Bifunctional cytotoxic agents containing the CTI pharmacophore

A compound of Formula (IIA):

• L-P (IIA)
• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• P is:
• F1-L1-T-L2-F2
• wherein:
• F1 and F2 are each independently selected from ring systems A, B, C and D:
• where:
• each R is independently selected from the group consisting of H, —C1-C20 alkyl, —C1-C8 alkenyl, —C1-C8 alkynyl, halo, deuterium, hydroxyl, alkoxy, —NH2, —NH(C1-C8 alkyl), —N(C1-C8 alkyl)2, —NO2, —C8-C14 aryl and —C8-C14 heteroaryl, wherein two or more R optionally join to form a ring or rings, and wherein said —C8-C14 aryl and —C8-C14 heteroaryl are optionally substituted with 1 to 5 substituents independently selected from —C1-C10 alkyl, —C1-C10 alkoxy, -halo, —C1-C10 alkylthio, -trifluoromethyl, —NH2, —NH(C1-C8 alkyl), —N(C1-C8 alkyl)2, —C1-C10 alkyl-N(C1-C8 alkyl)2, alkylthio, —NO2 or —C1-C10 heterocyclyl, for each ring system in which R appears;
• each V1 is independently a bond, O, N(R) or S, for each ring system in which V1 appears;
• each V2 is independently O, N(R) or S, for each ring system in which V2 appears;
• W1 and W2 are each independently H, —C1-C5 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 W1 and W2 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)RA, —C(S)RA, —C(O)ORA, —S(O)2ORA, —C(O)N(RA)2, —C(S)N(RA)2, glycosyl, —NO2, —P(O)(ORA)2, an amino acid, and a peptide, for each ring system in which Y appears, wherein each RA is independently selected from H, —C1-C20 alkyl, —C1-C8 heteroalkyl, —C6-C14 aryl, aralkyl, —C1-C10 heterocyclyl, —C3-C8 carbocyclyl, —C1-C20 alkylN(R)2, —C1-C20 alkylene, —C1-C8 heteroalkylene, —C6-C14 arylene, aralkylene, —C1-C10 heterocyclo, —C3-C8 carbocyclo and —C1-C20 alkylN(R)—, and RF where said RA 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,
• RF is —N(R6)QN(R5)C(O)— and is bonded to L at the carbonyl adjacent N(R5), wherein R5 and R6 are each independently selected from the group consisting of H, —C1-C8 alkyl, —C1-C8 heteroalkyl, —C6-C14 aryl, -aralkyl, —C1-C10 heterocyclyl and —C3-C8 carbocyclyl, or R5 or R6 joins with a substituted carbon on Q to form a —C1-C10 heterocyclic or —C6-C14 heteroaryl ring, or R5 and R6 join together to form a —C1-C10 heterocyclic or —C6-C14 heteroaryl ring system, and where Q is —C1-C8 alkylene-, —C1-C8 heteroalkylene-, —C6-C14 arylene-, -aralkylene-, —C1-C10 heterocyclo- or —C3-C8 carbocyclo-, wherein Q, R5 and R6 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, —C1-C8 alkyl, —C1-C8 heteroalkyl, —C6-C14 aryl, -aralkyl, —C1-C10 heterocyclyl, —C3-C8 carbocyclyl, —C(O)OC1-C8 alkyl, —C(O)N(C1-C8 alkyl)2, —C(O)OH, —C(O)NHNH2 and —C(O)-halo, and wherein said C1-C8 alkyl, —C1-C8 heteroalkyl, —C6-C14 aryl, -aralkyl, —C1-C10 heterocyclyl, —C3-C8 carbocyclyl, —C(O)OC1-C8 alkyl, —C(O)N(C1-C8 alkyl)2, —C(O)OH, —C(O)NHNH2 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;
• L1 and L2 are each independently selected from a direct bond;
• T is
• —C(A1)X1-T2-X1C(B1)—, where T2 is:
• wherein each X1 is independently a bond, —NRE—, —O— or —S—, wherein A1 and B1 are each independently ═O or ═S, wherein R1, R2, R3, and R4 are each independently RE or R1 and R2 form a ring system, or R3 and R4 form a ring system, or both R1 and R2, and R3 and R4, each independently form ring systems, or R1 and R3 form a ring system, or R2 and R4 form a ring system, or both R1 and R3, and R2 and R4, each independently form ring systems, where said ring systems are independently selected from —C1-C10 heterocyclyl or —C3-C8 carbocyclycl, or R1, R2, R3 and R4 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 —C1-C10 heterocyclo and —C3-C8 carbocyclo, where said —C1-C10 heterocyclo and —C3-C8 carbocyclo are optionally substituted with —RE, —C(O)RE, —C(O)ORE, —N(RE)2, —N(R)C(O)RE or —N(R)C(O)ORE, and D is additionally optionally substituted by 1 to 2 R,
• wherein each RE is independently selected from the group consisting of H, —C1-C8 alkyl, —C1-C8 heteroalkyl, -aryl, -aralkyl, —C1-C10 heterocyclyl, —C3-C8 carbocyclyl, —C(O)OC1-C8 alkyl, —C(O)N(C1-C8 alkyl)2, and —C(O)-halo, and wherein each RE is optionally substituted with 1 to 3 substitutents independently selected from R;
• L is LA-LB-(LC)1-3, wherein an LC is bound to Y and wherein LA is selected from the group consisting of -halo, —N(R)2, —CON(R)2, —S-aryl optionally substituted with —NO2 or —CON(R)2, —S-heteroaryl optionally substituted with —NO2, alkyl-SO2-heteroaryl, arylSO2-heteroaryl-,
• LB is LB1-LB2-LB3 wherein LB1 is absent or is one or more components selected from the group consisting of —C(O)—, —C(S)—, —C(O)NR—, —C(O)C1-C6alkyl-, —C(O)NRC1-C6alkyl-, —C1-C6alkyl(OCH2CH2)1-6—, —C(O)C1-C6alkylNRC(O)—, —C(O)C1-C6alkyl(OCH2CH2)1-6—, —C1-C6alkyl(OCH2CH2)1-6—C(O)—, —C1-C6alkyl-S—S—C1-C6alkylNRC(O)CH2—, —C1-C6alkyl(OCH2CH2)1-6NRC(O)CH2—, —C(O)C1-C6alkyl-NRC(O)C1-C6alkyl-, —N═CR-phenyl-O—C1-C6alkyl-, —N═CR-phenyl-O—C1-C6alkyl-C(O)—, —C(O)—C1-C6alkyl(OCH2CH2)1-6NRC(O)—, —C(O)C1-C6alkyl-phenyl(NR—C(O)C1-C6alkyl)1-4—, —C(O)C1-C6alkyl(OCH2CH2)1-6—NRC(O)C1-C6alkyl-, —C1-C6alkyl-, —S—, —C(O)—CH(NR—C(O)C1-C6alkyl)-C1-C6alkyl- and (—CH2—CH2—O—)1-20,
• wherein LB2 is AA0-12, wherein AA is a natural amino acid or a non-natural amino acid;
• LB3 is p-aminobenzoic acid, p-aminobenzyloxycarbonyl, —C(O)(CH2)0-50C(O)— or absent;
• LC is absent or independently selected from the group consisting of —C1-C6alkylene-, —NRC3-C8-heterocyclylNR—, —NRC3-C8-carbocyclylNR—, —NRC1-C6alkylNR—, —NRC1-C6alkylene-, —S—, —NR—, —NRNR—, —O(CR2)1-4S—S(CR2)1-4N(R)—, —NRC1-C6-alkylenephenyleneNR—, —NRC1-C6alkylenephenyleneSO2NR—, —OC1-C6alkylS-SC1-C6alkylC(COOR)NR—, —NRC(COOR)C1-C6alkylS-SC1-C6alkylO—,
• wherein
• XA is CR or N,
• XB is CH, CR(C(R)2)1-3NR, CR(C(R)2)1-3O, CR(C(R)2)1-3C(O)NR, CR—(C(R)2)1-3C(O)NRNR, CR(C(R)2)1-3SO2NR, CR(C(R)2)1-3NRNR, CR(C(R)2)1-3NRC(O) or N,
• each XC is R,
• each XD is —(CH2)1-5—, or is absent;
• XE is O, S, C(R)2, C(R)(C(R)2)1-3—NR2 or NR and
• each XF is (C(R)2)1-3—NR or C(R)2—(C(R)2)1-3—O.

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:
• F1-L1-T-L2-F2
• wherein:
• F1 and F2 are each independently selected from ring systems A, B, C and D:
• where:
• each R is independently selected from the group consisting of H, —C1-C20 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, halo, deuterium, hydroxyl, alkoxy, —NH2, —NH(C1-C8 alkyl), —N(C1-C8 alkyl)2, —NO2, —C6-C14 aryl and —C6-C14 heteroaryl, or wherein two or more R optionally join to form a ring or rings, and wherein said —C6-C14 aryl and —C6-C14 heteroaryl are optionally substituted with 1 to 5 substituents independently selected from —C1-C10 alkyl, —C1-C10 alkoxy, -halo, —C1-C10 alkylthio, -trifluoromethyl, —NH2, —NH(C1-C8 alkyl), —N(C1-C8 alkyl)2, —C1-C10 alkyl-N(C1-C8 alkyl)2, —C1-C3 alkylthio, —NO2 or —C1-C10 heterocyclyl, for each ring system in which R appears;
• each V1 is independently a bond, O, N(R) or S, for each ring system in which V1 appears;
• each V2 is independently O, N(R) or S, for each ring system in which V2 appears;
• W1 and W2 are each independently H, —C1-C5 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 W1 and W2 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)RA, —C(S)RA, —C(O)ORA, —S(O)2ORA, —C(O)N(RA)2, —C(S)N(RA)2, glycosyl, —NO2, —P(O)(ORA)2, an amino acid and a peptide for each ring system in which Y appears, wherein each RA is independently selected from H, —C1-C20 alkyl, —C1-C8 heteroalkyl, —C8-C14 aryl, aralkyl, —C1-C10 heterocyclyl, —C1-C8 carbocyclyl, —C1-C20 alkylN(R)2, —C1-C20 alkylene, —C1-C8 heteroalkylene, —C6-C14 arylene, aralkylene, —C1-C10 heterocyclo, —C3-C8 carbocyclo and —C1-C20 alkylN(R)—, and RF where said RA 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,
• RF is —N(R6)QN(R5)C(O)— and is bonded to L at the carbonyl adjacent N(R5), wherein R5 and R6 are each independently selected from the group consisting of H, —C1-C8 alkyl, —C1-C8 heteroalkyl, —C6-C14 aryl, -aralkyl, —C1-C10 heterocyclyl and —C3-C8 carbocyclyl, or R5 or R6 joins with a substituted carbon on Q to form a —C1-C10 heterocyclic or —C6-C14 heteroaryl ring, or R5 and R6 join together to form a —C1-C10 heterocyclic or —C6-C14 heteroaryl ring system, and where Q is —C1-C8 alkylene-, —C1-C8 heteroalkylene-, —C6-C14 arylene-, -aralkylene-, —C1-C10 heterocyclo- or —C3-C8 carbocyclo-, wherein Q, R5 and R6 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, —C1-C8 alkyl, —C1-C8 heteroalkyl, —C6-C14 aryl, -aralkyl, —C1-C10 heterocyclyl, —C3-C8 carbocyclyl, —C(O)OC1-C8 alkyl, —C(O)N(C1-C8 alkyl)2, —C(O)OH, —C(O)NHNH2 and —C(O)-halo, and wherein said C1-C8 alkyl, —C1-C8 heteroalkyl, —C6-C14 aryl, -aralkyl, —C1-C10 heterocyclyl, —C3-C8 carbocyclyl, —C(O)OC1-C8 alkyl, —C(O)N(C1-C8 alkyl)2, —C(O)OH, —C(O)NHNH2 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;
• L1 and L2 are each independently selected from a direct bond
• T is
• —C(A1)X1-T2-X1C(B1)—, where T2 is:
• wherein each X1 is independently a bond, —NRE—, —O— or —S—, wherein A1 and B1 are each independently ═O or ═S, wherein R1, R2, R3, and R4 are each independently RE or R1 and R2 form a ring system, or
• R3 and R4 form a ring system, or both R1 and R2, and R3 and R4, each independently form ring systems, or R1 and R3 form a ring system, or R2 and R4 form a ring system, or both R1 and R3, and R2 and R4, each independently form ring systems, where said ring systems are independently selected from —C1-C10 heterocyclyl or —C3-C8 carbocyclycl, or R1, R2, R3 and R4 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 —C1-C10 heterocyclo and —C3-C8 carbocyclo, where said —C1-C10 heterocyclo and —C3-C8 carbocyclo are optionally substituted with —RE, —C(O)RE, —C(O)ORE, —N(RE)2, —N(R)C(O)RE or —N(R)C(O)ORE, and D is additionally optionally substituted by 1 to 2 R, wherein each RE is independently selected from the group consisting of H, —C1-C8 alkyl, —C1-C8 heteroalkyl, -aryl, -aralkyl, —C1-C10 heterocyclyl, —C3-C8 carbocyclyl, —C(O)OC1-C8 alkyl, —C(O)N(C1-C8 alkyl)2, and —C(O)-halo, and wherein each RE is optionally substituted with 1 to 3 substitutents independently selected from R;
• L is LA-LB-(LC)1-3 wherein an LC is bound to Y;
• LA is selected from:
• a bond to AB, —NR-(bond to AB), -heteroaryl-(bond to AB),
• LB is LB1-LB2-LB3
• wherein LB1 is absent or is one or more components selected from the group consisting of —C(O)—, —C(S)—, —C(O)NR—, —C(O)C1-C6alkyl-, —C(O)NRC1-C6alkyl-, —C1-C6alkyl(OCH2CH2)1-6—, —C(O)C1-C6alkylNRC(O)—, —C(O)C1-C6alkyl(OCH2CH2)1-6—, —C1-C6alkyl(OCH2CH2)1-6—C(O)—, —C1-C6alkyl-S—S—C1-C6alkylNRC(O)CH2—, —C1-C6alkyl(OCH2CH2)1-6NRC(O)CH2—, —C(O)C1-C6alkyl-NRC(O)C1-C6alkyl-, —N═CR-phenyl-O—C1-C6alkyl-, —N═CR-phenyl-O—C1-C6alkyl-C(O)—, —C(O)—C1-C6alkyl(OCH2CH2)1-6NRC(O)—, —C(O)C1-C6alkyl-phenyl(NR—C(O)C1-C6alkyl)1-4-, —C(O)C1-C6alkyl(OCH2CH2)1-6—NRC(O)C1-C6alkyl-, —C1-C6alkyl-, —S—, —C(O)—CH(NR—C(O)C1-C6alkyl)-C1-C6alkyl- and (—CH2—CH2—O—)1-20;
• LB2 is AA0-12, wherein AA is a natural amino acid or a non-natural amino acid;
• LB3 is p-aminobenzoic acid, p-aminobenzyloxycarbonyl, —C(O)(CH2)0-50C(O)— or absent,
• LC is absent or is independently selected from the group consisting of —C1-C6alkylene-, —NRC3-C8-heterocyclylNR—, —NRC3-C8-carbocyclylNR—, —NRC1-C6alkylNR—, —NRC1-C6alkylene-, —S—, —NR—, —NRNR—, —O(CR2)1-4S—S(CR2)1-4N(R)—, —NRC1-C6-alkylenephenyleneNR—, —NRC1-C6alkylenephenyleneSO2NR—, —OC1-C6alkylS-SC1-C6alkylC(COOR)NR—, —NRC(COOR)C1-C6alkylS-SC1-C6alkylO—,
• wherein
• XA is CR or N,
• XB is CH, CR(C(R)2)1-3NR, CR(C(R)2)1-3O, CR(C(R)2)1-3C(O)NR, CR—(C(R)2)1-3C(O)NRNR, CR(C(R)2)1-3 SO2NR, CR(C(R)2)1-3 NRNR, CR(C(R)2)1-3 NRC(O) or N,
• each XC is R;
• each XD is —(CH2)1-5—, or is absent;
• XE is O, S, C(R)2, C(R)(C(R)2)1-3—NR2 or NR, and
• each XF is (C(R)2)1-3—NR or C(R)2—(C(R)2)1-3—O.

A compound of Formula (IIB):

• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• F1 and F2 are each independently selected from ring systems A, B, C and D:
• where:
• each R is independently selected from the group consisting of H, —C1-C20 alkyl, —C1-C8 alkenyl, —C1-C8 alkynyl, halo, deuterium, hydroxyl, alkoxy, —NH2, —NH(C1-C8 alkyl), —N(C1-C8 alkyl)2, —NO2, —C8-C14 aryl and —C8-C14 heteroaryl, wherein two or more R optionally join to form a ring or rings, and wherein said —C8-C14 aryl and —C8-C14 heteroaryl are optionally substituted with 1 to 5 substituents independently selected from —C1-C10 alkyl, —C1-C10 alkoxy, -halo, —C1-C10 alkylthio, -trifluoromethyl, —NH2, —NH(C1-C8 alkyl), —N(C1-C8 alkyl)2, —C1-C10 alkyl-N(C1-C8 alkyl)2, —C1-C3 alkylthio, —NO2 or —C1-C10 heterocyclyl, for each ring system in which R appears;
• each V1 is independently a bond, O, N(R) or S, for each ring system in which V1 appears;
• each V2 is independently O, N(R) or S, for each ring system in which V2 appears;
• W1 and W2 are each independently H, —C1-C5 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 W1 and W2 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, —C1-C8 alkyl-RA—C(O)RA, —C(S)RA, —C(O)ORA, —S(O)2ORA, —C(O)N(RA)2, —C(S)N(RA)2, glycosyl, —NO2, —PO(ORA)2, an amino acid and a peptide for each ring system in which Y appears, wherein each RA is independently selected from the group consisting of H, —C1-C20 alkyl, —C1-C8 heteroalkyl, —C6-C14 aryl, aralkyl, —C1-C10 heterocyclyl, —C1-C8 carbocyclyl and —C1-C20 alkylN(R)2, wherein said —C1-C20 alkyl, —C1-C8 heteroalkyl, —C8-C14 aryl, aralkyl, —C1-C10 heterocyclyl, —C3-C8 carbocyclyl and —C1-C20 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, —C1-C8 alkyl, —C1-C8 heteroalkyl, —C8-C14 aryl, -aralkyl, —C1-C10 heterocyclyl, —C1-C8 carbocyclyl, —C(O)OC1-C8 alkyl, —C(O)N(C1-C8 alkyl)2, —C(O)OH, —C(O)NHNH2 and —C(O)-halo, and wherein said C1-C8 alkyl, —C1-C8 heteroalkyl, —C8-C14 aryl, -aralkyl, —C1-C10 heterocyclyl, —C1-C8 carbocyclyl, —C(O)OC1-C8 alkyl, —C(O)N(C1-C8 alkyl)2, —C(O)OH, —C(O)NHNH2 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;
• L1 and L2 are each independently selected from a direct bond
• T is:
• —C(A1)X1-T2-X1C(B1)—, where T2 is:
• wherein each X1 is independently a bond, —NRE—, —O— or —S—, wherein A1 and B1 are each independently ═O or ═S, wherein R1, R2, R3, and R4 are each independently RE, or R1 and R2 form a ring system, or
• R3 and R4 form a ring system, or both R1 and R2, and R3 and R4 each independently form ring systems, or R1 and R3 form a ring system, or R2 and R4 form a ring system, or both R1 and R3, and R2 and R4 each independently form ring systems, where the ring systems are independently selected from —C1-C10 heterocyclyl or —C3-C8 carbocyclycl, or R1, R2, R3 and R4 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 —C1-C10 heterocyclo and —C3-C8 carbocyclo, where said —C1-C10 heterocyclo and —C3-C8 carbocyclo are substituted with one member of the group selected from N(RE)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 RE is independently selected from the group consisting of H, —C1-C8 alkyl, —C1-C8 heteroalkyl, -aryl, -aralkyl, —C1-C10 heterocyclyl, —C3-C8 carbocyclyl, —C(O)OC1-C8 alkyl, —C(O)N(C1-C8 alkyl)2, and —C(O)-halo, and wherein each RE is optionally substituted with 1 to 3 substitutents independently selected from R;
• L is LA-LB-(LC)1-3 where an LC is bond to T2;
• LA is selected from -halo, —N(R)2, —CON(R)2, —S-aryl optionally substituted with —NO2 or —CONR2, —S-heteroaryl optionally substituted with —NO2, alkyl-SO2-heteroaryl, arylSO2-heteroaryl-,
• LB is LB1-LB2-LB3
• wherein LB1 is absent or is one or more components selected from the group consisting of —C(O)—, —C(S)—, —C(O)NR—, —C(O)NRC1-C6alkyl-, —C1-C6alkyl(OCH2CH2)1-6—, —C(O)C1-C6alkylNRC(O)—, —C(O)C1-C6alkyl(OCH2CH2)1-6—, —C1-C6alkyl(OCH2CH2)1-6—C(O)—, —C1-C6alkyl-S—S—C1-C6alkylNRC(O)CH2—, —C1-C6alkyl(OCH2CH2)1-6NRC(O)CH2—, —C(O)C1-C6alkyl-NRC(O)C1-C6alkyl-, —N═CR-phenyl-O—C1-C6alkyl-, —N═CR-phenyl-O—C1-C6alkyl-C(O)—, —C(O)—C1-C6alkyl(OCH2CH2)1-6NRC(O)—, —C(O)C1-C6alkyl-phenyl(NR—C(O)C1-C6alkyl)1-4-, —C(O)C1-C6alkyl(OCH2CH2)1-6—NRC(O)C1-C6alkyl-, —C1-C6alkyl-, —S—, —C(O)—CH(NR—C(O)C1-C6alkyl)-C1-C6alkyl- and (—CH2—CH2—O—)1-20;
• LB2 is AA0-12, wherein AA is a natural amino acid or a non-natural amino acid;
• LB3 is p-aminobenzoic acid, p-aminobenzyloxycarbonyl, —C(O)(CH2)0-50C(O)— or absent;
• LC is absent or is independently selected from the group consisting of —C1-C6alkylene-, —NRC3-C8-heterocyclylNR—, —NRC3-C8-carbocyclylNR—, —NRC1-C6alkylNR—, —NRC1-C6alkylene-, —S—, —NR—, —NRNR—, —O(CR2)1-4S—S(CR2)1-4N(R)—, —NRC1-C6-alkylenephenyleneNR—, —NRC1-C6alkylenephenyleneSO2NR—, —OC1-C6alkylS-SC1-C6alkylC(COOR)NR—, —NRC(COOR)C1-C6alkylS-SC1-C6alkylO—,
• wherein
• XA is CR or N,
• XB is CH, CR(C(R)2)1-3NR, CR(C(R)2)1-3O, CR(C(R)2)1-3C(O)NR, CR—(C(R)2)1-3C(O)NRNR, CR(C(R)2)1-3SO2NR, CR(C(R)2)1-3NRNR, CR(C(R)2)1-3NRC(O) or N;
• each XC is R;
• each XC is —(CH2)1-5—, or is absent;
• XE is O, S, C(R)2, C(R)(C(R)2)1-3—NR2 or NR, and
• each XF is (C(R)2)1-3—NR or C(R)2—(C(R)2)1-3—O.

A compound of Formula (IIIB):

• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• AB is an antibody;
• F1 and F2 are each independently selected from ring systems A, B, C and D:
• where:
• each R is independently selected from the group consisting of H, —C1-C20 alkyl, —C1-C8 alkenyl, —C1-C8 alkynyl, halo, deuterium, hydroxyl, alkoxy, —NH2, —NH(C1-C8 alkyl), —N(C1-C8 alkyl)2, —NO2, —C8-C14 aryl and —C8-C14 heteroaryl, or wherein two or more R optionally join to form a ring or rings, and wherein said —C8-C14 aryl and —C8-C14 heteroaryl are optionally substituted with 1 to 5 substituents independently selected from —C1-C10 alkyl, —C1-C10 alkoxy, -halo, —C1-C10 alkylthio, -trifluoromethyl, —NH2, —NH(C1-C8 alkyl), —N(C1-C8 alkyl)2, —C1-C10 alkyl-N(C1-C8 alkyl)2, —C1-C3 alkylthio, —NO2 or —C1-C10 heterocyclyl, for each ring system in which R appears;
• each V1 is independently a bond, O, N(R) or S, for each ring system in which V1 appears;
• each V2 is independently O, N(R) or S, for each ring system in which V2 appears;
• W1 and W2 are each independently H, —C1-C5 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 W1 and W2 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, —C1-C6alkyl-RA—C(O)RA, —C(S)RA, —C(O)ORA, —S(O)2ORA, —C(O)N(RA)2, —C(S)N(RA)2, glycosyl, —NO, —PO(ORA)2, an amino acid and a peptide for each ring system in which Y appears, wherein each RA is independently selected from the group consisting of H, —C1-C20 alkyl, —C1-C8 heteroalkyl, —C8-C14 aryl, aralkyl, —C1-C10 heterocyclyl, —C3-C8 carbocyclyl and —C1-C20 alkylN(R)2, wherein said —C1-C20 alkyl, —C1-C8 heteroalkyl, —C8-C14 aryl, aralkyl, —C1-C10 heterocyclyl, —C3-C8 carbocyclyl and —C1-C20 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, —C1-C8 alkyl, —C1-C8 heteroalkyl, —C8-C14 aryl, -aralkyl, —C1-C10 heterocyclyl, —C1-C8 carbocyclyl, —C(O)OC1-C8 alkyl, —C(O)N(C1-C8 alkyl)2, —C(O)OH, —C(O)NHNH2 and —C(O)-halo, and wherein said C1-C8 alkyl, —C1-C8 heteroalkyl, —C6-C14 aryl, -aralkyl, —C1-C10 heterocyclyl, —C3-C8 carbocyclyl, —C(O)OC1-C8 alkyl, —C(O)N(C1-C8 alkyl)2, —C(O)OH, —C(O)NHNH2 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;
• L1 and L2 are each independently selected from a direct bond
• T is:
• —C(A1)X1-T2-X1C(B1)—, where T2 is:
• wherein each X1 is independently a bond, —NRE—, —O— or —S—, wherein A1 and B1 are each independently ═O or ═S, wherein R1, R2, R3, and R4 are each independently RE, or R1 and R2 form a ring system, or
• R3 and R4 form a ring system, or both R1 and R2, and R3 and R4 each independently form ring systems, or R1 and R3 form a ring system, or R2 and R4 form a ring system, or both R1 and R3, and R2 and R4 each independently form ring systems, where the ring systems are independently selected from —C1-C10 heterocyclyl or —C3-C8 carbocyclycl, or R1, R2, R3 and R4 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 —C1-C10 heterocyclo and —C3-C8 carbocyclo, where said —C1-C10 heterocyclo and —C3-C8 carbocyclo are substituted with one member of the group selected from N(RE)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 RE is independently selected from the group consisting of H, —C1-C8 alkyl, —C1-C8 heteroalkyl, -aryl, -aralkyl, —C1-C10 heterocyclyl, —C3-C8 carbocyclyl, —C(O)OC1-C8 alkyl, —C(O)N(C1-C8 alkyl)2, and —C(O)-halo, and wherein each RE is optionally substituted with 1 to 3 substitutents independently selected from R;
• L is LA-LB-(LC)1-3 wherein an LC is bound to T2;
• LA is selected from:
• a bond to AB, —NR-(bond to AB), -heteroaryl-(bond to AB),
• LB is LB1-LB2-LB3
• wherein LB1 is absent or is one or more components selected from the group consisting of —C(O)—, —C(S)—, —C(O)NR—, —C(O)C1-C6alkyl-, —C(O)NRC1-C6alkyl-, —C1-C6alkyl(OCH2CH2)1-6—, —C(O)C1-C6alkylNRC(O)—, —C(O)C1-C6alkyl(OCH2CH2)1-6—, —C1-C6alkyl(OCH2CH2)1-6—C(O)—, —C1-C6alkyl-S—S—C1-C6alkylNRC(O)CH2—, —C1-C6alkyl(OCH2CH2)1-6NRC(O)CH2—, —C(O)C1-C6alkyl-NRC(O)C1-6alkyl-, —N═CR-phenyl-O—C1-C6alkyl-, —N═CR-phenyl-O—C1-C6alkyl-C(O)—, —C(O)—C1-C6alkyl(OCH2CH2)1-6NRC(O)—, —C(O)C1-C6alkyl-phenyl(NR—C(O)C1-C6alkyl)1-4-, —C(O)C1-C6alkyl(OCH2CH2)1-6—NRC(O)C1-C6alkyl-, —C1-C6alkyl-, —S—, —C(O)—CH(NR—C(O)C1-C6alkyl)-C1-C6alkyl- and (—CH2—CH2—O—)1-20;
• LB2 is AA0-12, wherein AA is a natural amino acid or a non-natural amino acid;
• LB3 is p-aminobenzoic acid, p-aminobenzyloxycarbonyl, —C(O)(CH2)0-50C(O)— or absent;
• LC is absent or is independently selected from the group consisting of —C1-C6alkylene-, —NRC3-C8-heterocyclylNR—, —NRC3-C8-carbocyclylNR—, —NRC1-C6alkylNR—, —NRC1-C6alkylene-, —S—, —NR—, —NRNR—, —O(CR2)1-4S—S(CR2)1-4N(R)—, —NRC1-C6-alkylenephenyleneNR—, —NRC1-C6alkylenephenyleneSO2NR—, —OC1-C6alkylS-SC1-C6alkylC(COOR)NR—, —NRC(COOR)C1-C6alkylS-SC1-C6alkylO—,
• wherein
• XA is CR or N,
• XB is CH, CR(C(R)2)1-3NR, CR(C(R)2)1-3O, CR(C(R)2)1-3C(O)NR, CR—(C(R)2)1-3C(O)NRNR, CR(C(R)2)1-3SO2NR, CR(C(R)2)1-3NRNR, CR(C(R)2)1-3NRC(O) or N;
• each XC is R;
• each XC is —(CH2)1-5—, or is absent;
• XE is O, S, C(R)2, C(R)(C(R)2)1-3—NR2 or NR, and
• each XF is (C(R)2)1-3—NR or C(R)2—(C(R)2)1-3—O.

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 R7 is independently H or —C1-C20 alkyl,
• R8 is —C1-C20 alkyl, —C6-C14 aryl or —C6-C14 heteroaryl,
• Pg is H, acyl, PO3H2, a carbohydrate, an amino acid or a peptide,
• n=0-20, and
• m=0-20.