. 90 (s, 2 H), 8.29 (d, J=8. 1Hz, lH), 8.00 (s, 1H), 641 621 I-2, S 7.89 (m, 1 H), 7.78 (m, 2 H), 7.64 (m, 5 H), 7.08 (m, 2 H), 6.96 (d, J= 7.7 Hz 1 H), 6.64 (m, 1 H), 3.71 (m, 1 H), 1.82-1.03 (m, 10 H) p; MS (ES+) : 551. 33 'H NMR (DMSO-d6) : 8 13.87 (br s, 1 H), 9.07 (s, 2 H), g\0 8. 90 (s, 2 H), 8.48 (m, 1 H), 7.99 (s, 1 H), 7.89 (m, 1 H), 64m \=t 62m I-2, S 7.79 (m, 2H), 7.62 (m, 5H), 7.10 (m, 2H), 6.97 (d, J= CH3 7.9 Hz 1 H), 6.64 (m, 1 H), 2.73 (d, J= 4.5 Hz, 3 H); MS (ES+) : 483.2 Cpd. _R _R, Starting Method alytical Data -R-R ° . AnaIyttcatData No. From Used 'H NMR (DMSO-d6) : 5 9.08 (s, 2 H), 8.85 (s, 2 H), 8.26 eo (d, J= 8. 7 Hz, 1 H), 8.07 (s, 1 H), 7.91 (s, 1 H), 7.80 (m, cH3 2 H), 7.67 (m, 5 H), 7.09 (m, 3 H), 6.65 (m, 1 H), 3.89 64n 62n I-2, S =t\ CH3, (m, J= 7. 0 Hz, 1 H), 1.49 (m, J= 6. 9 Hz, 2 H), 1.10 (d, J= 6.6 Hz, 3 H), 0.85 (t, J= 7. 2 Hz, 3 H); MS (ES) : 525.2 IH NMR (DMSO-d6): 6 9. 19 (m, 2 H), 9.10 (s, 2 H), 8. 82 (s, 2 H), 8.19 (m, 1 H), 7. 94 (s, 1 H), 7. 83 (m, 2 H), 640 7. 68 (m, 4 H), 7. 33-7. 10 (m, 8 H), 6.66 (m, 1 H), 4.45 (d, J= 5.7 Hz, 2 Hz); MS (ES+) : 559.2 lH NMR (DMSO-d6) : 8 9.22 (m, 2 H), 9.09 (s, 2 H), 64p eo CF3 62p 1-2, S 8, 81 (s, 2 H), 8.17 (m, 1 H), 7.95 (s, 1 H), 7.82 (m, 2 H), 7. 68 (m, 4H), 7.16 (m, 4 H), 6.66 (m, 1 H), 4.06 (m, 2 H) ; MS (ES+) : 551.22 'H NMR (DMSO-d6) : 8 9.10 (s, 2 H), 8.86 (s, 2 H), 8.56 eo (m, 1 H), 8.13 (m, 1 H), 7.93 (s, 1 H), 7.82 (m, 2 H), 64q CH3 62q I-2, S 7.67 (m, 5 H), 7.15 (m, 3 H), 6.66 (m, 1 H), 3.19 (m, 2 H), 1.50 (m, 2 H), 1.28 (m, 4 H), 0.87 (t, J= 7.0 Hz, 3 H); MS (ES+) : 539. 3 4\0 IH NMR (DMSO-d6) : 8 9. 09 (s, 2 H), 8.90 (m, 2 H), 64r CH3 62r I-2, S 8. 15 (m, 2 H), 7.93 (s, 1 H), 7.81 (m, 3 H), 7.68 (m, 4 H), 7.13 (m, 3 H), 6.66 (m, 1 H), 3.83 (m, 1 H), 1.47 (m, 4 H), 1.25 (m, 4 H), 0.83 (m, 6 H); MS (ES+) : 567. 3 Cpd.-R-Rl Starting Method Analytical Data -R-R ° . Anatyttca! Data No. From Used 'H NMR (DMSO-d6) : 8 9.08 (s, 2 H), 8.86 (s, 2 H), 8.48 64s H3 62s I-2, S 7. 65 (m, 1 H), 7.79 (m, 2 H), 5 I 7. 12 (m, 2 H), 7.12 (m, 2H), H), 6.65 (m, 1 CH 3 H), 3. 22 (m, 2H), 1.42 (t, J=8. 2Hz, 2H), 0.91 (s, 9H) ; MS (ES+) :553.4 'H NMR (DMSO-d6) : 6 13.61 (br s, 1 H), 9.07 (s, 2 H), 9. 00 (s, 2 H), 8.52 (t, J= 5. 5 Hz, 1 H), 8.02 (s, 1 H), 7.90 64t pg 62t I-2, S d J-1. 9 Hz, 1 H), 7. 79 (m, 2 H), 7. 64 (m, 5 H), 7. 10 (m, 2 H), 7. 00 (d, J = 7. 7 Hz, I H), 6. 64 (m, 1H), 4.47 (t, J= 5. 3 Hz, 1 H), 3.43 (m, 2 H), 3.27 (m, 2 H), 1.64 (qui, J= 6. 8 Hz, 2 H) ; MS (ES+) : 527. 23 'H NMR (DMSO-d6) : 8 12. 7 (br s, 1 H), 9.09 (s, 2 H), \/8. 91 (s, 2 H), 8.57 (m, 1 H), 8.11 (s, 1H), 7. 92 (d, J= 64u OQ-,, OH 62u 1-2, S 1. 9 Hz, 1 H), 7.81 (m, 3H), 7.67 (m, 5H), 7.14 (m, 2 H), 6.66 (m, 1 H), 4.40 (t, J=5. 3Hz, lH), 3.39 (m, 2 H), 3.22 (m, 2 H), 1.48 (m, 4 H) ; MS (ES+) : 541.34 'H NMR (DMSO-d6) : 8 9. 16-8.89 (m, 4 H), 8.16 (m, 1 64 \/lE > 62v I2 S H), 7. 93 (s, 1H), 7.81 (m, 3 H), 7.67 (m, 4H), 7.56 (s, 1 H), 7. 15 (m, 5 H), 6.65 (m, lH), 6. 38 (m, lH), 6. 26 (m, 1 H), 4.42 (d, J=4. 9 Hz, 2 H) ; MS (ES+) : 549.27 'H NMR (DMSO-d6) : 8 11.59 (br s, 1 H), 9. 14 (s, 2 H), 8. 98 (s, 2 H), 8. 70 (t, J= 5. 7 Hz, 1 H), 8.24 (s, 1 H), 7.99 64w \ _/<N a 62w I-2 S (m, 2 H), 7. 87 (m, 3 H), 7.71 (m, 3 H), 7.36 (s, 1H), 7. 27 (m, 2 H), 7.10 (m, 2 H), 6.67 (m, lH), 4.07 (t, J= 6.9 Hz, 2 H), 3.24 (q, J=6. 5Hz, 2 H), 1.98 (qui, J= 6. 7 Hz, 2 H); MS (ES+) : 577.17 Cpd.-R-RI Starting Method Analytical Data No.From Used 'H NMR (DMSO-d6) : 5 13.72 (br s, 1 H), 9.13 (s, 2 H), 9. 06 (s, 2H), 8.50 (t, J=5. 7Hz, lH), 8.00 (d, J=1. 3 . 0 r Hz, 1 H), 7.89 (d, J= 1.9 Hz, 1 H), 7.78 (m, 2 H), 7.62 (m, 4 H), 7.08 (m, 2 H), 6.96 (d, J= 7. 9 Hz, 1 H), 6.64 (m, 1 H), 3.04 (t, J = 6.5 Hz, 2 H), 1. 72-1.43 (m, 6 H), 1. 25-1. 08 (m, 3 H), 0.88 (m, 2 H); MS (ES+) : 565.25 \o IH NMR (DMSO-d6) : 5 9.16-8.87 (m, 4 H), 8.09 (s, 1 64y 0 C', 62y 1-2, S H), 7. 91 (s, 1 H), 7.80 (m, 2 H), 7.65 (m, 5 H), 7.12 (m, 5 H), 6.65 (m, 1 H), 4.01 (m, 2 H), 3.10 (m, 1 H) ; MS (ES+) : 507. 2 'HNMR (DMSO-d6) : 6 9. 10 (s, 2 H), 8.97 (s, 2 H), 8.59 \ _/\/CH3 (t, J= 5.7 Hz, 1 H), 8.13 (s, 1 H), 7.93 (s, 1 H), 7.80 (m, 64z 62z 1-2, S 3H), 7.68 (m, 4H), 7.16 (m, 4H), 6.65 (m, 1 H), 3. 26 (qui, J= 6.0 Hz, 2 H), 1.10 (t, J= 7. 2 Hz, 3 H); MS (ES+) : 497.2 OH'H NMR (DMSO-d6) : 8 14.1 (br s, 1 H), 9.08 (s, 2 H), OH 8. 79 (s, 2 H), 8.45 (m, 1 H), 8.01 (s, 1 H), 7.90 (s, 1 H), 'OH 64aa 62aa 1-2, S 7. 79 (m, 3 H), 7.63 (m, 5 H), 7.09 (m, 2 H), 6.98 (m, 1 H), 6.65 (m, 1 H), 4.80 (d, J= 4.7 Hz, 1 H), 4.56 (t, J= 6.8 Hz, 1 H), 3.60 (m, 1H), 3. 32-2. 90 (m, 3 H) ; MS (ES+) : 543.2 /=\ IH NMR (DMSO-d6) : 8 10.34 (s, 1 H), 9.07 (s, 2 H), 64ab 62ab 1-2, S 8. 85 (s, 2 H), 8. 18 (s, 1 H), 7.93 (s, 1 H), 7.80 (m, 6 H), 7. 66 (m, 4 H), 7. 34 (m, 2 H), 7.11 (m, 4 H), 6.65 (m, 1 H) ; MS (ES+) : 545.2 Cpd. _R _R, Starting Method Analytical Data No. From Used No. From Used" 1H NMR (DMSO-d6) : 8 9.07 (m, 4 H), 8. 38 (d, J= 8. 5 Hz, 1 H), 8.10 (s, 1H), 7.92 (s, 1H), 7. 84-7. 62 (m, 7 H), 64ac 62ac I-2, S 7. 11 (m, 3 H), 6.66 (m, 1 H), 3.94 (m, 1 H), 1.88-1. 35 (m, 12 H) ; MS (ES+) : 565. 3 'H NMR (DMSO-d6) : 8 13. 71 (m, 2 H), 9.36-8.57 (m, 4 H), 8.50 (m, 1 H), 7.98 (s, 1 H), 7.89 (s, 1 H), 7.78 (2 64ad \H 62ad I-2, S H), 7. 61 (m, 5H), 7.08 (m, 2 H), 6.95 (d, J=7. 9Hz, l H), 6.63 (m, 1 H), 3.19 (m, 2 H), 2.16 (t, J= 7. 2 Hz, 2 o H), 1.48 (m, 4H), 1.28 (m, 2 H); MS (ES-): 581.2 'H NMR (DMSO-d6) : 8 9. 12 (s, 2 H), 8.89 (s, 2 H), 7.91 (m, 1 I, 7.81 (m, 2H), 7.70 (d, J=8. 7Hz, 2H), 7.62 /O NHR =N) 62 I 2 S (d, J=8. 9Hz, 2H), 7. 48 (m, 1H), 7.22 (m, 2 H), 7.11 (d, J = 3. 4 Hz, 1 H), 7. 05 (d,. I = 7. 2 Hz, 1 H), 6.65 (m, 1 H), 3.53 (m, 2 H), 3.08 (m, 2 H), 1.62-1.21 (m, 6 H); MS (ES+) : 537.20 1H NMR (DMSO-d6): 8 12. 81 (br s, 1 H), 9.13 (s, 2 H), 0 8. 82 (s, 2 H), 7.95 (s, 1H), 7.85 (m, 2H), 7.71 (m, 5H), 64af NHR =-N 62af I-2, S 7.43 (m, 1 H), 7.29 (m, 2 H), 7.13 (m, 1 H), 6.67 (m, 1 H), 3.49-2.97 (m, 4 H), 1.67-1.37 (m, 2 H), 1.. 08 (m, 1 H), 0.90 (m, 3 H), 0.61-0.26 (m, 4 H) ; MS (ES+) : 565. 3 Cpd.-R-Rv Starting Method Analytical Data T-R-R TT AjiatyttcatData No. From Used CH3 H NMR (DMSO-d6, D20) : 8 13.87 (br s, 1 H), 9.56 (m, 2 H) 9. 21 (s, 1 H), 8.74 (s, 1 H), 8.47 (m, 1 H), 7.97 (m, 1 H), 7.88 (s, 1 65 \/je 61 A-4, I-2, S H), 7.78 (m, 3H), 7.58 (m, 7H), 7.09 (m, 3H), 6.96 (m, 1H), 0 CH3 6.65 (m, 1 H), 3. 14 (m, 4 H), 1.77-0.80 (m, 18 H) ; MS (ES+) : 609.4 'H NMR (DMSO-d6) : 8 13.80 (br s, 1 H), 9.91 (s, 1 H), 9.41 (s, 1 71 \< 67 A 4 I-2 S H), 8. 63 (m, 2 H), 8.07 (s, 1 H), 7.98 (s, 1 H), 7.60 (m, 8 H), 6.90 (m, 3 H), 5.94 (d, J= 17. 7 Hz, 1 H), 4.37 (m, 1 H), 4.16 (m, 1 H), 2. 41-1.58 (m, 12 H) ; MS (ES+) : 537.4 'H NMR (DMSO-d6): 8 9.76 (s, 1 H), 9.41 (s, 1 H), 8.95 (s, 1 H), 8. 53 (m, 1 H), 8.07 (s, 1 H), 7.65 (m, 8 H), 7.08 (m, 2 H), 6.85 71b-CH=CH2 67 A-4, I-2, S (dd, J= 10.9 and 17.7 Hz, I H), 6.92 (m, 3 H), 5.97 (d, J= 17. 7 Hz, 1 H), 5.37 (d, J=10. 9 Hz, 1 H), 2.84 (m, 1 H), 2.70 (m, 1 H), 0.98-0.51 (m, 8H) ; MS (ES+) : 509. 4

Cpd., Starting Method No. From Used No. From Used' 'H NMR (DMSO-d6) : 8 12.51 (br s, 1 H), 9.59 (s, 1 H), 9.22 (s, 1 H), 8. 79 (s, 1 H), 8.58 (t, J= 5.5 Hz, 1 H), 8.17 (s, 1 H), 7.67 (m, 71c-CH=CH2 DCH3 67 A-4, I-2, S 8 H), 7.12 (m, 2 H), 6.86 (dd, J= 10. 9 and 17. 7 Hz, 1 H), 5.98 (d, J= 17.7 Hz, 1 H), 5. 38 (d, J= 10. 9 Hz, 1 H), 3.27 (m, 4 H), 1.20 (t, J= 7.2 Hz, 1 H), 1.09 (t, J= 7.2 Hz, 1 H); MS (ES+) : 485.3 Cpd.--,, Starting Method.,..,-. No. From Used No. From Used' 68a-CH3 zCH3 67 A-4 MS (ES+) : 599.4 CH, 68b-CH3 CH3 67 A-4 MS (ES+) : 641.4 CH3 68c-CH3 67 A-4 MS (ES+) : 625.3 68d-CH3 CH2 67 A-4 MS (ES+) : 583. 3 CH3 68e-CH3 CH3 67 A-4 MS (ES+) : 585.3 CH3 CHEZ 68f-CH3 67 A-4 MS (ES+) : 599.4 -CH

Cpd.-R-R'Fron Method Analytical Data No. From Used 68g-CH3 vCF3 67 A-4 MS (ES+) : 625.2 68h-CH3 67 A-4 MS (ES+) : 619.2 68i-CH3 OH 67 A-4 MS (ES+) : 615.3 68j-CH3 67 A-4 MS (ES+) : 597.3 68k-CH3 \CH3 67 A-4 MS (ES+) : 557. 3 3 681-CH3 CH3 67 A-4 MS (ES+) :571.4 68m-CH3 67 A-4 MS (ES+) : 639.4 CHZ 68n-CH3 67 A-4 Characterized in the next step 680-CH3 CH3 67 A-4 MS (ESj : 613.5 Cpd. _R-R, Starting Method Analytical Data' No. From Used CH3 68p-CH3 \XCH3 67 A-4 MS (ES+) : 613.5 3 'CH3 68q-CH3 67 A-4 MS (ES+) : 641.5 CH3 68r 68r-CH3 NBBoe 67 A-4 MS (ES+) : 714.5 68s-CH3 {) 67 A-4 MS (ES+) : 611.4 68t-CH3 » < OH 67 A-4 MS (ES+) : 641.4 68u-CH3 67 A-4 MS (ES+) : 583. 3 J 68v-CH3 67 A-4 MS (ES+) : 597.4 68w-CH3 mOH 67 A-4 MS (ES+) : 587.4 c3 68x-CH3 \\CH 67 A-4 MS (ES+) : 613.5 CH3 Cpd.-R (Position with Starting Method No. Respect to Phenyl-R'-R"From Used Analytical Data - Ring) Ring) 74-OCH3 (3)-CHO-CH3 73 + 3a D-2 MS (ES) : 368. 2 75a-OH (3)-CHO-CH3 74 V-2, W MS (ES-) : 354.1 75b-OH (3)-CHO-Bn 74 V-1, H MS (ES-) : 430.2 76a-OSO2CF3 (3)-CHO-CH3 75a B-2 MS (ES+) : 488.1 -CHO-Bn 75b B-2 MS (ES-) : 562. 3; MS (ES+) : 76b-OS02CF3 (3) 586. 3 (M+Na) 77a-CH=CH2 (3)-CHO-CH3 76a D-3 MS (ES+) : 366.38 77b-OCH2CO2C2Hs (3)-CHO-Bn 75b Characterized in the next step _ _. MS (ES : 487. 3 ; MS (ES+) : 77c-oCH2CONH2 (3)-CHO-Bn 75b X + 51135 (M+Na) 77d X (3)-CHO-Bn 76b D-2 Characterized in the next step S MS (ES+) : 530. 3 (M+Na) +) ; MS --o (ES-) : 506. 3 (ES-):506.3

-R (Position with No. Respect to Phenyl-R'-R"Starting Method Analytical Data Rang) Rj'ng) 77f-XoX<cH3-CHO-Bn 75b X MS (ES+) : 496. 3 (M+Na) + 77f 75b 77g 0 CH 3 (3)-CHO-Bn 75b X MS (ES+): 482.4 (M+Na)" CH3 77h 0 CH3 (3)-CHO-Bn 75b X MS (ES+) : 510.4 (M+Na) + CH3 HNMR (CDCl3) : 8 9.59 (s, 1 H), 8. 39 (d, J = 2 Hz, 1 H), 8.03 (m, 2 H), 7.84 (d, J = 8. 9 Hz, 1 H), 7.35 (d, J = 8 Hz, 1 H), 7. 28 (m, 2 H), 7. 12 (m, 2 H), 6 : 93 (dd, J = 2.5 77i 0 (3)-CHO-Bn 75b x and 8. 8-Hz, I H), 6. 64 (d, J = 2. 5 Hz, 1 H), 6. 31 (t, J = 6 and 5 Hz, Hz, 1 H), 6.31 (t, J = 6 and 5 Hz, 1 H), 5.06 (m, 2H), 4.42 (t, J= 4.5 Hz, 2 H), 4.13 (m, 2 H), 3. 34 (t, J =6. 8 Hz, 2 H), 2.11 (s, 3 H), 1.94 (m, 1 H), 1.01 (d, J = 6.8 Hz, 6 H) 78a-CH=CH2 (3)-CO2H-CH3 77a E MS (ES-) : 380.1 78b-OSOsCF3 (3)-CO2H-Bn 76b E Characterized in the next step 78c-OCH2CO2C2HS (3)-CO2H-Bn 77b E Characterized in the next step 78d-OCHzCONH2 (3)-CO2H-Bn 77c E MS (ES) : 527 : 35 (M+Na) + -R (Position wits Cpd. Respect to Phenyl _Rt _R"Starting Method Analytical Data No. *-.."From Used' Ring) 78e g3 (3)-CO2H-Bn 77d E MS (ES+) : 536.4 (M+Na) + (3) 78f _ o < (3)-CO2H-Bn 77e E MS (ES-) : 522.3 78g-OCH3 (3)-CO2H-CH3 E MS (ES-) : 384.1 78h/CH3 (3)-CO2H-Bn 77f E MS (ES) : 488. 3 OCH3 (3)-COZH-Bn 77g E MS (ES-) : 474.4 CH3 78j °) (3)-C02H-Bn 77h E MS (ES-) : 502.4 CH3 78k OAc (3)-C02H-Bn 77i E Characterized in the next step 'HNMR (CDC13) : 8 10.47 (s, 1 H), 8.36 (d, J = 2 Hz, 1 H), 7.96 (dd, J = 2.2 and 7.7 Hz, 1 H), 7.68 (m, 2 H), 7.46 (m, 5 H), 7.23 (d, J = 8 Hz, 1 H), 7.12 (d, J = 8. 7 Hz, 90-OBn (5)-CHO-CH3 89 + 3a D-2 1 H), 6.73 (d, J = 7.2 Hz, 1 H), 5.23 (q, J = 11 and 15 Hz, 2 H), 3.67 (s, 3 H), 3.31 (t, J = 6. 8 Hz, 2H), 1.94 (m, 1H), 1.01 (d, J= 6.8 Hz, 6 H), MS (ES+) 468. 2 (M+Na) + (ES-) 444.2 Cpd-R (Position with Starting Method No. Respect o j henyl-R-R From Used Analytical Data Ring) Ring) 'HNMR (CDC13): 8 8.22 (s, 1 H), 7.83 (d, J = 7. 2 Hz, 1 H), 7.34 (m, 8 H), 7.02 (d, J = 8. 1 Hz, I H), 91-OBn(5)-CO2H-CH3 90 E 6. 75 (d, J = 7. 4 Hz, I H), 5. 16 (s, 2 H), 3.66 (s, 3 H), 3.21 (t, J = 6. 8 Hz, 2 H), 1.85 (m, 1 H), 0.94 (d, J = 6.8 Hz, 6 H), MS (ES+) 484.1 (M+Na)+ 92-OBn (5)-CO2MEM-CH3 91 F MS (ES+) : 572.2 (M+Na) + 93-OH (5)-COzMEM-CH3 92 G MS (ES+) : 482. (M+Na) + 94-OSO2CF3 (5)-CO2MEM-CH3 93 B-2 MS (ES+) : 614. 3 (M+Na) + 95a \ ('5)-COzMEM-CHg 94 D-3 MS (ES+) 562. 3 (M+Na) + s 96a ' (5)-COH-CH3 95a 1-1 MS (ES+) 452.1 (M+Na) + S 101-OCH3 (2)-CHO-CH3 100 + 3a D-2 MS (ES+) 370.1 102-OCH3 (2)-C02H-CH3 101 E MS (ES-) 384.2; MS (ES+) 386.2 108-OBn (2)-CHO-CH3 107 + 3a D-2 MS (ES+) : 446.2 109-OBn (2)-CO2H-CH3 108 E MS (ES-) : 460.1 -1t (Position with Cpd. Respect to Phenyl-R'-"R Starting Method Analytical Data Rang) Ring) " 'HNMR (CDC13-di) : 8 9.79 (s, 1 H), 8. 39 (d, J =1. 88 Hz, 1 H), 8.02 (t, J = 6. 0 Hz, 2 H), 7.59 (m, 2 H), 738 (d, J = 7. 9 Hz, 1 H), 131-H-C 8. 1 Hz, 30 + 3a D-, 7.22 (d, J = 8.1 Hz, 1 H), 630 (b, 1 H), 3.72 (s, 3 H), 3.36 (t, J = 6. 6 Hz, 2 H), 1.96 (m, 1 H), 1.02 (d, J = 6.8 Hz, 6 H), MS (ES+) : 340.1 'HNMR (DMSO-d6) : 8 12.28 (b, 1 H), 8.52 (d, J = 6.03 Hz, 1 H), 8.12 (s, 1 H), 7.86 (d, J = 8.1 Hz, 1 H), 7.74 (d, J = 7.74 Hz, 1 H), 132-H-CO2H-CH3 131 E 7. 41 (t, J = 8. 67 Hz, 1 H), 7 31 (t, J = 7. 9 Hz, 1 H), 7.12 (d, J = 8. 1 Hz, 1 H), 6.97 (d, J = 7. 5 Hz, 1 H), 3.39 (s, 3H), 2.92 (t, J=6. 0 Hz, 2 H), 1.66 (m, 1 H), 0.78 (d, J = 7.4 Hz, 6 H), MS (ES-): 354.1 NH 193a-H I \-CH 196a + D-7 MS (ES+) : 560.5 6a NH NH 193b-H CH3 L NHBoc _Cg3 19b + D_7 MS (ES+) : 574.5) o a 0 cud-R (Position wits CNPod. Respect to Phenyt-R'-R"Strng Method Analytical Data -Ring) From Used Ring) 194a-H NH2-CH3 193a S-2 MS (ES+) : 460.3 zozo NH 194b-H CH3 XNH2-CH3 193b S-2 MS (ES+) : 474.3 'iso O 'HNMR (DMSO-d6) : 8 8.79 (bs, 4 H), 8.63 (t, J = 6. 5 Hz, I H), NH 8. 35 (s, 1 H), 7.85 (d, J = 6 Hz, 1 H), 7.62 (d, J = 8. 2 Hz, 2 H), 7.26 195a-H 4\t NHz-H 194a I-2 (m, 5 H), 7. 06 (m, 1 H), 5. 0 (m, 2 I H), 3.09 (t, J=6. 2Hz, 2H), 1.86 (m, 1 H), 0.89 (d, J = 6. 6 Hz, 6 H); MS (ES-): 444.3 and (ES+) 446. 3 -R (Position wits Cpd. Respect to Phenyl-R'-R"Starting Method Analytical Data No.".."From Used" RtBg) 1HNMR (DMSO-d6/DCl) : 8 8. 24 (d, J = 1. 6 Hz, 1 H), 7.91 (dd, J = 7.7 and 1. 6 Hz, 1 H), 7.56 (d, J = 8.7 Hz, 1 H), 7.48 (d, J = 8. 7 Hz, NH 1 H), 7. 32 (t, J = 8 Hz, 1 H), 7.16 (m, 3 H), 6.91 (t, J = 7. 5 Hz, 1 H), 195b-H CH3 NH,-H 194b I-2 6.76 (d, J = 8.5 Hz, 1 H), 6.66 (d, J = 8.5 Hz, 1 H), 4.99 (m, 1 H), 0 2.92 (d, J = 6.9 Hz, 2 H), 1.68 (m, 1 H), 1.33 (d, J = 6 Hz, 1.2 H), 1.27 (d, J = 6 Hz, 1.8 H), 0.71 (d, J = 6. 5 Hz, 6 H); MS (ES-): 458.2 and (ES+) 460. 3 NH 200-H CH3 vNHBoc-CH3 199 + 6a D-7 MS (ES+) : 573.5 A N H -R (Position with Cpd-RRespect to Phenyl-R'_R"Starting Method Analytical Data %, _. 1HNMR (DMSO-d6/DCI) : b 8.49 (t, J = 5. 6 Hz, 1 H), 8.18 (d, J = 6. 9 Hz, 1 H), 7.84 (t, J = 7.8 Hz, 1 N H), 7. 23 (m, 4 H), 7. 01 (m, 2 H), 6. 82 (d, J ==7Hz, 1 H), 6.22 (d, J CH, f 1 [MHBoc ocTj iTj\i<'r) T-R 201-H H Tnn 17-8. 5Hz, lH), 6. 1-) (d, J-S.-) Hz, 1 H), 3. 95 (m, 1 H), 2. 85 (t, J N = 5.8 Hz, 1 H), 1.62 (m, 1 H), 1. 23 (s, 9 H), 1. 1 (d, J = 6. 7 Hz, 1.2H), 1.05 (d, J=6. 7Hz, 1.8 H), 0.67 (d, J = 6. 6 Hz, 6 H) ; MS (ES+) : 559.4 NH 202-H P JjJ -H 201 S MS (ES+) : 459. 3 JAN H NH 203-OBn (4) 0 NHBoc-CH3 45 R MS (ES+) : 679.4 AU H NH 204-OBn (4) o n Jk NHBoc-H 203 I-2 MS (ES) : 663.4 ans N H cud-R (Position with Starting Method Cpd. "., ., , ,, Starting Method...., . No.. Respect to Phenyl-R'-R From Used alytical Data Riz Ring) Con O 209a-H f-CHs 132 A-7 MS (ES-) : 454. 3 H H H IHNMR (DMSO-d6) : 8 10. 72 (s, 1 H), 8. 65 (d, J = 6. 03 Hz, 1 H), C N 8. 24 (s, 1 H), 8.03 (d, J = 8.1 Hz, o/W 1 H), 7.75 (m, 6 H), 7.40 (d, J = Jt J< 7. 90 Hz, 1 H), 7. 34 (d, J = 8. 1 Hz, 209b-CH=CH2 (4) H-CH3 30f A-7 1 H), 6.88 (q, J =11. 2 Hz, 1 H), 6. 04 (d, J = 7.5 Hz, 1 H), 5.41 (d, J=ll. lHz, lH), 3.55 (s, 3H), 3.10 (t, J = 6. 6 Hz, 2 H), 1.86 (m, 1 H), 0.88 (d, J = 6. 6 Hz, 6 H) ; MS (ES-): 480.3 'HNMR (DMSO-d6) : 8 10.12 (s, 1 H), 9. 37 (b, 1 H), 8.48 (t, J=6.1 Hz, 1 H), 8.05 (d, J=1.9 Hz, 1 H), NH 7. 85 (d, J=7.9 Hz, 1 H), 7.56 (d, J=7. 8 Hz, 1 H), 7.49 (d, J=7.9 Hz, 0vNOH 1 H), 7. 36 (s, 4 H), 7. 21 (d, J=7. 9 210b-CH=CH2 (4) \ H-CH3 209b Y Hz, I H), 7.10 (d, J=2. 8 Hz, 1 H), AN/9/6. 69 (m, 1 H), 5.84 (d, J=15. 5 Hz, g 1 H), 5.60 (b, 1 H), 5.22 (d, J=11. 4Hz, lH), 3.38 (s, 3H), 2.91 (t, J = 6 Hz, 2 H), 1.66 (m, 1 H), 0.71 (d, J = 6.8 Hz, 6 H); MS (ES+)515.40 -R (Position. with Cpd. ,, ., ,-, Starting Method.,,., . "Respect to Phenyl-R'-R" irr Analytical Data ring) Ring) 'HNMR (DMSO-d6) : 8 12.62 (bs, 1H), 10.24 (s, 1 H), 8.48 (t, J=5.65 Hz, 1 H), 8.15 (s, 1 H), 7.81 (d, J=10. 9 Hz, 1 H), 7.61 (s, NH 1 H), 7.50 (d, J=7.9 Hz, 1 H), 211b-CH=CH2 (4) p/N-oH H 210b I-2 7. 49 (s, 6H), 7. 16 (d, J=8. 1Hz, l 0 N-OH H), 7. 08 (d, J=8. 1 Hz, 1 H), 6. 72 H (m, I H), 5. 85 (d, J=13. 7 Hz, 1 AN H), 5.24 (d, J=l 1.5 Hz, 1 H), H 2. 93 (t, J = 6 Hz, 2 H), 1.68 (m, 1 H), 0.72 (d, J = 6. 8 Hz, 6 H) ; MS (ES+) 501.40, (ES-) 499.2 'H NMR (DMSO): 5 8.70 (t, J = 5.6 Hz, 1 H), 8.36 (d, J= 1. 7 Hz, 1 H), 8.07 (dd, J = 8. 1,1.9 Hz, 1 C N H), 7.42 (m, 4H), 7.09 (d, J= 5.5 </Hz, 1 H), 7.04 (d, J= 7.7 Hz, 1 212-CH=CH2 (4)-CH3 187a A-E-5 H), 6. 74 (dd, J = 17. 5, 10. 9 Hz, I H), 6. 49 (d, J= 8. 8 Hz, 2 H),5.79 H (d, J= 17.7 Hz, 1 H), 5.27 (d, J= 10.9 Hz, 1 H), 4.0 (t, J= 6.0 Hz, 2H), 3.62 (s, 3H), 3.11 (t, J= 6.2,2H), 1.86 (m, 1 H), 0.90 (d, J= 6. 6 Hz, 6 H) Cpd.-R (Position with No. Respect to Phenyl-R'-R"Starting Method Analytical Data Ring) 'HNMR (DMSO): 8 9.23 (s, 1 H), 8.71 (t, J= 6.2 Hz, 1 H), 8.36 (d, J= 1. 9 Hz, 1 H), 8.09 (dd, J = 7.9,1.7 Hz, 1 H), 7.49 (d, J = 7.9 Hz, 2 H), 7.40 (d, J= 8. 3 Hz, 1 11 H), 7. 32 (d, J=8. 8Hz, 2H),7.04 (d, J = 7.9 Hz, 1 H), 6.73 (dd, J= 213-CH=CH2 (4) N-OH-CH3 212 Y 17.7,11. 1 Hz, 1 H), 6.40 (d, J= 8. 5 Hz, 2 H), 6.33 (t, J=7. 0Hz, 1 H), 5.78 (d, J= 17. 7 Hz, 1 H), 5. 58 (b, 1 H), 5.26 (d, J= 11. 1 Hz, 1 H), 3.96 (m. 2 H), 3.64 (s, 3 H), 3.11 (t, J=6. 4Hz, 2H), 1.86 (m"1 H), 0.90 (d, J=6. 8Hz, 6 H) ; MS (ES+) : 501.3 1HNMR (DMSO) : 5 8.76 (t, J= 5.8 Hz, 1 H), 8. 37 (s, 1 H), 8.04 (d, J=87Hz, 1H), 7.39 (m, 5 H), 7.06 (d, J= 8.3 Hz, 1 H), 6.72 (dd, J= 17.9,11.3 Hz, 1 H), 6.43 214-CH=CH2 (4) N-OH-H 213 I-2 (d, J=8. 5Hz, 3H), 5. 76 (d, J= /\ >< 17. 9 Hz, 1 H), 5. 24 (d, J= 11. 1 H Hz, 1 H), 3.98 (m. 2 H), 3.11 (t, J H = 6. 6 Hz, 2 H), 1.86 (h, 7=6. 8 Hz, 1 H), 0.90 (d, J= 6. 8,6 H); MS (ES+) : 487.2 cud-R (Position wits Cpd. '.. ., ,- Starting Method.,,., . Cpd. Resp Ring) Y-R"From Method AnalyticalData Rang) Ring) 'HNMR (DMSO-d6): 8 8.68-8.60 (m, 1 H), 8.50 (d, J = 2. 4 Hz, 1 H), 7.90-7.80 (m, 1 H), 7.76-7.70 /\ + (m, 1 H), 7.56-7.50 (m, 1 H), p-ff NH2 7. 48-7.42 (d, J = 7.7 Hz, 1 H), I'7. 30-7. 22 (d, J = 7.9 Hz, 1 H), N \ 237 + 7.10-7.02 (d, J = 7.7 Hz, 1 H), 238-CH=CH2 (4) H-H lga -2 6. 90-6. 75 (dd, J 17, 11 Hz, 1 H), 6.5 (bs, 1 H), 5.92-5.80 (d, J = 17 Hz, 1 H), 5.40-5.30 (d, 11 Hz, 1 H), 4.50-4.20 (m, 2 H), 3.20- 3.10 (t, J=6. 6Hz, 2H), 2. 10- 1.88 (m, 1 H), 1.2-0.94 (d, J = 6. 6 Hz, 6 H); MS (ES+) 471.3 NH 256-H !) ''255+6a D-6 MS (ES+) : 573. 3 H H NH 257-H)] -H 256 I-2. S MS (ES : 459. 1 N H Cpd., Starting Method No. 1 R From Used AnalyticaI Data ms 79a-CH=CH2 (3)-CH3 78a J MS (ES+) : 499.2 79b-OSO2CF3 (3)-CH2C6Hs 78b J Characterized in the next step 79c-OCH2CO2C2Hs (3)-CH2C6H5 78c J Characterized in the next step 79d-OCH2CONH2 (3)-CH2C6H5 78d J MS (ES+) : 622.4; (ES-) 620.4 79e 4 S 9 (3)-CH2C6H5 78e J Characterized in the next step S 79f o, \-CHZC6H5 78f J Characterized in the next step (3)

| i.- Cpd., Starting Method No. From Used No. From Used' 'HNMR (DMSO-d6) : 8 10. 6 (bs, 1 H), 9.29-9.32 (bs, 1 H), 9.06 (bs, 1 H), 8.82-8.75 (t, J = 5.84 Hz, 1 H), 8.32 (d, J = -OCH3 (3) 1. 88 Hz, 1 H), 8.13 (d, J = 1.7 Hz, 1 H), 7.83 (s, 4 H), 7.78 (d, 79g-CH3 78g J J = 8. 67 Hz, 1 H), 7.50 (d, J = 7.9 Hz, 1 H), 7.20-7.15 (dd, J = 8.67,2.3 Hz, 1 H), 6.92 (d, J = 2.4 Hz, 1 H), 3.94 (s, 3 H), 3.64 (s, 3 H), 3.21-3.14 (t, J = 6 Hz, 2 H), 2.0-1.86 (m, 1 H), 1.0-0.94 (d, J = 6.5 Hz, 6 H); MS (ES+) 503. 3 79h \oCH3 (3)-Bn 78h J MS (ES+) : 607. 3 'O^CH3 (3)-Bn 78i J MS (ES+) : 593.4 CH3 79j ° ~t (3)-Bn 78j J MS (ES+) : 621.4 CH3 79k-O-CH2-CH2-OAc (3)-Bn 78k J MS (ES+) : 651.4 'HNMR (DMSO-d6) : 8 9.1 (s, 2 H), 8.87 (s, 2 H), 8.53 (t, J = 6 Hz, 1 H), 8.02 (s, 1 H), 7.64 (m, 7 H), 7.1 (s, 1 H), 6.98 (d, 80a-H 79a I-2 7. 4 Hz, 1 H), 6.80 (dd, J = 11 Hz, J = 17. 6 Hz, 1 H), 5.90 (d, J = 17. 6 Hz, 1 H), 5.35 (d, J = 12 Hz, 1 H), 3.03 (t, 6 Hz, 2 H), 1.83 (m, 1 H), 0.86 (d, J = 6.7 Hz, 6 H); MS (ES+) 485.2 IHNMR (DMSO-d6) : 5 10.37 (s, 1 H), 9.20 (m, 3 H), 8.72 (t, OH (3) J = 6 Hz, 1 H), 8.2 (s, 1 H), 8.85 (m, 6 H), 7.65 (d, J = 8 Hz, 1 80b-H 79b 79b I-2 H), 7.12 (d, 8 Hz, 1 H), 7.02 (dd, J = 2. 5 Hz, J = 8 Hz, 1 H), 6.60 (d, J = 2. 5 Hz, 1 H), 3.25 (t, J = 6. 5 Hz, 2 H), 2.0 (m, 1 H), 1.07 (d, J = 6.8 Hz, 6 H); MS (ES+) 475.2 Cpd.-R-RI Starting Method Analytical Data No. From Used No. From Used" 'H NMR (DMSO-d6) : 6 12.7 (2H, bs, 1 H), 9.01,8.87 (2 bs, 4 80c-OCH2CO2H (3)-H 79c I-2 H), 8. 36 (m, 1H), 7.83 (s, 1H), 7.44 (m, 6 H), 6.75 (m, 2H), 6. 31 (d, J=2. 2 Hz, 1H), 4.42 (s, 2H), 2.84 (m, 2H), 1.63 (m, 1H), 0.67 (d, J=6.5 Hz, 6H); MS (ES+): 533.4 'H NMR (DMSO-d6) : 5 9.13 (bs, 5H), 8.59 (t, J=6.28 Hz, 1H), 8.14 (d, J = 1. 7 Hz, 1H), 7.63 (m, 9H), 7.42 (s, 1H), 7.09 80d-OCH2CONH2 (3)-H 79d G (d, J = 7.5 Hz, 1H), 7.03 (dd, J = 2.5,12.7 Hz, 1H), 6.70 (d, J =2.5 Hz, 1H), 4.48 (s, 2H), 3.05 (t, J= 6.6 Hz, 2H), 1.83 (m, 1H), 0.87 (d, J=6.8 Hz, 6H); MS (ES+): 532.4 'H NMR (DMSO-d6) : 5 12.6 (1H, bs, COOH), 8.98,8.67 (2 -H 79e I-2 bs, 4H), 8.46 (m, 1H), 8.08 (m, lH), 7.76 (m, 1H), 7.53 (m, 6 /H), 7.39 (m, 2H), 7.06 (m, lH), 7.04 (m, 1H), 2.89 (m, 2H), 1. 66 (m, 1H), 0.69 (d, J=6.5 Hz, 6H); MS (ES+): 541.4 'HNMR (DMSO-d6) : 6 9.14 (d, J = 10 Hz, 4 H), 8.60 (t, J = 6 Hz, 1 H), 8.22 (bs, 1 H), 7.87-7.62 (m, 7 H), 7.47 (t, J = 8 Hz, 80f o/\ 3-H 79f I-2 2 H), 7.26 (t, 7 Hz, 1 H), 7.22 (m, 4 H), 6.70 (bs, 1 H), 3.09 (t, /\=/J = 6 Hz, 2 H), 1.83 (m, 1 H), 0.91 (d, J = 6.8 Hz, 6 H) ; MS (ES+)551.4 'HNMR (DMSO-d6): 8 9.13 (bs, 2 H), 8.78 (bs, 2H), 8.65 (t, J = 6 Hz, 1 H), 8.25 (bs, 1 H), 7.78 (m, 1 H), 7.76 (m, 5 H), 80g-OCH3 (3)-H 79g I-2 7.25 (s, 1 H), 7.17 (m, 1 H), 6.73 (bs, 1 H), 3.83 (s, 3 H), 3.10 (t, J = 6 Hz, 2 H), 1.80 (m, 1 H), 0.88 (d, J = 6. 8 Hz, 6 H) ; MS (ES+) 489.3 Cpd. _R _R, Starting Method Analytical Data No. From Used No. From Used" 80h \/CH3 (3)-H 79h I-2 MS (ES+) : 517.7 80i 0 CH3 (3)-H 79i 1-2 MS (ES) : 503.4; MS (ES-) : 501.4 \ CH3 \ GHs 80j o y (-H 79j I-2 MS (ES+) : 531.4; MS (ES-) : 529.4 CH3 IHNMR (DMSO-d6): 6 13.52 (bs, 1 H), 9.16 (bs, 2 H), 9.03 (bs, 2 H), 8.50 (t, J = 6 Hz, 1 H), 7.96 (d, J = 1.7 Hz, 1 H), 7. 56 (m, 6 H), 7.00 (dd, J = 2.5 and 8.5 Hz, 1 H), 6.90 (d, J = 80k _O-CH2-CH2-OH (3)-H 79k 1-2 8 Hz, 1 H), 6.48 (d, J = 2. 5 Hz, 1 H), 4.91 (t, J = 5. 5 Hz, 1 H), 4. 00 (t, J = 4.5 Hz, 2 H), 3.69 (q, J = 5.5 and 10 Hz, 2 H), 3.05 (t, J = 6. 8 Hz, 2 H), 1.80 (m, 1 H), 0.84 (d, J = 6. 8 Hz, 6 H); MS (ES+) : 519. 3, (ES-) 517.3 'HNMR (DMSO-d6) : 6 9.15 (bs, 3 H), 8.65 (t, J = 6 Hz, 1 H), 86a-CH (OH) CH20H (3) 8. 12 (s, 2 H), 7.82-7.56 (m, 7 H), 7.55-6.96 (m, 4 H), 5.5 (bs, a, 1 H), 4.90 (bs, 1 H), 4.65 (bs, 1 H), 3.10 (t, J=6Hz, 2H),. 1.90 (m, 1 H), 0.92 (d, J = 6.8 Hz, 6 H); MS (ES+) 519.3 'HNMR (DMSO-d6) : 6 8.82 (bs, 2 H), 8.68 (bs, 2 H), 8.40 (t, -CHZOH (3) J = 6 Hz, 1 H), 7. 88 (bs, 1 H), 7. 53 (m, 5 H), 7. 45 (d, 8 Hz, 1 86b-H 84 S, I-2 H), 7. 25 (d, J = 8 Hz, 1 H), 6. 81 (m, 2 H), 5. 22 (d, J = 5. 5 Hz, 1 H), 4.41 (d, J = 5. 5 Hz, 2 H), 2.88 (t, J = 6 Hz, 2 H), 1.65 (m, 1 H), 0.71 (d, J = 6.8 Hz, 6 H); MS (ES+) 489.2 Cd., Starting Method No. From Used No. From Used' 'HNMR (DMSO-d6-D20) : 8 13.7 (bs, 1 H), 8.32 (t, J = 6 Hz, I-2 1 H), 7.63-7.17 (m, 7 H), 6.72 (d, 7. 0 Hz, 1 H), 2.81 (t, J = 6 <30<L,-'\2\-7-fl OJ tji"--. \ <-\i v r wnn/irn+\ Hz, 2 H), 1.53 (m, 1 H), 0.64 (d, J = 6.8 Hz, 6 H) ; MS (ES) 503. 2 97a-CH3 96a J MS (ES+) : 569.2 s(5) 'HNMR (DMSO-d6) : 5 10.62 (s, 1 H), 9.15 (bs, 2 H), 8.82 (bs, 2 H), 8.67 (t, J = 6 Hz, 1 H), 8.25 (d, J = 2 Hz, 1 H), 7.99 ci 91 J (dd, J = 8.1 and 2 Hz, 1 H), 7.69 (q, 8.8 and 16.2 Hz, 4 H), 7. 44 (m, 3 H), 7.28 (m, 3 H), 6.89 (d, J = 7. 7 Hz, 1 H), 5.5 (s, 2H), 3. 6 (s, 3 H), 3.08 (t, J = 5. 8 and 6. 8 Hz, 2 H), 1.83 (m, 1 H), 0.87 (d, J = 6.8 Hz, 6 H); MS (ES-) 577.2, (ES+) 579.3 'HNMR (DMSO-d6): 8 13. 45 (bs, 1 H), 9.06 (s, 2 H), 8.99 (s, 2 H), 8.51 (t, J = 6 and 5 Hz, 1 H), 7.99 (s, 1 H), 7.62 (m, 5 98a-H 97a I-2 H), 7.47 (s, 1 H), 7.36 (m, 2 H), 6.99 (m, 4 H), 4.26 (s, 2 H), S (5) 3.02 (t, J = 6. 8 Hz, 2 H), 1.80 (m, 1 H), 0.86 (d, J = 6. 8 Hz, 6 H); MS (ES-) 553.2, (ES+) 555.2 IHNMR (DMSO-d6): 8 13.52 (bs, 1 H), 9.09 (bs, 2 H), 9.04 (bs, 2 H), 8.48 (t, J = 6 Hz, 1 H), 7.94 (s, 1 H), 7.61 (m, 4 H), . 98b-OBn (5)-H 97b I-2 49 (s, 1 H), 7. 46 (s, 1 H), 7. 34 (m, 5 H), 7.15 (d, J = 8. 2 Hz, 1 H), 7. 00 (d, J = 8. 2,1 H), 6.02 (d, J = 7.4 Hz, 1 H), 5.21 (s, 2 H), 3.01 (t, J = 6. 8 Hz, 2 H), 1.80 (m, 1 H), 0.85 (d, J = 6. 8 Hz, 6 H); MS (ES-) 563.2, (ES+) 565.2 Cpd. Starting Method No. From Used No. From Used IHNMR (DMSO-d6) : 8 9.85 (s, 1 H), 9.07 (s, 2 H), 8.98 (s, 2 H), 8.50 (t, J = 6 and 5 Hz, 1 H), 7.99 (d, J =1. 7 Hz, 1 H), 98c-OH (5)-H 98b G 7. 63 (m, 5 H), 7. 20 (t, J=8Hz, 2H), 6. 90 (d, J=7. 9Hz, l H), 6.49 (d, J=7. 2Hz, lH), 3. 21 (t, J = 6. 8 Hz, 2 H), 1.80 (m, 1 H), 0.85 (d, J = 6.8 Hz, 6 H); MS (ES+) 475.2; (ES-) 473. 2 103-OCH3 (2)-CH3 102 J MS (ES+) 503.1 'HNMR (DMSO-d6) : 5 9.08 (bs, 2 H), 8.80 (bs, 2 H), 8.52 (t, 104-OCH3 (2)-H 103 I-2 J-6 Hz, 1 H), 8. 02 (s, lH), 7. 64 (m, 5H), 7. 16 (m, 2H), 7. 03 (m, 2 H), 3.84 (s, 3 H), 3.03 (t, J = 6. 8 Hz, 2 H), 1.81 (m, 1 H), 0.86 (d, J = 6.8 Hz, 6 H); MS (ES-) 487.3, (ES+) 489. 3 110-OBn (2)-CH3 109 J MS (ES+) : 579.3 111-OH (2)-CH3 110 G MS (ES+) : 489. 3 126-OC2Hs (3)) both-CH3 118b J Characterized in the next step -OBn(4) - 'H NMR (DMSO-d6): 6 9.06-9.09 (m, 3H), 8.56-8.50 (m, 1H), 8.05 (s, 1H), 7.71-7.58 (m, 6H), 7.55-7.28 (m, 6H), 7.10- 127-OC2H5 (3-H 126 I-2 7.01 (m, IH), 6.63 (s, 1H), 5.19 (s, 2H), 4.05-3.97 (m, 2H), -OBn (4) J 3.05-3.01 (m, 2H), 1.86-1.77 (m, 1H), 1.29 (t, J=6. 7 Hz, 3H), 0. 87 (d, J=6. 8 Hz, 6H) H NMR (DMSO-d6) : 13.64 (br s, 1 H), 8.99 (br s, 2 H), 8.49 (t, J= 5. 1 Hz, 1 H), 7. 99 (s, 1 H), 7. 73-7. 56 (m, 5 H), 7. 32- -H 128 I-2, S 129 -CH (OH) CH3 (4) (m, I H), 3. 75 (s, 1H), 5. 17 (d, J=4. 3Hz, lH), 5. 01 129-CH (OH) CH3 (4) 8 I-, S (m, 1 H), 3. 75 (s, 3 H), 3. 03 (t, J= 6. 0 Hz, 1 H), 1. 81 (m, 1 H), 1.32 (d, J= 6.2 Hz, 3 H), 0.86 (d, J= 6.6 Hz, 6 H); MS (ES+) : 533. 4 (100% M+l) Cpd. -R (With Respexct to Starting Method No. Phenyl Ring) From Used Analytical Data 81 0-CH=CH2 (3) 79a R MS (ES-): 597.2 82 -CH(OH)CH2OH(3) 81 L MS (ES-1): 631.3 83 -CH=O (3) 82 M MS (ES+): 601.3 84 -CH2OH (3) 83 K MS (ES-1): 601.4 85 -CO2H (3) 83 E MS (ES-1): 615.3 128 -OCH3 N93) # both 124a R MS (ES+): 629.4 -CH=CH2 (4)

Cpd. Starting Method No. -R -R1 -R2 -R3 -R4 From Used Analytical Data 1HNMR (CDCl3): # 10.48 (s, 1 H), 7.42 -7.25 (m, 7 H), 7.00 (dd, J = 2 and .4 88 -Br -H -H -H -OBn 87 X Hz, 1 H), 5.19 (s, 2 H); IR (KBr) 1701, 1585, 1452, 1262, 1009 cm-1; MS (ES+) 313.0, 315.0 (M+Na)+ 1HNMR (CDCl3): # 10.61 (s, 1 H), 7.65 (d, J = 7.2 Hz, 1 H), 7.60 (t, J = 7.9 and 89 -B(OH)2 -H -H -H -OBn 88 T, U-1 7.2 Hz, 1 H), 7.41 (m, 5 H), 7.19 (d, J = 7.9 Hz, 1 H), 6.81 bs, 2 H), 5.20 (s, 2 H) 1HNMR (DMSO-d6): # 10.2 (s, 1 H), 100 -B(OH)2 -OCH3 -H -H -H 99 T, U-3 8.34 (s, 2 H), 7.92 (d, J=94 Hz, 1 H), 7.13 (m, 2 H), 3.92 (s 3 H); MS (ES-) 179.0 1HNMR (DMSO-d6): # 10.1 (s, 1 H), 107 -B(OH)2 -OBn -H -H -H 106 T, U-1 7.3-7.6 (m, 8 H), 5.3 (m, 2 H) 114a -Br -H -OCH3 -OH -H 113 Z MS (ES-): 229.0 and 231.0) 114b -Br -H -OC2H5 -OH -H 113 Z-1 MS (ES-): 242.9 and 244.9 114c -Br -H -OCH(CH3)2 -OH -H 113 Z-1 MS (ES-): 257.0 and 259.0 115a -Br -H -OCH3 -OBn -H 114a X MS (ES+): 321.0 and 323.0 115b -Br -H -OC2H5 -OBn -H 114b X MS (ES+): 335.0 and 337.0 115c -Br -H -OCH(CH3)2 -OBn -H 114c X MS (ES+): 349.0 and 351.0

l Cpd. _R _ _ _R3-R4 Starting Method alytical Data No. From Used 0 115d-Br-H \ <-OBn-H 115a AH Characterized in the next step o C (CH3) 3 116a-B (OH) 2-H-OCH3-OBn-H 115a T, U-1 Characterized in the next step 116b-B (OH) 2-H-OC2H5-OBn-H llSb T, U-1 Characterized in the next step 116c-B (OH) 2-H-OCH (CH3) 2-OBn-H 115c T, U-1 Characterized in the next step Cpd. Starting Method No. From Used Analytical Data 1HNMR (DMSO-d6); # 11.28 (s, 1 H), 9.31 (s, 2 H), 9.0 (s, 2 H), 8.88 (d, J = 11.30 Hz, 1 H), 8.82 (d, J = 1.88 Hz, 1 H), 8.25 (d, J = 1.88 Hz, 1 H), 8.18 (d, J = 1.88 Hz, 1 H), 112 111 I-2 8.04 (d, J = 8.47 Hz, 1H), 7.92 (m, J = 24.48 Hz, 2 H), 7.75 (m, J = 15.82, 1 H)M, 7.75 (m, J = 8.28 Hz, 1 H), 7.55 (m, J = 8.66 Hz, 1 H), 3.10 (m J = 12.6 Hz, 1 H), 2.5 (m, J = 3.5 Hz, 1 H), 1.8 (m, J = 19.9 Hz, 2 H), 0.88 (m, J = 6.6 Hz, 6 H).

Cpd. , ., Startmg Method.,.., , Cpd.-R-Rl-R"-Rtv 1 Starting Method Analytical Data No. From Used CH3 117a-CH3-OBn-CHO lX6a D-2 MS (ES) : 474.2 CH3 CH3 117b-C2H5-OBn-CHO 1CH3 lla6+b D-2 MS (ES) : 488.2 CH3 CI43 117c-CH (CH3) 2-OBn-CHO 3a+ D-2 MS (ES) : 502.3 c3 'HNMR (CDC13) : 6 9. 56 (s, 1 H), 8.34 (d, J=1. 7Hz, 1 H), 8.5 (s, 1 H), 8.01 (dd, J = 7.9 and 1.9 117d-C-OBn-CHO P D-2 '/-J'- 117d-CH3-OBn-CHO CH3 3b + D-2 Hz, 1 H), 7. 40 (m, 7 H), 6. 9 (s, 1 116a H), 5.24 (m, 2 H), 4.2 (m, l H), ."KCH 3 3.80 (s, 3 H), 3.52 (s, 3 H), 1.02 (d, J=7Hz, 6H) ; MS (ES+) : 484.3 (M+Na)

Cpd. Starting Method Analytical Data No. From Used" No. From Used 'HNMR (DMSO-d6) : 88. 43 (d, J IHNMR (DMSO-d6) : 6 8. 43 (d, J = 1. 65 Hz, 1 H), 8.31 (d, J = 8.66 Hz, 1), 8.12 (dd, J = 1. 69 Hz, 1H), 7.98 (s, 1H), 7.41 (d, J = 8 CH and 10 Hz, 1H), 7.19 (d, J = 8.1 117e-CH3-OBn-CHO C4 3c+ D-2 Hz, IH), 5. 20 (dd, 3 = 6. 2 Hz, 116a 1H), 3.98 (dd, J = 7.75 Hz, 3H), 3.94 (s, 3H), 3.42 (m, 3H), 3.32 (m, 3H), 3.19 (s, 3H), 2.5 (m, 3H), 2.0 (s, 4H), 1. 5 (m, 2H), 1.28 (m, 3H), 0.88 (d, J = 6. 59 Hz, 3H) ; MS (ES+) : 664. 3 IHNMR (CDC13) : 6 9.50 (s, 1 H), 8.40 (d, J = 2. 1 Hz, 1 H), 8.04 (dd, J= 8.1,2.1 Hz, 1 H), 7.57 (s, 1 H), 7.48 (m, 5 H), 7.38 (m, 5 117f-CH3-OBn-CHO H3 3d + D_2 H), 6. 67 (s, 1 H), 6. 50 (broad, 1 116a H),) 5. 27 (d, J=11. 9 Hz, 1 H), 5.22 (dd, J= 11. 7,1 H), 4.63, (m, 3H) 4.17 (m, 4 H), 3.92 (s, 3 H), 3.66 (s, 3 H) ; MS (ES-) : 488.3 1HNMR (CDCI3) : 8 9.50 (s, 1 H), 8.40 (d, J = 2. 1 Hz, 1 H), 8.04 (dd, J = 8. 1,2.1 Hz, 1 H), 7. 57 (s, 1 H), 7.48 (m, 2 H), 7.38 117g-CH3-OBn-CHO 116 D-2 (m, 3 H), 6.67 (s, 1 H), 6.50 (broad, 1 H), 5.27 (d, J= 11. 9 Hz, 1 H), 5.22 (dd, J= 11. 7,2 H), 4.17 (m, 2 H), 3.92 (s, 3 H), 3.66 (s, 3 H); MS (ES-) : 500 Cpd.-R-R'-R"-R."'StFarting MUeshedd Analytical Data No. From Used 'HNMR (CDC13): 6 9.56 (s, 1 H), 8.34 (d, J=1. 7Hz, 1 H), 8.01 (dd, J= 7. 9,1.9 Hz,'1 H), 7.57 (s, 1 H), 7.50 (dd, J= 7.2, 117h-CH3-OBn-CHO 3e+ D-2 1. 5, 2 14), 7. 40 (m, 4 H), 6. 67 (s, CH3 =2. 8Hz, 2H), 3. 92 (s, 3H), 3. 65 = 2.8 Hz, 2 H), 3.92 (s, 3 H), 3.65 (s, 3 H), 3.52 (m, 2 H), 1.65 (m, 2 H), 1.46 (m, 2 H), 0.99 (t, J = 7. 3 Hz, 3 H. IHNMR (CDC13) : 8 9.57 (s, 1 H), 8.37 (d, J=1. 9 Hz, 1 H), 8.03 (dd, J= 7. 9,1.9 Hz, 1 H), 7.58 (s, 1 H), 7.50 (d, J= 7.2 Hz, 3g+ 2H), 7.38 (m, 3H), 6.68 (s, 1 H), 117i-CH3-OBn-CHO 116a D-2 6.33 (broad, 1 H), 5.26 (d, J= 11. 5 Hz, 1 H), 5.21 (d, J=11. 9 Hz, lH), 3.92 (s, 3H), 3.65 (s, 3 H), 3.37 (dd, J=7. 2,5.3Hz, 2 H), 1. 09 (m, 1 H), 0.60 (m, 2 H), 0.32 (m, 2 H) ; MS (ES+) : 474.2 'H NMR (CDC13) : 6 9.55 (s, 1 H), 8.32 (d, J=1. 9Hz, 1H), 8.00 (dd, J= 1. 9 and 7.9 Hz, 1 3h + H), 7.59-7.30 (m, 7 H), 6.67 (s, 1 116a H), 5. 23 (m, 2 H), 4. 45 (q, J= 7. 0 Hz, 1 H), 3.91 (s, 3 H), 3.64 (s, 3 H), 2.21-1.46 (m, 8 H); MS (ES+) : 510. 3 (M+Na) + S Cpd.-1t'-R"From MUthedd Analytical Data No. From Used 'H NMR (CDC13) : 6 9. 56 (s, 1 H), 8. 35 (d, J= 1. 9 Hz, 1 H), 8.02 (dd, Y= 1. 9 and 7. 9 Hz, 1 3i + H), 7.58-7. 33 (m, 7 H), 6.68 (s, 1 11-l-CH3 116a H), 5. 24 (m, 2 H), 3.92 (s, 3 H), 3. 65 (s, 3 H), 3.56 (m, 2 H), 1.30 (t, J= 7.2 Hz, 3 H); MS (ES+) : 470.3(M+Na) 'H NMR (CDCI3) : 8 9.56 (s, 1 H), 8. 35 (d, J= l. 9 Hz, 1 H), 8. 02 (dd, J=1. 9 and 7. 9 Hz, 1 3j + H), 7. 58-733 (m, 7 H), 6.68 (s, 1 11 1-CH3.-OBn-CHO \, D-2 CH3 116a H), 524 (m, 2 H), 3.92 (s, 3 H), 3.65 (s, 3 H), 3.40 (m, 2 H), 1.80- 0.94 (m, 9 H); MS (ES+) : 512.2 (M+Na) + 'HNMR (DMSO-d6) : 8 9.73 (s, 1 H), 8.86 (t, J = 5. 7 Hz, 1 H), 8.52 (d, J = 1. 5 Hz, 1 H), 8.22 (dd, J = O CH3 8 and 2 Hz, 1 H), 7.79 (s, 1 H), I' (J = 8 Hz, 1 H), 7.5 (m, 5 JLi/m JJL-Uou-J-iU ie, 4 Tj'700/r. iuc< T-n 117m Jk-OBn-CHO X 1CH 115d D-6 H), 7. 22 (s, 1 H), 535 (q, J =11 33 and 17 Hz, 1 H), 3.70 (s, 3 H), 3.23 (t, J = 6.5 Hz, 2 H), 1.98 (m, 1 H), 1.3 (s, 9 H), 1.01 (d, J = 6. 8 Hz, 6 H); MS (ES+) : 546.4 CH3 118a-CH3-OBn-CO2H XCH3 117a E MS (ES-): 490.2 "-CH, --R-R'-R"-R'"Starting Method Analytical Data No. From Used CH3 118b-C2H5-OBn-C02H < CH3 117b E MS (ES-) : 504.2 CH3 ICH3 118c-CH (CH3) 2-OBn-CO2H > 13 117c E MS (ES-) : 518.2 \ CH3 118d-CH3-OBn-C02H l CH3 117d E Characterized in the next step CH3 /-CHg 118e-CH3-OBn-C02H 117e E MS (ES+) : 534.3 CH3 118f-CH3-OBn-CO2H mCH3 117f E MS (ES+) : 506. 3 118g-CH3-OBn-CO2H/\CF3 117g E Characterized in the next step 3 118h-CH3-OBn-CO2H vCH3 117h E MS (ES-') : 490.2 118i-CH3-OBn-C02H 117i E MS (ES-1) : 488. 3 Cpd.-R-Rl-R"-Rl"Starting Method Analytical Data No. From Used 'H NMR (DMSO-d6) : 812. 19 (br s, 1 H), 8.50 (d, J= 7.4 Hz, 1 H), 8. 31 (d, J= 1. 9 Hz, 1 H), 118j-CH3-OBn-c02H 117j E 8. 02 (dd, J= 1. 7 and 7. 9 Hz, 1 H), 7. 58-7. 29 (m, 7 H), 6. 71 (s, I H), 5.17 (s, 2H), 4.27 (q, J=6. 4 Hz, 1 H), 3.80 (s, 3 H), 3.57 (s, 3 H), 1.97-1.51 (m, 8 H) 118k-CH3-OBn-COzH/'CH3 117k E MS (ES) : 462. 3 'H NMR (CDC13) : 8 8. 30 (d, J= 1.9 Hz, 1. I, 7.95 (dd, J=1. 7 and 7.9 Hz, 1 H), 7.66 (s, 1 H), CH3 7. 52-7. 27 (m, 6 H), 6. 62 (s, 1 H), 1181-CH3-OBn-COZH 1171 E CH3 6. 49 (m, 1 H), 521 (s, 2 H), 3.88 (s, 3 H), 3.61 (s, 3 H), 3.38 (m, 2 H), 1.79-0.94 (m, 9 H); MS (ES-) : 504.4 O CH3 118m t-OBn-CO2H l 117m E Characterized in the next step C(CH3) 3 mCH3 _ CH3 119a-CH3-OBn-CO2MEM 118a F MS (ES-) : 578. 3 CH3 CH3 119b-C2H5-OBn-COZMEM 118b F MS (ES-) : 592.3 ""CH Cpd. ,, ,, ,,, Startms Method...., . Cpd. _R-R'-R"_R Startiug Method alytical Data No. From Used CH3 119c-CH (CH3) 2-OBn-C02MEM . Jk 118c F MS (ES) : 606. 3 C3 CH3 ll9d-CH3-OBn-CO2MEM/\ 118d F MS (ES) : 564.2 CH3 CH3 119e-CH3-OBn-C02MEM CH3 118e F MS (ES-) : 620.1 c3 119f-CH3-013n-CO2MEM CH3 118f F MS (ES-) : 592. 3 ll9g-CH3-OBn-CO2MEM/\CF3 118g F Characterized in the next step 3 1HNMR (CDCI3) : 8 8.32 (d, J= 1.9 Hz, 1 H), 7.96 (dd, J= 7. 9, 1. 9 Hz, 1 H), 7.68 (s, 1 H), 7.50 (m, 2 H), 7.35 (m, 4 H), 6.62 (s, 1 119h-CH3-OBn-COzMEM % Cg3 118h F H), 6.33 (t, J= 5.4 Hz, 1 H), 5.24 (m, 4H), 3.88 (s, 3H), 3.63 (s, 3 H), 3.46 (m, 6 H), 3.34 (s, 3 H), 1.63 (m, 2 H), 1.44 (m, 2 H), 0.98 (t,J=7. 3Hz, 3H) --R-R'-R"-R'"Starting Method Analytical Data No. From Usez HNMR (CDC13) : 8 8.34 (d, J= 1.9 Hz, 1 H), 8.00 (dd, J= 7. 9, 2.1 Hz, 1 H), 7.68 (s, 1 H), 7.50 (m, 2 H), 7.36 (m, 4 H), 6.63 (s, 1 119i-CH3-OBn-C02MEM 118i F H), 6.42 (broad, 1 H), 5. 24 (m, 4 H), 3.89 (s, 3 H), 3.64 (s, 3 H), 3.45 (s, 3 H), 3. 35 (m, 5 H), 1.07 (m, 1 H), 0.58 (m, 2 H), 0. 30 (m, 2H) 'H NMR (DMSO-d6) : 8 8.55 (d, J= 7. 4 Hz, 1 H), 8.39 (d, J=1. 9 Hz, 1 H), 8.10 (dd, J=1. 7and 7. 9 Hz, 1 H), 7.63-7. 35 (m, 7 H), ll9j-CH3-OBn-CO2MEM a \ 118j F 6.81 (s, 1 H), 5. 25-5. 12 (m, 4 H), 4. 31 (q, J= 6.4 Hz, 1 H), 3.86 (s, 3 H), 3.62 (s, 3 H), 3.3 (s, 3 H), 3.23 (s, 3 H) 1.99-1.53 (m, 8 H); MS (ES+) : 614. 3 (M+Na) + 'H NMR (DMSO-d6) : 8 8.70 (t, J=5. 5Hz, lH), 8.35 (d, J=1. 9 Hz, 1 H), 8.05 (dd, J= 1. 7 and 7.9 Hz, 1 H), 7.59-7. 30 (m, 7 H), ll9k-CH3-OBn-CO2MEM/\ 118k F 6.77 (s, 1 H), 5.21-5.08 (m, 4 H), CH3 3. 82 (s, 3 H), 3.58 (s, 3 H), 3.40- 3.29 (m, 6 H), 3.18 (s, 3 H), 1.14 (t, J=7. 2Hz, 3H) ; MS (ES+) : 574. 3 (M+Na) + CNod-R |-R'-R"-R"'1 starting 1 Method AnalyticalData No. From Used --. 1H NMR (DMSO-d6) : 8 8.68 (t, J=5. 8Hz, lH), 8. 35 (d, J=1. 9 Hz, 1 H), 8.05 (dd, J= 1. 7 and cl3 7. 9 Hz, 1 H), 7.63-7.33 (m, 7 H), CH3 6. 77 (s, 1 H), 5. 22-5.08 (m, 4 H), 1191-CH3-OBn-COZMEM 3 1181 F','' 3.82 (s, 3H, 3.58 (s, 3H), 3.39- 3.22 (m, 6H), 3.18 (s, 3 H), 1. 56 (qui, J= 7.0 Hz, 2 H), 1.27 (m, 1 H), 0.94-0.75 (m, 6 H); MS (ES+) : 616. 3 (M+ Na) + 'HNMR (DMSO-d6) : 8 8.72 (t, J = 5. 6 Hz, 1 H), 8.38 (d, J = 1. 8 Hz, 1 H), 8.70 (dd, J-1. 8 and 8.1 Hz, 1H), 7. 71 (s, 1 H), 7.40 O CH3 (m, 6 H), 7.02 (s, 1 H), 5.20 (m, 4 119m I I-OBn-CO2MEM 118m F H), 3.59 (s, 3 H), 3.37 (m, 2 H), /\C (CH) CH 3.31 (m, 2 H), 3.17 (s, 3 H), 3.12 (t, J = 6. 5 Hz, 2 H), 1.87 (m, 1 H), 1.21 (s, 9 H), 0.91 (d, J = 6. 8 Hz, 6 H); MS (ES+): 650.4 and 672.3(M+ Na) + CH3 120a-CH3-OH-COZMEM 119a G MS (ES) : 488.1 CH3 120b-C2H5-OH-CO2MEM 119b G MS (ES-): 502.2 " CH, Cpd.-R-R'-R"Starting Method Analytical Data No. From Used CH3 120c-CH (CH3) 2-OH-CO2MEM 119c G MS (ES-): 516. 3 CH3 CH, IZOd-CH3-OH-COZMEM 1 119d G MS (ES) : 474.3 CHC H3 CH3 120e-CH3-OH-CO2MEM 119e G MS (ES-) : 530.4 CH3 120f-CH3-OH-CO2MEM/oCH3 ll9f G MS (ES-) : 502.3 120g-CH3-OH-CO2MEM/\CF3 ll9g G Characterized in the next step 120h-CH3-OH-CO2MEM CH3 119h G Characterized in the next step 120i-CH3-OH-CO2MEM ll9i G MS (ES-): 486. 3 120j-CH3-OH-CO2MEM < ll9j G MS (ES+) : 524.3 (M+ Na) + 120k-CH3-OH-CO2MEM/\CH3 ll9k G MS (ES+) : 484.2 (M+Na) + Cpd.-R-RI-R"-R"f Starting Method Analytical Data No. From Used No. From Used' CH3 CH3 1201-CH3-OH-CO2MEM ZIN/CH3 1191 G MS (ES-) : 502.3 3 'HNMR (DMSO-d6) : 8 10.83 (bs, 1 H), 8.77 (t, J=5. 6Hz, lH), 8.42 (d, J = 1. 8 Hz, 1 H), 8.12 (dd,J =1. 8 and 8. 1 Hz, 1 H), CH3 7. 68 (s, 1 H), 7.41 (d, J = 8.1 Hz, 1 H), 6.73 (s, 1 H), 5.21 (q, J = 120m JQ-OH-CO2MEM CH3 ll9m G 21 and 6 Hz, 2 H), 3.65 (s, 3 H), C (CH3) 3 3.48 (m, 2 H), 3.37 (m, 2 H), 3.24 33 . o e (s, 3H), 3.18 (t, J=6. 5Hz, 2H), 1.94 (m, 1 H), 1.39 (s, 9 H), 0.97 (d, J = 6.8 Hz, 6 H); MS (ES+): 560.5 and 582.4 (M+ Na) +, (ES-) 558. 4 CHg 121a-CH3-OSO2CF3-CO2MEM 1 120a B-2 MS (ES+) : 644.1 (M+Na) + J CH, 121b-C2Hs-OSOzCF3-CO2MEM CH 3 120b B-2 MS (ES+) : 658.2 (M+Na) + CHr CH 121c-CH (CH3) z-OSO2CF3-CO2MEM < 120c B-2 MS (ES+) : 672.2 (M+Na) + CH3 Cpd. Tr,, ,, ,.. Startms Method.,,., . Cpd. _R-R'-R"_R Starting Method alyticalData No. From Used 'HNMR (DMSO-d6) : 8 8.43 (d, J =1. 9Hz, lH), 8. 31 (s, 1 H), 8. 12 CH3 (d, J = 1. 69 Hz, 1 H), 7.98 (s, 1 H), 7.41 (d, J = 8. 1 Hz, 1 H), 7.19 -CH 120d B-2 (s, 1 H), 5. 20 (m, 2 H), 3.98 (m, 1 CH3 H), 3.94 (s, 3 H), 3.42 (s, 3 H), 3.19 (s, 3 H), 2.50 (m, 2 H), 1.08 (d, J = 6.59,6 H); MS (ES+) 608.3 'HNMR (DMSO-d6) : 8 8.49 (s, 1 H), 8. 34 (d, J = 1. 8 Hz, 1 H), 8.2 (d, J=1. 8Hz, lH), 7.97 (s, 1 H), CH3 7.4 (d, J = 7.8 Hz, 1 H), 7.2 (s, 1 121e-CH3-OSO2CF3-CO2MEM < 120e B-2 H), 5.2 (q, J = 6 and 10 Hz, 2 H), CH3 4. 0 (m, 3 H), 3.6 (s, 3 H), 3.4 (m, 4H), 3.2 (s, 3H), 1.5 (m, 4H), 1.3 (m, 4H), 0.85 (m, 6H) ; MS (E+) : 664. 3 'HNMR (DMSO-d6): 8 8.83 (d, J = 5.46,1 H), 8.55 (d, J = 1. 88 Hz, 1 H), 8.23 (dd, J = 1. 88 Hz, 1 H), 8.19 (s, 1 H), 7.73 (d, J = 7. 93 /vCH3 Hz, 1 H), 7. 29 (s, 1 H), 5.29 (dd, 121f-CH3-OSO2CF3-CO2MEM 120f B-2 J = 6. 217 Hz, 2 H), 4.06 (s, 3 H), 3.71 (s, 2 H), 3.54 (m, 5 H), 2.62 (t, J = 3. 57 Hz, 3 H), 1. 66 (t, J = 6.59Hz, 2H), 1.42 (m, 6H), 0.99 (t, J = 6.79 Hz, 3 H); MS (ES+)636.6 J Cpd.-R-Rl-R"-Rt"Starting Method Analytical Data No. From Used 'HNMR (CDCl3) : 8 8.43 (d, J= 1. 9Hz, lH), 8.03 (dd, J=7. 9 Hz, 2.1 Hz, 1 H), 8.00 (s, 1 H), 7.35 (d, V= 7. 9 Hz, 1 H), 6.79 121g-CH3-OSO2CF3-CO2MEM nCF 120g B-2 (m, 2 H), 5.29 (d, J= 6. 2 Hz, 1 H), 526 (d, J 6. 2 Hz, 1 H), 4.16 (m, 2 H), 3.94 (s, 3 H), 3.67 (s, 3H), 3.48 (m, 4H), 3. 36 (s, 3 H) ; MS (ES-) : 646.3 IHNMR (CDC13) : 8 8.41 (s, 1 H), 7.96 (d, J = 8. 3 Hz, 2 H), 7.8 (m, lH), 6.80 (s, 1 H), 6.34 (m, 121h-CH3-OSO2CF3-CO2MEM 120h B-2 1 H), 5 32 (m, 2 H), 3. 90 (s, 3 CH H), 3.66 (s, 3 H), 3.55 (m, 6 H), 3. 4 (s, 3H), 1.7 (m,. 2H), 1.45 (m, 2H), 0.98 (t, J=7. 3Hz, 3 H); MS (ES-): 620 'H NMR (CDC13) : 8 8.41 (d, J= 2.1 Hz, 1 H), 8.03 (dd, J= 7. 9, 1.9 Hz, 1 H), 8.00 (s, 1 H), 7. 32 (d, J= 7.9 Hz, 1 H), 6.43 (t, J= 121i-CH3-OSO2CF3-CO2MEM/120i B-2 4. 9 Hz, 1 H) 5.30 (q, J= 6. 0 Hz, 2 H), 3. 94 (s, 3 H), 3.67 (s, 3 H), 3. 55 (m, 2 H), 3.48 (m, 2 H), 3.35 (m, 5 H), 1.09 (m, 1 H), 0.59 (m, 2 H), 0.31 (m, 2 H) ; MS (ES-) : 618.4 No. | |-R'|-R"|-R"'starting | Method | AnalyticalData No. From Used 'H NMR C13) : 8 8. 35 (d, J= 1.9 Hz, 1 H), 8.00 (m, 2 H), 7. 31 (d, J= 7.9 Hz, 1 H), 6.77 (s, 1 H), 12lj-CH3-OS02CF3-CO2NMM 120j B-2 6. 27 (m, 1 H), 5. 29 (m, 2 H), 4. 44 (q, J= 7.0 Hz, 1 H), 3_94 (s, 3 H), 3.66 (s, 3 H), 3.57-3.45 (m, 4 H), 3.35 (s, 3 H), 2.19-1.45 (m, 8 H); MS (ES+) : 656. 3 (M+ Na) + "H NMR (CDC13) : 8 8. 38 (s, 1 H), 8.00 (m, 2 H), 7.31 (d, J= 7. 9 Hz, 1 H), 6.78 (s, 1 H), 6. 37 (m, 1 121k-CH3-OSO2CF3-CO2MEM 120k B-2 H), 5.27 (m, 2 H), 3.94 (s, 3 H), CH3 3. 66 (s, 3 H), 3.59-3.43 (m, 6 H), 3.35 (s, 3 H), 1.28 (t, J= 7. 2 Hz, 3 H); MS (ESt) : 616. 3 (M+Na) + 'H NMR (CDC13) : 6 8. 38 (s, 1 H), 8.00 (m, 2 H), 7.31 (d, J= 7. 9 Hz, 1 H), 6.78 (s, 1 H), 6. 37 (m, 1 1211-CH3-OS02CF3-CO2MEM 3 1201 B-2 H), 5.27 (m, 2 H), 3.94 (s, 3 H), 3.66 (s, 3 H), 3.57-3.25 (m, 9 H), 1.78-0.92 (m, 9 H); MS (ES+) : 658.4(M+ Na) + Cpd.,"", Starting Method No. From Used No. From Used" 'HNMR (DMSO-d6)-5 8.75 (t, J = 5. 6 Hz, 1 H), 8.45 (d, J=1. 8 Hz, 1 H), 8.11 (dd, J=1. 8and 8. 1 Hz, 1 H), 8.04 (s, 1 H), 7.57 (s, 1 H), 7.42 (d, J = 8. 1 Hz, 1 H), 121m k-OSO2CF3-CO2MEM X 121m B-2 5. 23 (q, J = 21 and 6 Hz, 2 H), /C (CH) CH3 3.60 (s, 3 H), 3.41 (m, 2 H), 3. 32 33 (m, 2 H), 3.17 (s, 3H), 3.13 (t, J = 6. 5 Hz, 2 H), 1.87 (m, 1 H), 1.37 (s, 9 H), 0.91 (d, J = 6.8 Hz, 6 H); MS (ES-) : 690.4 CH3 122a-CH3-CH=CH2-CO2MEM e 121a D-3 Characterized in the next step CH3 CH 122b-C2Hs-CH=CH2-CO2MEM sXCH3 121b D-3 MS (ES+) : 536.3 (M+Na) + -CHO CH3 122c-CH (CH3) 2-CH=CH2-CO2MEM o13 121e D-3 MS (ES+) : 550.3 (M+Na) + cl3 CHEZ 122d-CH3-CH=CH2-CO2MEM 1 121d D-3 MS (ES+) : 486.2 CH3 CH3 122e-CH3-CH=CH2-CO2MEM 121 e D-3 MS (ES+) : 564.5 (M+ Na) + cl --R-R'-R"-R'"Starting Method Analytical Data No. From Used CH3 122f-CH3-CH=CH2-CO2MEM 121f D-3 MS (ES+) : 514.4 (M+Na) + 122g-CH3-CH=CH2-CO2MEM/\CF3 121g D-3 Characterized in the next step 122h-CH3-CH=CH2-CO2MEM/sCH3 121h D-3 Characterized in the next step 122i-CH3-CH=CH2-C02MEM 121i D-3 Characterized in the next step 122j-CH3--CH=CH2-CO2MEM O 121j D-3 MS (ES) : 422.3 [(M-MeM)-l] 122k-CH3-CH=CH2-C02MEM 121K D-3 MS (ES+) : 494.2 (M+ Na) + CH3 -tirr J c'THr 1221 yCH3-CH=CHZ-COzMEM \ v CH3 1211 D-3 MS (ES+) : 536.42 (M+ Na) + Cpd. TQ, ,, ,,,, Starting Method.,,., . Cpd. _R-R'-R"_R Starting Method Analytical Data No. From Used 'HNMR (DMSO-d6) : 8 8.73 (t, J =5. 6Hz, lH), 8.43 (d, J = 1. 8 Hz, 1 H), 8.11 (dd, J= 1. 8 and 8.1 Hz, 1 H), 7.61 (s, 1 H), 7.57 CHs (s, 1 H), 7.42 (d, J = 8.1 Hz, 1 H), l l Jo 6. 72 (dd, J = 11 and l7. 5 Hz, 1 CH H), 6.03 (d, J= 17. 5Hz. lH), 122m/\CCH)-CH=CHZ-COzMEM 3 121m D-3 Hz 1 H 5. 19 3 3 5.52 (d, J =11,), (q, J = 18 and 6 Hz, 2 H), 3.60 (s, 3 H), 3.41 (m, 2 H), 3.32 (m, 2 H), 3.18 (s, 3H), 3.13 (t, J = 6. 5 Hz, 2 H), 1.89 (m, 1 H), 1.38 (s, 9 H), 0.91 (d, J = 6.8 Hz, 6 H); MS (ES-) : 480.4 [(M-MEM)-1] CH3 123a-CH3-CH=CH2 CO2H \tCH3 122a I-1 MS (ES) : 410.2 CH3 CH, 123b-C2H5-CH=CH2 CO2H 1CH3 122b I-1 MS (ES-) : 424.2 CH3 CHEZ 123c-CH (CH3) 2-CH=CH2 COZH 122c I-1 MS (ES) : 438. 2 CH 3 CH3 123d-CH3-CH=CH2 CO2H 1 122d I-1 MS (ES-) : 396.2 CH3 Cpd.,"", Starting Method No. From Used No. From Used" CH3 123e-CH3-CH=CH2 CO2H 122e 1-1 MS (ES+) : 454. 3 CL 123f-CH3-CH=CH2 COsH v CH3 122f I-1 MS (ES+) : 426.3 IHNMR (DMSO): 8 12.37 (s, 1 H), 9. 35 (t, J= 6. 0 Hz, 1 H), 8.42 (d, J= 1.7 Hz, 1 H), 8.10 (dd, J= 8.1 Hz, 1.9 Hz, 1 H), 8.06 (s, 1 H), 7.40 (d, J= 7. 9 Hz, 1 I, 123g-CH3-CH=CH2 COzH 122g I-1 6.98 (dd, J= 17. 9,11.5 Hz, 1 H), CF3 6. 77 (s, 1 H), 5. 89 (dd, J= 17. 7, 1.3 Hz, 1 H), 5. 37 (dd, J= 11. 1, 1.3 Hz, 1 H), 4.14 (m, 2 H), 3.84 (s, 3 H), 3.61 (s, 3 H); MS (ES-): 436.3 'H NMR (DMSO): 8 8.66 (t, J= 5.5 Hz, 1 H), 8.35 (d, J=1. 7Hz, 1 H), 8.05 (s, 1 H), 8.03 (dd, J= 8.1,1.9 Hz, 1 H), 7. 34 (d, J= 7. 9 Hz, 1 H), 6.98 (dd, J= 17. 9,11.3 123h-C-CH=CH2 COH 122h 1-1 ''-'' Hz, 1 H), 6. 75 (s, 1 H), 5.88 (dd, % CH3 J=17.7,1.3,1H), 5. 36 (dd, J= 3 11. 3, 1. 3Hz, 1 H), 3.84 (s, 3H), 3.60 (s, 3 H), 3.30 (q, J= 5.6 Hz, 2 H), 1.52 (m, 2 H), 1.33 (m, 2 H), 0.96 (t, J= 7. 3 Hz, 3 H); MS (ES-) : 410. 4 Cpd. , ,,, .,, Startmg Method...., . Cpd.-R-RI-R"-Rl"Starting Method Analytical Data No. From Used 'HNMR (DMSO): 6 12.34 (s, 1 H), 8.80 (t, J=6. 1Hz, 1H), 8. 37 (d, J= 1. 9 Hz, 1 H), 8.06 (dd, J= 9.8,7.9 Hz, 1 H), 8.05 (s, 1 H), 7.36 (d, J= 7.9 Hz, 1 H), 6.98 123i-CH3-CH=CH2 CO2H < 122i I-1 (dd, J) 179,11. 3 Hz, 1 H), 6.76 (s, 1 H), 5.89 (dd, J= 17. 9,1.5 Hz, 1 H), 5.36 (dd, J= 10. 9,1.5 Hz, 1 H), 3.84 (s, 3 H), 3.60 (s, 3 H), 3.18 (t, 6.2,2H), 1.06 (m, 1 H), 0.45 (m, 2 H), 0.25 (m, 2 H); MS (ES-) : 408. 4 'H NMR (DMSO-d6) : 512. 31 (br s, 1 H), 8.52 (d, J= 7. 3 Hz, 1 H), 8. 34 (d, J= 1. 7 Hz, 1 H), 8.05 (m, 2 H), 7. 34 (d, J= 7. 9 ./Hz, 1 H), 6.97 (dd, J= 11. 5 and 123j-CH3-CH=CH2 CO2H X J 122j I-1 17.9 Hz, 1 H), 6.74 (s, 1 H), 5.89 (d, J= 17. 9 Hz, 1 H), 5.37 (d, J= 11.5 Hz, 1 H), 4.27 (q, J= 7. 3 Hz, 1 H), 3.84 (s, 3 H), 3.60 (s, 3 H), 1.98-1.50 (m, 8 H); MS (ES-) : 422. 3 'H NMR (DMSO-d6) : 8 12.27 (br s, 1 H), 8.58 (m, 1 H), 8.23 (s, 1 H), 7.92 (m, 2 H), 7.47 (m, 1 H), 7. 22 (m, 1 H), 6. 84 (m, 1 H), CH 6.63 (s, 1 H), 5. 76 (d, J= 17. 9 Hz, 1 H), 5.24 (d, J=11. 5 Hz, 1 H), 3.71 (s, 3H), 3.47 (s, 3H), 1. 02 (m, 3 H) ; MS (ES') : 382. 2 Cpd.-R-Rl-R"-Rttv Starting Method Analytical Data No. From Used 'H NMR (DMSO-d6) : 8 30 (br s, 1 H), 8.52 (d, J= 6. 0 Hz, 1 H), 8.33 (d, J=1. 7 Hz, 1 H), 8. 02 (m, 2 H), 7.31 (d, J=7. 9 1 3 Hz, 1 H), 6.95 (dd, J= 11. 5 and 1231-CH3-CH=CH2 CO2H CH3 1221 I-1 17.9 Hz, 1 H), 6.73 (s, 1 H), 5.86 (d, J=17. 9Hz, lH), 5. 33 (d, J= 11. 5 Hz, 1 H), 3.81 (s, 3H), 3.57 (s, 3 H), 3.14 (m, 2 H), 1.65 (m, 1 H), 1.39 (m, 1 H), 1. 11 (m, 1 H), 0. 87 (m, 6 H) HNMR (DMSO-d6) : 612. 81 (bs, 1 H), 8.72 (t, J = 5. 6 Hz, 1 H), 8.38 (d, J=1. 8Hz, lH), 8.08 (dd, J= 1. 8 and 8. 1 Hz, 1 H), CH3 7.61 (s, 1 H), 7.57 (s, 1 H), 7.39 123m-CH=CH2-C02H 122m 1-1 (d, J = 8 Hz, I H), 6. 72 (dd, J = O CH 11 and 17. 5 Hz, 1 H), 5.99 (d, J= 17. 5 Hz, 1 H), 5.49 (d, J = I I Hz, AC (CH3) 3 1 H), 3. 57 (s, 3 H), 3.13 (t, J = _C CH 33 6.5 Hzj 2 H), 1.87 (m, 1 H), 1.37 (s, 9 H), 0. 91 (d, J = 6. 8 Hz, 6 H) ; MS (ES-): 480. 3 Cpd.,"Starting Method No.From Used CH 124a-CH3-CH3, 123a J MS (ES+) : 529. 3 cl 3 CH 124b-CzHy-CH3 ! 123b J MS (ES) : 543. 3 cl 3 CH3 124c-CH (CH3) Z-CH3 123c J MS (ES : 557. 3 CH 3 CH3 124d-CH3-CH3 1CH3 123d J Characterized in the next step CH, -CH, 124e-CH3-CH3 I23e J MS (ES+) : 571. 6 C3

Cpd. |-R s-R'] R"| Starting | Method | AnalyticalData NôStarting Method No. From Used C3 CH, 124f-CH3-CH3 123f J MS (ESt : 543.6 'H NMR (DMSO): 5 10.62 (s, 1 H), 9.35 (t, J= 6.6 Hz, 1 H), 9.20 (s, 2 H), 8.90 (s, 2 H), 8.30 (d, J= /N 1. 9 Hz, 1 H), 8.11 (dd, J= 8.1,1.9 Hz, 1 H), 7.86 124g-CHs-CH3 123g J (s, 1 H), 7.76 (s, 4 H), 7.50 (d, J= 8. 1 Hz, 1 H), 7.04 (dd, J= 17. 9,11.5 Hz, 1 H), 6.94 (s, 1 H), 6.01 (dd, J= 17. 7,1.3,1 H), 5.42 (dd, J= 11. 3,1. 3 Hz, 1 H), 4.11 (m, 2 H), 3.89 (s, 3 H), 3. 57 (s, 3 H) 'HNMR (DMSO): 8 9.03 (broad, 3 H), 8.49 (broad, 1 H), 8.04 (s, 1 H), 7.65 (m, 6 H), 6.99 (m, 124h-CH3-CH3'cH3 123h J 2 H), 6.61 (s, 1 H), 5.90 (d, J= 17.5 Hz, 1 H), 5.35 (d, 3 123h (d, J= 11. 5 Hz, 1 H), 3.78 (s, 3 H), 3.20 (m, 2 H), 1.46 (m, 2 H), 1.28 (m, 2 H), 0.87 (t, J= 7. 3 Hz, 3 H) 124i-CH3-CH3 123i J MS (ES+) : 527.4 124j-CH3-CH3 J 123j J MS (ES+) : 541.4 124k-CH3-CH3/\CH3 123K J MS (ESi) : 501. 3 CH 1241-CH3-CH3 CH3 1231 J MS (ES+) : 543.3 Cpd.,"Starting Method Analytical Data No. From Used 6 'HNMR (DMSO-d6) : 8 10.67 (s, 1H), 9.19 (bs, 2 H), 8.88 (bs, 2 H), 8.71 (t, J = 5.6 Hz, 1 H), 8.25 (d, J = 1. 8 Hz, 1 H), 8.07 (dd, J = 1.8 and 8.1 Hz, 1 H), 7.73 (m, 4 H), 7.65 (s, 1 H), 7.50 (d, J = 8 Hz, 124m O-CH3 l H3 123m J 1 H), 7.45 (s, 1 H), 6.73 (dd, J =11 and 17.5 Hz, 1 H), 6.03 (d, J = 17. 5 Hz, 1 H), 5.49 (d, J = 11 Hz, 1 CH 3 H), 3. 56 (s, 3 H), 3. 09 (t, J = 6.5 Hz, 2 H), 1.85 (m, C (CH3) 3 1 H), 1. 37 (s, 9 H), 0. 89 (d, J = 6.8 Hz, 6 H); MS (ES-) : 597. 3 and (ES+) 599.5 'HNMR (DMSO): 6 13.40 (bs, 1H), 9.26 and 9.03 CH3 (2s, 4H), 8.53-8.49 (t, J = 6 Hz, 1H), 8.02 (d, l J=1. 28 Hz, 1H), 7.71-7.53 (m, 6H), 7.0-6.9 (m, 125a-CH3-H 124a 1-2 2H), 6. 5 (s, 1H), 5.89 (d, J=17. 6 Hz, 1H), 5. 33 (d, 125a-CH3-H /\. CH 124a I-2 2H), 3 J=12. 4 Hz, 1H), 3.77 (s, 3H), 3.04-2.99 (m, 2H), 1.85-1.75 (m, 1H), 0.86-0.84 (d, J=76. 8 Hz, 6H); MS (ES+) : 515. 3 'HNMR (DMSO): 5 9.17 and 8.92 (s, 3H), 8.67- 8.63 (m, 1H), 8.28 (s, 1H), 7.95-7.93 (m, 1H), 7.83 CH3 (s, 1H), 7.73 (s, 5H), 7.29 (d, J=8. 1 Hz, 1H), 7.02 1 I 2 (dd, J=17. 7 Hz, 11.3 Hz, 1H), 6.82 (s, 1H), 6.00 (d, CH3 17. 7 Hz, 1H), 5. 38 (d, 11.3 Hz, 1H), 4.14-4.06 (m, 2H), 3.11-3.04 (q, J=6. 8 Hz, 2H), 1.89-1.80 (m, 1H), 1.35 (t, J=6. 8 Hz, 3H), 0.88 (d, J=6. 8 Hz, 6H) ; MS (ES+) : 529.2 'HNMR (DMSO): 8 13.74 (s, 1H), 8.99 (s, 3H), OH 8.59-8.41 (m, 1H), 7.95 (s, 1H), 7.69 (s, 1H), 7.65- 7. 53 (m, 6H), 7.06-6.91 (m, 2H), 6.53 (s, 1H), 5.89 125c-CH (CH3) 2-H H\ 124c I-2 (d, J=17. 7 Hz, 1H), 5.32 (d, J=11. 5 Hz, 1H), 4.62- CH3 4. 54 (m, 1H), 3.03-2.99 (m, 2H), 1.87-1.71 (m, 1H), 1.25 (d, J=6. 1 Hz, 6H), 0.85 (d, J=6. 8 Hz, 6H); MS (ES-) : 541.2 Cpd. Starting Method -R-R'R' From Used a13'trcal Data No. From Used' IHNMR (DMSO-d6) : 6 8. 9 (d, J = 33. 74, 4 H), CH3 8.08 (d, J = 7.91,1 H), 7.81 (s, 1 H), 7.51 (s, 1 H), 125d-CH3-H l 124d I-2 7. 41 (s, 4 H), 6.78 (s, 1 H), 6.3 (s, 2 H), 5.70 (d, J = ./\CH 7. 78 Hz, 1 H), 5. 15 (d, J = 11. 8 Hz, 2 H),) 3. 82 (m, CH 3 J = 20. 34 Hz, 2 H), 3. 56 (bs, 3 H) 0. 92 (d, 6H) ; ""3 J=20.34Hz, 2H), 3.56 (bs, 3H) 0.92 (d, 6H); MS (ES+) 501.3 'HNMR (DMSO-d6): 8 9.05 (s, 2 H), 8.85 (s, 2 H), 7.96 (d, J = 9. 04 Hz, 1 H), 7.88 (s, 1 H), 6,86 (m, J CH3 = 17. 8 Hz, 3 H), 7.62 (m, 1 H), 7.24 (d, J = 7. 8 Hz, 125e-CH3-H 124e I-2 1 H), 6.95 (d, J = 7.8 Hz, 1 H), 7.45 (m, J = 28.63 CH3 Hz, 5 H), 7.55 (s, 1 H), 5.75 (d, J = 17. 5 Hz, 1 H) ; 5. 61 (d, J= 11. 11, 1 H) 3.61 (s, 3H) 1. 30 (bs, 3 H) 1.05 (s, 4 H) 0.66 (m, 6 H); MS (ES+) 555. 3 (100% M+I) 'H NMR (DMSO-d6) : 8 12.7 (bs, 1H), 9.01 (bs, 2H), 8.87 (bs, 2H), 8.36 (t, J = 6 Hz, 1H), 7.83 (s, 125f-CH3-H cH3 124f I-2 1H), 7.44 (m, 6H), 6.75 (m, 2H), 6.31 (d, J = 2.2 Hz, 1H), 5. 7 (d, J = 17 Hz, 1H), 5. 1 (d, J = 11 Hz, 1H), 3.5 (s, 3H), 2.84 (m, 2H), 1. 3 (m, 2H), 1. 1 (m, 4H), 0.7 (m, 3H) ; MS (ES+): 529.4 'HNMR (DMSO): 8 9.22 (broad, 1 H), 9.09 (s, 2 H), 8.9 (s, 2 H), 8.18 (s, 1 H), 7.80 (m, 2 H), 7.66 125g-CH3-H 1-1---CF3 I H), 6. 70 (s, 1 H), 5. 94 (d, J= 17. 7 Hz, 1 H), 5. 37 3 1 H), 6. 70 (s, 1 H), 5. 94 (d, J= 17. 7 Hz, 1 H), 5. 37 (d, J=10. 9Hz, 1 H), 4.07 (m, 2 H), 3.81 (s, 3 H) ; MS (ES-) 539.3 Cpd. Starting Method No. From Used No. From Used" 'HNMR(DMSO) : S 9. 03 (bs, 4 H), 8. 49 (bs, 1 No.. From Used H), 8. 04 (s, 1 H), 7. 65 (m,-6 H), 6. 99 (m, 2 H), H), 8. 04 (s, 1 H), 5. 90 (d, J=17. 5 Hz, 1 H), 5. 35 (d, J = 11. 5 Hz, 1 H), 3. 78 (s, 3 H), 3. 20 (m, 2 H), 1. 46 (m, 2 H), 1.28 (m, 2 H), 0.87 (t, J= 7. 3 Hz, 3 H) ; MS (ES+) 515.4 'HNMR (DMSO) : 8 8.86 (s, 2 H), 8.78 (s, 2 H), 8. 44 (broad, 1 H), 7.89 (s, 1 H), 7.53 (m, 2 H), 7. 43 (m, 4 H), 6.86 (s, 1 H), 6.78 (dd, J= 17. 5, 125i-CH3-H 124i I-2 11. 3 Hz, 1 H), 6.44 (s, 1 H), 5.71 (d, J = 17. 5 Hz, 1 H), 5. 14 (d, J = 11. 1 Hz, 1 H), 3.59 (s, 3 H), 2.89 (m, 2H), 0.79 (m, 1 H), 020 (m, 2 H), 0. 01 (m, 2 H); MS (ES-) 513.4 'HNMR (DMSO): 6 13.14 (br s, 1 H), 8.84 (m, 3 H), 8.12 (d, J= 7.3 Hz, 1 H), 7.79 (s, 1 H), 7.40 125j-CH3-H 124i 1-2 (m, 8 H), 6. 74 (m, 2 H), 6. 33 (s, 1 H), 5. 66 (d, J= 19. 2 Hz, 1 H), 5.10 (d, J-11. 7Hz. lH), 3.94 (m, 1 H), 3.54 (s, 3 H), 1.66-0.93 (m, 8 H); MS (ES+) 527.4 'H NMR (DMSO): 8 9.25 (m, 4 H), 8.73 (t, J= 5.7 Hz, 1 H), 8.28 (s, 1 H), 7.86 (m, 7 H), 6.84 (s, 125k-CH3-H 124k I-2 1 H), 6.10 (d, J= 17. 7 Hz, 1 H), 5.55 (d, J= 11. 3 '-----CH3 Hz, 1 H), 3.99 (s, 3 H), 3.43 (qui, J= 6.2 Hz, 2 H), 1.28 (t, J= 7.2 Hz, 3 H); MS (ES+) : 487.2 'H NMR (DMSO): 8 8.91 (m, 4 H), 8. 38 (t, J= 5.5 Hz, CH3 1 H), 7.96 (s, 1 H), 7.53 (m, 5 H), 6.86 (m, 2 H), 6.52 1251-CH3-H 1241 1-2 (s, 1 H), 5.77 (d, J= 17. 7 Hz, 1 H), 5.21 (d, J= 11. 5 CH3 Hz, 1 H), 3.65 (s, 3 H), 2.94 (m, 1 H), 1.57-0.56 (m, 11 H); MS (ESt : 529.3 Cpd. Starting Method No. From Used No. I From Used 'HNMR (DMSO-d6) : 8 10.07 (bs, 1H), 9.05 (bs, 2 H), 8.98 (bs, 2 H), 8.49 (t, J = 5. 6 Hz, 1 H), 7.96 (s, CH3 1 H), 7. 62 (m, 5 H), 7.06 (s, 1 H), 7.03 (s, 1 H), 125m-H-H 124m I-2 6.94 (dd, J = 11 and 18 Hz, 1 H), 5.78 (d, J 18 CH3 Hz, 1 H), 5.26 (d, J = 11 Hz, 1 H), 3.02 (t, J = 5.7 Hz, 2 H), 1.81 (m, 1 H), 0.85 (d, J = 6. 8 Hz, 6 H); MS (ES-) : 499.2 and (ES+) 501.3 Cpd.-R-Rl-R"Starting Method Analytical Data No. From Used H H N 133a-N N-)-H-CHs 132 A-5 MS (ES+) : 506.4 N :) H NU H 133b N _H-CH3 132 J v X N H 133c N-H-CH3 132 A-5 Characterized in the next step H/ F H 133d xN CF3-H-CH3 132 A-5 Characterized in the next step 133e \ CF3-H-CH3 132 A-5 Characterized in the next step NH... H

Cpd. |-R | Rf | R | Starting | Method | AnalyticalData Cpd.,"Starting Method No. From Usez CF3 133i \-H-CH3 132 A-5 Characterized in the next step H H CF3 133g H-H-CH3 132 A-5 Characterized in the next step N-6 F 133h H-H-CH3 132 A-5 Characterized in the next step N 133i-N 0-H-CH3 132 A-5 Characterized in the next step F 133j H-H-CH3 132 A-5 Characterized in the next step / N 133k A D-H-CH3 132 J MS (ES+) : 502.3 N Cpd. -,- Startmg Method.,... . Cpd. Starting Method Analytical Data No. From Used' 1331 H NH-H-CH3 132 J MS (ES+) : 470.2 N 133m-H-H-CH3 132 J MS (ES+) : 437.3 , N N 133n. N- ! !-H-CHs 132 J MS (ES+) : 518. 2 Orme 1330 N N-H-CH3 132 J MS (ES+) : 501.3 H N 133p N-H-CH3 4 132 J C 0 Zon N H H N-CH 132 J MS (ES-) : 469.1; MS (ES+) : 471.2 . 133r /\ 2-H-CH3 132 A-5 Characterized in the next step N H Cpd.,"Starting Method No. From Used No. From Used' OH 133s H-H-CH3 132 A-5 MS (ES+) : 483.2 (M+Na) /N N- 133u-H-CH3 132 A-5 MS (ES) : 432.2 133V xNw-H-CH3 132 A-5 MS (ES+) : 432.2 Hop 133w/-H-CH3 132 A-5 MS (ES+) : 447.2 OH N 133x N-H-CH3 132 A-5 Characterized in the next step H N 133y \/-H-CH3 132 A-5 MS (ES+) : 446.3 N H 133z N =-H-CH3 132 A-5 MS (ES+) : 446. 2 H H Cpd. Starting Method a.-R-R'-R' grorn Used Analytical Data No. From Used 133aa N OH-H-CH3 132 A-4 MS (ES+) : 475. 3 N< OH 133ab/N oH _H-CH3 132 J MS (ES+) : 499. 3 (M+Na) OH N N-- 133ac/-H-CH3 132 A-4 MS (ES-): 483.2; MS (ES+) : 485.2 / H, C H3c 133ad N N-H-CH3 132 A-4 MS (ES+) : 497.2; MS (ES-) : 495. 2 H Zu 133ae X/<\ XJ-H-CH3 132 A-4 MS (ES-) : 483.2; MS (ES+) : 485.2 NN H 133af S- zu Ac-H-CH3 132 J MS (ESi) : 5113 (M+r1a) + ; MS (ES-) : 487.3 Cpd.,"Starting Method No. From Used No. I li'rom Used I N OH N < OH 133ag/\=e-H-CH3 132 J MS (ES) : 451. 3 CH CH3 133ai t-H-CH3 132 J MS (ES-): 584.4 i 'Nso IHNMR (DMSO-d6) : 5 13.13 (bs, 1 H), 8.76 (t, J = 6 and 5 Hz, 1 H), 8.32 (m, 2 H), 8.02 (dd, J = 134a N-H-H 133a I-2 1. 9 and 8. 1 Hz, 1 H), 7.42 (m, 4 H), 7.25 (m, 1 -N N H), 3.62-3.19 (m, 12 H), 3.11 (t, J = 6.8 Hz, 2 H), -\ D 1. 87 (m, 1 H), 1.76 (m, 2 H), 0.90 (d, J = 6.8 Hz, N 6 H); MS (ES-) 490. 3 ; (ES+) 492. 3 'HNMR (DMSO-d6) : b 13.82 (bs, 1 H), 10.57 (bs, 2 H), 8.50 (t, J = 6 and 5 Hz, 1 H), 7.99 (d, J =1. 5 Hz, 1 H), 7.83 (s, 1 H), 7.8 (s, 1 H), 7.59 H 134b N < X-H-H 133b I-2 (m, 4 H), 7.46 (m, 2 H), 7.03 (m, 1 H), 6.92 (d, J = 7. 9 Hz, 1 H), 3.89 (s, 4 H), 3.02 (t, J = 6. 8 Hz, H 2 H), 1. 81 (m, I H), 0.8 (d, J = 6. 8 Hz, 6 H) ; MS (ES-) : 483.3; MS (ES+) : 485.4 IHNMR (DMSO-d6) : 6 8.71 (t, J=5.5 Hz, 1 H), 8. 40 (t, J=5. 3 Hz, 1H), 8.30 (s, 1 H), 8.00 (d, J= 7. 8 Hz, I H), 7.63 (d, J=4.3 Hz, 2 H), 7.40 (d, 134c N-H-H 133c I-2 J=7.4 Hz, 4 H), 7.27 (d, J=8.1 Hz, 1 H), 7.18 (s, 1 H), 6.91 (d, J=7.1 Hz, 1 H), 4.42 (b, 2 H), 3.13 (t, CF3 J = 6.5 Hz, 2 H), 1.93 (m, 1 H), 0.91 (d, J = 6.8 Hz, 6 H); MS (ES-) 497.3 Cpd. Starting Method No.-R-Rv-Rly From Used Analytical Data No. From Used' 'HNMR (DMSO-d6) : 6 10.45 (s, 1 H), 8.63 (s, 1 H H), 8. 2 7 (s, 1 H), 7.93 (d, J=8. IHz, 1 H), 7.67 (t, 134d/3-H-H 133d I-2 J=6.8 Hz, 2 H), 7.55 (m, 2 H), 7.27 (m 3 H), 7.12 (m, 2 H), 3.06 (t, J = 6 Hz, 2 H), 1.82 (m, 1 H), 0.86 (d, J = 6.8 Hz, 6 H); MS (ES-) 483. 3 'HNMR (DMSO-d6): 8 12.92 (bs, 1 H), 8.71 (t, J=5. 8Hz, 1 H), 8.49 (t, J=6.2 Hz, 1 H), 8. 32 (s, 1 -H'-H \\p H), 8. 01 (d, J=7. 7. 8 Hz, I H), 7.52 (m, 5 H), 7.27 134e N 3-H-H 133e I-2 (d, J=7.9 Hz, 1 H), 7.18 (m, 1 H), 7.08 (d, J=8.2 H Hz, 2 H), 4. 32 (d, J=4.2 Hz, 2 H), 3.12 (t, J = 6. 5 Hz, 2 H), 1. 88 (m, 1 H), 0. 91 (d, J = 6. 8 Hz, 6 H); MS (ES-) 498.2 CF3'HNMR (DMSO-d6) : 8 8.66 (t, J=5.7 Hz, 1 H), 8. 27 (s, 1 H), 7.92 (d, J=8.1 Hz, 1 H), 7.45 (m, 7 134f//a-H-H 133f I-2 H), 7.18 (m, 3 H), 4.32 (d, J=5. 9 Hz, 2 H), 3.12 N (t, J = 6 Hz, 2 H), 1.89 (m, 1 H), 0. 91 (d, J = 6. 8 H Hz, 6 H); MS (ES-) 497.2 CF'HNMR (DMSO-d6) : 8 13.1 (s, 1 H), 9.58 (s, 1 H), 8.65 (s, 1 H), 8.29 (s, 1 H), 7.98 (d, J=5. 9Hz, 134g N -H-H 133g I-2 1 H), 7.75 (d, J=5. 2Hz, 2H), 7. 30 (d, J=8Hz, 2 N H), 7.12 (d, J=12.0 Hz, 1 H), 7.12 (m, 4 H), 3.06 (t, J = 6 Hz, 2 H), 1.85 (m, 1 H), 0.86 (d, J = 6.8 Hz, 6 H); MS (ES-) 483.2 'HNMR (DMSO-d6) : 8 10.31 (s, 1 H), 8.65 (t, F J=6. 2 Hz, 1 H), 8.31 (s, 1 H), 7.98 (d, J= 7.9 Hz, 1 H), 7.66 (m, 1 H), 7.53 (m, 3 H), 7.27 (m, 4 H), 134h H4/\%-H-H 133h 6. 85 (m, 1 H), 3.09 (t, J = 6. 5 Hz, 2 H), 1. 86 (m, I H), 0.89 (d, J = 6.8 Hz, 6 H); MS (ES-) 433. 1 (M-') Cpd.,"Starting Method No. From Used No. From Used" IHNMR (DMSO-d6) : 8 8_71 (t, J=5. 7 Hz, 1 H), No. From Used 'HNMR (DMSO-d6) : 6 8. 71 (t, J=5. 7 Hz, 1 H), 8. 31 (s, 1 H), 8.01 (d, J= 7.9 Hz, 1 H), 7.46 (m, 2 134i \-H-H 133i I-2 H), 7. 39 (m, 2 H), 7.24 (s, 1 H), 3.38 (b, 8 H), 3.11 (t, J = 6. 5 Hz, 2 H), 1.86 (m, 1 H), 0. 91 (d, J = 6.8 Hz, 6 H); MS (ES-) 409.3 'HNMR (DMSO-d6) : 6 9. 61 (s, 1 H), 8. 67 (t, J=5. 5 Hz, 1 H), 8. 32 (s, 1 H), 7.98 (d, J= 7.9 Hz, 134j H 8 %. I2 lH), 7.71 (m, 2H), 7.54 (m, 2H), 7.29 (d, J=7.9 /Hz, 1 H), 7.04 (m, 4 H), 3.10 (t, J = 6. 5 Hz, 2 H), 1. 86 (m, 1 H), 0.89 (d, J = 6. 8 Hz, 6 H) ; MS (ES- )433. 3 IHNMR. (DMSO-d6) : 5 8.59 (t, J = 6 and 5 Hz, 1 N H), 8.3 (d, J = 5 Hz, 2 H), 8. 18 (s, I H), 7. 86 (d, J 134k-N-H-H 233k I-2 gng (s, 1 H), 7.86 (d, J / = 8 Hz, 1 H), 7. 36 (m, 5 H), 6. 6 (t, J = 4. 7 Hz, 1 H), 4.0 (m, 1 H), 3.75 (m, 2 H), 3. 37 (m, 5 H), 3. 07 (t, J = 6. 8 Hz, 2 H), 1.81 (m, 1 H), 0.85 (d, J =6. 8Hz, 6H) 'HNMR (DMSO-d6) : 6 10.92 (bs, 1 H), 8.55 (t, J = 6 and 5 Hz, 1 H), 8.14 (s, 1 H), 7.76 (d, J = 7 Hz, 1 H), 7.68 (m, 1 H), 7.62 (m, 1 H), 7.45 (m, 1341-H-H 1331 I 2 2 H), 7.24 (t, J = 2. 6 Hz, 1 H), 7.19 (s, 1 H), 7.15 1341-H-H 1331 I-2 H n I (s, lH), 7.10 (m, 2H), 6.95 (dd, J=1. 5and8. 7 N Hz, 1 H), 6. 28 (s, 1 H), 3. 04 (t, J = 6.8 Hz, 2 H), 1. 82 (m, 1 H), 0.86 (d, J = 6.8 Hz, 6 H); MS (ES- ) 454.3; (ES+) 456. 3 'HNMR (DMSO-d6) : 613. 13. 30 (bs, 1 H), 8.62 (t, J = 6 and 5 Hz, 1 H), 8.18 (s, 1 H), 7.87 (d, J=7. 9. 134m H-H-H. 133m I-2 Hz, 1 H), 7. 42 (m, 3 H), 7. 09 (m, 2 H), 3. 03 (m, N 1 H), 3. 1 (t, J = 6. 8 Hz, 2 H), 1.86 (m, 1 H), 1.4 (m, 4 H), 1.09 (m, 1 H), 0.89 (d, J = 6.8 Hz, 6 H); MS (ES-) 421.2; (ES+) 423.2 Cpd. Starting Method No. From Used No. From Used" 'HNMR (DMSO-d6) : 6 15.89 (bs, 1 H), 8.56 (t, J N = 6 and 5 Hz, 1 H), 8.06 (s, 1 H), 7.67 (m, 2 H), j 7. 54 (d, J = 8. 8 Hz, 1 H), 7.48 (m, 4 H), 7.05 (m, 134n/N----C I/-H-H 133n I-2 1 H), 6. 96 (m, 2 H), 3. 77 (s, 3 H), 3. 03 (t, J = 6. 8 S OMe Hz, 2 H), 1.81 (m, 1 H), 0.84 (d, J = 6. 8 Hz, 6 H); MS (ES-) 502. 3 ; (ES+) 504.3 'HNMR (DMSO-d6) : 8 13.07 (bs, 1 H), 8.63 (t, J = 6 and 5 Hz, 1 H), 8.26 (s, 1 H), 8.05 (d, J = 4 Hz, 1 H), 7.94 (d, J=8Hz, 1 H), 7.43 (m, 5H), 134o-H-H 133o 1-2 7.28 (m, 1 H), 6.72 (d, J = 8.8 Hz, 1 H), 6.62 (dd, J = 5, 5 and 6. 5 Hz, 1 H), 3. 34 (m, 8 H), 3. 07 (t, J = 6.8 Hz, 2 H), 1.82 (m, 1 H), 0.85 (d, J = 6.8 Hz, 6 H); MS (ES-) 486. 3 ; (ES+) 488. 3 '14NMR (DMSO-d6): 8 12.94 (bs, 1 H), 10.20 (bs, 1 H), 8.63 (t, J = 6 and 5 Hz, 1 H), 8.28 (d, J 1 H), 7.96 (m, 2 H), 7.92 (d, J = 8. 3 H =l. SHz, 1H), 7.52 (m, 2H, 7.4 m, 1 134p 8 -H-H 133p I-2 Hz, 1 H), 7.4 (m, 1 , zN H), 7. 3 (m, 2 H), 7.24 (m, 1 H), 3.08 (t, J = 6. 8 Hz, 2 H), 1.84 (m, 1 H), 0.88 (d, J = 6.8 Hz, 6 H); MS (ES-) 455. 2; (ES+) 479.2 (M+Na) 'HNMR (DMSO-d6) : 8 12.84 (bs, 1 H), 10.45 (bs, 1 H), 8.62 (t, J = 6 and 5 Hz, 1 H), 8.27 (d, J =, 1.5 Hz, 1 H), 8.01 (s, 1 H), 7.93 (s, 2 H), 7.9 g-H (d, J =1. 5 Hz,, 1 H) 7. 57 (d J = 1 H) 7. 69 (m,,, 134q/N\\//N-H-H 133q I-2 8. 7 Hz, 1 H), 7.52 (m, 2 H), 7.29 (d, J = 8 Hz, 1 nN H), 7.23 (m, 1 H), 7. 02 (dd, J = 1. 5 and 8.7 Hz, 1 H), 3.07 (t, J = 6.8 Hz, 2 H), 1.83 (m, 1 H), 0.87 (d, J = 6.8 Hz, 6 H), MS (ES-) 455.2; (ES+) 479.3 (M+Na) Cpd. Starting Method Analytical Data No. From Used IHNMR (DMSO-d6) : 5 8.64 (t, J=5.5 Hz, 1 H), 8. 16 (s, 1 H), 7.87 (d, J=7. 1 Hz, 1H), 7.50 (m, 1 134r"N/--. NH2-H-H 133r 1-2 H), 7. 40 (d, J=4.1 Hz, 2 H), 7.19 (b, 3 H), 7.07 (m, 2 H), 6.51 (m, 2 H), 6.35 (d, J=7.8 Hz, 2 H), H 3. 97 (d, J=5.6 Hz, 2 H), 3.13 (t, J = 6. 5 Hz, 2 H), 1. 90 (m, 1 H), 0. 91 (d, J = 6. 8 Hz, 6 H) OH'HNMR (DMSO-d6) : 8 9.53 (bs, 1 H), 8. 67 (t, J=4. 7 Hz, 1 H), 8.32 (s, 1 H), 7.99 d, J=8.1 Hz, 1 134s-H-H 133s 1-2 H), 7. 70 (d, J=7. 6 Hz, 1 H), 7.52 (m, 2 H), 7.46 (d, J=l 1. 5 Hz, I H), 7.32 (m, 3 H), 7.18 (m, 3 H), N 4. 33 (s, 2H), 3.10 (t, J=6. 5Hz, 2H), 1.86 (m, 1 H), 0. 89 (d, J = 6.8 Hz, 6 H); MS (ES-) 445. 2 1HNMR (DMSO-d6) : 8 12.57 (b, 1 H), 8.69 (t, J=5.6 Hz, 1 H), 8.36 (s, 1 H), 7.99 (d, J= 7. 9 Hz, 1 H), 7.92 (d, J=7. 7 Hz, 1 H), 7.57 (t, J=7.5 Hz, 134t-OH-H-H 132 I-2 1H), 7.46 (t, J=7. 7 Hz, 1H), 7.23 (d, J=5. 2 Hz, 1H), 7.17 (d, J=7.5 Hz, 1H), 3.12 (t, J = 6.5 Hz, 2 H), 1.88 (m, 1 H), 0.91 (d, J = 6.8 Hz, 6 H); MS (ES-)340.2 'HNMR (DMSO-d6): 8 8.56 (t, J=5. 0 Hz, 1 H), 8.16 (d, J=7. 0 Hz, 2 H), 7.94 (d, J=8. 4 Hz, 1 H), 7. 75 (d, J=7. 4 Hz, 1 H), 7.63 (m, 2 H), 7.46 (m, 2 134u N--H-H 133u I-2 H H), 7. 21 (b, I H), 7. 07 (s, 2 H), 6. 99 (t, J=5. 1 Hz, xN 1 H), 3. 05 (t, J = 6.5 Hz, 2 H), 1.83 (m, 1 H), 0. 86 (d, J = 6. 8 Hz, 6 H); MS (ES-) 416.3 'HNMR (DMSO-d6) : 6 8.60 (t, J=5.6 Hz, 1 H), 8. 32 (d, J=5.3 Hz, 2 H), 8.11 (s, 1 H), 7.78 (d, 134v/-H-H 133v Z-2, J- Hz, 1 H), 7. 65 (d, J=5. 5 Hz, 1 H), 7. 55 (m, N__C\ N 2 H), 7.43 (d, J=4.5 Hz, 2 H), 7.14 (m, 3 H), 3.06 (t, J = 6. 5 Hz, 2 H), 1.83 (m, 1 H), 0.86 (d, J = 6. 8 Hz, 6 H); MS (ES-) 416.2 Cpd. Tr., Tr.,, Starttns Method.,.., .. Cpd. |-R |-R'-R''Starti g Method Allalytical Data No. From Used IHNMR (DMSO-d6) : 8 10.10 (bs, 1 H), 9.31 (s, 1 H), 8.65 (t, J=5.7 Hz, 1 H), 8.27 (s, 1 H), 7.93 (d, H__p J=8. 1 Hz, 1 H), 7.62 (d, J=5. 3 Hz, 1 H), 7.48 (m, H, 2 H), 7.28 (s, 1 H), 7.20 (d, J=12.0 Hz, 1 H), 7.09 134w/-H-H 133w I-2 (s, 1 H), 6.98 (d, J=7.0 Hz, 1 H), 6.81 (d, J=7. 3 OH Hz, 1 H), 6.37 (t, J=7.6 Hz, 1 H), 3.09 (t, J = 6.5 Hz, 2 H), 1.85 (m, 1 H), 0. 90 (d, J = 6. 8 Hz, 6 H); MS (ES-) 431. 1 IHNMR (DMSO-d6) : 8 10.28 (bs, 1 H), 8.63 (t, J=5.3 Hz, 1 H), 8.34 (d, J=4.7 Hz, 1 H), 8.06 (s, N 1 H), 7.82 (d, J=6.6 Hz, 1 H), 7.53 (m, 1 H), 7.42 /\E H 3 I 2 (m, 2 H), 7.34 (t, J=8.6 Hz, 1 H), 7.18 (s, 1 H), 7. 07 (d, J=2.7Hz, 2 H), 6.10 (b; 1 H), 4.43 (b; 1 H H), 4.12 (b, 1 H), 3.12 (t, J = 6.5 Hz, 2 H), 1.89 (m, 1 H), 0. 90 (d, J = 6. 8 Hz, 6 H); MS (ES+) 432. 3, (ES-)430.2 'HNMR (DMSO-d6) : 6 9.79 (bs, 1 H), 8.62 (t, J=6.0 Hz, 1 H), 8. 31 (d, J=4.5 Hz, 1 H), 8.20 (s, 1 H), 8.08 (s, 1 H), 7.78 (d, J=2.1 Hz, 1 H), 7.51 134y X e f-H-H 133y I-2 (m, 1 H), 7.42 (m, 2 H), 7.06 (m, 3 H), 6.88 (m, 1 N \=/H), 4.02 (b, 2 H), 3.13 (t, J = 6.5 Hz, 2 H), 1.90 H (m, 1 H), 0.93 (d, J = 6.8 Hz, 6 H); MS (ES+) 432. 3, (ES-) 430.3 'HNMR (DMSO-d6) : 8 10.71 (bs, 1 H), 8.64 (t, J=5. 9 Hz, 1 H), 8.21 (d, J=5.2 Hz, 2 H), 8.05 (s, 1 H), 7.81 (d, J=7.7 Hz, 1 H), 7.51 (m, 1 H), 7.42 134z/-H-H 133z I-2 (m, 2 H), 7.18 (s, 1 H), 7.04 (t, J=1. 4Hz, 2 H), N (b, 1 H), 3.13 6. 51 (b, 2H), 4.41 (b, 1 H), 4. 01 (b, 1 H), 3. 13 (t, H J=6. 5Hz, 2H), 1.91 (m, 1 H), 0. 91 (d, J=6. 8 Hz, 6 H) ; MS (ES+) 432. 2, (ES-) 430. 2 Cpd."Starting Method Analytical Data No. From Usez HMMR (DMSO-d6) : 8 10. 02 (bs, 1 H), 8. 65 (t, J = 5. 7 Hz, 1 H), 8. 26 (s, 1 H), 7. 94 (d, J= 7. 7 Hz, 1 H H), 7, 66 (d, J=5. 8 Hz, I H), 7.51 (m, 2 H), 7. 36 (d, J=8. 4 Hz, 2 H), 729 (d, J=7. 9 Hz, 1 H), 7.22 (d, l3aa/OH-H-H 133aa I-2 134aa 5 Hz, 1 H), 7. 07 (d, J=8. 3 Hz, 2 H), 4. 57 (t, J=9.0 Hz, 1 H), 3.51 (m, 2 H), 3.09 (t, J = 6. 5 Hz, 2 H), 2.62 (t, J=6.6 Hz, 2 H), 1.85 (m, 1 H), 0. 90 (d, J = 6. 8 Hz, 6 H), MS (ES-) 459. 2 'HNMR (DMSO-d6) : 8 9.05 (s, 1 H), 8.70 (t, H J=5. 7 Hz, 1 H), 8.56 (s, 1 H), 8.36 (s, 1 H), 8.12 N OH (m, 2 H), 7.79 (m, 1 H), 7.60 (m, 1 H), 7.44 (s, 2 134ab-H-H 133ab I-2 H), 7.09 (m, 2 H), 6.56 (d, J=8. 9 Hz, 1 H), 4.89 OH (t, J=4.4 Hz, 1 H), 4.38 (d, J=5. 6 Hz, 2 H), 3.11 (t, J = 6. 5 Hz, 2 H), 1.84 (m, 1 H), 0. 90 (d, J = 6. 8 Hz, 6 H), MS (ES-) 461.1 'HNMR (DMSO-d6) : 6 8.60 (t, J = 6 and 5 Hz, 1 N/s H), 8.13 (s, 2 H), 7.85 (d, J = 2 Hz, 1 H), 7.46 H (m, 4 H), 7. 36 (d, J = 7. 7 Hz, 1 H), 7.16 (m, 4 H), 134ac/N/-H-H 133ac I-2 , lp (m, 1 H), 3. 17 (s, 3 H), 3. 08 (t, J = b. 8 Hz, 2 H), 1.85 (m, 1 H), 0.89 (d, J = 6. 8 Hz, 6 H), MS H, C (ES-) 469.2; (ES+) 471. 3 'HNMR (DMSO-d6): 8 8.55 (t, J = 6 and 5 Hz, 1 /1-N H), 8.10 (s, 2 H), 7.73 (d, J = 7. 2 Hz, 1 H), 7. 54 134ad _j-H-H 133ad 1-2 (m, 4 H), 7.46 (m, 5 H), 7.08 (m, 3 H), 3.04 (t, J = 6. 8 Hz, 2 H), 1.82 (m, 1 H), 0.86 (d, J = 6. 8 Hz, 6 H), MS (ES-) 481.1; (ES+) 483.3 Cpd. Starting Method No. From Used No. From Used 'HNMR (DMSO-d6) : 6 9.66 (bs, 1H), 8. 54 (t, J = H 6andSHz, lH), 8.12 (s, 2H), 7.77 (dd, J=8 and 2 Hz, 1 H), 7.6 (dd, J = 7 and 2 Hz, I H), 134ae \/<\ XJ-H-H 133ae I-2 7. 45 (m, 5 H), 7.10 (m, 4 H), 4.36 (bs, 2 H), 3.09 N N (t, J=6. 8Hz, 2H), 1.86 (m, 1 H), 0.89 (d, J = 6. 8 Hz, 6 H), MS (ES-) 469.2; (ES+) 471.3 'HNMR (DMSO-d6) : 5 9.76 (s, 1 H), 9.17 (s, 1 H), 8.63 (t, J=5. 0 Hz, 1 H), 8. 29 (s, 1 H), 7.90 (d, J=1. 6 Hz, 1 H), 7.60 (s, 1 H), 7.51 (d, J=8 Hz 1 134af N < OH-H-H 133af I-2 H), 7.30 (d, J=3. 6 Hz, 2 H), 7.28 (d, J=8.2Hz, 1 /H), 7.22 (t, 3 H), 6.60 (d, J=8. 9 Hz, 1 H), 3.06 (t, J = 6 Hz, 2 H), 1.85 (m, 1 H), 0.86 (d, J = 6.8 Hz, 6 H); MS (ES-) 431.2 'HNMR (DMSO-d6) : 8 9.64 (s, 1 H), 9.06 (s, 1 H), 8.66 (t, J=5.6 Hz, 1 H), 8.29 (s, 1 H), 7.95 (d, H J=7. 9 Hz, 1 H), 7.63 (m, 1 H), 7.50 (m, 2 H), NH) sOH 7 29 (d, J=3. 1 Hz, 1 H), 7.20 (d, J=8. 9 Hz, I H), 134ag/\=<-H-H 133ag I-2 7 11 (m, 1 H), 7.03 (m, 1 H), 6.60 (d, J=8. 9 Hz, 1 CH3 H), 3.08 (t, J = 6 Hz, 2 H), 2.05 (s, 3 H), 1.85 (m, 1 H), 0.86 (d, J = 6.8 Hz, 6 H); MS (ES-) 445. 2, MS (ES+) 469.3 (M+Na) N < H N H 134ai/\=/l-H-H 133ai I-2, S MS (ES+) : 472.2; MS (ES-) : 470.2 N- N NH2 N'---"'----, N N . 135a H N-CH=CH2-CH3 30f A-4 MS (ES+) : 489. 3 Cpd. Starting Method No. From Used- H H N L nL o CS m. MS (ES) : 4753 ; MS (ES : 4733 NON H N y 135c AX NHBoc-CH=CH2-CH3 30f J MS (ES+) : 573. 5 ; MS (ES) 571.3 N zon 135d xNt \NH2-CH=CH2-CH3 30f A-4 MS (ES-): 472.2 N cl 135 s-CH=CH3-CH3 0 30f J W N H 135f/N -CH=CHZ-CH3 30f J MS (ES-) : 498. 1 NEZ 135g/N cHzcN-H=CHZ-CH3 30f J MS (ES-) : 494. 3 135h/5 <CH2NHBoc-CH CH2-CH3 30f J MS (ES-) : 584.2 Cpd. Starting Method Analytical Data No. From Used 'HNMR (DMSO-d6) : 8 8.66 (t, J =. 55 Hz, 1 H), 8.35 (t, J = 4 and 6.4 Hz, l H), 8.28 (d, J = 2 Hz, 1 H), 7.95 (dd, J = 7.9 and 2 Hz, 1 H), 7.69 (s, 1 H), 7.59 (m, 2 H), 7. 25 (d, J = 8.1 Hz, 2 H), 7.15 N N (m, 2 H), 6. 93 (s, 1 H), 6. 88 (dd, J = 17. 7 and /11. 5 Hz, 1 H), 5. 95 (d, J = 17. 7 Hz, 1 H), 5. 37 (d, J=11. 5HzalH), 3.76 (t, J = 6. 8 Hz, 2 H), 3.10 (t, J = 6. 4 Hz, 2 H), 2.96 (m, 2 H), 1.86 (m, 1 H), 1.67 (m, 2 H), 0.89 (d, J = 6.8 Hz, 6 H); MS (ES-) 473. 3 ; (ES+) 475. 3 'HNMR (DMSO-d6) : 8 8.64 (t, 1 H), 8.51 (s, 1 H H), 8.21 (s, 1 H), 7.88 (d, J=7.8 Hz, 1 H), 7. 74 (s, N 1 H), 7. 56 (s, 2 H), 7.15 (m, 2 H), 6.80 (t, 2 H), 136b X, Jt/>-CH=CH2-H 135b I-2 5.90 (d, J=17 Hz, 1 H), 5. 36 (d, J=ll. OHz, 1 H), N N 3. 18 (m, 2 H), 3.06 (t, J = 6 Hz, 2 H), 2.43 (m, 2 H), 1.85 (m, 1 H), 0.86 (d, J = 6. 8 Hz, 6 H) ; MS (ES+) 461. 2, MS (ES-) 459.2 'HNMR (DMSO-d6/D20) : 8 8.71 (t, 1 H), 8.27 (d, J= 3 Hz, 1 H), 8.21 (d, J=3 Hz, 1 H), 7.96 (q, 1 H), 7.79 (q, 1 H), 7.72 (s, 1 H), 7.63 (d, J=8 Hz 1 136c N-"-NH,-CH=CH2-H 135c 1-2, S H), 7. 30 (d, J=6 Hz, 1 H), 7.24 (d, J=7 Hz, 1 H), 6. 87 (q, 2 H), 6.00 (d, J=8 Hz, 1 H), 5.41 (d, J=8 Hz, 1 H), 3.06 (t, J = 6 Hz, 2 H), 1.85 (m, 1 H), 0. 86 (d, J = 6. 8 Hz, 6 H) ; MS (ES+) 459.2 p Starting Method No. From Used No. From Used- 'HNMR (DMSO-d6) : 6 12.86 (bs, 1 H), 9.17 (s, 1 H), 8.65 (t, J = 6 Hz, 1 H), 8.29 (d, J = 2 Hz, 1 H), 8.26 (s, 2 H), 7.97 (dd, J = 8 and 2 Hz, 1 H), 7. 76 (s, 1 H), 7.63 (d, 8 Hz, 1 H), 7.31 (d, J = 8 136d NX \<NH-CH=CH2-H 135d I-2 Hz, 1 H), 7.24 (d, J = 8 Hz, 1 H), 6.86 (dd, J = /\=/2 10.7 and 17. 5 Hz, 1 H), 6.49 (s, 1 H), 5.99 (d, J = N 17. 5, 1 H), 5.40 (d, J = 10. 7 Hz, 1 H), 3.10 (t, J = 6.8 Hz, 2 H), 1.86 (m, 1 H), 0.89 (d, J = 6. 8 Hz, 6 H); MS (ES-) 458.2, (ES+) 460. 3 'HNMR (DMSO-d6): 6 12.72 (s, broad, 1 H), 8. 65 (t, J=5. 7 Hz, 1 H), 8.29 (s, 1 H), 7.93 (d, Cl J=7. 9 Hz, 1 H), 7.74 (m, 2 H), 7.65 (d, J=6 Hz 1 136e H n-CH=CH2-H 135e I-2 H), 7. 42 (d, J=7. 9 Hz, 1 H), 7.24 (m, 3 H), 7.11 (m, 1 H), 6.84 (q, J=l 1. 1, 17.8 Hz, 1 H), 5.97 (d, /, T=18 Hz, I H), 5.58 (d, 1 H), 5.41 (d, I H), 3.08 (t, J = 6 Hz, 2 H), 1.85 (m, 1 H), 0.86 (d, J = 6. 8 Hz, 6 H); MS (ES-) 475.1 'HNMR (DMSO-d6) : 8 8.67 (t, J=6.06 Hz, 1 H), 8.28 (s, 1 H), 7.90 (d, J=7.7Hz, 1 H), 7.67 (m, 4 /mS o H), 7. 32 (m, 5H), 7.09 (d, J=7.9HzlH), 6.89 136f NA A-CH=CH2-H 135f I-2 (q, J=10.9 & 18.0 Hz, 1 H), 5.99 (d, J=17.5Hz, 1 /\-/\H H), 5.42 (d, J=11 Hz, 1 H), 3.08- (t, J=6.3 Hz, 2 H), 1.88 (m, 1 H), 0.87 (d, J = 6. 8 Hz, 6 H) ; MS (ES-) 484. 2 Cpd. Starting Method No. From Used No. From Used" 'HNMR (DMSO-d6) : 8 10. 38 (s, 1 H), 8.66 (t, J=6.06 Hz, 1 H), 8.29 (s, 1 H), 7.95 (d, J=6.1 Hz, 1 H), 7.75 (s, 1 H), 7.63 (d, 2 H), 7.43 (d, 2 H), 7. 26 (m, 3 H), 7.00 (d, J=7.7 Hz, I H), 6.85 (q, N _CHCN J=10. 9 & 18. 0 Hz, 1 H), 5. 98 (d, J=17.5Hz, 1 H), 5. 40 (d, J=11 Hz, 1 H), 3.98 (s, 2 H), 3.08 (t, J=6. 3 Hz, 2 H), 1.86 (m, 1 H), 0.88 (d, J = 6. 8 Hz, 6 H); MS (ES-) 480. 2 'HNMR (DMSO-d6) : 8 8.55 (t, J=6.06 Hz, 1 H), 8.02 (s, 1 H), 7.60 (m, 4H), 7.21 (t, J=7. 1,2 H), H 6. 99 (m, 2 H), 6.83 (d, J=6.8 Hz, 1H), 6.81 (q, 136h/N<=tCH2NH2-CH=CH2-H 135h S, I-2 J=10. 9 & 18.0 Hz, 1H), 5.92 (d, J=17.5Hz, 1 H), 5. 35 (d, J=11 Hz, 1 H), 3.89 (s, 2H), 3.03 (t, J=6.3 Hz, 2 H), 1.36 (m, 1 H), 0.86 (d, J = 6. 8 Hz, 6 H) Cpd.,"Starting Method No. From Used No. From Used 'H NMR (DMSO-d6) : 6 10.65 (s, 1 H), 10.15 (s, 1 H), 9. 19 (s, 2 H), 8.88 (s, 2 H), 8.10 (d, J=2. 1 Hz, 1 H), 148a-CH3 CH3 7. 92 (s, 1 H), 7.93-7.75 (m, 6 H), 7.31 (dd, J= 8.4 and 148a ¢3-CH3 X Jt 147a J 23. 9 Hz, 1 H), 7.12 (d, J= 3.5 Hz, 1 H), 6.67 (m, 1 H), O N CH3 3.53 (s, 3 H), 2.20 (d, J= 7. 0 Hz, 2 H), 2.07 (m, 1 H), 0.94 (d, J= 6. 3 Hz, 6 H). 'H NMR (DMSO-d6) : 5 10.65 (s, 1 H), 10.09 (s, 1 H), 9.17 (s, 1 H), 8.83 (s, 1 H), 8.10 (d, J= 2. 0 Hz, 1 O CH3 H), 7.85 (d, J= 2.0 Hz, 2 H), 7.81 (d, J= 2.0 and 7.9 , - Hz, 2H), 7.76 (m, 5H), 7.66 (d, J=3. 9Hz, 1 H), 7.62 148b -3"N""CH,"'"'' (d, J=4. 9Hz, lH), 7. 31 (d, J= 7. 9 Hz, 1 H), 7.26 (d, S H J= 7. 9 Hz, 1 H), 7.19 (t, J= 3. 9 Hz, 1 H), 3.53 (s, 1 H), 2. 19 (d, J= 6.9 Hz, 2 H), 2.06 (m, J= 6.9 Hz, 1 H), 0.92 (d, J= 6.9 Hz, 6 H); MS (ES+) : 555.67 0 CH3 148c-CH=CH2-CH3 J ! L 147c J Characterized in the next step H H

Cpd.Starting Method *-R-R-R""., AnatyttcatData No. From Used qn O CH3 149a '-H jj J. 148a I-2 MS (ESt : 525.3 O NH CH3 HL IH NMR (DMSO-d6) : 8 13.95 (s, 1 H), 9.79 (s, 1 H), A o CH3 8. 87 (s, 4 H), 7.76 (s, 1 H), 7.65 (m, 8 H), 7.46 (dd, J= 149b (\-H \ 148b I-2 2-1 and 8. 4 Hz, 1 H), 7. 16 (t, J= 4. 2 Hz, 1 H), 7. 04 (d, g H CH3 J= 7. 7 Hz, 1 H), 6.76 (d, J= 8. 4 Hz, I H), 2.13 (d, J= 7. 0 Hz, 2 H), 2.03 (m, J= 6.3 and 7.0 Hz, I H), 0.90 (d, J= 6.3 Hz, 6 H); MS (ES+) : 541.62 O CH3 jj ' 149c-CH=CH2-H N v 148c I-2 MS (ES+) : 485.6 N CH, N CH3 { ?'H NMR (DMSO-d6) : 6 8.81 (m, 4 H), 8.37 (t, J= 6.0 175-H-CH3 N c3 14 J Hz, 1 H), 7.74-7.23 (m, 11 H), 4. 31 (d, J= 6. 2 Hz, 2 H-ly H), 3.51 (s, 3 H), 2.44 (m, 1 H), 1.04 (d, J= 7. 0 Hz, 6 CH3 H); MS (ES% : 473.3 R 1H NMR (: DMSO-d6) : 5 13.79 (br s, 1 H), 9.03 (m, 3 176-H-H--"N CH 3 175 1-2 H), 8. 25 (m, 1 H), 7.78-7. 35 (m, 7 H), 6.99 (m, 2 H), g ! 6. 79 (m, 1 H), 4.20 (br s, 2 H), 3.51 (s, 3 H), 2.39 (m, CH3 1 H), 1.00 (d, J= 6.8 Hz, 6 H); MS (ES+) : 459.3 /s CH3'H NMR (DMSO-d6) : 6 8.96 (m, 2 H), 7. 79-7. 38 (m, CH () 7.79-7.38 (m, 182-H-CH3 Nv 178 J 9 H), 7.29 (dd, J= 7. 5 md 1. 7 Hz, 2 H), 4.42 (s, 2 H), I CH 3. 50 (S, 3 H), 2.97 (s, 2 H), 1.87 (m, 1 H), 1. 36 (m, 9 Boc 3 H), 0.81 (d, J= 6.8 Hz, 6 H); MS (ES'') : 559.5 Cpd. Starting Method No.-From Used No l From Vsed n A CH3'H NMR (DMSO-d6) : 8 9.11 (m, 4 H), 7.86 (s, 1 H), N-f 182 I2 S 7. 66 (m, 5H), 7.49 (m, 2H), 7. 38 (m, 1H), 7.08 (m, 2 183-H-H H 182 I-2, S cH H), 4.12 (s, 2 H), 2.59 (m, 2 H), 1.87 (m, 1 H), 0.81 (d, J= 6.6 Hz, 6 H); MS (ES) : 445.32 N (in Ring Cpd. With Starting Method No. Respect to From Used Phenyl) 151 3-CHO-CH3 D-9 MS (ES-): 339.3 'H NMR (CDC13) : 8 8.69 (t, J= 5.8 Hz, 1 H), 8.50 (d, J= 4.9 Hz, 1 H), 8. 33 (d, J=1. 7 Hz, 1 152 3-C02H-CH3 151 E H), 8.24 (s, 1 H), 8.01 (dd, J= 7.9,1.9 Hz, 1 H), 7. 53 (d, J= 5. 1 Hz, 1 H), 7.34 (d, J= 8. 1 Hz, 1 H), 3.56 (s, 3 H), 3.12 (m, 2 H), 1.87 (m, 1 H), 0.91 (d, J=6. 6Hz, 6H) NH HNMR (CD30D) : 6 8.75 (d, J = 4.7 Hz, 2 H), 8. 55 (s, 1 H), 8.42 (d, J= 1.9 Hz, 1 H), 8.07 (dd, 153 3 o o rNH, J=8. 1, 1. 9,1 H), 7.74 (s, 3 H), 7.70 (d, J= 5. 1 Hz, 1 H), 7.51 (d, J= 8. 1 Hz, 1 H), 3.69 (s, 3 H), 3. 21 (m, 2 H), 1.94 (m, 1 H), 0.98 (d, J= 6.6 Hz, H 6 H) ; MS (ES+) : 474

N (in Ring Cpd. With Starting Method No. Respect to From Used Phenyl) IHNMR (DMSO) : 8 11. 18 (s, 1 H), 9.31 (s, 2 NH H), 9.10 (s, 2 H), 8.92 (d, J= 5.1 Hz, 1 H), 8.78 (m, 2 H), 8.43 (d, J=1. 5 Hz, 1 H), 8.07 (dd, J= 154 4\/\NH2 I-2 7.9,1. 3 Hz, 1 H), 7.97 (d, J= 5. 3 Hz, 1 H), 7.82 ff L JJ (d, J=8. 7Hz, 2H), 7.72 (d, J= 8. 8 Hz, 2 H), AN 7. 50 (d, J= 7.9 Hz, 1 H), 3.10 (t, J= 6.0 Hz, 2 H H H), 1.86 (m, 1 H), 0.89 (d, J=6.6 Hz, 6 H); MS ES+) 460 156 4-CHO-CH3 155+ 3a D-9 MS (ESt : 341.4 tHNMR (CDC13) : 8 8.80 (s, 1 H), 8.46 (d, J= 5.1 Hz, 1 H), 8.29 (s, 1 H), 7.85 (d, J= 7.9 Hz, 1 157 4-CO2H-CH3 156 E H), 7. 13 (d, J = 7. 9 Hz, I H), 7. 00 (d, J = 5. 1 Hz, 1 H), 6.83 (bs, 2 H), 3.45 (s, 3 H), 3.15 (m, 2 H), 1.84 (m, 1 H), 0.90 (d, J= 6.6 Hz, 6 H); MS (ES- ) : 355.2 NH'HNMR (CD30D) : 8 8.85 (s, 1 H), 8.75 (d, J= 53 Hz, 1 H), 8.41 (d, J = 1. 9 Hz, 1 H), 8.07 (dd, 158 vNH2 C J J = 8. 1,2.1,1 H), 7.74 (s, 4 H), 7.48 (d, J= 8. 1 Hz, 1 H), 7.45 (d, J= 5. 1 Hz, 1 H), 3.69 (s, 3 H), AN 3. 21 (m, 2 H), 1. 94 (m, 1 H), 0.97 (d, J= 6.8 Hz, 6 H); MS (ES-): 472.4 NH IHNMR (DMSO): 8 10. 97 (s, 1 H), 9.24 (s, 2 0 NH2 H), 8.96 (s, 3 H), 8.79 (m, 2 H), 8.40 (d, J=1. 8 159 4-H 158 1-2 Hz, 1 H), 8. 06 (d, J= 7. 7 Hz, 1 H), 7. 77 (s, 4 H), J 7. 52 (m, lH), 7. 38 (d, V= 7. 5 Hz, 1H), 3. 10 (m, NH 2 H), 1.85 (m, 1 H), 0.89 (d, J= 5. 3, 6 H); MS (ES) 460. 2

Cpd. Starting Method No. -R -R' From Used Analytical Data 1H NMR (DMSO-d6): # 10.55 (s, 1H), 9.00 (bs, 2H), 8.68 (t, J = 5.8 Hz, 1H)M, 8.24 (d, J = 1.9 Hz, 1H), 8.04 (d, J = 8.1 Hz, 1h), 7.91 (d, J= 8.8 Hz, 2H), 7.77 (d, J=1.3 Hz, 1H), 7.67 (m 3H), 7.40 (d, J = 7.9 Hz, 161a -CH3 -CH3 31f AB-2 1H), 7.29 (d J = 7.9 Hz, 1H), 6.90 (dd, J=17.7, 11.) Hzm, 1H), 6.03 (d, J = 17.7 Hz, 1H), 5.42 (d, J=11.0 Hz, 1H), 3.61 (s, 3H), 3.56 (s, 3H), 3.10 (t, J = 6.4 Hz, 2H), 1.85 (m, 1H, 0.90 (d, J=6.5 Hz, 6H); MS (ES+): 557.3 1H NMR (DMSO-d6): # 10.54 (s, 1H), 9.20 (bs, 4H), 8.67 (t, J=6 Hz, 1H), 8.24 (1H), 8.02 (1h), 7.91 (2H), 7.77 (1H), 7.66 (m, 3H), 7.40 161b -C2H5 -CH3 31f AB-2 (1H)m, 7.29 (1H), 6.88 (dd, j=17.3, 10.7 Hz, 1H), 6.0-3 (d, J=17.3 Hz, 1H), 5.42 (d, J=10.7 Hz, 1H), 3.56 (s, 3H), 3.5 (m, 3H), 3.09 (2H), .85 (m, 1H), 0.89 (6H): MS (ES+): 571.3 1H NMR (DMSO-d6): # 10.54 (s, 1H), 9.20 (bs, 2h), 8.68 (t. J=5.8 Hz, 1H), 8.24 (d, J = 1.9 Hz, 1H)_, 8.03 (d, j = 8.1 Hz, 1H), 7.92 (d, J = 8.8 Hz, 2H), 7.77 (s, 1H), 7.68 (m, 4H), 7.36 (m, 6H), 6.89 (dd, J = 161c -CH2C6H5 -CH3 31f Ab-2 17.7, 11.2 Hz, 1H), 5.05 (s, 2H), 6.03 (d, J = 17.7 Hz, 1H), 5.42 (d, J = 11.2 Hz, 1H), 3.56 (s, 3H), 3.09 (t, J =6.6 Hz 2H)m, 1.84 (m, 1h), 0.89 (d, J = 6.6 Hz, 6H); MS (ES+): 633.3 Cpd. _R ^R, Starting Method Analytical Data -R-R' ° . AnatytcatData No. From Used 161d-C (CH3) 3-CH3 31f AB-2 MS (ES) : 599. 3 and 499. 3 'HNMR (DMSO-d6): 8 10.59 (s, 1H), 9.24 (s, 2H), 8.68 (t, J = 5.6 Hz, 1H), 8.24 (d, J = 1. 8 Hz, 1H), 8.03 (dd, J = 8.9,1.9 Hz, 1H), 7.96 (d, J = 8.9 Hz, 2H), 7.79 (d, J = 1. 5 Hz, 1H), 7.69 (m, 3H), 7.41 (d, J = 8.1 161e-CH2-CC13-CH3 31f AB-2 Hz, 1H), 7.29 (d, J = 8.0 Hz, 1H), 6.89 (dd, J = 17. 7,11.1 Hz, IH), 6.03 (d, J = 17. 7 Hz, 1H), 5.42 (d, J = 11. 1 Hz, 1H), 4.88 (s, 2H), 3.56 (s, 3H), 3.10 (t, J = 6.6 Hz, 2H), 1.85 (m, 1H), 0.89 (d, J = 6.6 Hz, 6H); MS (ES+): 674.97 'H NMR (DMSO-d6): 8 10.58 (s, 1H), 9.15 (s, 2H), 8.69 (t, J = 5.4 Hz, 1H), 8.25 (d, J = 1. 8 Hz, 1H), 8.04 (dd, J = 8.1,1.9 Hz, 1H), 7.95 (d, J /R = 8. 9 Hz, 2H), 7.78 (s, 1H), 7.68 (m, 3H), 7.40 (d, J = 8.0 Hz, 1H), 7.29 161f OMe-CH3 31f AB-2 (d, J = 8. 0 Hz, 1H), 7.07 (d, J = 8. 8 Hz, 2H), 6.93 (d, J = 8. 8 Hz, 2H), 6. 89 (dd, J = 17. 7,11.1 Hz, 1H), 6.03 (d, J = 17. 7 Hz, 1H), 5.42 (d, J = 11. 1 Hz, 1H), 3.75 (s, 3H), 3.57 (s, 3H), 3.10 (t, J = 6. 6 Hz, 2H), 1.85 (m, 1H), 0.89 (d, J = 6.6 Hz, 6H); MS (ES+): 649.3 H NMR (DMSO-d6): 8 10.59 (s, 1H), 9.19 (s, 2H), 8.68 (t, J = 5.7 Hz, 1H), 8.25 (d, J = 1. 8 Hz, 1H), 8.03 (dd, J = 8.1,1.9 Hz, 1H), 7.95 (d, J /=\ = 8. 9 Hz, 2H), 7.78 (d, J = 1. 7 Hz, 1H), 7.70 (m, 3H), 7.41 (d, J = 8.1 16lg-CH3 31f AB-2 Hz, 1H), 7.29 (d, J = 7.9 Hz, 1H), 7.20 (m, 4H), 6.90 (dd, J = 17. 9,11.1 Hz, 1H), 6.03 (d, J = 17. 9 Hz, 1H), 5.42 (d, J = 11. 1 Hz, 1H), 3.57 (s, 3H), 3.10 (t, J = 6.8Hz, 2H), 1.85 (m, 1H), 0.89 (d, J = 6.6 Hz, 6H); MS (ES+):637.5 Cpd. Starting Method No. From Used No. From Used' 'H NMR (DMSO-d6): 8 10.58 (s, 1H), 9.00 (bs, 2H), 8.68 (t, J = 5.9 0 Hz, 1H), 8.24 (d, J = 1. 9 Hz, 1H), 8.03 (d, J = 8. 1 Hz, 1H), 7.94 (d, J = 8. 9 Hz, 2H), 7.78 (d, J = 1. 5 Hz, 1H), 7.68 (m, 3H), 7.40 (d, J = 8. 1 Hz, 161h/\o CH3-CH3 31f AB-1 1H), 7.29 (d, J = 8.1 Hz, 1H), 6.89 (dd, J = 17. 5,11.0 Hz, 1H), 6.03 (d, J = 17. 5 Hz, 1H), 5.71 (s, 2H), 5.42 (d, J = 11. 0 Hz, 1H), 3.56 (s, 3H), 3.10 (t, J = 6. 2 Hz, 2H), 2.07 (s, 3H), 1.85 (m, 1H), 0.89 (d, J = 6. 6 Hz, 6H); MS (ES+): 615. 3 'H NMR (DMSO-d6): 8 10.57 (s, 1H), 9.22 (s, 2H), 8.67 (t, J = 5. 9 Hz, 0 1H), 8.24 (d, J = 1.9 Hz, 1H), 8.03 (dd, J = 8.1,1.9 Hz, 1H), 7.94 (d, J -1CCH = 8.9 Hz, 2H), 7.78 (d, J = 1. 5 Hz, 1H), 7.69 (m, 3H), 7.41 (d, J = 7.9 161i O X 3-CH3 31f AB-1 Hz, 1H), 7. 29 (d, J = 7.9 Hz, 1H), 6.89 (dd, J= 17. 7,11. 1 Hz, IH), 6.03 3 (d, J = 17.7 Hz, 1H), 5.73 (s, 2H), 5.42 (d, J = 11. 1 Hz, 1H), 3.56 (s, 3H), 3.09 (t, J = 6.6 Hz, 2H), 1. 85 (m, 1H), 1.14 (s, 9H), 0.89 (d, J = 6.7 Hz, 6H); MS (ES+): 657.52 CH 0'H NMR (DMSO-d6): 8 10.57 (s, 1H), 9.24 (s, 1 H), 9.17 (s, 1H), 8.68 1H 7.94 d J = (t, J = 6.2 Hz, 1H), 8.25 (s, 1H), 8.04 (d, J = 8. 2Hz, 1H), 7. 94 (d, J = /S ACH 7.5 Hz, 2H), 7.67 (s, 1H), 7.67 (m, 3H), 7.40 (d, J = 7.9 Hz, 1H), 7. 29 CH3 _CH 31f AB-1 (d, J = 7.9 Hz, 1H), 6.90 dd J = 17. 8 11.1 Hz, 1H), 6.71 (q, J = 5.5 161J 3 (> >) > >) q Hz, 1H), 6.03 (d, J = 17. 7 Hz, 1H), 5.42 (d, J = 11. 1 Hz, 1H), 3.56 (s, 3H), 3.10 (t, J = 6. 6 Hz, 2H), 2.00 (s, 3H), 1.85 (m, 1H), 1. 43 (d, J = 5. 5 Hz, 3H), 0.89 (d, J = 6.7 Hz, 6H); MS (ES+): 629.4 Cpd. Starting Method No. -R -R' From Used Analytical Data 1H NMR (DMSO-d6): # 9.04 (bs, 3H)m, 8.57 (t J = 5.4 Hz, 1H), 8.16 (s, 1H) 7.86 (d, J = 8.5 Hz, 2H), 7.79 (d, J = 7.9 Hzm, 1H), 7.72 (s, 1H), 7.58 (m, 3H), 7.12 (d, J = 8. Hz, 2H), 6.87 (dd, J = 17.7 11.0 Hz 1H), 162a -CH3 -H 161a I-2 5.97 (d, J = 17.7 Hz, 1H), 5.37 (d, J = 11.0 Hz, 1H), 3.59 (s, 3H) 3.05 (t, J = 6.6 Hz, 2H), 1.83 (m, 1h), 0.87 (d, J = 6.6 Hz, 6H); MS (ES+) 543.38 1H NMR(DMSO-d6): # 12.8 (bs, 1H), 10.8 (bs, 1H), 9.20 (bs, 2H), 8.68 (t, J=5.9 Hz, 1H), 8.24 (d, J = 1.9 Hz, 1H), 7.91 (m, 3H), 7.77 (d, J = 1.5 Hz, 1 H), 7.64 (m, 3H), 7.38 (d, J = 8.1 Hz, 1H), 7.22 (d, J = 8.1 162b -C2H5 -H 161b I-2 Hz, 1H), 6.87 (dd, J = 17.7 11.4 Hz, 1h), 6.01 (d, J = 17.7 Hz, 1H)m, 5.42 (d, J = 11.4 Hz, 1H), 4.05 (q, J = 7.2 Hz, 2H), 3.08 (t, J = 6.4 Hz, 2H), 1.84 (m, 1H), 1.21 (t, J = 7.2 Hz, 3H), 0.88 (d, J = 6.6 Hz, 6H); MS (ES-): 555.2 1H NMR (DMSO-d6): # 12.7 (bs, 1H), 10.75 (bs, 1H), 9.15 (b, 2H), 8.63 (t, J = 5.8 Hz, 1H), 8.27 (bs, 1H), 7.90 (d, J = 8.3 Hz, 2H), 7.77 (s, 1H), 7.43-7.15 (m, 8H), 7.40 (d, J = 8.1 Hz, 1H), 7.29 (d, J=8.1 Hz, 162c -CH2C6H5 -H 161c I-2 1H), 6.87 (dd, J=17.4, 11.0 Hz, 1H), 6.03 (d, J = 17.5 Hz, 1H) 5.71 (s 2H), 5.42 (d, J = 11.0 Hz, 1H), 5.09 (s, 2H), 3.08 (t, J = 6.4 Hz, 2H), 1,.85 (m, 1H), 0.88 (d, J = 6.6 Hz, 6H); MS (ES+1): 619.2 1H NMR (DMSO-d6): #12.6 (bs, 1H), 11.0 (bs, 1H), 9.04 (b, 2H), 8.62 (t, J = 5.4 Hz, 1H), 8.24 (s, 1H), 7.86 (m, 3H), 7.77 (s, 1H), 7.62 (m, 162d -C(CH3)3 -H 161d I-2 3H), 7.24 (d, J = 8.2 Hz, 1h), 7.20 (d, J = 8.0- Hz, 1H), 6.87 (dd, J = 17.2, 11. Hz, 1h),. 6.00 (d, J = 17.7 Hz, 1H), 5.40 (d, J = 11.0 hz, 1H), 3.07 (t, J = 6.3 Hz, 2H), 1.84 (m, 1H), 1.44 (s, 9H), 0.88 (d, J = 6.6 Hz, 6H); MS (ES+1): 585.4 Cpd. Starting Method No.'From Used No. From Used" 'HNMR (DMSO-d6) : 6 9.58 (s, 1 H), 7.91 (dd, J = 1.2,8.0 Hz, 1 H), 7.71 (dt, J = 1. 2 and 7.4 Hz, 1 H), 164-CHO-CH3 163+130 D-2 7. 58 (t, J=7. 4Hz, lH), 7.41 (m, 2H), 7. 38 (m, l H), 7. 32 (d, 3 = 8 Hz, 1 I, 7.24 (d, J=7. 4Hz, lH), 3.52 (q, J = 16 and 26 Hz, 2 H), 3.35 (s, 3 H); MS (ES+) : 255.32 165-CO2H-CH3 164 E Characterized in the next step NH IHIHNMR (DMSO-d6) : 8 10.34 (s, 1 H), 9.18 (s, 2 H), 166 o NH2-CH3 165 1 8. 92 (s, 2 H), 7.72-7. 5 (m, 7 H), 7.34-7.14 (m, 5 H), 11 l ll-3 3.60 (q, J=17&40Hz, 2H), 3.48 (s, 3H) ; MS N (ES+) 388.67 H H NH IHNMR (DMSO-d6) : 8 11.74 (bs, 1 H), 9.90 (s, 1 ! i H), 8.79 (bs, 2 H), 7. 64 (m, 1 H), 7.50 (m, 7 H), 7.33 O < NH 6 I 2 (d, J = 8. 6 Hz, 1 H), 7.26 (d, J = 7. 4 Hz, 1 H), 7.12 (t, J = 7. 4 Hz, 1 H), 7.02 (t, J = 7. 4 Hz, 1 H), 6.89 (d, N J = 6.8 Hz, 1 H), 3.83 (d, J =15 Hz, 2 H); MS (ES+) H 374. 79

Cpd. _R-R'-R"_R", Starting Method A, nalytical Data No. From Used NH CH3 188a-CH=CH2 (4) NH2 CH_,-H 187a AE-3 MS (ES+) : 485.4 (100% M+1) PV NH'HNMR (DMSO-d6/D20) : 8 8. 5 (d ; ll J2Hz, 1 H), 8.17 (dd, J=8Hz, 2 . . k. H), 7. 65 (s, lH), 7. 63 (s, lH), 7. 54 NH2 d, J = 8 Hz, I H), 7.49 (bs, 2 H), f W NH2 (d, J = 8 Hz, 1 H), 7. 49 (bs, 2 H), J =11 and 17 Hz, 1 H), 6. 62 (d, J= 9 hz, 1 H), 5.83 (d, J = 17 hz, 1 H), 5.33 (d, J = 11 hz, 1 H), 4.17 (d, J = 9 hz, 1 H), 4.12 (s, 2 H); MS (ES+) : 497. 3

Cpd.-R-R5-R"-R"'starting Method A-nalytical Data No. From Used 'HNMR (DMSO-d6/D20) : 8 8.6 (MI 3 H), 8. 3 (m, 3 H), 7. 9 (d, J = 7. 9 Hz, 1 H), 7.45 (d, J = 8. 8 Hz, 1 C/W NH2 H), 7. 3 (m, 3 H), 7.1 (m, 1 H), 7.0 2 188c-CH=CB2 (4)-_"_CH 3-H 187c AE-3 (d, J = 8. 1 Hz, I H), 6. 6 (dd, J = 6 and 28 Hz, 1 H), 6. 4 (d, J = 8. 8 Hz, 2 H), 5.7 (d, J = 17 Hz, 1 H), 5.15 (d, J 11 Hz, 1 H), 3.9 (m, 2 H), 3. 25 (m, 2 H), 1.1 (t, J = & Hz, 3 H) ; MS (ES+) : 443. 3 'HNMR (DMSO-d6) : 6 8.8 (m, 2 NH H), 8.7 (m, 1 H), 8.4 (m, 2 H), 8.1 11 (m, 1 H), 7. 6 (m, 2 H), 7.5 (m, 3 H), 7. 3 (m, 1 H), 7.2 (m, 1 H), 6.8 188d-CH=CH2 (4) NH2 H 187d AE-3 (m, 1 H), 6.6 (m, 2 H), 5.8 (m, 1 H), 5.3 (m, 1 H), 4.1 (m, 2 H), 3.31 /R/ (m, 1 H), 3.2 (m, I H), 1.7 (m, I H), 1.6 (m, I H), 1.3 (m, I H), 1.0 (m, 6 H); MS (ES+): 485 'HNMR (DMSO-d6) : 8 8.60 (t, J = NH 6 Hz, 1 H), 8.39 (bs, 2 H), 8.28 (bs, 1 H), 7. 78 (m, 1 H), 7.56 (m, 1 H), a\ A CH3 AE-4, 7. 43 (dd, J = 5. 8 Hz,3.8 Hz, 2 H), CH3-H 74 1-2 7. 18 (m, 2 H), 6.80 (m, 3 H), 6.51 (bs, 1 H), 4.10 (m, 1 H), 3.85 (m, 1 H), 3.70 (s, 3 H), 3.17 (t, J = 6 Hz, 2 H), 1.80 (m, 1 H), 0.89 (d, J = 6.8 Hz, 6 H); MS (ES+) 475.2- Cpd. _R-R'-R"_g", Starting Method Analytical Data No. From Used 'HNMR (DMSO-d6/D20) : 8 8. 24 (d, J = 1.5 Hz, I H), 7.86 (d, J = 7 Hz, 1 H), 7.49 (m, 2 H), 7. 36 (m, 4 CH H), 7. 26 (d, J=8. 3Hz, I H), 6.94 189b-OBn fTNH,)' i AE. (m, 3H), 6.66 (d, J = 8. 7 Hz, 2 Hz, 4.06 J =16 . I X CH3 2 H), 5.03 (s, 2 H), 4. 06 (q, J= 16 and 21 Hz, 2 H), 3.02 (d, J = 7 Hz, 2H), 1.86 (m, lH), 0.89 (d, J=6. 8 Hz, 6 H); MS (ES-) : 549.2 and ES+551.4 'HNMR (DMSO-d6) : 6 11. 3 (bs, 1 H), 9.07 (s, 1 H), 8.46 (t, J = 6 Hz, NH 1 H), 8.27 (bs, 2 H), 8.15 (bs, 2 H), 7. 66 (d, J=7. 7Hz, 1 H), 7.36 (d, J = 8.5 Hz, 2 H), 7.03 (d, J = 8.1 Hz, NHz CH3 1 H), 6. 77 (m, 2 H), 6. 68 (d, J = 8. 3 189c-OH ( ) -H I89b G _c3 Hz, 2 Hz, 2 H), 6.6 (s, 1 H), 6.47 9d, J = 8.2 Hz, 1 H), 4.05 (d, J = 14 Hz, 1 H), 3.09 (d, J = 14 Hz, I H), 3.01 (t, J = 7 Hz, 2 H), 1.79 (m, 1 H), 0.82 (d, J = 6.8 Hz, 6 H); MS (ES-): 459.2 and (ES+) 461.4 NH CH 189d-H-H 131 AE-3 MS (ES+) : 445. 4 ; MS (ES-): 443.3 l CH3 , w- Cpd. _R-R'-R"_R", Starting Method alytical Data No.From Used 89e-E S XNH2 > cg |-H | 131 | b3 | M' (ES) : 446 46 ; MS ES) : NH CH3 MS (ESt) : 446. 46 ; MS (ES-) : 189e-H , NFi2 CHZ 131 W3 444. 45 e N Cpd. _R ^R, Starting Method A. nalytical Data No. From Used No. From Used" 'HNMR (DMSO-d6) : 8 11.04 (s, 0.6 H), 10.97 (bs, 0.4 H), 8.66 (t, J = 5.6 Hz, O 0.6 H), 8.56 (t, J = 5.6 Hz, 0.4 H), 8.22 (s, 1 H), 8.11 (d, J = 2 Hz, 0.6 H), 8.03 (4 H) 7.40 (m, 8 205-Boc 204 A-4 (d, J = 2 Hz, 0.4 H), 7.94 (dd, J = 2 and 8 Hz, 1 H), 7.82 (m, 4 H), 7. 40 (m, 8 /S H H), 7. 18 (m, 2H), 7. 04 (m, 2H), 5. 21 (s, 0. 8H), 5. 11 (s, 1. 2H), 3. 11 (t, J=6. 2 NH2 Hz, 1. 2 H), 3. 06 (t, J 6. 2 Hz, 0. 8 H), 1. 84 (m, I H), 1. 43 (s, 5. 4 H), 1. 42 (s, "2 Hz, 1.2 H), 3.06 (t, J = 6.2 Hz, 0.8 H), 1.84 (m, 1 H), 1.43 (s, 5.4 H), 1.42 (s, 3.6 H), 0.91 (d, J = 6.8 Hz, 3.6 H), 0.88 (d, J = 6.8 Hz, 2.4 H) ; MS (ES+) : 665.5 'HNMR (DMSO-d6) : 8 12.15 (bs, 1 H), 11.07 (bs, 1 H), 10.69 (s, 1 H), 10. 38 (bs, 1 H), 8.68 (t, J = 5. 6 Hz, I H), 8.12 (d, J = 1. 7 Hz, 1 H), 8.00 (dd,-1. 8,8 Hz, 206-CH20H-Boc 204 A 6 1 H), 7.68 (m, 4 H), 7.46-7. 30 (m, 6 H), 7.16 (d, J = 2.8 Hz, 1 H), 7.01 (d, J = -2 oc 8. 5 Hz, 1 H), 6. 86 (dd, J = 8. 5 and 2. 8 Hz, 1 H), 5.07 (s, 2 H), 4.30 (d, J =7. 4 Hz, 2 H), 3.15 (t, J = 6. 2 Hz, 2 H), 1.86 (m, 1 H), 1.53 (s, 9 H), 0.89 (d, J = 6. 8 Hz, 6 H); MS (ES-): 649.4 'HNMR (DMSO-d6/D20) : 6 10.66 (s, 1 H), 9.19 (bs, 2 H), 8.86 (bs, 2 H), 8.69 (t, J = 5.5 Hz, 1 H), 8.13 (d, J = 2 Hz, 1 H), 8.02 (dd, J = 8 and 2 Hz, 1 H), 7.72 S-2 (m, 4 H), 7.38 (m, 6 H), 7.17 (d, J = 2. 6 Hz, 1 H), 7.03 (d, J = 8. 5 Hz, 1 H), 6. 87 (dd, J = 8. 5 and 2. 5 Hz, 1 H), 5. 39 (t, J = 4. 7 Hz, 1 H), 5.08 (s, 2 H), 4. 30 (m, 2 H), 3.13 (t, J = 6. 5 Hz, 2 H), 1.87 (m, 1 H), 0. 91 (d, J = 6. 5 Hz, 6 H) ; MS (ES+)551.4

Cpd. _R _R, Starting Method aiytical Data No.From Used IHNMR (DMSO-d6) : 6 11. 26 (s, 0.6 H), 11.20 (bs, 0. 4 H), 9. 15 (bs, 1.2 H), O 9.11 (bs, 0.8 H), 8.84 (bs, 1.2 H), 8.82 (bs, 0.8 H), 8.67 (t, J = 5. 6 Hz, 0.6 H), 8. 58 (t, J = 5.6 Hz, 0.4 H), 8. 3 (s, 1 H), 8.12 (d, J = 2 Hz, 0.6 H), 8.04 (d, J = 2 208-H 205 S-2 Hz, 0.4 H), 7.96 (dd, J = 2 and 8 Hz, 1 H), 7.84 (m, 1 H), 7.70 (m, 2 H), 7.57 2 (m, 3H), 7.40 (m, 4 H), 7.22 (m, 2 H), 7.02 (m, 2 H), 5. 21 (s, 0.8 H), 5. 11 (s, 1.2 H), 3.12 (t, J = 6. 5 Hz, 1.2 H), 3.06 (t, J = 6. 5 Hz, 0.8 H), 1.84 (m, 1 H), 0. 90 (d, J = 6. 5 Hz, 3.6 H), 0.86 (d, J = 6.5 Hz, 2.4 H); MS (ES+) : 564.5 Cpd. _R-R'-R"Starting Method Analytical Data No. From Used' CH3'H NMR (DMSO-d6) : 8 8.48 (t, J = 6.2 Hz, 1 H), 1 3 8. 06 (d, J= 8. 3 Hz, 1 H), 7.69 (d, J= 8. 5 Hz, 1 -OCH3-Br 216 A-3 H), 4.01 (s, 3 H), 3.15 (t, J= 6. 5 Hz, 2 H), 1.91 CH3 (m, 1 H), 0.91 (d, J= 6.6 Hz, 6 H); MS (ES+) : 0 287. 1 IH NMR (CDC13) : 8 8.08 (m, 2 H), 7.20 (m, 2 H 3 H), 6.39 (dd, J= 2.0 and 17. 3 Hz, 1 H), 5. 53 (dd, 1 H) 5.53 dd 218-OCH3 N s-CH=CH2 217 D-12 J=2. 0 and 10. 9 Hz, 1 H), 4.01 (s, 3 H), 3.15 (t, J cH3 = 6. 5 Hz, 2 H), 1.91 (m, 1 H), 0.91 (d, J= 6. 6 Hz, 0 6 H) CH3'H NMR (DMSO-d6) : 8 11.05 (s, 1 H), 8.48 (t, J H N V = 6. 2 Hz, 1 H), 8.06 (d, J= 8. 7 Hz, 1 H), 7.53 (d, 219-OH v CH3-COzCH3 218 E-2, V-J-8. 5 Hz, 1 H), 3.90 (s, 3 H), 3.12 (t, J= 6.6 Hz, "-""2 H), 1.85 (m, 1 H), 0.86 (d, J= 6.6 Hz, 6 H); MS (ES'') : 253.2 CH3 H 220-OSO2CF3 NCH-CO2CH3 219 B-2 MS (ES+) : 407.2 (M+Na) + 0 NH 237---NH2-H 236 AF-1 MS (ES+) : 137.1 NH2

Cpd. Starting Method -R -R' -R" Analytical Data No. From Used 1H NMR (CDCl3): # 9.77 (s, 1 H), 8.40 (d, J=7.9 Hz, 1 H), 8.13 (d, J= 6.8 Hz, 1 H), 7.83 (d, J=7.9 Hz, 1 H), 7.61 (d, J=2.60 Hz, 1 H), 7.20 (m, 5 221 -CHO -OBn -CH3 220+6 D-2 H), 7.21 (m, 1 H), 7.18 (d, J=8.3 Hz, 1 H), 5.18 (s, 2 H), 3.72 (s, 3 H), 3.35 (q, J=5.8 Hz, 2 H), 1.96 (m, 1 H), 1.01 (d, J=6.8 Hz, 6 H); MS (ES+): 447.4 222 -CO2H -OBn -CH3 221 E MS (ES-): 461.3 223 -CO2MEM -OBn -CH3 222 F MS (ES+): 573.33 (M+Na)+ 224 -CO2MEM -OH -CH3 223 G MS (ES+): 461.36 225 -CO2MEM -OSO2CF3 -CH3 224 B-2 MS (ES+): 615.58 (M+Na)+ 226 -CO2MEM -CH=CH2 -CH2 225 D-3 or D-12 MS (ES-): 381.35 [(M-MEM)-1] 227 -CO2H -CH=CH2 -CH3 226 I-1 MS (ES-): 381.35

Cpd. -,,-, Startjmg Method.,,., ,, Cpd.-R-Rl-R"Starting Method Analytical Data No. From Used NH 228 j)"-CH=CH2-CH3 227 J MS (ESt : 500. 35 H H NH 229 ) ! 2-CH=CH2-H 228 1-2 MS (ES+) : 486. 32 N- H 245-CHO-OH-CH3 221 AD MS (ES+) : 357.40 246-CHO-OSO2CF3-CH3 245 B-2 Characterized in the next step 247-CHO-CH=CH2-CH3 246 D-3 MS (ES+) : 367.42 NH -CH=CH2-H 247 AE-3 MS (ES+) : 472. 39 zu NH 249 j \H2-OBn-CH3 222 J MS (ES+) : 580.4 AN H Cpd. _R-R'_R, Starting Method alytical Data No.From Used NU NH 0 f"NH MS (ES"): 566.4 250 O N 2-OBn-H 249 I-2 MUS (ES-): 564. 3 H NU NH 251 0 NH,-OH-H 250 G MS (ES+) : 476.3 MS (ES) : 474. 2 'kan H H H/\/ MS (ES+) : 473. 44 252 \. N-/)---CH=CH2-H 247 AE-3 N NH 2 z Cpd. Starting Method -R Analytical Data No. From Used 1H NMR (CDCl3): # 10.17 (d, J = 0.75 Hz, 1 H), 231b -CO2CH3 230 AG-3 7.62 (d, J=8.3 Hz, 1 H), 6.94 (dd, J=8.3, 0.75 Hz, 1 H), 6.51 (s, 1 H), 3.90 (s, 3 H)

Cpd. Starting Method -R -R' -R" Analytical Data No. From Used 1HNMR (CDCl3): # 9.64 (s, 1 H), 8.44 (d, J= 2 Hz, 1 H), 8.02 (dd, J=8 and 2 Hz, 1 H), 7.60 (d, J=8.3 Hz, 1 H), 7.40 (d, J=8 Hz, 1 H), 232a -H -CHO -CH3 231a+6a D-6 or D-7 6.96 (d, J=8 Hz, 1 H), 6.32 (t, J=6 and 5 Hz, 1 H), 6.01 (s, 2H), 3.72 (s, 3 H), 3.33 (t, J= 6.5 Hz, 2 H), 1.93 (m, 1 H), 1.00 (d, J=6.8 Hz, 6 H); MS (ES+): 384.3 AND 406.3 (M+Na)+ 1HNMR (DMSO-d6): # 9.87 (s, 1 H), 9.49 (s, 1 H), 8.64 (d, J=2 Hz, 1 H), 8.3 (s, 1 H), 7.97 (d, J=8 Hz, 1 H), 7.43 (dd, J=8 and 2.6 Hz, 1 232b -CH2H -CHO -CH3 231b+6a D-6 or D-7 H), 7.35 (m, 2 H), 6.94 (m, 1 H), 6.05 (s, 0.4 H), 5.98 (s, 0.6 H), 3.55 (s, 1.8 H), 3.52 (s, 1.2 H), 3.02 (t, J=6.5 Hz, 2 H), 1.78 (m, 1 H), 0.81 (d, J=6.6 Hz, 6 H); MS (ES-): 426.2 1HNMR (DMSO-d6): # 12.29 (bs, 1 H), 8.69 (t, J=5.5 Hz, 1 H), 8.38 (d, J=2 Hz, 1 H), 8.03 (dd, J=8 and 2 Hz, 1 H), 7.58 (d, J=8.5 Hz, 1 233a -H -CO2H -CH3 232a E H), 7.36 (d, J=8 Hz, 1 H), 7.00 (d, J=8.5 Hz, 1 H), 6.02 (s, 2 H), 3.64 (s, 3 H), 3.12 (t, J= 6.5 Hz, 2 H), 1.87 (m, 1 H), 0.91 (d, J=6.8 Hz, 6 H); MS (ES-): 398.2

Cpd. Starting Method No. From Used- Mb. From Used' 'HNMR (DMSO-d6) : 8 8.64 (t, J = 5.5 Hz, 1 H), 8.38 (d, J = 4 Hz, 1 H), 8.00 (dd, J = 8.5 and 4 Hz, 1 H), 7.59 (dd, J = 8.5 and 4 Hz, 1 233b-CO2H-CO2H-CH3 232b E H), 7. 30 (dd, J = 8 and 2.5 Hz, 1 H), 6.52 (s, 0.5 H), 6.48 (s, 0.5 H), 3.60 (s, 1.5 H), 3.58 (s, 1.5 H), 3.08 (t, J = 6.5 Hz, 2 H), 1.84 (m, 1 H), 0.88 (d, J=6. 8Hz, 6H) NH 234a-H H !) ! ' 233a J MS (ES+) : 517.4 'iNe N H (DMSO-d6) : 8 12.41 (bs, 1 H), 11.09 (s, 1 H), 10.96 (s, 1 H), 9. 22 (bs. 2 H), 8.96 (bs, 2 H), 8.70 (m, 1 H), 8. 38 (dd, J = 2 and 13 Hz, 1 H), 8.04 (d, J = 8 Hz, 1 H), 7.82 (m, 4 234b-CO2H R C W-CH3 233b J H), 7.65 (dd, J = 8 and 5 Hz, 1 H), 7.39 (dd, J 'KN& = 8 and 2 : 5 Hz, 1 H), 7.11 (dd, J = 8.5 and 1.7 NH Hz, 1 H), 6.05 (s, 1 H), 3.67 (s, 1.5 H), 3.50 (s, 1.5 H), 3.10 (t, J = 6. 5 Hz, 2 H), 1. 88 (m, I H), 0. 90 (d, J=6. 8Hz, 6H) 1HNMR (DMSO-d6+DCl one drop): 8 8. 34 (d, NH J = 2 Hz, 1 H), 7.97 (dd, J = 8 and 2 Hz, 1 H), 7. 75 (m, 4 H), 7. 33 (dd, J = 3.8 and 8.1 Hz, 2 235a-H o vNH2-H 234a I-2 H), 7.04 (d, J = 8. 1 Hz, 1 H), 6.01 (d, J = 6 Hz, 2 H), 3.07 (t, J = 6. 5 Hz, 2 H), 1.83 (m, 1 H), 0. 86 (d, J = 6.8 Hz, 6 H); MS (ES-) 501. 3 ; H (ES+) 503. 3 Cpd. Starting Method -R -R' -R" Analytical Data No. From Used 1H NMR (DMSO-d6): # 10.47 (s, 1H), 9.07 (s, 2H), 8.72 (t, J=5.7 Hz, 1H), 8.29 (d, J=2 Hz, 1H), 8.08 (dd, J=8.0, 2 Hz, 1H), 7.95 (s, 1H), 7.92 (s, 1 H), 7.67 (m, 2 H), 7.62 (d, J=6.5 Hz, 1 H), 240 -CH(OH)-CH2OH -Boc -CH3 161d L 7.46 (d, J=8 Hz, 1H), 7.31 (d, J=8 Hz, 1H), 5.50 (d, J=4.5 Hz, 1H), 4.91 (t, J=5.7 Hz, 1H), 4.74 (m, 1 H), 4.25 (s, 1 H), 3.63 (s, 3H), 3.15 (t, J=6.4 Hz, 2H), 1.91 (m, 1H), 1.50 (s, 9 H), 0.95 (d, J = 6.7 Hz, 6H) 1H NMR (DMSO-d6): # 10.69 (s, 1H), 10.17 (s, 1 H), 9.10 (bs, 2 H), 8.72 (t, J=5.7 Hz, 1H), 8.30 (d, J = 1.5 Hz, 1H), 8.22 (d, J=1.5 Hz, 1H), 8.22 (dd, 241 -CHO -Boc -CH3 240 M J=1.5 and 8 Hz, 1 H), 8.07 (dd, J=1.5 and 8 Hz, 1 H), 7.89 (s, 1H), 7.86 (s, 1 H), 7.65 (s, 1 H), 7.62 (s, 1 H), 7.57 (d, J=8 Hz, 1H), 7.44 9d, J=8 Hz, 1H), 3.57 (s, 3H), 3.11 (t, J=6.4 Hz, 2H), 1.85 (m, 1H), 1.44 (s, 9 H), 0.89 (d, J=6.7 Hz, 6H) 242-CH(OH)-CH=CH2 -Boc -CH3 241 AG MS (ES+): 629.39 243 -CH(OH)-CH=CH2 -H -CH3 242 S MS (ES+): 529.38 244 -CH(OH)-CH=CH2 -H -H 243 I-2 MS (ES-): 515.35

Cpd. |-R Starting I Method Analytical Data -R ° . AmaIyttcaIData No.From Used NU 254 H_G4 253 AE-3 MS (ES+) : 318. 2,320.2 NH- NU 255 H 254 R MS (ES) : 418 Boc I I BOG, I I

The following non-limiting examples are presented to further illustrate the present invention.

2'- [ ( {4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4- [ (isobutylamino) carbonyl]-4'-thien-2-yl-1,1'-biphenyl-2-carboxylic acid 2'- [ ( {4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4- [ (isobutylamino) carbonyl]-4'-thien-3-yl-1, 1'-biphenyl-2-carboxylic acid 2'- [ ( {4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4- [(isobutylamino) carbonyl]-1, 1': 4', 1"-terphenyl-2-carboxylic acid 2'- [ ( {4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4'-(3-furyl)-4- [ (isobutylamino) carbonyl]-1,1'-biphenyl-2-carboxylic acid 2'- [ ( {4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4- [(isobutylamino) carbonyl]-4'-pyridin-4-yl-1, 1'-biphenyl-2-carboxylic acid 2'- [({4-[Amino (imino) methyl] phenyl} amino) carbonyl]-4- [(isobutylamino) carbonyl]-4'-(lH-pyrrol-2-yl)-1, 1'-biphenyl-2-carboxylic acid 2'- [ ( {4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4'- [2- (hydroxymethyl) thien- 3-yl]-4-[(isobutylamino)carbonyl]-1,1'-biphenyl-2-carboxylic acid 2'- [ ( {4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4'- [3- (hydroxymethyl) thien- 2-yl]-4- [ (isobutylamino) carbonyl]-1,1'-biphenyl-2-carboxylic acid 2'- [ ( {4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4- [(isobutylamino) carbonyl]-4'-vinyl-1, 1'-biphenyl-2-carboxylic acid 4'-Allyl-2'-[( {4-[amino (imino) methyl] phenyl} amino) carbonyl]-4- [(isobutylamino) carbonyl]-1, 1'-biphenyl-2-carboxylate 2'- [ ({4-[Amino (imino) methyl] phenyl} amino) carbonyl]-4- [(isobutylamino) carbonyl]-4'-(1, 3-thiazol-2-yl)-1, 1'-biphenyl-2-carboxylic acid 2'- [({4-[Amino(imino) methyl] phenyl} amino) carbonyl]-4'- [3- (hydroxymethyl)-2- furyl]-4- [ (isobutylamino) carbonyl]-l, 1'-biphenyl-2-carboxylic acid 2'- [ ( {4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4- [(isobutylamino) carbonyl]-4'-prop-1-ynyl-1, 1'-biphenyl-2-carboxylic acid 2'- [({4-[Amino (imino) methyl] phenyl} amino) carbonyl]-4'- (3-hydroxy-3-methylbut- 1-ynyl)-4-[(isobutylamino) carbonyl]-1, 1'-biphenyl-2-carboxylic acid 2'- [({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(3- methylbutanoyl) amino]-4'-vinyl-1,1'-biphenyl-2-carboxylic acid 2'- [({4-[Amino (imino) methyl] phenyl} amino) carbonyl]-4'- (4-hydroxybut-1-ynyl)-4- [(isobutylamino)carbonyl]-1,1'-biphenyl-2-carboxylic acid 2'- [ ( {4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4- [(isobutylamino)carbonyl]-4'-[(1E)-3-methylbuta-1,3-dienyl]- 1,1'-biphenyl-2- carboxylic acid 2'- [ ( {4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4'- (3-hydroxyprop-1-ynyl)- 4- [ (isobutylamino) carbonyl]-1,1'-biphenyl-2-carboxylic acid 2'- [ ( f4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4'- (2-furyl)-4- [(propylamino) carbonyl]-1, 1'-biphenyl-2-carboxylic acid 2'- [ ( {4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4- [ (sec- butylamino) carbonyl]-4'-(2-furyl)-1, 1'-biphenyl-2-carboxylic acid '-[({4-[Amino(imino) methyl] phenyl} amino) carbonyl]-4'- (2-furyl)-4- { [ (2, 2,2- trifluoroethyl) amino] carbonyl}-1, 1'-biphenyl-2-carboxylic acid 2'- [({4-[Amino(imino) methyl] phenyl} amino) carbonyl]-4'- (2-furyl)-4- { [ (4- hydroxybutyl) amino] carbonyl}-1, 1'-biphenyl-2-carboxylic acid 2'- [ ( {4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4-[(ethylamino) carbonyl]-4'- (2-furyl)-1, 1'-biphenyl-2-carboxylic acid 2'- [({4-[Amino (imino) methyl] phenyl} amino) carbonyl]-4- [(isobutylamino) carbonyl]-5'-methoxy-4'-vinyl-1, 1'-biphenyl-2-carboxylic acid 2'- [ ( f4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4- [(isobutylamino) carbonyl]-4'-(thien-2-ylmethyl)-1, 1'-biphenyl-2-carboxylic acid 2-{3-[({4-[Amino (imino) methyl] phenyl} amino) carbonyl] pyridin-4-yl}-5- [ (isobutylamino) carbonyl] benzoic acid 2'- [ ( {4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4- [(cyclopentylamino) carbonyl]-4'-vinyl-1, 1'-biphenyl-2-carboxylic acid 2'- {4-[Amino (imino) methyl] phenyl} amino) carbonyl]-5'-ethoxy-4- [(isobutylamino) carbonyl]-4'-vinyl-1, 1'-biphenyl-2-carboxylic acid Methyl 2'-[({4-[({[(acetyloxy) methoxy] carbonyl} amino) (imino) methyl] phenyl} amino)carbonyl]-4-[(isobutylamino)carbonyl]-4'-vinyl-1,1'-bi phenyl-2-carboxylate Methyl 2'-[({4-[{[(benzyloxy) carbonyl] amino} (imino) methyl] phenyl} amino) carbonyl]-4- [ (isobutylamino) carbonyl]-4'-vinyl-1,1'-biphenyl-2-carboxylate Nl- {4- [Amino (imino) methyl] phenyl}-N8-isobutyl-6-oxo-6H-benzo [c] chromene- 1,8-dicarboxamide 2'- [ (f 4- [Amino (imino) methyl] phenyl} amino) methyl]-4-[(isobutylamino) carbonyl]- 4'-vinyl-1, 1'-biphenyl-2-carboxylic acid 2'- ( { [4- (4, 5-Dihydro-1 H-imidazol-2-yl) phenyl] amino} carbonyl)-4- [ (isobutylamino) carbonyl]-l, l'-biphenyl-2-carboxylic acid 2'- [({4-[Amino (imino) methyl] phenyl} amino) carbonyl]-4- [(isobutylamino)carbonyl]-5'-thien-2-yl-1,1'-biphenyl-2-carb oxylic acid 2'- [ ( {4- [Amino (imino) methyl] phenyl} amino) carbonyl]-5'- (2-amino-2-oxoethoxy)-4- [ (isobutylamino) carbonyl]-1,1'-biphenyl-2-carboxylic acid 2'- [ ( {4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4'-ethoxy-4- [(isobutylamino)carbonyl]-1,1'-biphenyl-2-carboxylic acid 2- {5- [({4-[Amino(imino)methyl]phenyl} amino) carbonyl]-1, 3-benzodioxol-4-yl}-5- [ (isobutylamino) carbonyl] benzoic acid 2'- [1- ( {4- [Amino (imino) methyl] phenyl} amino) ethyl]-4-[(isobutylamino) carbonyl]- 1,1'-biphenyl-2-carboxylic acid 3- [2- [ ( {4- [Amino (imino) methyl] phenyl} amino) carbonyl]-4- (benzyloxy) phenyl]-6- [ (isobutylamino) carbonyl] pyridine-2-carboxylic acid <BR> <BR> 3- [2- (4-Carbamimidoyl-phenylcarbamoyl)-4-vinyl-phenyl]-6-isobutyl carbamoyl- pyridine-2-carboxylic acid <BR> <BR> 2'- [ (5-Carbamimidoyl-pyridin-2-ylamino)-methyl]-4-isobutylcarbam oyl-4'-vinyl- biphenyl-2-carboxylic acid 2'- {[4-(N-Hydroxycarbamimidoyl)-phenylamino]-methyl}-4-isobutyl carbamoyl-4'- vinyl-biphenyl-2-carboxylic acid 2'- { [4- (N-Hydroxycarbamimidoyl)-phenylamino]-methyl}-4-isobutylcarb amoyl-4'- vinyl-biphenyl-2-carboxylic acid methyl ester 3- {2-[(4-Carbamimidoyl-phenylamino)-methyl]-4-vinyl-phenyl}-6- isobutylcarbamoyl-pyridine-2-carboxylic acid

Biological Assay Methods In Vitro Assay for Inhibition of TF/FVIIa To assess the inhibition of the test compounds against the target enzyme, TF/FVIIa, an amidolytic assay based upon the absorbance of p-Nitroanalide (pNA) at OD405 was utilized. The ICso of the test compounds was determined by using KC4A data reduction software (Bio-Tek Instruments) to interpolate percent inhibition from observed Vmax values.

TF/FVIIa assay reactions were performed in a 200 LL mixture containing 4 nM FVIIa, 10 nM lipidated tissue factor, in an assay buffer containing 100 mM Tris, pH 7.2, 150 mM NaCl, 5 mM calcium chloride, 0.1 % bovine serum albumin (BSA), and 10% dimethyl sulfoxide (DMSO). TF and FVIIa were allowed to equilibrate at room temperature for 15 minutes. Test compounds dissolved in DMSO were incubated at varied concentrations with TF/FVIIa for 10 minutes, followed by addition of 500 CM substrate Spectrozyme-FVIIa. Reactions were incubated for 5 minutes at room temperature prior to measuring the change in OD405 nm for 10 minutes at 21 second intervals with a Powerwave x (Bio-Tek Instruments) microplate reader.

In Vitro Assay for Human Thrombin This colorimetric assay was used to assess the ability of the test compounds to inhibit the human thrombin enzyme. ICso of the test compounds was determined by using KC4A data reduction software (Bio-Tek Instruments) to interpolate percent inhibition from observed Vmax values.

Thrombin assay reactions were performed in a 200 gel mixture containing human thrombin at (1 U/mL) in an assay buffer containing 100 mM HEPES, 10 mM calcium

chloride, and 10 % DMSO, pH 7.5. Test compounds dissolved in DMSO were added to thrombin enzyme reactions at varied concentrations, followed by the addition of substrate Na-Benzoyl-Phe-Val-Arg p-Nitroanilide at a final concentration of 1 mM. Reactions were incubated for 5 minutes at room temperature prior to measuring the change in OD4os nm for 10 minutes at 21 second intervals with a Powerwave x (Bio-Tek Instruments) microplate reader.

In Vitro Assay for Human Trypsin This enzymatic assay was employed to evaluate the ability of the test compounds to inhibit human pancreatic trypsin. IC50 of the test compounds was determined by using KC4A data reduction software (Bio-Tek Instruments) to interpolate percent inhibition from observed Vmax values.

Trypsin assay reactions were performed in a 200 ; je mixture containing human pancreatic trypsin at 1 llg/mL in an assay buffer containing 200 mM triethanolamine (TEA), 10 mM calcium chloride, 10 % DMSO, pH 7.8. Test compounds dissolved in DMSO were added to trypsin enzyme reactions at varied concentrations, followed by the addition of substrate Na-Benzoyl-L-Arginine p-Nitroanilide (L-BAPNA) at a final concentration of (0.25 mg/mL). Reactions were incubated for 5 minutes at room temperature prior to measuring the change in OD405 nm for 10 minutes at 21 second intervals with a Powerwave x (Bio-Tek Instruments) microplate reader.

Biological Data

IC50 Values of Some Selected Compounds on Different Serine Protease Enzymes R (With Respect to TF/FVIIa TlYPS2D Thrombin Phenyl Ring . _. CH3 -1, CH, ich CH3 OH(4)-1, CH3 ++ + + S U wCHs I J (4) ++ + + N 3 k13 CH3 OH (4) CH3 ++ CL3 Cl3 c3 cl3 CH3 S CH3 O so\ ? ++ + CH3 CH, q, +++ ++ + 0 (4) CH, C02H ich2 (4) ! ++ + -"CH IC50 values: + means >1 µM ; ++ means >100 nM; +++ means <100 nM

A comparison of Examples with R group and without R group illustrates the greatly-enhanced activity achieved pursuant to the present invention.

Compounds of the present invention are useful as inhibitors of trypsin-like serine protease enzymes such as thrombin, factor VIIa, TF/FVIIa, and trypsin.

These compounds may be employed to inhibit the coagulation cascade and prevent or limit coagulation.

These compounds may be used to inhibit the formation of emboli or thromboli in blood vessels.

These compounds may be used to treat thrombolymphangitis, thrombosinusitis, thromboendocarditis, thromboangitis, and thromboarteritis.

These compounds may be used to inhibit thrombus formation following angioplasty. These may be used in combination with other antithrombolytic agents such as tissue plasminogen activators and their derivatives, streptokinase and its derivatives, or urokinase and its derivatives to prevent arterial occlusion following thrombolytic therapy.

These compounds may also be used in matastatic diseases, or for any disease where inhibition of coagulation is indicated.

These compounds may be used as diagnostic reagents in vitro for inhibiting clotting of blood in the tubes.

These compounds may be used alone or in combination with other compounds such as heparin, aspirin, or warfarin and any other anticoagulant agents.

These compounds may be used as anti-inflammatory agents.

According to a further aspect of the invention, compounds may be employed in preventing ex vivo coagulation such as that encountered in the extracorporeal perfusion of blood through for example artificial valves, prothesis, stents or catheters. According to this aspect of the invention the extracorporeal device may be coated with the compositions of the invention resulting in a lower risk of clot formation due to extrinsic pathway activation.

Dosage and Formulation The compounds of this invention can be administered by any means that produces contact of the active agent's site of action with factor VIIa and other serine proteases in the body of a human, mammal, bird, or other animal. They can be administered by any conventional means, such as oral, topical, transdermal, parenteral, subcutaneous, intraperitoneal, intrapulmonary, and intranasal, available for use in conjunction with pharmaceuticals, either as individual therapeutic agents or in a combination of therapeutic agents. Parenteral infusion includes intramuscular, intravenous, and intraarterial. They can be administered alone, but generally administered with a pharmaceutical carrier elected on the basis of the chosen route of administration and standard pharmaceutical practice.

The dosage administered will, or course, vary depending upon known factors, such as the pharmacodynamic characteristics of the particular agent and its mode and route of administration; the age, health and weight of the recipient; the nature and extent of the symptoms, the kind of concurrent treatment; the frequency of treatment; and the effect desired. A daily dosage of active ingredient can be expected to be about 0.0001 to 1000 milligram (mg) per kilogram (kg) of body weight, with the preferred dose being 0.1 to about 30 mg/kg.

Dosage forms (compositions suitable for administration) contain from about mg to about 500 mg of compound per unit. In these pharmaceutical compositions, the compound of the present invention will ordinarily be present in an amount of about 0.5- 95% by weight based on the total weight of the composition.

The daily dose of the compounds of the invention that is to be administered can be a single daily dose or can be divided into several, for example, two, three or four, part administrations. The pharmaceutical compositions or medicaments of the invention can be administered orally, for example in the form of pills, tablets, lacquered tablets, coated tablets, granules, hard and soft gelatin capsules, solutions, syrups, emulsions, suspensions or aerosol mixtures. Administration, however, can also be carried out rectally, for example in the form of suppositories, or parenterally, for example intravenously, intramuscularly or subcutaneously, in the form of injection solutions or infusion solutions, microcapsules, implants or rods, or percutaneously or topically, for example in the form of ointments, solutions or tinctures, or in other ways, for example in the form of aerosols or nasal sprays.

Gelatin capsules contain a compound of the present invention and powdered carriers, such as lactose, starch, cellulose derivatives, biocompatible polymers, magnesium stearate, stearic acid, and the like. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of medication over a period of hours.

Compressed tablets can be sugar coated to mask by unpleasant taste and protect the tablet from the atmosphere, or enteric coated for selective disintegration in the gastrointestinal tract.

Liquid dosage forms for oral administration can contain coloring and flavoring to increase patient acceptance. They may also contain buffering agents, surfactants and

preservatives. Liquid oral products can be developed to have sustained-release properties. They may also contain cyclodextrin derivatives to enhance the solubility of the active ingredient and to promote its oral uptake.

In general, water, a suitable oil, saline, aqueous dextrose (glucose), and related sugar solutions and glycols such as propylene glycol or polyethylene glycols are suitable carriers for parenteral solutions. Solutions for parenteral administration preferably contain a water-soluble salt of the active ingredient, suitable stabilizing agents, and, if necessary, buffering agents. Antioxidizing agents such as sodium bisulfite, sodium sulfite, or ascorbic acid, either alone or combined, are suitable stabilizing agents. Also used are citric acid and its salts and sodium EDTA. In addition, parenteral solutions can contain preservatives, such as benzalkonium chloride, methyl-or propylparaben, and chlorobutanol.

Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, Mack Publishing Company and in the Handbook of Pharmaceuticals Excipients, American Pharmaceutical Association, both standard reference texts in this field.

Useful pharmaceutical dosage forms for administration of the compounds according to the present invention can be illustrated as follows: Hard Shell Capsules A large number of unit capsules are prepared by filling standard two-piece hard gelatin capsules each with 100 mg of powdered 1500 mg of lactose, 50 mg of cellulose, and 6 mg of magnesium stearate.

Soft Gelatin Capsules A mixture of active ingredient in a digestible oil such as soybean oil, cottonseed oil, or olive oil is prepared and injected by means of a positive displacement pump into molten gelatin to form soft gelatin capsules containing 100 mg of the active ingredient.

The capsules are washed and dried. The prodrug can be dissolved in a mixture of polyethylene glycol, glycerin and sorbitol to prepare a water miscible medicine mix.

Tablets A large number of tablets are prepared by conventional procedures so that the dosage unit was 100 mg of active ingredient, 0.2 mg of colloidal silicon dioxide, 5 mg of magnesium stearate, 275 mg of microcystalline cellulose, 11 mg of starch, and 9.98 mg of lactose. Appropriate aqueous and non-aqueous coatings may be applied to increase palatability improve elegance and stability or delay absorption.

Immediate Release Tablets/Capsules These are solid oral dosage forms made by conventional and novel processes.

These units are taken orally without water for immediate dissolution and delivery of the medication. The drug is mixed containing ingredient such as sugar, gelatin, pectin, and sweeteners. These liquids are solidified into solid tablets or caplets by freeze drying and solid thermoelastic sugars and polymers or effervescent components to produce porous matrices intended for immediate release, without the need of water.

Moreover, the compounds of the present invention can be administered in the form of nose drops, metered dose nasal or buccal inhalers. The drug is delivered from a nasal solution as a fine mist or from a powder as an aerosol.

In another embodiment of the invention, a compound of the invention can be used in an assay to identify the presence of factor VIIa and other serine protease or to isolate factor VIIa and other serine protease in a substantially purified form. For example, the compound of the invention can be labeled with, for example, a radioisotope, and the labeled compound is detected using a routine method useful for detecting the particular label. In addition, á compound the invention can be used advantageously as a probe to detect the location or amount of factor VIIa and other serine protease activity in vivo, in vitro or ex vivo.

Various modifications of the invention in addition to those shown and described herein will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims.

The foregoing disclosure includes all the information deemed essential to enable those skilled in the art to practice the claimed invention. The foregoing description of the invention illustrates and describes the present invention. Additionally, the disclosure shows and describes only the preferred embodiments of the invention but, as mentioned above, it is to be understood that the invention is capable of use in various other combinations, modifications, and environments and is capable of changes or modifications within the scope of the inventive concept as expressed herein, commensurate with the above teachings and/or the skill or knowledge of the relevant art.

The embodiments described hereinabove are further intended to explain best modes known of practicing the invention and to enable others skilled in the art to utilize the invention in such, or other, embodiments and with the various modifications required by the particular applications or uses of the invention. Accordingly, the description is not intended to limit the invention to the form disclosed herein. Also, it is intended that the appended claims be construed to include alternative embodiments.