1 . An immunoconjugate comprising an antibody (Ab), or a functional fragment thereof, coupled to an agonist of Stimulator of Interferon Genes (STING) receptor (D) via a linker (L), wherein the linker optionally comprises one or more cleavage elements.

2. The immunoconjugate of claim 1 comprising Formula (I):

Ab-(L-(D)_m)_n (Formula (I))

wherein:

Ab is an antibody or a functional fragment thereof;

L is a linker comprising one or more cleavage elements;

D is a drug moiety that has agonist activity against STING receptor;

m is an integer from 1 to 8; and

n is an integer from 1 to 20.

3. The immunoconjugate of claim 1 comprising Formula (I):

Ab-(L-(D)_m)_n (Formula (I))

wherein:

Ab is an antibody or a functional fragment thereof;

L is a linker;

D is a drug moiety that binds to STING receptor;

m is an integer from 1 to 8; and

n is an integer from 1 to 20;

wherein D, or a cleavage product thereof, that is released from the immunoconjugate has STING agonist activity.

The immunoconjugate of claim 1 comprising Formula (I):

Ab-(L-(D)_m)_n (Formula (I))

wherein:

Ab is an antibody or a functional fragment thereof;

L is a linker; D is a drug moiety that binds to STING receptor;

m is an integer from 1 to 8; and

n is an integer from 1 to 20;

wherein the immunoconjugate delivers D, or a cleavage product thereof, to a cell targeted by the Ab, and wherein D, or the cleavage product thereof, has STING agonist activity.

5. The immunoconjugate of claim 1 comprising Formula (I):

Ab-(L-(D)_m)_n (Formula (I))

wherein:

Ab is an antibody or a functional fragment thereof;

L is a linker comprising one or more cleavage elements;

D is a drug moiety that binds to STING receptor;

m is an integer from 1 to 8; and

n is an integer from 1 to 20;

wherein the immunoconjugate releases D, or a cleavage product thereof, in a cell targeted by the Ab, and wherein D, or the cleavage product thereof, has STING agonist activity.

6. The immunoconjugate of claim 1 comprising Formula (I):

Ab-(L-(D)_m)_n (Formula (I))

wherein:

Ab is an antibody or a functional fragment thereof;

L is a linker comprising one or more cleavage elements;

D is a drug moiety that has agonist activity against STING receptor;

m is an integer from 1 to 8; and

n is an integer from 1 to 20;

wherein the immunoconjugate releases D, or a cleavage product thereof, in a cell targeted by the Ab, and wherein D, or the cleavage product thereof, has STING agonist activity in the cell.

7. The immunoconjugate of claim 1 for delivery of a STING receptor agonist to a cell, the immunoconjugate comprising Formula (I):

Ab— (L— (D)_m)_n (Formula (I)) wherein:

Ab is an antibody or a functional fragment thereof;

L is a linker comprising one or more cleavage elements;

D is a drug moiety that binds to STING receptor;

m is an integer from 1 to 8; and

n is an integer from 1 to 20;

wherein the immunoconjugate specifically binds to an antigen expressed on the cell surface and is internalized into the cell, and wherein D, or a cleavage product thereof, is cleaved from L and has STING agonist activity as determined by one or more STING agonist assays selected from: an interferon stimulation assay, a hSTING wt assay, a THP1 -Dual assay, a TANK binding kinase 1 (TBK1) assay, or an interferon-v-inducible protein 10 (IP-10) secretion assay.

8. The immunoconjugate of any one of the preceding claims, wherein D, or the cleavage product thereof, has STING agonist activity if it binds to STING and is able to stimulate production of one or more STING-dependent cytokines in a STING-expressing cell at least 1 .1 - fold, 1 .2-fold, 1 .3-fold, 1 .4-fold, 1 .5-fold, 1 .6-fold, 1 .7-fold, 1 .8-fold, 1.9-fold, 2-fold or greater than an untreated STING-expressing cell.

9. The immunoconjugate of claim 8, wherein the STING-dependent cytokine is selected from interferon, type 1 interferon, IFN-a, IFN-β, type 3 interferon, IFN , IP10, TNF, IL-6, CXCL9, CCL4, CXCL1 1 , CCL5, CCL3, or CCL8.

10. The immunoconjugate of any one of claims 1 -7, wherein D, or the cleavage product thereof, has STING agonist activity if it binds to STING and is able to stimulate phosphorylation of TBK1 in a STING-expressing cell at least 1 .1 -fold, 1 .2-fold, 1 .3-fold, 1 .4-fold, 1 .5-fold, 1 .6-fold, 1 .7- fold, 1 .8-fold, 1 .9-fold, 2-fold or greater than an untreated STING-expressing cell.

1 1 . The immunoconjugate of any one of claims 1 -7, wherein D, or the cleavage product thereof, has STING agonist activity if it binds to STING and is able to stimulate expression of a STING- dependent transcript selected from any one of the transcripts listed in Fig. 1A - Fig. 10 and Fig. 2A - Fig. 2L in a STING-expressing cell at least 5-fold or greater than the expression level in an untreated STING-expressing cell.

12. The immunoconjugate of claim 1 1 , wherein expression of the STING-dependent transcript is increased 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 1 1 -fold, 12-fold, 13-fold, 14-fold, 15-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 70-fold, 80-fold, 90-fold, 100-fold, 200-fold, 300-fold, 400-fold, 500-fold, 700-fold or greater.

13. The immunoconjugate of any one of claims 1 -7, wherein D, or the cleavage product thereof, has STING agonist activity if it binds to STING and is able to stimulate expression of a luciferase reporter gene controlled by interferon (IFN)-stimulated response elements in a STING-expressing cell at an EC50 of 20 micromolar (μΜ), 15 μΜ , 10 μΜ, 9 μΜ , 8 μΜ , 7 μΜ, 6 μΜ , 5 μΜ , 4 μΜ, 3 μΜ , 2 μΜ , 1 μΜ , or less.

14. The immunoconjugate of any one of claims 1 -7, wherein D, or the cleavage product thereof, has STING agonist activity if it binds to STING and is able to stimulate expression of a luciferase reporter gene controlled by interferon (IFN)-stimulated response elements in a STING-expressing cell to a level equal to or greater than the level of stimulation of 50 μΜ of 2'3'-cGAMP.

15. The immunoconjugate of claim 13 or 14, wherein the STING-expressing cell is THP1 -Dual cell, and the luciferase reporter gene is the IRF-Lucia reporter gene in THP1 -Dual cell, and optionally the STING agonist activity is determined by the THP1 -Dual assay described for Table 7.

16. The immunoconjugate of claim 13 or 14, wherein the luciferase reporter gene is the

5xlSRE-mlFNb-GL4 reporter gene and the STING-expressing cell is a cell expressing wild-type human STING protein, and optionally the STING agonist activity is determined by the hSTING wt assay described in Table 7.

17. The immunoconjugate of any one of claims 1 -7, wherein the immunoconjugate stimulates IP-10 secretion from a STING-expressing cell targeted by the Ab at an EC50 of 5 nanomolar

(nM) or less in an IP-10 secretion assay.

18. The immunoconjugate of anyone of the preceding claims, wherein the immunoconjugate is parenterally administered.

19. The immunoconjugate of any one of the preceding claims, wherein the Ab specifically binds a target antigen.

20. The immunoconjugate of claim 19, wherein the target antigen is a tumor antigen.

21 . The immunoconjugate of any one of the preceding claims, wherein the Ab is human or humanized.

22. The immunoconjugate of any one of the preceding claims, wherein the Ab is a monoclonal antibody.

23. The immunoconjugate of any one of the preceding claims, wherein the Ab comprises a modified Fc region.

24. The immunconjugate of claim 23, wherein the Ab comprises cysteine at one or more of the following positions, which are numbered according to EU numbering: (a) positions 152, 360 and 375 of the antibody heavy chain, and

(b) positions 107, 159, and 165 of the antibody light chain.

25. The immunconjugate of any one of the preceding claims, wherein L is attached to the Ab via conjugation to one or more modified cysteine residues in the Ab.

26. The immunoconjugate of claim 25, wherein L is conjugated to the Ab via modified cysteine residues at positions 152 and 375 of the heavy chain of the Ab, wherein the positions are determined according to EU numbering.

27. The immunconjugate of claims 24 to 26, wherein L is conjugated via a maleimide linkage to the cysteine.

28. The immunoconjugate of any one of the preceding claims, wherein D is a dinucleotide.

29. The immunoconjugate of any one of the preceding claims, wherein D is a cyclic dinucleotide (CDN).

30. The immunoconjugate of any of the preceding claims, wherein D is a compound selected from any one of the compounds of Table 1 , Table 2, Table 3, or Table 4.

31. The immunoconjugate of any of the preceding claims, wherein D is a compound selected from

and

32. The immunoconjugate of any of the preceding claims, wherein L is a cleavable linker comprising one or more cleavage elements.

33. The immunoconjugate of claim 32, wherein L comprises two or more cleavage elements, and each cleavage element is independently selected from a self-immolative spacer and a group that is susceptible to cleavage.

34. The immunoconjugate of claim 33, wherein the cleavage is selected from acid-induced cleavage, peptidase-induced cleavage, esterase-induced cleavage, glycosidase-induced cleavage, phosphodiesterase-induced cleavage, phosphatase-induced cleavage, protease- induced cleavage, lipase-induced cleavage, or disulfide bond cleavage.

35. The immunoconjugate of claim 32, where L has a structure selected from: I (L_c)_x C_E D _ -HL_c)x-C_E— (L_c)y-C_E-D _{^ and} ^~^((L_c)_x^"C_E)p-^"(L_c)_y^~C_E^~D _^ wherein:

Lc is a linker component and each Lc is independently selected from a linker component as shown in Embodiments 70 to 75;

x is an integer selected from 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19 and 20;

y is an integer selected from 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19 and 20; p is an integer selected from 1 , 2, 3, 4, 5, 6, 7, 8, 9 and 10;

D is the compound of claims 28 to 31 ;

and each cleavage element (C_E) is independently selected from a self-immolative spacer and a group that is susceptible to cleavage selected from acid-induced cleavage, peptidase-induced cleavage, esterase-induced cleavage, glycosidase induced cleavage, phosphodiesterase induced cleavage, phosphatase induced cleavage, protease induced cleavage, lipase induced cleavage or disulfide bond cleavage.

36. The immunoconjugate of any one of the preceeding claims, wherein L comprises a structure selected from:

and o

37. The immunoconjugate of any one of the preceding claims, wherein the immunoconjugate is selected from the following:

Formula (BB-a) Formula (BB-b)

637

Formula (CC-e) Formula (CC-f)

639

Formula (FF-a) Formula (FF-b)

Formula (FF-e) Formula (FF-f)

Formula (FF-i) Formula (FF-j)

Formula (FF-k);

wherein:

each Gi is independently selected from and

where * indicates the point of attachment to -CR⁸R⁹-;

X_A is C(=0)-, -C(=S)- or -C(=NR¹¹)- and each Ζ is NR¹²;

X_B is C, and each Z₂ is N;

G₂ is , where * indicates the point of attachment to -CR^8aR^9a-;

Xc is C(=0)-, -C(=S)- or -C(=NR¹¹)- and each Z₃ is NR¹²;

YI is -0-, -S-, -S(=0)-, -SO2-, -CH₂-, or -CF₂-;

Y₂ is -0-, -S-, -S(=0)-, -SO2-, -CH₂-, or -CF₂-;

Y₃ is OH, 0^", OR¹⁰, N(R¹⁰)₂, SR¹⁰, SeH, Se^", BH₃, SH or S^";

Y₄ is OH, 0^", OR¹⁰, N(R¹⁰)₂, SR¹⁰, SeH, Se^", BH₃, SH or S^";

Ys is -CH₂-, -NH-, -0- or -S;

Y₆ is -CH₂-, -NH-, -0- or -S;

Y₈ is 0 or S; Y₉ is -CH₂-, -NH-, -O- or -S;

Y₁₀ is -CH2-, -NH-, -O- or -S;

Y11 is -0-, -S-, -S(=0)-, -SO2-, -CH₂-, or -CF₂-;

q is 1 , 2 or 3;

R¹ is a partially saturated or aromatic monocyclic heterocyclyl or partially saturated or

aromatic fused bicyclic heterocyclyl containing from 5-10 ring members selected from carbon atoms and 1 to 5 heteroatoms, and each heteroatoms is independently selected from O, N or S, or a tautomer thereof, wherein R¹ is substituted with 0, 1 , 2, 3 or 4 substituents independently selected from -NHL,R¹¹⁵, F, CI, Br, OH, SH, NH₂, D, CD₃, CrC₆alkyl, CrC₆alkoxyalkyl, CrC₆hydroxyalkyl, C₃-C₈cycloalkyl, a 3 to 6 membered heterocyclyl having 1 to 2 heteroatoms independently selected from O, N and S, -0(C_r C₆alkyl), -0(C₃-C₈cycloalkyl), -S(CrC₆alkyl), -S(CrC₆aminoalkyr), -S(CrC₆hydroxyalkyl), -S(C₃-C₈cycloalkyl), -NH(C C₆alkyl), -NH(C₃-C₈cycloalkyl), -N(CrC₆alkyl)₂, -N(C C₆alkyl) (C₃-C₈cycloalkyl), -CN, -P(=0)(OH)₂, -(CH₂)₁.₁₀C(=O)OH,- -NHC(0)(Ci-C₆alkyl), -NHC(0)(C₃-C₈cycloalkyl), -

NHC(0)(phenyl), and -N(C₃-C₈cycloalkyl)₂;

R^1a is a partially saturated or aromatic monocyclic heterocyclyl or partially saturated or

aromatic fused bicyclic heterocyclyl containing from 5-10 ring members selected from carbon atoms and 1 to 5 heteroatoms, and each heteroatoms is independently selected from O, N or S, or a tautomer thereof, wherein R^1a is substituted with 0, 1 , 2, 3 or 4 substituents independently selected from -NHLiR¹¹⁵, F, CI, Br, OH, SH, NH₂, D, CD₃, CrC₆alkyl, CrCealkoxyalkyl, CrC₆hydroxyalkyl, C₃-C₈cycloalkyl, a 3 to 6 membered heterocyclyl having 1 to 2 heteroatoms independently selected from O, N and S, -0(C_r C₆alkyl), -0(C₃-C₈cycloalkyl), -S(CrC₆alkyl), -S(CrC₆aminoalkyr), -S(CrC₆hydroxyalkyl), -S(C₃-C₈cycloalkyl), -NH(C C₆alkyl), -NH(C₃-C₈cycloalkyl), -N(CrC₆alkyl)₂, -N(C

C₆alkyl) (C₃-C₈cycloalkyl), -CN, -P(=0)(OH)₂, -O(CH₂)₁.₁₀C(=O)OH, -(CH₂)₁.₁₀C(=O)OH,- CH=CH(CH₂)₁.₁₀C(=O)OH, -NHC(0)(C C₆alkyl), -NHC(0)(C₃-C₈cycloalkyl), - NHC(0)(phenyl), and -N(C₃-C₈cycloalkyl)₂;

R^1b is a partially saturated or aromatic monocyclic heterocyclyl or partially saturated or

aromatic fused bicyclic heterocyclyl containing from 5-10 ring members selected from carbon atoms and 1 to 5 heteroatoms, and each heteroatoms is independently selected from O, N or S, or a tautomer thereof, wherein R^1b is substituted with 0, 1 , 2, 3 or 4 substituents independently selected from -NHLiR¹¹⁵, F, CI, Br, OH, SH, NH₂, D, CD₃, CrC₆alkyl, CrCealkoxyalkyl, CrC₆hydroxyalkyl, C₃-C₈cycloalkyl, a 3 to 6 membered heterocyclyl having 1 to 2 heteroatoms independently selected from O, N and S, -0(C_r

C₆alkyl), -0(C₃-C₈cycloalkyl), -S(CrC₆alkyl), -S(CrC₆aminoalkyl), -S(CrC₆hydroxyalkyl), -S(C₃-C₈cycloalkyl), -NH(CrC₆alkyl), -NH(C₃-C₈cycloalkyl), -N(CrC₆alkyl)₂, -N(C_r C₆alkyl) (C₃-C₈cycloalkyl), -CN, -P(=0)(OH)₂,

-NHC(0)(C C₆alkyl), -NHC(0)(C₃-C₈cycloalkyl), - NHC(0)(phenyl), and -N(C₃-C₈cycloalkyl)₂;

each R² is independently selected from the group consisting of H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, C Cealkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-

C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - O(CH₂)₁.₁₀C(=O)OH, -O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R² and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl,

CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C C₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R² are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

each R³ is independently selected from the group consisting of -OI_iR¹¹⁵, H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrCealkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - -OC(0)Ophenyl, -OC(0)OCi-C₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R³ and the

CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R³ are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

each R⁴ is independently selected from the group consisting of -OLiR¹¹⁵, H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(Ci-C₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - O(CH₂)₁.₁₀C(=O)OH, -O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, -

OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R⁴ and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R⁴ are substituted by

0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃; each R⁵ is independently selected from the group consisting of -OLiR¹¹⁵, H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrCealkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - O(CH₂)₁.₁₀C(=O)OH, -O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R⁵ and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C C₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R⁵ are substituted by 0,1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

each R⁶ is independently selected from the group consisting of H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrCealkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂- C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - -OC(0)Ophenyl, -OC(0)OCi-C₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R⁶ and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R⁶ are substituted by 0,1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

each R⁷ is independently selected from the group consisting of -OLiR¹¹⁵, H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - O(CH₂)₁.₁₀C(=O)OH, -O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R⁷ and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R⁷ are substituted by 0,1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

each R⁸ is independently selected from the group consisting of H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂- C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - O(CH₂)₁.₁₀C(=O)OH, -O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R⁸ and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C Cehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C C₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R⁸ are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

each R⁹ is independently selected from the group consisting of H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, C Cealkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂- C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - O(CH₂)₁.₁₀C(=O)OH, -O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R⁹ and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(Ci-C₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R⁹ are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

R^2a is selected from the group consisting of H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C_r C₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, -O(CH₂)₁.₁₀C(=O)OH, - O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, - OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and - OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R^2a and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂- C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), - OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R^2a are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃

R^3a is selected from the group consisting of -OL^R¹¹⁵, H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂-C₆haloalkenyl, C₂- C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - O(CH₂)₁.₁₀C(=O)OH, -O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R^3a and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R^3a are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

R^4a is selected from the group consisting of -OL^R¹¹⁵, H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂-C₆haloalkenyl, C₂- C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - O(CH₂)₁.₁₀C(=O)OH, -O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R^4a and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C Cehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C C₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R^4a are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

R^5a is selected from the group consisting of -OI_iR¹¹⁵, H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂-C₆haloalkenyl, C₂- C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - -OC(0)Ophenyl, -OC(0)OCi-C₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R^5a and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the C Cealkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C Cehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C C₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R^5a are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

R^6a is selected from the group consisting of H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, C C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C_r Csalkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OC C₆alkyl, -OC(0)OC₂-C₆alkenyl, - OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)C C₆alkyl, -OC(0)C₂-C₆alkenyl and - OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R^6a and the C C₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the C Cealkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂- C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), - OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R^6aare substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃; R^7a is selected from the group consisting of -OL^R¹¹⁵, H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂-C₆haloalkenyl, C₂- C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - O(CH₂)₁.₁₀C(=O)OH, -O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R^7a and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C Cehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C C₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R^7a are substituted by 0,1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

R^8a is selected from the group consisting of H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, C C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C_r C₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, -O(CH₂)₁.₁₀C(=O)OH, - -OC(0)Ophenyl, -OC(0)OCi-C₆alkyl, -OC(0)OC₂-C₆alkenyl, - OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)C C₆alkyl, -OC(0)C₂-C₆alkenyl and - OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R^8a and the C C₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the Ci-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, Ci-C₆haloalkyl, C₂- C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C C₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), - OC(0)OC C₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)C C₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R⁸ are substituted by 0,1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

R^9a is selected from the group consisting of H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, C C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C_r C₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, -O(CH₂)₁.₁₀C(=O)OH, - O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OC C₆alkyl, -OC(0)OC₂-C₆alkenyl, - OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)C C₆alkyl, -OC(0)C₂-C₆alkenyl and - OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R^9a and the Ci-C₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the C Cealkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂- C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), - OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R^9a are substituted by 0,1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃; each R¹⁰ is independently selected from the group consisting of H, CrC₁₂alkyl, C_r

C₆heteroalkyl, , wherein the

C₁₂alkyl and CrC₆heteroalkyl of R¹⁰ is substituted by 0, 1 , 2 or 3 substituents independently selected from -OH, CrC₁₂alkoxy, -S-C(=0)C₁-C₆alkyl, halo, -CN, C_r C₁₂alkyl, -O-aryl, _0-heteroaryl, -O-cycloalkyl, oxo, cycloalkyl, heterocyclyl, aryl, or heteroaryl, -OC(0)OCrC₆alkyland C(0)OCrC₆alkyl, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is substituted by 0, 1 , 2 or 3 substituents independently selected from CrC₁₂ alkyl, 0-CrC₁₂alkyl, CrCeheteroalkyl, halo, CN, OH, oxo, aryl, heteroaryl, O-aryl, O-heteroaryl,

C₁₂alkyl, -OC(=0)OC₁-C₁₂alkyl, -C(=0)N(R¹¹)-C₁-C₁₂alkyl, -N(R¹¹)C(=0)-C₁-C₁₂alkyl; - OC(=0)N(R^{1 1})-C₁-C₁₂alkyl, -C(=0)-aryl, -C(=0)-heteroaryl, -OC(=0)-aryl, -C(=0)0-aryl, OC(=0)-heteroaryl, -C(=0)0-heteroaryl, -C(=0)0-aryl, -C(=0)0-heteroaryl, - C(=0)N(R¹¹)-aryl, -C(=0)N(R¹¹)-heteroaryl, -N(R¹¹)C(0)-aryl, -N(R¹¹)2C(0)-aryl, - N(R¹¹)C(0)-heteroaryl, and S(0)₂N(R¹¹)-aryl;

each R^{1 1} is independently selected from H and CrC₆alkyl;

each R¹² is independently selected from H and C Cealkyl;

optionally R³ and R⁶ are connected to form CrC₆alkylene, C₂-C₆alkenylene, C₂-

C₆alkynylene, -0-CrC₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R³ and R⁶ are connected, the O is bound at the R³ position

optionally R^3a and R^6a, are connected to form CrC₆alkylene, C₂-C₆alkenylene, C₂- C₆alkynylene, -0-CrC₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R^3a and R^6a are connected, the O is bound at the R^3a position;

optionally R² and R³ are connected to form CrC₆alkylene, C₂-C₆alkenylene, C₂-

C₆alkynylene, -0-CrC₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R² and R³ are connected, the O is bound at the R³ position;

optionally R^2a and R^3a, are connected to form CrC₆alkylene, C₂-C₆alkenylene, C₂- C₆alkynylene, -0-CrC₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R^2a and R^3a are connected, the O is bound at the R^3a position;

optionally R⁴ and R³ are connected to form CrC₆alkylene, C₂-C₆alkenylene, C₂-

C₆alkynylene, -0-CrC₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R⁴ and R³ are connected, the O is bound at the R³ position;

optionally R^4a and R^3a, are connected to form CrC₆alkylene, C₂-C₆alkenylene, C₂- C₆alkynylene, -0-CrC₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R^4a and R^3a are connected, the O is bound at the R^3a position; optionally R⁵ and R⁶ are connected to form CrCalkylene, C₂-C₆alkenylene, C₂-

C₆alkynylene, -0-CrC₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R⁵ and R⁶ are connected, the O is bound at the R⁵ position;

optionally R^5a and R^6a, are connected to form CrC₆alkylene, C₂-C₆alkenylene, C₂- C₆alkynylene, -0-CrC₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R^5a and R^6a are connected, the O is bound at the R^5a position;

optionally R⁵ and R⁷ are connected to form C Cealkylene, C₂-C₆alkenylene, C₂-

C₆alkynylene, -0-CrC₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R⁵ and R⁷ are connected, the O is bound at the R⁵ position;

optionally R^5a and R^7a, are connected to form C Cealkylene, C₂-C₆alkenylene, C₂- C₆alkynylene, -0-CrC₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R^5a and R^7a are connected, the O is bound at the R^5a position;

optionally R⁸ and R⁹ are connected to form a CrC₆alkylene, C₂-C₆alkenylene, C₂- C₆alkynylene, and

optionally R^8a and R^9a are connected to form a CrC₆alkylene, C₂-C₆alkenylene, C₂-

, , , -C(=0)-, -ON=***, -S-, -NHC(=0)CH₂-***, -

S(=0)₂CH₂CH₂-***, -(CH₂)₂S(=0)₂CH₂CH₂-***, -NHS(=0)₂CH₂CH₂..., -NHC(=0)CH₂CH₂- piio

where *** indicates the point of attachment to Ab;

R¹³ is H or methyl;

R¹⁴ is H, -CH₃ or phenyl;

each R^{1 10} is independently selected from H, Ci-C₆alkyl, F, CI, and -OH;

each R^{1 11} is independently selected from H, C C₆alkyl, F, CI, -NH₂, -OCH₃, -OCH₂CH₃, -

N(CH₃)₂, -CN, -N0₂ and -OH;

each R^{1 12} is independently selected from H, Ci_-6alkyl, fluoro, benzyloxy substituted with -

C(=0)OH, benzyl substituted with -C(=0)OH, substituted with -C(=0)OH and

C_1-4alkyl substituted with -C(=0)OH;

Ab is an antibody or a functional fragment thereof; and

y is 1 , 2, 3, 4, 5, 6, 7, 8, 9 or 10. The immunoconjugate of any one of the preceding claims comprising a structure selected from:

654

656

658

664

665

666

667

668

670



673



676

39. The immunoconjugate of any one of the preceding claims, wherein the immunoconjugate has in vivo anti-tumor activity.

40. A pharmaceutical composition comprising the immunconjugate according to any one of the preceding claims and a pharmaceutically acceptable excipient.

41 . A composition comprising the immunoconjugate according to any one of the preceding claims in combination and one or more additional therapeutic agents.

42. The composition of claim 41 , wherein the additional therapeutic agent is selected from the group consisting of an inhibitor of a co-inhibitory molecule, an activator of a co-stimulatory molecule, a cytokine, an agent that reduces cytokine release syndrome (CRS), a chemotherapy, a targeted anti-cancer therapy, an oncolytic drug, a cytotoxic agent, an immune-based therapy, a vaccine, or a cell therapy.

43. The composition of claim 41 , wherein the additional therapeutic agent is an inhibitor of a co- inhibitory molecule, an activator of a co-stimulatory molecule, or a cytokine, wherein:

(i) the co-inhibitory molecule is selected from Programmed death-1 (PD-1), Programmed death-ligand 1 (PD-L1), Lymphocyte activation gene-3 (LAG-3), or T-cell immunoglobulin domain and mucin domain 3 (TIM-3),

(ii) the co-stimulatory molecule is Glucocorticoid-induced TNFR-related protein (GITR), and

(iii) the cytokine is IL-15 complexed with a soluble form of IL-15 receptor alpha (IL-

15Ra).

44. A method of treating cancer comprising administering to a patient in need thereof a therapeutically effective amount of the immunconjugate of any one of claims 1 -39, the pharmaceutical composition of claim 40, or the composition of claims 41 -43.

45. Use of the immunconjugate of any one of claims 1 -39, the pharmaceutical composition of claim 40, or the composition of claims 41 -43 for treatment of a cancer in a subject in need thereof.

46. The immunconjugate of any one of claims 1 -39, the pharmaceutical composition of claim 40, or the composition of claims 41 -43, for use in the treatment of cancer.

47. Use of the immunconjugate of any one of claims 1 -39, the pharmaceutical composition of claim 40, or the composition of claims 41 -43 in the manufacture of a medicament for treatment of a cancer in a subject in need thereof.

48. The method according to claim 43, the use according to claim 44 or 46, or the

immunoconjugate of claim 45, wherein the cancer is selected from sarcomas,

adenocarcinomas, blastomas, carcinomas, liver cancer, lung cancer, non-small cell lung cancer, small cell lung cancer, breast cancer, lymphoid cancer, colon cancer, renal cancer, urothelial cancer, prostate cancer, cancer of the pharynx, rectal cancer, renal cell carcinoma, cancer of the small intestine, esophageal cancer, melanoma, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, colorectal cancer, cancer of the anal region, cancer of the peritoneum, stomach or gastric cancer, esophageal cancer, salivary gland carcinoma, testicular cancer, uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, penile carcinoma, glioblastoma, neuroblastoma, cervical cancer , Hodgkin lymphoma, non-Hodgkin lymphoma, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, chronic or acute leukemias including acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, solid tumors of childhood, lymphocytic lymphoma, cancer of the bladder, cancer of the kidney or ureter, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brain stem glioma, pituitary adenoma, Kaposi's sarcoma, neuroendocrine tumors (including carcinoid tumors, gastrinoma, and islet cell cancer), mesothelioma, schwannoma (including acoustic neuroma), meningioma, epidermoid cancer, squamous cell cancer, T-cell lymphoma, environmentally induced cancers including those induced by asbestos, leukemia, lymphoma, acute

myelogenous leukemia (AML), acute lymphoid leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphoid leukemia (CLL), myelodysplasia syndromes, B-cell acute lymphoid leukemia ("BALL"), T-cell acute lymphoid leukemia ("TALL"), B cell prolymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, diffuse large B cell lymphoma, Follicular lymphoma, Hairy cell leukemia, small cell- or a large cell-follicular lymphoma, malignant lymphoproliferative conditions, MALT lymphoma, mantle cell lymphoma, Marginal zone lymphoma, multiple myeloma, myelodysplasia, myelodysplasia syndrome, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, and Waldenstrom macroglobulinemia.

49. The method according to claim 43, the use according to claim 44 or 45, or the

immunoconjugate of claim 45, wherein the immunoconjugate is administered to the subject intravenously, intratumorally, or subcutaneously.

50. The immunconjugate of any one of claims 1-39, the pharmaceutical composition of claim 40, or the composition of claims 41-43, for use as a medicament.

51. A method of manufacturing the immunoconjugate of any one of claims 1-38 comprising the steps of:

a) Reacting D and L to form (L— (D)_m; and

b) Reacting (L— (D)_mwith Ab to form the immunoconjugate Ab— (L— (D)_m)_n (Formula (I)).

52. A compound having a structure selected from Formula (A), Formula (B), Formula (C), Formula (D), Formula (E), or Formula (F) or stereoisomers or pharmaceutically acceptable salts thereof,

Formula (C) Formula (D)

Formula (E) Formula (F) wherein:

each Gi is independently selected from

indicates the point of attachment to -CR⁸R⁹-;

XA is C(=0)-, -C(=S)- or -C(=NR¹¹)- and each is NR¹²;

wwhheerree ** indicates the point of attachment to -CR^8aR^9a-;

Xc is C(=0)-, -C(=S)- or -C(=NR¹¹)- and each Z₃ is NR¹²;

YI is -0-, -S-, -S(=0)-, -SO₂-, -CH₂-, or -CF₂-;

Y₂ is -0-, -S-, -S(=0)-, -S0₂-, -CH₂-, or -CF₂-;

Y₃ is OH, 0^", OR¹⁰, N(R¹⁰)₂, SR¹⁰, SeH, Se^", BH₃, SH or S^";

Y₄ is OH, 0^", OR¹⁰, N(R¹⁰)₂, SR¹⁰, SeH, Se^", BH₃, SH or S^";

Ys is -CH₂-, -NH-, -0- or -S;

Y₆ is -CH₂-, -NH-, -0- or -S;

Y₈ is 0 or S;

Y₉ is -CH₂-, -NH-, -0- or -S; Y₁₀ is -CH₂-, -NH-, -O- or -S;

Y₁₁ is -0-, -S-, -S(=0)-, -SO2-, -CH_r, or -CF₂-;

q is 1 , 2 or 3;

R¹ is a partially saturated or aromatic monocyclic heterocyclyl or partially saturated or

aromatic fused bicyclic heterocyclyl containing from 5-10 ring members selected from carbon atoms and 1 to 5 heteroatoms, and each heteroatoms is independently selected from O, N or S, or a tautomer thereof, wherein R¹ is substituted with 0, 1 , 2, 3 or 4 substituents independently selected from -NHL,R¹⁵, F, CI, Br, OH, SH, NH₂, D, CD₃, C C₆alkyl, CrC₆alkoxyalkyl, CrC₆hydroxyalkyl, C₃-C₈cycloalkyl, a 3 to 6 membered heterocyclyl having 1 to 2 heteroatoms independently selected from O, N and S, -0(C_r

C₆alkyl), -0(C₃-C₈cycloalkyl), -S(CrC₆alkyl), -S(CrC₆aminoalkyr), -S(CrC₆hydroxyalkyl), -S(C₃-C₈cycloalkyl), -NH(C C₆alkyl), -NH(C₃-C₈cycloalkyl), -N(CrC₆alkyl)₂, -N(C C₆alkyl) (C₃-C₈cycloalkyl), -CN, -P(=0)(OH)₂,

CH=CH(CH₂)₁.₁₀C(=O)OH, -NHC(0)(C C₆alkyl), -NHC(0)(C₃-C₈cycloalkyl), - NHC(0)(phenyl), and -N(C₃-C₈cycloalkyl)₂;

R^1a is a partially saturated or aromatic monocyclic heterocyclyl or partially saturated or

aromatic fused bicyclic heterocyclyl containing from 5-10 ring members selected from carbon atoms and 1 to 5 heteroatoms, and each heteroatoms is independently selected from O, N or S, or a tautomer thereof, wherein R^1a is substituted with 0, 1 , 2, 3 or 4 substituents independently selected from -NHLiR¹⁵, F, CI, Br, OH, SH, NH₂, D, CD₃, C

C₆alkyl, CrCealkoxyalkyl, CrCehydroxyalkyl, C₃-C₈cycloalkyl, a 3 to 6 membered heterocyclyl having 1 to 2 heteroatoms independently selected from O, N and S, -0(C_r C₆alkyl), -0(C₃-C₈cycloalkyl), -S(CrC₆alkyl), -S(CrC₆aminoalkyl), -S(CrC₆hydroxyalkyl), -S(C₃-C₈cycloalkyl), -NH(CrC₆alkyl), -NH(C₃-C₈cycloalkyl), -N(CrC₆alkyl)₂, -N(C_r C₆alkyl) (C₃-C₈cycloalkyl), -CN, -P(=0)(OH)₂, -O(CH₂)₁.₁₀C(=O)OH, -(CH₂)₁.₁₀C(=O)OH,-

CH=CH(CH₂)₁.₁₀C(=O)OH, -NHC(0)(CrC₆alkyl), -NHC(0)(C₃-C₈cycloalkyl), - NHC(0)(phenyl), and -N(C₃-C₈cycloalkyl)₂;

R^1b is a partially saturated or aromatic monocyclic heterocyclyl or partially saturated or

aromatic fused bicyclic heterocyclyl containing from 5-10 ring members selected from carbon atoms and 1 to 5 heteroatoms, and each heteroatoms is independently selected from O, N or S, or a tautomer thereof, wherein R^1b is substituted with 0, 1 , 2, 3 or 4 substituents independently selected from -NHLiR¹⁵, F, CI, Br, OH, SH, NH₂, D, CD₃, C_r C₆alkyl, CrC₆alkoxyalkyl, CrC₆hydroxyalkyl, C₃-C₈cycloalkyl, a 3 to 6 membered heterocyclyl having 1 to 2 heteroatoms independently selected from O, N and S, -0(C_r C₆alkyl), -0(C₃-C₈cycloalkyl), -S(CrC₆alkyl), -S(CrC₆aminoalkyl), -S(CrC₆hydroxyalkyl),

-S(C₃-C₈cycloalkyl), -NH(CrC₆alkyl), -NH(C₃-C₈cycloalkyl), -N(CrC₆alkyl)₂, -N(C_r C₆alkyl) (C₃-C₈cycloalkyl), -CN, -P(=0)(OH)₂, -O(CH₂)₁.₁₀C(=O)OH, -(CH₂)₁.₁₀C(=O)OH,- CH=CH(CH₂)i-i₀C(=O)OH,-NHC(O)(C₁-C₆alkyl), -NHC(0)(C₃-C₈cycloalkyl), - NHC(0)(phenyl), and -N(C₃-C₈cycloalkyl)₂;

each R² is independently selected from the group consisting of H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrCealkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂- Cehaloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, -

O(CH₂)₁.₁₀C(=O)OH, -O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R² and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C C₆alkyl), -0(C₂-C₆alkenyl), -

0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R² are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

each R³ is independently selected from the group consisting of -OLiR¹⁵, H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, Ci-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl,

C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - O(CH₂)₁.₁₀C(=O)OH, -O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)Ci-C₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R³ and the CrCealkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the C C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl,

CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R³ are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

each R⁴ is independently selected from the group consisting of -OLiR¹⁵, H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - -OC(0)Ophenyl, -OC(0)OCi-C₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R⁴ and the

CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R⁴ are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

each R⁵ is independently selected from the group consisting of -OLiR¹⁵, H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - O(CH₂)₁.₁₀C(=O)OH, -O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R⁵ and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C Cehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C C₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R⁵ are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

each R⁶ is independently selected from the group consisting of H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrCealkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂- C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - O(CH₂)₁.₁₀C(=O)OH, -O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R⁶ and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCi-C₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R⁶ are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

each R⁷ is independently selected from the group consisting of -OLiR¹⁵, H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - O(CH₂)₁.₁₀C(=O)OH, -O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R⁷ and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(Ci-C₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R⁷ are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

each R⁸ is independently selected from the group consisting of H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂- C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - O(CH₂)₁.₁₀C(=O)OH, -O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R⁸ and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C Cehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C C₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R⁸ are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

each R⁹ is independently selected from the group consisting of H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, C Cealkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, Ci-C₆haloalkyl, C₂-C₆haloalkenyl, C₂- C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, - O(CH₂)₁.₁₀C(=O)OH, -O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, - OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R⁹ and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C Cehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C C₆alkyl), -0(C₂-C₆alkenyl), - 0(C₂-C₆alkynyl), -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, - OC(0)Ci-C₆alkyl, -OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R⁹ are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

R^2a is selected from the group consisting of H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, C C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, Ci-C₆haloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(Cr C₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, -O(CH₂)₁.₁₀C(=O)OH, - O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OC C₆alkyl, -OC(0)OC₂-C₆alkenyl, - OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)C C₆alkyl, -OC(0)C₂-C₆alkenyl and - OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R^2a and the C C₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the C Cealkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂- C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C C₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), - OC(0)OC C₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)C C₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R^2a are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃

R^3a is selected from the group consisting of -OI_iR¹⁵, H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, Ci C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, 0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, -O(CH₂)₁.₁₀C(=O)OH, O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, - OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and - OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R^3a and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂- C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), - OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R^3a are substituted by 0,1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

R^4a is selected from the group consisting of -OL^R¹⁵, H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, C C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, - OCd-Csalkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, -O(CH₂)₁.₁₀C(=O)OH, -

O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OC C₆alkyl, -OC(0)OC₂-C₆alkenyl, - OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)C C₆alkyl, -OC(0)C₂-C₆alkenyl and - OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R^4a and the C C₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂- Cehaloalkenyl, C₂-C₆haloalkynyl, -0(C C₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -

OC(0)OC C₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)C C₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R^4a are substituted by 0,1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

R^5a is selected from the group consisting of -OL^R¹⁵, H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, C C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, Ci-C₆haloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -

OCd-Csalkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, -O(CH₂)₁.₁₀C(=O)OH, - O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OC C₆alkyl, -OC(0)OC₂-C₆alkenyl, - OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)Ci-C₆alkyl, -OC(0)C₂-C₆alkenyl and - OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R^5a and the C C₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-

C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C C₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), - OC(0)OC C₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)C C₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R^5a are substituted by 0,1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

R^6a is selected from the group consisting of H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, C C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C_r C₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, -O(CH₂)₁.₁₀C(=O)OH, - -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, - OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and - OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R^6a and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂- C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), - OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R^6aare substituted by 0,1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

R^7a is selected from the group consisting of -OL^R¹⁵, H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, C_r C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, - 0(Ci-C_ealkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OC C₆alkyl, -OC(0)OC₂-C₆alkenyl, - OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)C C₆alkyl, -OC(0)C₂-C₆alkenyl and - OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R^7a and the C C₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂- C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C C₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), - OC(0)OC C₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)C C₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R^7a are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

R^8a is selected from the group consisting of H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, C C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C_r C₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, -O(CH₂)₁.₁₀C(=O)OH, - O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OC C₆alkyl, -OC(0)OC₂-C₆alkenyl, - OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)C C₆alkyl, -OC(0)C₂-C₆alkenyl and - OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R^8a and the Ci-C₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrCehaloalkyl, C₂- C₆haloalkenyl, C₂-C₆haloalkynyl, -0(CrC₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), - OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R⁸ are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

R^9a is selected from the group consisting of H, -OH, F, CI, Br, I, D, CD₃, CN, N₃, CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂-C₆haloalkenyl, C₂-C₆haloalkynyl, -0(C_r C₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), -OP(=0)(OH)₂, -O(CH₂)₁.₁₀C(=O)OH, - O(CH₂)₁.₁₀P(=O)(OH)₂, -OC(0)Ophenyl, -OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, - OC(0)OC₂-C₆alkynyl, -OC(0)phenyl, -OC(0)CrC₆alkyl, -OC(0)C₂-C₆alkenyl and - OC(0)C₂-C₆alkynyl, wherein the -OC(0)Ophenyl of R^9a and the CrC₆alkyl, C₂-C₆alkenyl and C₂-C₆alkynyl of the CrC₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, CrC₆haloalkyl, C₂- C₆haloalkenyl, C₂-C₆haloalkynyl, -0(Ci-C₆alkyl), -0(C₂-C₆alkenyl), -0(C₂-C₆alkynyl), - OC(0)OCrC₆alkyl, -OC(0)OC₂-C₆alkenyl, -OC(0)OC₂-C₆alkynyl, -OC(0)CrC₆alkyl, - OC(0)C₂-C₆alkenyl and -OC(0)C₂-C₆alkynyl of R^9a are substituted by 0, 1 , 2 or 3 substituents independently selected from F, CI, Br, I, OH, CN, and N₃;

each R¹⁰ is independently selected from the group consisting of H, CrC₁₂alkyl, C_r

Ceheteroalkyl, , wherein the Ci

C₁₂alkyl and CrC₆heteroalkyl of R¹⁰ is substituted by 0, 1 , 2 or 3 substituents independently selected from -OH, CrC₁₂alkoxy, -S-C(=0)C₁-C₆alkyl, halo, -CN, C_r C₁₂alkyl, -O-aryl, _0-heteroaryl, -O-cycloalkyl, oxo, cycloalkyl, heterocyclyl, aryl, or heteroaryl, -OC(0)OCrC₆alkyland C(0)OCrC₆alkyl, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is substituted by 0, 1 , 2 or 3 substituents independently selected from CrC₁₂ alkyl, 0-CrC₁₂alkyl, CrC₁₂heteroalkyl, halo, CN, OH, oxo, aryl, heteroaryl, O-aryl, O-heteroaryl, -C(=0)C₁-C₁₂alkyl, -OC(=0)C₁-C₁₂alkyl, -C(=0)OC C₁₂alkyl, -OC(=0)OC₁-C₁₂alkyl, -C(=0)N(R¹¹)-C C₁₂alkyl, -N(R¹¹)C(=0)-C₁-C₁₂alkyl; - OC(=0)N(R^{1 1})-C C₁₂alkyl, -C(=0)-aryl, -C(=0)-heteroaryl, -OC(=0)-aryl, -C(=0)0-aryl, - OC(=0)-heteroaryl, -C(=0)0-heteroaryl, -C(=0)0-aryl, -C(=0)0-heteroaryl, - C(=0)N(R¹¹)-aryl, -C(=0)N(R¹¹)-heteroaryl, -N(R¹¹)C(0)-aryl, -N(R¹¹)2C(0)-aryl, -

N(R¹¹)C(0)-heteroaryl, and S(0)₂N(R¹¹)-aryl;

each R^{1 1} is independently selected from H and CrC₆alkyl;

each R¹² is independently selected from H and C Cealkyl;

optionally R³ and R⁶ are connected to form CrC₆alkylene, C₂-C₆alkenylene, C₂- C₆alkynylene, -0-Ci-C₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R³ and R⁶ are connected, the O is bound at the R³ position

optionally R^3a and R^6a, are connected to form CrC₆alkylene, C₂-C₆alkenylene, C₂-

C₆alkynylene, -0-Ci-C₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R^3a and R^6a are connected, the O is bound at the R^3a position;

optionally R² and R³ are connected to form C Cealkylene, C₂-C₆alkenylene, C₂-

C₆alkynylene, -0-CrC₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R² and R³ are connected, the O is bound at the R³ position;

optionally R^2a and R^3a, are connected to form CrC₆alkylene, C₂-C₆alkenylene, C₂-

C₆alkynylene, -0-CrC₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R^2a and R^3a are connected, the O is bound at the R^3a position;

optionally R⁴ and R³ are connected to form CrC₆alkylene, C₂-C₆alkenylene, C₂-

C₆alkynylene, -0-CrC₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R⁴ and R³ are connected, the O is bound at the R³ position;

optionally R^4a and R^3a, are connected to form CrC₆alkylene, C₂-C₆alkenylene, C₂- C₆alkynylene, -0-CrC₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R^4a and R^3a are connected, the O is bound at the R^3a position;

optionally R⁵ and R⁶ are connected to form CrC₆alkylene, C₂-C₆alkenylene, C₂-

C₆alkynylene, -0-CrC₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R⁵ and R⁶ are connected, the O is bound at the R⁵ position;

optionally R^5a and R^6a, are connected to form CrC₆alkylene, C₂-C₆alkenylene, C₂-

C₆alkynylene, -0-CrC₆alkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R^5a and R^6a are connected, the O is bound at the R^5a position; optionally R⁵ and R⁷ are connected to form Ci-Cealkylene, C₂-C₆alkenylene, C₂-

C₆alkynylene, -O-C Cealkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R⁵ and R⁷ are connected, the O is bound at the R⁵ position;

optionally R^5a and R^7a, are connected to form C Cealkylene, C₂-C₆alkenylene, C₂-

C₆alkynylene, -O-CrCealkylene, -0-C₂-C₆alkenylene, -0-C₂-C₆alkynylene, such that when R^5a and R^7a are connected, the O is bound at the R^5a position;

optionally R⁸ and R⁹ are connected to form a Ci-Cealkylene, C₂-C₆alkenylene, C₂- C₆alkynylene, and

optionally R^8a and R^9a are connected to form a C Cealkylene, C₂-C₆alkenylene, C₂- C₆alkynylene,

-C(=0)0(CH₂)_mNR¹¹C(=0)X₁X₂C(=0)(CH₂)_m-^**;

-C(=0)OC(R¹²)₂(CH₂)_mNR¹¹C(=0)X₁X₂C(=0)(CH₂)_m-**;

-C(=0)0(CH₂)_mNR¹¹C(=0)X₁X₂C(=0)(CH₂)_mO(CH₂)_m-**;

-C(=0)0(CH₂)_mNR¹¹C(=0)X₁X₂C(=0)(CH₂)_mO(CH₂)_mC(=0)-**;

-C(=0)0(CH₂)_mNR¹¹C(=0)X₄C(=0)NR¹¹(CH₂)_mNR¹¹C(=0)(CH₂)_mO(CH₂)_m-^**; -

C(=0)0(CH₂)_mNR¹¹C(=0)X₅C(=0)(CH₂)_mNR¹¹C(=0)(CH₂)_m-**;

-C(=0)X₄C(=0)NR¹¹(CH₂)_mNR¹¹C(=0)(CH₂)_mO(CH₂)_m-**;

-C(=0)(CH₂)_mNR¹¹C(=0)X₁X₂C(=0)(CH₂)_m-**; -C(=0)(CH₂)_mNR¹¹C(=0)X₂C(=0)(CH₂)_m-^**; -C(=0)0(CH₂)_mX₆C(=0)X₁X₂C(=0)(CH₂)_m-^**,

-C(=0)(CH₂)_mNR¹¹C(=0)((CH₂)_mO)_n(CH₂)_m-^**,

-C(=0)0(CH₂)_mXsC(=0)(CH₂)_m-**,

-C(=0)0(CH₂)_mX₆C(=0)(CH₂)_mO(CH₂)_m-**,

-C(=0)0(CH₂)_mX₆C(=0)X₁X₂C(=0)(CH₂)_m-^**,

-C(=0)0(CH₂)_mX₆C(=0)X₁X₂C(=0)(CH₂)_mO(CH₂)_m-**,

-C(=0)0(CH₂)_mX₆C(=0)X₁X₂C(=0)(CH₂)_mO(CH₂)_mC(=0)- **,

-C(=0)0(CH₂)_mXeC(=0)X₄C(=0)NR¹¹(CH₂)_mNR¹¹C(=0)(CH₂)_mO(CH₂)_m-^**,

-C(=0)X₄C(=0)X₆(CH₂)_mNR¹¹C(=0)(CH₂)_mO(CH₂)_m-**,

-C(=0)(CH₂)_mX₆C(=0)X₁X₂C(=0)(CH₂)_m-*^*,

-C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)(CH₂)_m-**;

-C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)(CH₂)_mNR¹¹C(=0)(CH₂)_m-^**;

-C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)(CH₂)_mX₃(CH₂)_m-**;

-C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)((CH₂)_mO)_n(CH₂)_m-^**;

-C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹ C(=0)X₅C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)(CH₂)_m-**;

-C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)(CH₂)_mX₃(CH₂)_m-

C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0))X₅C(=0)((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_n -C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)(CH₂)_mNR¹¹C(=0)((CH₂)_mO)_n(CH₂)_m-**;

-C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)(CH₂)_mNR¹¹C(=0)((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-

_**.

-C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅(CH₂)_mX₃(CH₂)_m-**;

-C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅((CH₂)_mO)_n(CH₂)_m-**;

-C(=0)0((CH2)mO)n(CH2)mNR1 1 C(=0)X5((CH2)mO)n(CH2)mNR1 1 C(=0)(CH2)m-**;

-C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)(CH₂)_mX₃(CH₂)_m-**;

-C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-**;

-C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅(CH₂)_mNR¹¹ ((CH₂)_mO)_n(CH₂)_m-**; - C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)(CH₂)_mNR¹¹ ((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-**;

-C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅(CH₂)_m-**;

-C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)((CH₂)_mO)_n(CH₂)_m-**;

-C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅(CH₂)_mX₃(CH₂)_m-**; -C(=0)0(CH₂)_m-**;

-C(=0)0((CH₂)_mO)_n(CH₂)_m-**; -C(=0)0(CH₂)_mNR^{1 1}(CH₂)_m-**;

-C(=0)0(CH₂)_mNR¹¹(CH₂)_mC(=0)X₂XiC(=0)-**;

-C(=0)0(CH₂)_mX₃(CH₂)_m-**; -C(=0)0(CH₂)_mX₆C(=0)X₁X₂C(=0)((CH₂)_mO)_n(CH₂)_m-**, -

C(=0)0((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-**;

-C(=0)0((CH₂)_mO)n(CH₂)_mNR¹¹C(=0)(CH₂)_m-**;

-C(=0)0(CH₂)_mNR¹¹C(=0(CH₂)_mX₃(CH₂)_m-**;

-C(=0)0((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)(CH₂)_mX₃(CH₂)_m-**;

-C(=0)0((CH₂)_mO)_nX₃(CH₂)_m-**; -C(=0)0((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-**;

-C(=0)0((CH₂)_mO)_n(CH₂)_mC(=0)NR¹¹ (CH₂)_m-**; -C(=0)0(CH₂)_mC(R¹²)₂-**;

-C(=0)OCH₂)_mC(R¹²)₂SS(CH₂)_mNR¹¹C(=0)(CH₂)_m-**;

-C(=0)0(CH₂)_mC(=0)NR¹¹ (CH₂)_m-**; -C(=0)(CH₂)_m-**; -C(=0)((CH₂)_mO)_n(CH₂)_m-**;

-C(=0)(CH₂)_mNR¹¹ (CH₂)_m-**; -C(=0)(CH₂)_mNR¹¹ (CH₂)_mC(=0)X₂X₁C(=0)-**;

-C(=0)(CH₂)_mX₃(CH₂)_m-**; -C(=0)((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-**;

-C(=0)(CH₂)_mNR¹¹C(=0)(CH₂)_m-**; -C(=0)((CH₂)_mO)_n(CH₂)_mNR^{1 1}C(=0)(CH₂)_m-**; -

C(=0)(CH₂)_mNR¹¹C(=0(CH₂)_mX₃(CH₂)_m-**; -(CH₂)_mNR¹¹C(=0)X₁X₂C(=0)(CH₂)_m-**;

-(CH₂)_m(CHOH)(CH₂)_mNR¹¹C(=0)X₁X₂C(=0)(CH₂)_m**;

-C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)(CH₂)_mX₃(CH₂)_m-**; -C(=0)((CH₂)_mO)_nX₃(CH₂)_m-**;

-C(=0)((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-**; -C(=0)((CH₂)_mO)_n(CH₂)_mC(=0)NR¹¹ (CH₂)_m-**; -

C(=0)(CH₂)_mC(R¹²)₂-**; -C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)(CH₂)_m-**;

-C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)(CH₂)_mNR¹¹C(=0)(CH₂)_m-**;

-C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)(CH₂)_mX₃(CH₂)_m-**;

-C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)((CH₂)_mO)_n(CH₂)_m-**;

-C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)(CH₂)_m-**;

-C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)(CH₂)_mX₃(CH₂)_m-** -C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0))X₅C(=0)((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-**;

-C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)(CH₂)_mNR¹¹ C(=0)((CH₂)_mO)_n(CH₂)_m-**;

-C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)(CH₂)_mNR¹¹ C(=0)((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-**; -C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅(CH₂)_mX₃(CH₂)_m-**;

-C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅((CH₂)_mO)_n(CH₂)_m-**;

-C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅((CH₂)_mO)_n(CH₂)_mNR¹¹ C(=0)(CH₂)_m-**;

-C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅((CH₂)_mO)_n(CH₂)_mNR¹¹ C(=0)(CH₂)_mX₃(CH₂)_m-**; -C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-**;

-C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅(CH₂)_mNR^{1 1} ((CH₂)_mO)_n(CH₂)_m-**; - C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)(CH₂)_mNR¹¹ ((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-**;

-C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅(CH₂)_m-**; - C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅C(=0)((CH₂)_mO)_n(CH₂)_m-**;

-C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)X₅(CH₂)_mX₃(CH₂)_m-**; -

C(=0)(CH₂)_mC(R¹²)₂SS(CH₂)_mNR¹¹ C(=0)(CH₂)_m-**; -C(=0)(CH₂)_mC(=0)NR¹¹ (CH₂)_m-**; -C(=0)X₁X₂C(=0)(CH₂)_m-**; -C(=0)X₁X₂C(=0)(CH₂)_mNR¹¹C(=0)(CH₂)_m-**;

-C(=0)X₁X₂C(=0)(CH₂)_mX₃(CH₂)_m-**; -C(=0)X₁X₂C(=0)((CH₂)_mO)_n(CH₂)_m-**;

-C(=0)X₁X₂C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)(CH₂)_m-**;

-C(=0)X₁X₂C(=0)((CH₂)_mO)n(CH₂)_mNR¹¹C(=0)(CH₂)_mX₃(CH₂)_m-**;

-C(=0)X₁X₂C(=0)((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-**;

-C(=0)X₁X₂C(=0)(CH₂)_mNR¹¹ C(=0)((CH₂)_mO)_n(CH₂)_m-**;

-C(=0)X₁X₂C(=0)(CH₂)_mNR¹¹ C(=0)((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-**;

-C(=0)X₁X₂(CH₂)_mX₃(CH₂)_m-**; -C(=0)X₁X₂((CH₂)_mO)_n(CH₂)_m-**;

-C(=0)X₁X₂((CH₂)_mO)_n(CH₂)_mNR¹¹ C(=0)(CH₂)_m-**;

-C(=0)X₁X₂((CH₂)_mO)_n(CH₂)_mNR¹¹ C(=0)(CH₂)_mX₃(CH₂)_m-**;

-C(=0)X₁X₂((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-**;

-C(=0)X₁X₂(CH₂)_mNR¹¹ ((CH₂)_mO)_n(CH₂)_m-**; -

C(=0)X₁X₂C(=0)(CH₂)_mNR¹¹ ((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-**;

-C(=0)NR¹¹ (CH₂)_m-**; -C(=0)NR¹¹ (CH₂)_mX₃(CH₂)_m-**;

-C(=0)NR¹¹ (CH₂)_mNR¹¹ C(=0)X₁X₂C(=0) (CH₂)_m-**;

-C(=0)NR¹¹ (CH₂)_mNR¹¹ C(=0)0(CH₂)_m-**; -C(=0)NR¹¹ (CH₂)_mNR¹¹C(=0)X₁X₂-**; -

C(=0)NR¹¹ (CH₂)_mNR¹¹C(=0)X₅-; -C(=0)NR¹¹ (CH₂)_mNR¹¹ C(=0)(CH₂)_mX₅(CH₂)_m-**; -

C(=0)X₁ C(=0)NR¹¹ (CH₂)_mX_s(CH₂)_m-**; -C(=0)X₆C(=0)(CH₂)mNR¹¹ C(=0)X₁X₂C(=0)(CH₂)_m-

**; -C(=0)NR¹¹ (CH₂)_mNR¹¹ C(=0)(CH₂)_m-**; -C(=0)NR¹¹ (CH₂)_mNR¹¹ C(=0)(CH₂)_mO(CH₂)_m-**;

-C(=0)NR¹¹ (CH₂)_mNR¹¹ C(=0)X₁X₂C(=0)(CH₂)_mO(CH₂)_m-**;

-C(=0)NR¹¹ (CH₂)_mNR¹¹ C(=0)X₁X₂C(=0)(CH₂)_mO(CH₂)_mC(=0)-**;

-C(=0)NR¹¹ (CH₂)_mNR¹¹ C(=0)X₄C(=0)NR¹¹ (CH₂)_mNR¹¹ C(=0)(CH₂)_mO(CH₂)_m-**; -C(=0)NR¹¹ (CH₂)_mNR¹¹C(=0)X₁X₂C(=0)(CH₂)_m-**; -

C(=0)NR¹¹ (CH₂)_mNR¹¹ C(=0)X₅C(=0)(CH₂)_m-**;

-C( =0)NR^{1 1} (CH₂)_mNR^{1 1}C(=0)X₅C(=0)(CH₂)_mNR¹¹C(=0)(CH₂)_m-**;

-C( =0)NR^{1 1} (CH₂)_mNR^{1 1}C(=0)X₅C(=0)(CH₂)_mX₃(CH₂)_m-**;

-C( =0)NR^{1 1} (CH₂)_mNR^{1 1}C(=0)X₅C(=0)((CH₂)_mO)_n(CH₂)_m-**;

-C( =0)NR^{1 1} (CH₂)_mNR^{1 1}C(=0)X₅C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)(CH₂)_m-**;

-C( =0)NR^{1 1} (CH₂)_mNR^{1 1}C(=0)X₅C(=0)((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)(CH₂)_mX₃(CH₂)_m-

-C( =0)NR^{1 1} (CH₂)_mNR^{1 1}C(=0)X₅C(=0)((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-**;

-C( =0)NR^{1 1} (CH₂)_mNR^{1 1}C(=0)X₅C(=0)(CH₂)_mNR¹¹C(=0)((CH₂)_mO)_n(CH₂)_m-**;

-C( =0)NR^{1 1} (CH₂)_mNR^{1 1}C(=0)X₅C(=0)(CH₂)_mNR¹¹C(=0)((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-

-C( =0)NR^{1 1} (CH₂)_mNR^{1 1}C(=0)X₅(CH₂)_mX₃(CH₂)_m-**;

-C( =0)NR^{1 1} (CH₂)_mNR^{1 1}C(=0)X₅((CH₂)_mO)_n(CH₂)_m-**;

-C( =0)NR^{1 1} (CH₂)_mNR^{1 1}C(=0)X₅((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)(CH₂)_m-**;

-C( =0)NR^{1 1} (CH₂)_mNR^{1 1}C(=0)X₅((CH₂)_mO)_n(CH₂)_mNR¹¹C(=0)(CH₂)_mX₃(CH₂)_m-**;

-C( =0)NR^{1 1} (CH₂)_mNR^{1 1}C(=0)X₅((CH₂)_mO)n(CH₂)_mX₃(CH₂)_m-**;

-C( =0)NR^{1 1} (CH₂)_mNR^{1 1} C(=0)X₅(CH₂)_mNR¹¹ ((CH₂)_mO)_n(CH₂)_m-**; -

C(^: =0)NR¹¹ (CH₂)_mNR¹¹ C(=0)X₅C(=0)(CH₂)_mNR¹¹ ((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-**;

-C( =0)NR^{1 1} (CH₂)_mNR^{1 1}C(=0)X₅(CH₂)_m-**; -

C(^: =0)NR¹¹ (CH₂)_mNR¹¹ C(=0)X₅C(=0)((CH₂)_mO)_n(CH₂)_m-**;

-C( =0)NR^{1 1} (CH₂)_mNR^{1 1}C(=0)X₅(CH₂)_mX₃(CH₂)_m-**; -

C(^: =0)X₁C(=0)NR¹¹ (CH₂)_mNR^{1 1}C(=0)(CH₂)_m-**;

=0)X₁C(=0)NR¹¹(CH₂)_mX₃(CH₂)_m-**; -C(=0)NR¹¹(CH₂)_mNR¹¹C(=0)(CH₂)_n

=0)NR¹¹(CH₂)_mNR¹¹C(=0)(CH₂)_mX₃(CH₂)_m-* -C(=0)NR¹¹(CH₂)_mNR¹¹C(=0)-*

(=0)X₁X₂(CH₂)_m-**; -C(=0)X₁X₂C(=0)((CH₂)_mO)_n(CH₂)_m-**;

(=0)X₁X₂(CH₂)_mX₃(CH₂)_m-**; -C(=0)NR¹¹(CH₂)_mX₃(CH₂)_m-**; - C(=0)NR¹¹((CH₂)_mO)_n(CH₂)_mX₃(CH₂)_m-**; -C(=0)X₁X₂C(=0)((CH₂)_mO)_n(CH₂)_m- -C(=0)X₁X₂C(=0)(CH₂)_m-**; -C(=0)X₁C(=0)(CH₂)_mNR¹¹C(=0)(CH₂)_m-**; and

=0)X₁C(=0)(CH₂)_mNR¹¹C(=0)((CH₂)_mO)n(CH₂),

S(=0)₂(CH=CH₂), -(CH₂)₂S(=0)₂(CH=CH₂), -NHS(=0)₂(CH=CH₂), -NHC(=0)CH₂Br, - =0)CH₂l, , -C(0)NHNH₂

or where the * indicates the point of attachment to x₂; X₂ i

* indicates the point of attachment to Xi

-0(CH₂)_nSSC(R¹²)₂(CH₂)_n- or -(CH₂)_nC(R¹²)₂SS(CH₂)_nO-;

Xs is where the indicates orientation toward the Drug moiety; X₆ is , ^¾ , or or, where the ** indicates orientation toward the Drug moiety;

R¹⁷ is 2-pyridyl or 4-pyridyl;

each R^{1 1} is independently selected from H and CrCealkyl;

each R¹² is independently selected from H and Ci-C₆alkyl;

each m is independently selected from 1 , 2, 3, 4, 5, 6, 7, 8, 9 and 10; and

each n is independently selected from 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17 and 18.

each R^{1 10} is independently selected from H, C Cealkyl, F, CI, and -OH;

each R^{1 11} is independently selected from H, C C₆alkyl, F, CI, -NH₂, -OCH₃, -OCH₂CH₃, - N(CH₃)₂, -CN, -N0₂ and -OH;

each R^{1 12} is independently selected from H, C_1-6alkyl, fluoro, benzyloxy substituted with - C(=0)OH, benzyl substituted with -C(=0)OH, d.₄alkoxy substituted with -C(=0)OH and C_1-4alkyl substituted with -C(=0)OH;

and provided at least one of R¹ , R^1a or R^{1 b} is substituted with -NHL^R¹⁵, or at least one of R³, R⁴, R⁵, R⁷, R^3a, R^4a, R^5a or R^7a is -OLiR¹⁵.

53. The com ound of claim 52 wherein:

**; -C(=0)0(CH₂)_mNR¹¹C(=0)X₁X₂C(=0)(CH₂)_m-**; - C(=0)OC(R¹²)₂(CH₂)_mNR¹¹C(=0)X₁X₂C(=0)(CH₂)_m-**; -

C(=0)0(CH₂)_mNR⁸C(=0)X₁X₂C(=0)(CH₂)_mO(CH₂)_m-**; - C(=0)0(CH₂)_mNR¹¹C(=0)X₁X₂C(=0)(CH₂)_mO(CH₂)_mC(=0)-**; - C(=0)0(CH₂)_mNR¹¹C(=0)X₄C(=0)NR¹¹ (CH₂)_mNR¹¹C(=0)(CH₂)_mO(CH₂)_m-**; - C(=0)0(CH₂)_mNR¹¹C(=0)X₅C(=0)(CH₂)_mNR¹¹C(=0)(CH₂)_m-**; - C(=0)0(CH₂)_mX₆C(=0)X₁X₂C(=0)((CH₂)_mO)_n(CH₂)_m-**; -

(CH₂)_mNR¹¹C(=0)X₁X₂C(=0)(CH₂)_m-**; - (CH₂)_m(CHOH)(CH₂)_mNR¹¹C(=0)X₁X₂C(=0)(CH₂)_m**; - C(=0)X₆C(=0)(CH₂)mNR¹¹C(=0)X₁X₂C(=0)(CH₂)_m-**;- C(=0)X₄C(=0)NR¹¹(CH₂)_mNR¹¹C(=0)(CH₂)_mO(CH₂)_m-**; - C(=0)(CH₂)_mNR¹¹C(=0)X₁X₂C(=0)(CH₂)_m-**; -

C(=0)0(CH₂)_mX₆C(=0)X₁X₂C(=0)(CH₂)_m-**, or - C(=0)(CH₂)_mNR¹¹C(=0)((CH₂)_mO)_n(CH₂)_m-**,

where the ** indicates the point of attachment to R¹⁵.

54. The compound of claim 52 or claim 53 selected from:

(C23b)

698 (C38)

(C45).

55. The compound of claim 52 or claim 53 selected from:

(C42a)

56. The compound of claim 52 or claim 53 selected from: