IP Library › Granted Patent US 10,870,706

Granted Patent B2

US 10,870,706 · App. 15/070,549 · Granted Dec 22, 2020

Bifunctional cytotoxic agents containing the CTI pharmacophore

Inventors: Andreas Maderna (San Diego, CA); Chakrapani Subramanyam (South Glastonbury, CT); Lawrence N. Tumey (Pawcatuck, CT); Zecheng Chen (New City, NY); Jeffrey M. Casavant (Franklin, CT)

Assignee: PFIZER INC.

C07K16/32 A61K47/65 A61K47/6803 A61K47/6807 A61K47/6849 A61K47/6863 A61K47/6865 A61K47/6869 A61K47/6871 C07B59/002 C07D495/04 C07D519/00 C07F9/6561 C07K5/06052 C07K5/0815 C07K16/2803 C07K16/2866 C07B2200/05

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Quick Facts

Patent No.: US 10,870,706
App. No.: 15/070,549
Granted: Dec 22, 2020
Kind: B2

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Abstract

The present invention is directed to novel bifunctional CTI-CTI and CBI-CTI dimers of the formula: F 1 -L 1 -T-L 2 -F 2 where F 1 , L 1 , T, L 2 and F 2 are as defined herein, useful for the treatment for proliferative diseases, where the inventive dimers can function as stand-alone drugs, payloads in antibody-drug-conjugates (ADCs), and linker-payload compounds useful in connection with the production or administration of such ADCs; and to compositions including the aforementioned dimers, linker-payloads and ADCs, and methods for using these dimers, linker-payloads and ADCs, to treat pathological conditions including cancer.

Claims (202)

1. A compound of Formula (I):

F 1 L 1 T-L 2 -F 2 (I)

or a pharmaceutically acceptable salt or solvate thereof, wherein:

F 1 and F 2 are each independently selected from ring systems A, B, C and D:

where:

each R is independently selected from the group consisting of H, —C 1 -C 20 alkyl, —C 2 -C 6 alkenyl, —C 2 -C 6 alkynyl, halo, deuterium, hydroxyl, alkoxy, —NH 2 , —NH(C 1 -C 8 alkyl), —N(C 1 -C 8 alkyl) 2 , —NO 2 , —C 6 -C 14 aryl and —C 6 -C 14 heteroaryl, or wherein two or more R optionally join to form a ring or rings, and wherein said —C 6 -C 14 aryl and —C 6 -C 14 heteroaryl are optionally substituted with 1 to 5 substituents independently selected from —C 1 -C 10 alkyl, —C 1 -C 10 alkoxy, -halo, —C 1 -C 10 alkylthio, -trifluoromethyl, —NH 2 , —NH(C 1 -C 8 alkyl), —N(C 1 -C 8 alkyl) 2 , —C 1 -C 10 alkyl-N(C 1 -C 8 alkyl) 2 , —C 1 -C 3 alkylthio, —NO 2 or —C 1 -C 10 heterocyclyl, for each ring system in which R appears;

each V 1 is independently a bond, O, N(R) or S, for each ring system in which V 1 appears;

each V 2 is independently O, N(R) or S, for each ring system in which V 2 appears;

W 1 and W 2 are each independently H, —C 1 -C 5 alkyl, -phenyl, —C(O)OR, —C(O)SR, —C(O)NHN(R) 2 or —C(O)N(R) 2 for each ring system in which W 1 and W 2 appear;

each X is independently —OH, —O-acyl, azido, halo, cyanate, thiocyanate, isocyanate, thioisocyanate,

for each ring system in which X appears;

each Y is independently selected from the group consisting of H, —C 1 -C 6 alkyl-R A , —C(O)R A , —C(S)R A , —C(O)OR A , —S(O) 2 OR A , —C(O)N(R A ) 2 , —C(S)N(R A ) 2 , glycosyl, —NO 2 , —PO(OR A ) 2 , an amino acid, and a peptide, for each ring system in which Y appears, wherein each R A is independently selected from the group consisting of H, —C 1 -C 20 alkyl, —C 1 -C 8 heteroalkyl, —C 8 -C 14 aryl, aralkyl, —C 1 -C 10 heterocyclyl, —C 1 -C 8 carbocyclyl and —C 1 -C 20 alkylN(R) 2 , wherein said —C 1 -C 20 alkyl, —C 1 -C 8 heteroalkyl, —C 8 -C 14 aryl, aralkyl, —C 1 -C 10 heterocyclyl, —C 3 -C 8 carbocyclyl and —C 1 -C 20 alkylN(R) 2 are optionally substituted with 1 to 3 substitutents independently selected from R;

each Z is independently selected from the group consisting of H, —C 1 -C 8 alkyl, —C 1 -C 8 heteroalkyl, —C 8 -C 14 aryl, -aralkyl, —C 1 -C 10 heterocyclyl, —C 1 -C 8 carbocyclyl, —C(O)OC 1 -C 8 alkyl, —C(O)N(C 1 -C 8 alkyl) 2 , —C(O)OH, —C(O)NHNH 2 , and —C(O)-halo, and wherein said C 1 -C 8 alkyl, —C 1 -C 8 heteroalkyl, —C 8 -C 14 aryl, -aralkyl, —C 1 -C 10 heterocyclyl, —C 1 -C 8 carbocyclyl, —C(O)OC 1 -C 8 alkyl, —C(O)N(C 1 -C 8 alkyl) 2 , —C(O)OH, —C(O)NHNH 2 and —C(O)-halo are each optionally substituted with 1 to 3 substitutents independently selected from R, for each ring system in which Z appears;

L 1 and L 2 are each independently selected from a direct bond,

T is

—C(A 1 )X 1 -T 2 -X 1 C(B 1 )—, where T 2 is:

where said ring systems are independently selected from —C 1 -C 10 heterocyclyl or —C 3 -C 8 carbocyclycl, or R 1 , R 2 , R 3 and R 4 are each bonds to different carbons on D, wherein g and j are each independently an integer from 0 to 50 and m is an integer from 1 to 50, and wherein D is selected from the group consisting of —C 1 -C 10 heterocyclo and —C 3 -C 8 carbocyclo, where said —C 1 -C 10 heterocyclo and —C 3 -C 8 carbocyclo are optionally substituted with —R E , —C(O)R E , —C(O)ORE, —N(R E ) 2 , —N(R)C(O)R E or —N(R)C(O)ORE, and D is additionally optionally substituted by 1 to 2 R

wherein each R E is independently selected from the group consisting of H, —C 1 -C 8 alkyl, —C 1 -C 8 heteroalkyl, —C 6 -C 14 aryl, -aralkyl, —C 1 -C 10 heterocyclyl, —C 3 -C 8 carbocyclyl, —C(O)OC 1 -C 8 alkyl, —C(O)N(C 1 -C 8 alkyl) 2 , and —C(O)-halo, and wherein each R E is optionally substituted with 1 to 3 substitutents independently selected from R.

2. A compound of Formula (IIA):

L-P (IIA)

or a pharmaceutically acceptable salt or solvate thereof, wherein:

P is:

F 1 -L 1 -T-L 2 -F 2

wherein:

F 1 and F 2 are each independently selected from ring systems A, B, C and D:

where:

each R is independently selected from the group consisting of H, —C 1 -C 20 alkyl, —C 1 -C 8 alkenyl, —C 1 -C 8 alkynyl, halo, deuterium, hydroxyl, alkoxy, —NH 2 , —NH(C 1 -C 8 alkyl), —N(C 1 -C 8 alkyl) 2 , —NO 2 , —C 8 -C 14 aryl and —C 8 -C 14 heteroaryl, wherein two or more R optionally join to form a ring or rings, and wherein said —C 8 -C 14 aryl and —C 8 -C 14 heteroaryl are optionally substituted with 1 to 5 substituents independently selected from —C 1 -C 10 alkyl, —C 1 -C 10 alkoxy, -halo, —C 1 -C 10 alkylthio, -trifluoromethyl, —NH 2 , —NH(C 1 -C 8 alkyl), —N(C 1 -C 8 alkyl) 2 , —C 1 -C 10 alkyl-N(C 1 -C 8 alkyl) 2 , alkylthio, —NO 2 or —C 1 -C 10 heterocyclyl, for each ring system in which R appears;

each V 1 is independently a bond, O, N(R) or S, for each ring system in which V 1 appears;

each V 2 is independently O, N(R) or S, for each ring system in which V 2 appears;

W 1 and W 2 are each independently H, —C 1 -C 5 alkyl, -phenyl, —C(O)OR, —C(O)SR, —C(O)NHN(R) 2 or —C(O)N(R) 2 for each ring system in which W 1 and W 2 appear;

each X is independently selected from —OH, —O-acyl, azido, halo, cyanate, thiocyanate, isocyanate, thioisocyanate, or

for each ring system in which X appears;

each Y is independently selected from a bond, H, —C(O)R A , —C(S)R A , —C(O)OR A , —S(O) 2 OR A , —C(O)N(R A ) 2 , —C(S)N(R A ) 2 , glycosyl, —NO 2 , —P(O)(OR A ) 2 , an amino acid, and a peptide, for each ring system in which Y appears, wherein each R A is independently selected from H, —C 1 -C 20 alkyl, —C 1 -C 8 heteroalkyl, —C 6 -C 14 aryl, aralkyl, —C 1 -C 10 heterocyclyl, —C 3 -C 8 carbocyclyl, —C 1 -C 20 alkylN(R) 2 , —C 1 -C 20 alkylene, —C 1 -C 8 heteroalkylene, —C 6 -C 14 arylene, aralkylene, —C 1 -C 10 heterocyclo, —C 3 -C 8 carbocyclo and —C 1 -C 20 alkylN(R)—, and RF where said R A is optionally substituted with 1 to 3 substituents independently selected from R, and wherein at least one Y-containing Ring System is present and is divalent and is bonded to L,

R F is —N(R 6 )QN(R 5 )C(O)— and is bonded to L at the carbonyl adjacent N(R 5 ), wherein R 5 and R 6 are each independently selected from the group consisting of H, —C 1 -C 8 alkyl, —C 1 -C 8 heteroalkyl, —C 6 -C 14 aryl, -aralkyl, —C 1 -C 10 heterocyclyl and —C 3 -C 8 carbocyclyl, or R 5 or R 6 joins with a substituted carbon on Q to form a —C 1 -C 10 heterocyclic or —C 6 -C 14 heteroaryl ring, or R 5 and R 6 join together to form a —C 1 -C 10 heterocyclic or —C 6 -C 14 heteroaryl ring system, and where Q is —C 1 -C 8 alkylene-, —C 1 -C 8 heteroalkylene-, —C 6 -C 14 arylene-, -aralkylene-, —C 1 -C 10 heterocyclo- or —C 3 -C 8 carbocyclo-, wherein Q, R 5 and R 6 are each independently optionally substituted with 1 to 3 substituents independently selected from R;

each Z is independently selected from the group consisting of H, —C 1 -C 8 alkyl, —C 1 -C 8 heteroalkyl, —C 6 -C 14 aryl, -aralkyl, —C 1 -C 10 heterocyclyl, —C 3 -C 8 carbocyclyl, —C(O)OC 1 -C 8 alkyl, —C(O)N(C 1 -C 8 alkyl) 2 , —C(O)OH, —C(O)NHNH 2 and —C(O)-halo, and wherein said C 1 -C 8 alkyl, —C 1 -C 8 heteroalkyl, —C 6 -C 14 aryl, -aralkyl, —C 1 -C 10 heterocyclyl, —C 3 -C 8 carbocyclyl, —C(O)OC 1 -C 8 alkyl, —C(O)N(C 1 -C 8 alkyl) 2 , —C(O)OH, —C(O)NHNH 2 and —C(O)-halo are each optionally substituted with 1 to 3 substitutents independently selected from R, for each ring system in which Z appears;

L 1 and L 2 are each independently selected from a direct bond;

T is

—C(A 1 )X 1 -T 2 -X 1 C(B 1 )—, where T 2 is:

wherein each X 1 is independently a bond, —NR E —, —O— or —S—, wherein A 1 and B 1 are each independently ═O or ═S, wherein R 1 , R 2 , R 3 , and R 4 are each independently R E or R 1 and R 2 form a ring system, or R 3 and R 4 form a ring system, or both R 1 and R 2 , and R 3 and R 4 , each independently form ring systems, or R 1 and R 3 form a ring system, or R 2 and R 4 form a ring system, or both R 1 and R 3 , and R 2 and R 4 , each independently form ring systems, where said ring systems are independently selected from —C 1 -C 10 heterocyclyl or —C 3 -C 8 carbocyclycl, or R 1 , R 2 , R 3 and R 4 are each bonds to different carbons on D, wherein g and j are each independently an integer from 0 to 50 and m is an integer from 1 to 50, and wherein D is selected from the group consisting of —C 1 -C 10 heterocyclo and —C 3 -C 8 carbocyclo, where said —C 1 -C 10 heterocyclo and —C 3 -C 8 carbocyclo are optionally substituted with —R E , —C(O)R E , —C(O)ORE, —N(R E ) 2 , —N(R)C(O)R E or —N(R)C(O)OR E , and D is additionally optionally substituted by 1 to 2 R,

wherein each R E is independently selected from the group consisting of H, —C 1 -C 8 alkyl, —C 1 -C 8 heteroalkyl, -aryl, -aralkyl, —C 1 -C 10 heterocyclyl, —C 3 -C 8 carbocyclyl, —C(O)OC 1 -C 8 alkyl, —C(O)N(C 1 -C 8 alkyl) 2 , and —C(O)-halo, and wherein each R E is optionally substituted with 1 to 3 substitutents independently selected from R;

L is L A -L B -(L C ) 1-3 , wherein an L C is bound to Y and wherein L A is selected from the group consisting of -halo, —N(R) 2 , —CON(R) 2 , —S-aryl optionally substituted with —NO 2 or —CON(R) 2 , —S-heteroaryl optionally substituted with —NO 2 , alkyl-SO 2 -heteroaryl, arylSO 2 -heteroaryl-,

L B is L B1 -L B2 -L B3 wherein L B1 is absent or is one or more components selected from the group consisting of —C(O)—, —C(S)—, —C(O)NR—, —C(O)C 1 -C 6 alkyl-, —C(O)NRC 1 -C 6 alkyl-, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —, —C(O)C 1 -C 6 alkylNRC(O)—, —C(O)C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —C(O)—, —C 1 -C 6 alkyl-S—S—C 1 -C 6 alkylNRC(O)CH 2 —, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 NRC(O)CH 2 —, —C(O)C 1 -C 6 alkyl-NRC(O)C 1 -C 6 alkyl-, —N═CR-phenyl-O—C 1 -C 6 alkyl-, —N═CR-phenyl-O—C 1 -C 6 alkyl-C(O)—, —C(O)—C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 NRC(O)—, —C(O)C 1 -C 6 alkyl-phenyl(NR—C(O)C 1 -C 6 alkyl) 1-4 —, —C(O)C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —NRC(O)C 1 -C 6 alkyl-, —C 1 -C 6 alkyl-, —S—, —C(O)—CH(NR—C(O)C 1 -C 6 alkyl)-C 1 -C 6 alkyl- and (—CH 2 —CH 2 —O—) 1-20 ,

wherein L B2 is AA 0-12 , wherein AA is a natural amino acid or a non-natural amino acid;

L B3 is p-aminobenzoic acid, p-aminobenzyloxycarbonyl, —C(O)(CH 2 ) 0-50 C(O)— or absent;

L C is absent or independently selected from the group consisting of —C 1 -C 6 alkylene-, —NRC 3 -C 8 -heterocyclylNR—, —NRC 3 -C 8 -carbocyclylNR—, —NRC 1 -C 6 alkylNR—, —NRC 1 -C 6 alkylene-, —S—, —NR—, —NRNR—, —O(CR 2 ) 1-4 S—S(CR 2 ) 1-4 N(R)—, —NRC 1 -C 6 -alkylenephenyleneNR—, —NRC 1 -C 6 alkylenephenyleneSO 2 NR—, —OC 1 -C 6 alkylS-SC 1 -C 6 alkylC(COOR)NR—, —NRC(COOR)C 1 -C 6 alkylS-SC 1 -C 6 alkylO—,

wherein

X A is CR or N,

X B is CH, CR(C(R) 2 ) 1-3 NR, CR(C(R) 2 ) 1-3 O, CR(C(R) 2 ) 1-3 C(O)NR, CR—(C(R) 2 ) 1-3 C(O)NRNR, CR(C(R) 2 ) 1-3 SO 2 NR, CR(C(R) 2 ) 1-3 NRNR, CR(C(R) 2 ) 1-3 NRC(O) or N,

each X C is R,

each X D is —(CH 2 ) 1-5 —, or is absent;

X E is O, S, C(R) 2 , C(R)(C(R) 2 ) 1-3 —NR 2 or NR and

each X F is (C(R) 2 ) 1-3 —NR or C(R) 2 —(C(R) 2 ) 1-3 —O.

3. A compound of Formula (IIIA):

AB-(L-P) 1-20 (IIIA)

or a pharmaceutically acceptable salt or solvate thereof, wherein:

AB is an antibody;

P is:

F 1 -L 1 -T-L 2 -F 2

wherein:

F 1 and F 2 are each independently selected from ring systems A, B, C and D:

where:

each V 1 is independently a bond, O, N(R) or S, for each ring system in which V 1 appears;

each V 2 is independently O, N(R) or S, for each ring system in which V 2 appears;

W 1 and W 2 are each independently H, —C 1 -C 5 alkyl, -phenyl, —C(O)OR, —C(O)SR, —C(O)NHN(R) 2 or —C(O)N(R) 2 for each ring system in which W 1 and W 2 appear;

each X is independently selected from —OH, —O-acyl, azido, halo, cyanate, thiocyanate, isocyanate, thioisocyanate, or

for each ring system in which X appears;

each Y is independently selected from a bond, H, —C(O)R A , —C(S)R A , —C(O)OR A , —S(O) 2 OR A , —C(O)N(R A ) 2 , —C(S)N(R A ) 2 , glycosyl, —NO 2 , —P(O)(OR A ) 2 , an amino acid and a peptide for each ring system in which Y appears, wherein each R A is independently selected from H, —C 1 -C 20 alkyl, —C1-C 8 heteroalkyl, —C 8 -C 14 aryl, aralkyl, —C 1 -C 10 heterocyclyl, —C 1 -C 8 carbocyclyl, —C 1 -C 20 alkylN(R) 2 , —C 1 -C 20 alkylene, —C 1 -C 8 heteroalkylene, —C 6 -C 14 arylene, aralkylene, —C 1 -C 10 heterocyclo, —C 3 -C 8 carbocyclo and —C 1 -C 20 alkylN(R)—, and R F where said R A is optionally substituted with 1 to 3 substituents independently selected from R, and wherein at least one Y-containing Ring System is present and is divalent and is bonded to L,

L 1 and L 2 are each independently selected from a direct bond

T is

—C(A 1 )X 1 -T 2 -X 1 C(B 1 )—, where T 2 is:

R 3 and R 4 form a ring system, or both R 1 and R 2 , and R 3 and R 4 , each independently form ring systems, or R 1 and R 3 form a ring system, or R 2 and R 4 form a ring system, or both R 1 and R 3 , and R 2 and R 4 , each independently form ring systems, where said ring systems are independently selected from —C 1 -C 10 heterocyclyl or —C 3 -C 8 carbocyclycl, or R 1 , R 2 , R 3 and R 4 are each bonds to different carbons on D, wherein g and j are each independently an integer from 0 to 50 and m is an integer from 1 to 50, and wherein D is selected from the group consisting of —C 1 -C 10 heterocyclo and —C 3 -C 8 carbocyclo, where said —C 1 -C 10 heterocyclo and —C 3 -C 8 carbocyclo are optionally substituted with —R E , —C(O)R E , —C(O)OR E , —N(R E ) 2 , —N(R)C(O)R E or —N(R)C(O)OR E , and D is additionally optionally substituted by 1 to 2 R, wherein each R E is independently selected from the group consisting of H, —C 1 -C 8 alkyl, —C 1 -C 8 heteroalkyl, -aryl, -aralkyl, —C 1 -C 10 heterocyclyl, —C 3 -C 8 carbocyclyl, —C(O)OC 1 -C 8 alkyl, —C(O)N(C 1 -C 8 alkyl) 2 , and —C(O)-halo, and wherein each R E is optionally substituted with 1 to 3 substitutents independently selected from R;

L is L A -L B -(L C ) 1-3 wherein an L C is bound to Y;

L A is selected from: a bond to AB, —NR-(bond to AB), -heteroaryl-(bond to AB),

L B is L B1 -L B2 -L B3

wherein L B1 is absent or is one or more components selected from the group consisting of —C(O)—, —C(S)—, —C(O)NR—, —C(O)C 1 -C 6 alkyl-, —C(O)NRC 1 -C 6 alkyl-, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —, —C(O)C 1 -C 6 alkylNRC(O)—, —C(O)C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —C(O)—, —C 1 -C 6 alkyl-S—S—C 1 -C 6 alkylNRC(O)CH 2 —, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 NRC(O)CH 2 —, —C(O)C 1 -C 6 alkyl-NRC(O)C 1 -C 6 alkyl-, —N═CR-phenyl-O—C 1 -C 6 alkyl-, —N═CR-phenyl-O—C 1 -C 6 alkyl-C(O)—, —C(O)—C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 NRC(O)—, —C(O)C 1 -C 6 alkyl-phenyl(NR—C(O)C 1 -C 6 alkyl) 1-4 -, —C(O)C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —NRC(O)C 1 -C 6 alkyl-, —C 1 -C 6 alkyl-, —S—, —C(O)—CH(NR—C(O)C 1 -C 6 alkyl)-C 1 -C 6 alkyl- and (—CH 2 —CH 2 —O—) 1-20 ;

L B2 is AA 0-12 , wherein AA is a natural amino acid or a non-natural amino acid;

L B3 is p-aminobenzoic acid, p-aminobenzyloxycarbonyl, —C(O)(CH 2 ) 0-50 C(O)— or absent,

L C is absent or is independently selected from the group consisting of —C 1 -C 6 alkylene-, —NRC 3 -C 8 -heterocyclylNR—, —NRC 3 -C 8 -carbocyclylNR—, —NRC 1 -C 6 alkylNR—, —NRC 1 -C 6 alkylene-, —S—, —NR—, —NRNR—, —O(CR 2 ) 1-4 S—S(CR 2 ) 1-4 N(R)—, —NRC 1 -C 6 -alkylenephenyleneNR—, —NRC 1 -C 6 alkylenephenyleneSO 2 NR—, —OC 1 -C 6 alkylS-SC 1 -C 6 alkylC(COOR)NR—, —NRC(COOR)C 1 -C 6 alkylS-SC 1 -C 6 alkylO—,

wherein

X A is CR or N,

X B is CH, CR(C(R) 2 ) 1-3 NR, CR(C(R) 2 ) 1-3 O, CR(C(R) 2 ) 1-3 C(O)NR, CR—(C(R) 2 ) 1-3 C(O)NRNR, CR(C(R) 2 ) 1-3 SO 2 NR, CR(C(R) 2 ) 1-3 NRNR, CR(C(R) 2 ) 1-3 NRC(O) or N,

each X C is R;

each X D is —(CH 2 ) 1-5 —, or is absent;

X E is O, S, C(R) 2 , C(R)(C(R) 2 ) 1-3 —NR 2 or NR, and

each X F is (C(R) 2 ) 1-3 —NR or C(R) 2 —(C(R) 2 ) 1-3 —O.

4. A compound of Formula (IIB):

or a pharmaceutically acceptable salt or solvate thereof, wherein:

F 1 and F 2 are each independently selected from ring systems A, B, C and D:

where:

each R is independently selected from the group consisting of H, —C 1 -C 20 alkyl, —C 1 -C 8 alkenyl, —C 1 -C 8 alkynyl, halo, deuterium, hydroxyl, alkoxy, —NH 2 , —NH(C 1 -C 8 alkyl), —N(C 1 -C 8 alkyl) 2 , —NO 2 , —C 8 -C 14 aryl and —C 8 -C 14 heteroaryl, wherein two or more R optionally join to form a ring or rings, and wherein said —C 8 -C 14 aryl and —C 8 -C 14 heteroaryl are optionally substituted with 1 to 5 substituents independently selected from —C 1 -C 10 alkyl, —C 1 -C 10 alkoxy, -halo, —C 1 -C 10 alkylthio, -trifluoromethyl, —NH 2 , —NH(C 1 -C 8 alkyl), —N(C 1 -C 8 alkyl) 2 , —C 1 -C 10 alkyl-N(C 1 -C 8 alkyl) 2 , —C 1 -C 3 alkylthio, —NO 2 or —C 1 -C 10 heterocyclyl, for each ring system in which R appears;

each V 1 is independently a bond, O, N(R) or S, for each ring system in which V 1 appears;

each V 2 is independently O, N(R) or S, for each ring system in which V 2 appears;

W 1 and W 2 are each independently H, —C 1 -C 5 alkyl, -phenyl, —C(O)OR, —C(O)SR, —C(O)NHN(R) 2 or —C(O)N(R) 2 for each ring system in which W 1 and W 2 appear;

each X is independently —OH, —O-acyl, azido, halo, cyanate, thiocyanate, isocyanate, thioisocyanate, or

for each ring system in which X appears;

each Y is independently selected from the group consisting of H, —C 1 -C 8 alkyl-R A —C(O)R A , —C(S)R A , —C(O)OR A , —S(O) 2 OR A , —C(O)N(R A ) 2 , —C(S)N(R A ) 2 , glycosyl, —NO 2 , —PO(OR A ) 2 , an amino acid and a peptide for each ring system in which Y appears, wherein each R A is independently selected from the group consisting of H, —C 1 -C 20 alkyl, —C 1 -C 8 heteroalkyl, —C 6 -C 14 aryl, aralkyl, —C 1 -C 10 heterocyclyl, —C 1 -C 8 carbocyclyl and —C 1 -C 20 alkylN(R) 2 , wherein said —C 1 -C 20 alkyl, —C 1 -C 8 heteroalkyl, —C 8 -C 14 aryl, aralkyl, —C 1 -C 10 heterocyclyl, —C 3 -C 8 carbocyclyl and —C 1 -C 20 alkylN(R) 2 are optionally substituted with 1 to 3 substitutents independently selected from R;

each Z is independently selected from the group consisting of H, —C 1 -C 8 alkyl, —C 1 -C 8 heteroalkyl, —C 8 -C 14 aryl, -aralkyl, —C 1 -C 10 heterocyclyl, —C 1 -C 8 carbocyclyl, —C(O)OC 1 -C 8 alkyl, —C(O)N(C 1 -C 8 alkyl) 2 , —C(O)OH, —C(O)NHNH 2 and —C(O)-halo, and wherein said C 1 -C 8 alkyl, —C 1 -C 8 heteroalkyl, —C 8 -C 14 aryl, -aralkyl, —C 1 -C 10 heterocyclyl, —C 1 -C 8 carbocyclyl, —C(O)OC 1 -C 8 alkyl, —C(O)N(C 1 -C 8 alkyl) 2 , —C(O)OH, —C(O)NHNH 2 and —C(O)-halo are each optionally substituted with 1 to 3 substitutents independently selected from R, for each ring system in which Z appears;

L 1 and L 2 are each independently selected from a direct bond

T is:

—C(A 1 )X 1 -T 2 -X 1 C(B 1 )—, where T 2 is:

wherein each X 1 is independently a bond, —NR E —, —O— or —S—, wherein A 1 and B 1 are each independently ═O or ═S, wherein R 1 , R 2 , R 3 , and R 4 are each independently R E , or R 1 and R 2 form a ring system, or

R 3 and R 4 form a ring system, or both R 1 and R 2 , and R 3 and R 4 each independently form ring systems, or R 1 and R 3 form a ring system, or R 2 and R 4 form a ring system, or both R 1 and R 3 , and R 2 and R 4 each independently form ring systems, where the ring systems are independently selected from —C 1 -C 10 heterocyclyl or —C 3 -C 8 carbocyclycl, or R 1 , R 2 , R 3 and R 4 are each bonds to different carbons on D, wherein g and j are each independently an integer from 0 to 50 and m is an integer from 1 to 50, and wherein D is selected from the group consisting of —C 1 -C 10 heterocyclo and —C 3 -C 8 carbocyclo, where said —C 1 -C 10 heterocyclo and —C 3 -C 8 carbocyclo are substituted with one member of the group selected from N(R E )C(O)— where the carbonyl is bonded to L, and —C(O)— where the carbonyl is bonded to L, and additionally optionally substituted by 1 to 2 R;

where each R E is independently selected from the group consisting of H, —C 1 -C 8 alkyl, —C 1 -C 8 heteroalkyl, -aryl, -aralkyl, —C 1 -C 10 heterocyclyl, —C 3 -C 8 carbocyclyl, —C(O)OC 1 -C 8 alkyl, —C(O)N(C 1 -C 8 alkyl) 2 , and —C(O)-halo, and wherein each R E is optionally substituted with 1 to 3 substitutents independently selected from R;

L is L A -L B -(L C ) 1-3 where an L C is bond to T 2 ;

L A is selected from -halo, —N(R) 2 , —CON(R) 2 , —S-aryl optionally substituted with —NO 2 or —CONR 2 , —S-heteroaryl optionally substituted with —NO 2 , alkyl-SO 2 -heteroaryl, arylSO 2 -heteroaryl-,

L B is L B1 -L B2 -L B3

wherein L B1 is absent or is one or more components selected from the group consisting of —C(O)—, —C(S)—, —C(O)NR—, —C(O)NRC 1 -C 6 alkyl-, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —, —C(O)C 1 -C 6 alkylNRC(O)—, —C(O)C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —C(O)—, —C 1 -C 6 alkyl-S—S—C 1 -C 6 alkylNRC(O)CH 2 —, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 NRC(O)CH 2 —, —C(O)C 1 -C 6 alkyl-NRC(O)C 1 -C 6 alkyl-, —N═CR-phenyl-O—C 1 -C 6 alkyl-, —N═CR-phenyl-O—C 1 -C 6 alkyl-C(O)—, —C(O)—C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 NRC(O)—, —C(O)C 1 -C 6 alkyl-phenyl(NR—C(O)C 1 -C 6 alkyl) 1-4 -, —C(O)C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —NRC(O)C 1 -C 6 alkyl-, —C 1 -C 6 alkyl-, —S—, —C(O)—CH(NR—C(O)C 1 -C 6 alkyl)-C 1 -C 6 alkyl- and (—CH 2 —CH 2 —O—) 1-20 ;

L B2 is AA 0-12 , wherein AA is a natural amino acid or a non-natural amino acid;

L B3 is p-aminobenzoic acid, p-aminobenzyloxycarbonyl, —C(O)(CH 2 ) 0-50 C(O)— or absent;

wherein

X A is CR or N,

X B is CH, CR(C(R) 2 ) 1-3 NR, CR(C(R) 2 ) 1-3 O, CR(C(R) 2 ) 1-3 C(O)NR, CR—(C(R) 2 ) 1-3 C(O)NRNR, CR(C(R) 2 ) 1-3 SO 2 NR, CR(C(R) 2 ) 1-3 NRNR, CR(C(R) 2 ) 1-3 NRC(O) or N;

each X C is R;

each X C is —(CH 2 ) 1-5 —, or is absent;

X E is O, S, C(R) 2 , C(R)(C(R) 2 ) 1-3 —NR 2 or NR, and

each X F is (C(R) 2 ) 1-3 —NR or C(R) 2 —(C(R) 2 ) 1-3 —O.

5. A compound of Formula (IIIB):

or a pharmaceutically acceptable salt or solvate thereof, wherein:

AB is an antibody;

F 1 and F 2 are each independently selected from ring systems A, B, C and D:

where:

each R is independently selected from the group consisting of H, —C 1 -C 20 alkyl, —C 1 -C 8 alkenyl, —C 1 -C 8 alkynyl, halo, deuterium, hydroxyl, alkoxy, —NH 2 , —NH(C 1 -C 8 alkyl), —N(C 1 -C 8 alkyl) 2 , —NO 2 , —C 8 -C 14 aryl and —C 8 -C 14 heteroaryl, or wherein two or more R optionally join to form a ring or rings, and wherein said —C 8 -C 14 aryl and —C 8 -C 14 heteroaryl are optionally substituted with 1 to 5 substituents independently selected from —C 1 -C 10 alkyl, —C 1 -C 10 alkoxy, -halo, —C 1 -C 10 alkylthio, -trifluoromethyl, —NH 2 , —NH(C 1 -C 8 alkyl), —N(C 1 -C 8 alkyl) 2 , —C 1 -C 10 alkyl-N(C 1 -C 8 alkyl) 2 , —C 1 -C 3 alkylthio, —NO 2 or —C 1 -C 10 heterocyclyl, for each ring system in which R appears;

each V 1 is independently a bond, O, N(R) or S, for each ring system in which V 1 appears;

each V 2 is independently O, N(R) or S, for each ring system in which V 2 appears;

W 1 and W 2 are each independently H, —C 1 -C 5 alkyl, -phenyl, —C(O)OR, —C(O)SR, —C(O)NHN(R) 2 or —C(O)N(R) 2 for each ring system in which W 1 and W 2 appear;

each X is independently —OH, —O-acyl, azido, halo, cyanate, thiocyanate, isocyanate, thioisocyanate, or

for each ring system in which X appears;

each Y is independently selected from the group consisting of H, —C 1 -C 6 alkyl-R A —C(O)R A , —C(S)R A , —C(O)OR A , —S(O) 2 OR A , —C(O)N(R A ) 2 , —C(S)N(R A ) 2 , glycosyl, —NO, —PO(OR A ) 2 , an amino acid and a peptide for each ring system in which Y appears, wherein each R A is independently selected from the group consisting of H, —C 1 -C 20 alkyl, —C 1 -C 8 heteroalkyl, —C 8 -C 14 aryl, aralkyl, —C 1 -C 10 heterocyclyl, —C 3 -C 8 carbocyclyl and —C 1 -C 20 alkylN(R) 2 , wherein said —C 1 -C 20 alkyl, —C 1 -C 8 heteroalkyl, —C 8 -C 14 aryl, aralkyl, —C 1 -C 10 heterocyclyl, —C 3 -C 8 carbocyclyl and —C 1 -C 20 alkylN(R) 2 are optionally substituted with 1 to 3 substitutents independently selected from R;

each Z is independently selected from the group consisting of H, —C 1 -C 8 alkyl, —C 1 -C 8 heteroalkyl, —C 8 -C 14 aryl, -aralkyl, —C 1 -C 10 heterocyclyl, —C 1 -C 8 carbocyclyl, —C(O)OC 1 -C 8 alkyl, —C(O)N(C 1 -C 8 alkyl) 2 , —C(O)OH, —C(O)NHNH 2 and —C(O)-halo, and wherein said C 1 -C 8 alkyl, —C 1 -C 8 heteroalkyl, —C 6 -C 14 aryl, -aralkyl, —C 1 -C 10 heterocyclyl, —C 3 -C 8 carbocyclyl, —C(O)OC 1 -C 8 alkyl, —C(O)N(C 1 -C 8 alkyl) 2 , —C(O)OH, —C(O)NHNH 2 and —C(O)-halo are each optionally substituted with 1 to 3 substitutents independently selected from R, for each ring system in which Z appears;

L 1 and L 2 are each independently selected from a direct bond

T is:

—C(A 1 )X 1 -T 2 -X 1 C(B 1 )—, where T 2 is:

L is L A -L B -(L C ) 1-3 wherein an L C is bound to T 2 ;

L A is selected from: a bond to AB, —NR-(bond to AB), -heteroaryl-(bond to AB),

L B is L B1 -L B2 -L B3

wherein L B1 is absent or is one or more components selected from the group consisting of —C(O)—, —C(S)—, —C(O)NR—, —C(O)C 1 -C 6 alkyl-, —C(O)NRC 1 -C 6 alkyl-, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —, —C(O)C 1 -C 6 alkylNRC(O)—, —C(O)C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —C(O)—, —C 1 -C 6 alkyl-S—S—C 1 -C 6 alkylNRC(O)CH 2 —, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 NRC(O)CH 2 —, —C(O)C 1 -C 6 alkyl-NRC(O)C 1-6 alkyl-, —N═CR-phenyl-O—C 1 -C 6 alkyl-, —N═CR-phenyl-O—C 1 -C 6 alkyl-C(O)—, —C(O)—C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 NRC(O)—, —C(O)C 1 -C 6 alkyl-phenyl(NR—C(O)C 1 -C 6 alkyl) 1-4 -, —C(O)C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —NRC(O)C 1 -C 6 alkyl-, —C 1 -C 6 alkyl-, —S—, —C(O)—CH(NR—C(O)C 1 -C 6 alkyl)-C 1 -C 6 alkyl- and (—CH 2 —CH 2 —O—) 1-20 ;

L B2 is AA 0-12 , wherein AA is a natural amino acid or a non-natural amino acid;

L B3 is p-aminobenzoic acid, p-aminobenzyloxycarbonyl, —C(O)(CH 2 ) 0-50 C(O)— or absent;

wherein

X A is CR or N,

X B is CH, CR(C(R) 2 ) 1-3 NR, CR(C(R) 2 ) 1-3 O, CR(C(R) 2 ) 1-3 C(O)NR, CR—(C(R) 2 ) 1-3 C(O)NRNR, CR(C(R) 2 ) 1-3 SO 2 NR, CR(C(R) 2 ) 1-3 NRNR, CR(C(R) 2 ) 1-3 NRC(O) or N;

each X C is R;

each X C is —(CH 2 ) 1-5 —, or is absent;

X E is O, S, C(R) 2 , C(R)(C(R) 2 ) 1-3 —NR 2 or NR, and

each X F is (C(R) 2 ) 1-3 —NR or C(R) 2 —(C(R) 2 ) 1-3 —O.

6. The compound of claim 1 , wherein:

each R is independently selected from the group consisting of H, deuterium, —C 1 -C 20 alkyl and —NH 2 ;

each V 1 is independently O or N(R) for each ring system in which V 1 appears;

each V 2 is independently O or N(R) for each ring system in which V 2 appears;

W 1 and W 2 are each independently H, —C 1 -C 5 alkyl, —C(O)OR, or —C(O)NR 2 for each ring system in which W 1 and W 2 appear;

each X is independently halo, for each ring system in which X appears;

each Y is independently selected from the group consisting of H, —C(O)R A , —C(O)N(R A ) 2 , glycosyl, —NO 2 , —PO(OR A ) 2 a cathepsins and a matrix metalloproteinase for each ring system in which Y appears, wherein each R A is independently selected from the group consisting of H, —C 1 -C 20 alkyl, —C 1 -C 8 heteroalkyl, —C 3 -C 8 carbocyclyl and —C 1 -C 20 alkylN(R) 2 , wherein said —C 1 -C 20 alkyl, —C 1 -C 8 heteroalkyl, —C 3 -C 8 carbocyclyl and —C 1 -C 20 alkylN(R) 2 are optionally substituted with 1 to 3 substitutents independently selected from R;

L 1 and L 2 are each independently selected from a direct bond; and

T is:

—C(A 1 )X 1 -T 2 -X 1 C(B 1 )—, where T 2 is:

wherein each X 1 is a bond, wherein A 1 and B 1 are each independently ═O, wherein R 1 , R 2 , R 3 , and R 4 are each independently H or R 1 and R 2 form a ring system, or R 3 and R 4 form a ring system, or both R 1 and R 2 , and R 3 and R 4 , each independently form ring systems, or R 1 and R 3 form a ring system, or R 2 and R 4 form a ring system, or both R 1 and R 3 , and R 2 and R 4 , each independently form ring systems, where said ring systems are independently selected from —C 1 -C 10 heterocyclyl or —C 3 -C 8 carbocyclycl, and wherein D is a bond or is selected from the group consisting of —C 1 -C 10 heterocyclo and —C 3 -C 8 carbocyclo, where said —C 1 -C 10 heterocyclo and —C 3 -C 8 carbocyclo are optionally substituted with —NH 2 , —N(R)C(O)H or —N(R)C(O)OH.

7. The compound of claim 3 , wherein where two or more R optionally join to form a ring or rings.

8. The compound of claim 5 , wherein where two or more R optionally join to form a ring or rings.

9. The compound of claim 2 , wherein:

L A is selected from the group consisting of -halo, —N(R) 2 , —CON(R) 2 , —S-aryl optionally substituted with —NO 2 or —CON(R) 2 , —S-heteroaryl optionally substituted with —NO 2 , alkyl-SO 2 -heteroaryl, arylSO 2 -heteroaryl-, and

L B is L B1 -L B2 -L B3 wherein L B1 is absent or is one or more components selected from the group consisting of —C(O)—, —C(S)—, —C(O)NR—, —C(O)C 1 -C 6 alkyl-, —C(O)NRC 1 -C 6 alkyl-, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —, —C(O)C 1 -C 6 alkylNRC(O)—, —C(O)C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —C(O)—, —C 1 -C 6 alkyl-S—S—C 1 -C 6 alkylNRC(O)CH 2 —, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 NRC(O)CH 2 —, —C(O)C 1 -C 6 alkyl-NRC(O)C 1 -C 6 alkyl-, —C(O)—C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 NRC(O)—, —C(O)C 1 -C 6 alkyl-phenyl(NR—C(O)C 1 -C 6 alkyl) 1-4 -, —C(O)C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —NRC(O)C 1 -C 6 alkyl-, —C 1 -C 6 alkyl-, —S—, —C(O)—CH(NR—C(O)C 1 -C 6 alkyl)-C 1 -C 6 alkyl- and (—CH 2 —CH 2 —O—) 1-20 , wherein L B2 is AA 0-12 , wherein AA is a natural amino acid or a non-natural amino acid, and L B3 is p-aminobenzoic acid, p-aminobenzyloxycarbonyl, —C(O)(CH 2 ) 0-50 C(O)— or absent; and

L C is absent.

10. The compound of claim 4 , wherein:

L B is L B1 -L B2 -L B3 wherein L B1 is absent or is one or more components selected from the group consisting of —C(O)—, —C(S)—, —C(O)NR—, —C(O)C 1 -C 6 alkyl-, —C(O)NRC 1 -C 6 alkyl-, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —, —C(O)C 1 -C 6 alkylNRC(O)—, —C(O)C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —C(O)—, —C 1 -C 6 alkyl-S—S—C 1 -C 6 alkylNRC(O)CH 2 —, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 NRC(O)CH 2 —, —C(O)C 1 -C 6 alkyl-NRC(O)C 1 -C 6 alkyl-, —C(O)—C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 NRC(O)—, —C(O)C 1 -C 6 alkyl-phenyl(NR—C(O)C 1 -C 6 alkyl) 1-4 -, —C(O)C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —NRC(O)C 1 -C 6 alkyl-, —C 1 -C 6 alkyl-, —S—, —C(O)—CH(NR—C(O)C 1 -C 6 alkyl)-C 1 -C 6 alkyl- and (—CH 2 —CH 2 —O—) 1-20 , wherein L B2 is AA 0-12 , wherein AA is a natural amino acid or a non-natural amino acid, and L B3 is p-aminobenzoic acid, p-aminobenzyloxycarbonyl, —C(O)(CH 2 ) 0-50 C(O)— or absent; and

L C is absent.

11. The compound of claim 3 , wherein:

L A is selected from: a bond to AB, —NR-(bond to AB), -heteroaryl-(bond to AB),

L B is L B1 -L B2 -L B3 wherein L B1 is absent or is one or more components selected from the group consisting of —C(O)—, —C(S)—, —C(O)NR—, —C(O)C 1 -C 6 alkyl-, —C(O)NRC 1 -C 6 alkyl-, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —, —C(O)C 1 -C 6 alkylNRC(O)—, —C(O)C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —C(O)—, —C 1 -C 6 alkyl-S—S—C 1 -C 6 alkylNRC(O)CH 2 —, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 NRC(O)CH 2 —, —C(O)C 1 -C 6 alkyl-NRC(O)C 1 -C 6 alkyl-, —C(O)—C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 NRC(O)—, —C(O)C 1 -C 6 alkyl-phenyl(NR—C(O)C 1 -C 6 alkyl) 1-4 -, —C(O)C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —NRC(O)C 1 -C 6 alkyl-, —C 1 -C 6 alkyl-, —S—, —C(O)—CH(NR—C(O)C 1 -C 6 alkyl)-C 1 -C 6 alkyl- and (—CH 2 —CH 2 —O—) 1-20 , wherein L B2 is AA 0-12 , wherein AA is a natural amino acid or a non-natural amino acid, and L B3 is p-aminobenzoic acid, p-aminobenzyloxycarbonyl, —C(O)(CH 2 ) 0-50 C(O)— or absent; and

L C is absent.

12. The compound of claim 5 , wherein:

L A is selected from: a bond to AB, —NR-(bond to AB), -heteroaryl-(bond to AB),

L B is L B1 -L B2 -L B3 wherein L B1 is absent or is one or more components selected from the group consisting of —C(O)—, —C(S)—, —C(O)NR—, —C(O)C 1 -C 6 alkyl-, —C(O)NRC 1 -C 6 alkyl-, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —, —C(O)C 1 -C 6 alkylNRC(O)—, —C(O)C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —C(O)—, —C 1 -C 6 alkyl-S—S—C 1 -C 6 alkylNRC(O)CH 2 —, —C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 NRC(O)CH 2 —, —C(O)C 1 -C 6 alkyl-NRC(O)C 1 -C 6 alkyl-, —C(O)—C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 NRC(O)—, —C(O)C 1 -C 6 alkyl-phenyl(NR—C(O)C 1 -C 6 alkyl) 1-4 -, —C(O)C 1 -C 6 alkyl(OCH 2 CH 2 ) 1-6 —NRC(O)C 1 -C 6 alkyl-, —C 1 -C 6 alkyl-, —S—, —C(O)—CH(NR—C(O)C 1 -C 6 alkyl)-C 1 -C 6 alkyl- and (—CH 2 —CH 2 —O—) 1-20 , wherein L B2 is AA 0-12 , wherein AA is a natural amino acid or a non-natural amino acid, and L B3 is p-aminobenzoic acid, p-aminobenzyloxycarbonyl, —C(O)(CH 2 ) 0-50 C(O)— or absent; and

L C is absent.

13. A compound, or a pharmaceutically acceptable salt or solvate thereof, selected from:

14. A compound, or a pharmaceutically acceptable salt or solvate thereof, selected from:

where Pg is H, acyl, PO3H2, a carbohydrate, an amino acid or a peptide.

15. A compound, or a pharmaceutically acceptable salt or solvate thereof, selected from:

16. A compound, or a pharmaceutically acceptable salt or solvate thereof, consisting of a payload and a linker, said payload selected from:

and said linker is selected from:

where

P represents the point of attachment to said payload,

each R 7 is independently H or —C 1 -C 20 alkyl,

R 8 is —C 1 -C 20 alkyl, —C 6 -C 14 aryl or —C 6 -C 14 heteroaryl,

Pg is H, acyl, PO 3 H 2 , a carbohydrate, an amino acid or a peptide,

n=0-20, and

m=0-20.

17. A compound, or a pharmaceutically acceptable salt or solvate thereof, selected from:

where AB is an antibody.

18. The compound of claim 17 , wherein said antibody AB is selected from trastuzumab, trastuzumab mutants, oregovomab, edrecolomab, cetuximab, a humanized monoclonal antibody to the vitronectin receptor (αvβ3), alemtuzumab, anti HLA DR antibodies, 131I Lym 1, anti HLA Dr10 antibodies, anti cd33 antibodies, anti cd22 antibodies, labetuzumab, bevacizumab, ibritumomab tiuxetan, ofatumumab, panitumumab, rituximab, tositumomab, ipilimumab, and gemtuzumab.

19. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, and pharmaceutically acceptable excipient.

Assignments (1)

ASSIGNEE ADDRESS CORRECTION Recorded Mar 20, 2023

From: PFIZER INC.

To: PFIZER INC.

Reel/Frame 063119/0087 →