# US 10,870,706 B2 · Bifunctional cytotoxic agents containing the CTI pharmacophore

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- Number: US 10,870,706 B2
- Document ID: US10870706B2
- Status: Granted
- Kind: B2
- Application number: 15/070,549
- Filed: 2016-03-15
- Published: 2016-09-22
- Granted: 2020-12-22
- Earliest claimed: 2015-03-20
- Assignees: Pfizer Inc.
- Applicants: Pfizer Inc.
- Inventors: Andreas Maderna; Chakrapani Subramanyam; Lawrence N. Tumey; Zecheng Chen; Jeffrey M. Casavant
- Web page: https://patentgrep.com/patent/US10870706B2

## CPC

- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- A61K 47/65: Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
- A61K 47/6803: {Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates}
- A61K 47/6807: {the drug or compound being a sugar, nucleoside, nucleotide, nucleic acid, e.g. RNA antisense}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6863: {the tumour determinant being from stomach or intestines cancer cell}
- A61K 47/6865: {the tumour determinant being from skin, nerves or brain cancer cell}
- A61K 47/6869: {the tumour determinant being from a cell of the reproductive system: ovaria, uterus, testes, prostate}
- A61K 47/6871: {the antibody targeting an enzyme}
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- C07B 59/002: {Heterocyclic compounds}
- C07D 495/04: Ortho-condensed systems
- C07F 9/6561: containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07K 5/06052: {Val-amino acid}
- C07K 5/0815: {with the first amino acid being basic}
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- C07K 16/32: against translation products of oncogenes
- C07B 2200/05: Isotopically modified compounds, e.g. labelled
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The present invention is directed to novel bifunctional CTI-CTI and CBI-CTI dimers of the formula: F1-L1-T-L2-F2 where F1, L1, T, L2 and F2 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

### Claim 1

A compound of Formula (I):
F1L1T-L2-F2 (I)
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, —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 —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-C6 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, —C8-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 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, —C6-C14 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.

### Claim 2

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.

### Claim 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:
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.

### Claim 4

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.

### Claim 5

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.

### Claim 6 (depends on 1)

The compound of claim 1, wherein:
each R is independently selected from the group consisting of H, deuterium, —C1-C20 alkyl and —NH2;
each V1 is independently O or N(R) for each ring system in which V1 appears;
each V2 is independently O or N(R) for each ring system in which V2 appears;
W1 and W2 are each independently H, —C1-C5 alkyl, —C(O)OR, or —C(O)NR2 for each ring system in which W1 and W2 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)RA, —C(O)N(RA)2, glycosyl, —NO2, —PO(ORA)2 a cathepsins and a matrix metalloproteinase 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, —C3-C8 carbocyclyl and —C1-C20 alkylN(R)2, wherein said —C1-C20 alkyl, —C1-C8 heteroalkyl, —C3-C8 carbocyclyl and —C1-C20 alkylN(R)2 are optionally substituted with 1 to 3 substitutents independently selected from R;
L1 and L2 are each independently selected from a direct bond; and
T is:
—C(A1)X1-T2-X1C(B1)—, where T2 is:
wherein each X1 is a bond, wherein A1 and B1 are each independently ═O, wherein R1, R2, R3, and R4 are each independently H 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, and wherein D is a bond or 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 —NH2, —N(R)C(O)H or —N(R)C(O)OH.

### Claim 7 (depends on 3)

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

### Claim 8 (depends on 5)

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

### Claim 9 (depends on 2)

The compound of claim 2, 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-, and
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-, —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, and LB3 is p-aminobenzoic acid, p-aminobenzyloxycarbonyl, —C(O)(CH2)0-50C(O)— or absent; and
LC is absent.

### Claim 10 (depends on 4)

The compound of claim 4, 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, and
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-, —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, and LB3 is p-aminobenzoic acid, p-aminobenzyloxycarbonyl, —C(O)(CH2)0-50C(O)— or absent; and
LC is absent.

### Claim 11 (depends on 3)

The compound of claim 3, wherein:
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-, —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, and LB3 is p-aminobenzoic acid, p-aminobenzyloxycarbonyl, —C(O)(CH2)0-50C(O)— or absent; and
LC is absent.

### Claim 12 (depends on 5)

The compound of claim 5, wherein:
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-, —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, and LB3 is p-aminobenzoic acid, p-aminobenzyloxycarbonyl, —C(O)(CH2)0-50C(O)— or absent; and
LC is absent.

### Claim 13

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

### Claim 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.

### Claim 15

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

### Claim 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 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.

### Claim 17

A compound, or a pharmaceutically acceptable salt or solvate thereof, selected from:
where AB is an antibody.

### Claim 18 (depends on 17)

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.

### Claim 19 (depends on 1)

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