or where a R 7 , R 8 , R 9 , or R 10 is attached to a G or G′ that is N, such R 7 , R 8 , R 9 , or R 10 is absent; the dotted lines in ring C of formula (Ib) indicate the optional presence of a C1-C2, C2-C3, or C2-R 11 double bond; R 11 is H, ═O, ═CH 2 , ═CH(C 1 -C 5 alkyl), CH═CH(CH 2 ) 1-5 X 2 , C≡C(CH 2 ) 1-5 X 2 , C 1 -C 5 alkyl, OH, O(C 1 -C 5 alkyl), cyano, NO 2 , F, Cl, Br, O(CH 2 CH 2 O) 1-8 (C 1-3 alkyl), (CH 2 ) 0-5 X 2 , 4- to 7-membered cycloalkyl, or heterocycloalkyl unsubstituted or substituted with (CH 2 ) 0-5 X 2 , O(CH 2 ) 2-5 X 2 , 3- to 7-membered cycloalkyl or heterocycloalkyl unsubstituted or substituted with (CH 2 ) 0-5 X 2 or O(CH 2 ) 2-5 X 2 , 5- to 6-membered aryl or heteroaryl unsubstituted or substituted with (CH 2 ) 0-5 X 2 or O(CH 2 ) 2-5 X 2 ; R 11′ is absent if a C1-C2, C2-C3, or C2-R 11 double bond is present and otherwise is H; each X 2 is independently H, F, Cl, Br, OH, O(C 1 -C 3 alkyl), O(C 1 -C 3 alkylene), CO 2 H, N 3 , CN, NO 2 , CO 2 (C 1 -C 3 alkyl), NH 2 , NH(C 1 -C 5 alkyl), N(C 1 -C 5 alkyl) 2 , SH, CHO, N(CH 2 CH 2 ) 2 N(C 1 -C 3 alkyl), NHNH 2 , or C(═O)NHNH 2 ; each Y is independently CH 2 , C═O, or CHR 12 ; wherein each R 12 is independently F, Cl, Br, or C 1 -C 3 alkyl; and Y′ and Y″ are independently CH 2 , C═O, or CHR 12 ; wherein each R 12 is independently F, Cl, Br, or C 1 -C 3 alkyl, with the proviso that at least one of Y′ and Y″ is present; wherein a heterocycloalkyl group has 1 to 2 carbons replaced with a heteroatom independently selected from N, O, or S, where the N and S optionally may be oxidized and the N optionally may be quaternized; and wherein a heteroaryl group has 1 to 4 heteroatoms independently selected from N, O, or S, where the N and S optionally may be oxidized and the N optionally may be quaternized; or a pharmaceutically acceptable salt thereof.
and X 3 is H, OH, OMe, Me, CH 2 OH, O(allyl), Cl, or CO 2 Me.
R 11′ is absent if a C1-C2, C2-C3, or C2-R 11 double bond is present and otherwise is H; X 3 is H, OH, OMe, Me, CH 2 OH, O(allyl), Cl, or CO 2 Me; at least one of the double lines in a diazepine ring system is a double bond; R 5 is H if the double line to the N to which it is attached is a single bond and absent if the double line is a double bond; and R 6 is H if the double line to the C to which it is attached is a single bond and absent if the double line is a double bond.
wherein one G′ is N and the others are C; at least one of the double lines in a diazepine ring system is a double bond; R 5 is H if the double line to the N to which it is attached is a single bond and absent if the double line is a double bond; and R 6 is H if the double line to the C to which it is attached is a single bond and absent if the double line is a double bond.
or where a R 7 , R 8 , R 9 , or R 10 is attached to a G or G′ that is N, such R 7 , R 8 , R 9 , or R 10 is absent; the dotted lines in ring C of formula (Ib) indicate the optional presence of a C1-C2, C2-C3, or C2-R 11 double bond; R 11 is H, ═O, ═CH 2 , ═CH(C 1 -C 5 alkyl), CH═CH(CH 2 ) 1-5 X 2 , C≡C(CH 2 ) 1-5 X 2 , C 1 -C 5 alkyl, OH, O(C 1 -C 5 alkyl), cyano, NO 2 , F, Cl, Br, O(CH 2 CH 2 O) 1-8 (C 1-3 alkyl), (CH 2 ) 0-5 X 2 , 4- to 7-membered cycloalkyl, or heterocycloalkyl unsubstituted or substituted with (CH 2 ) 0-5 X 2 , O(CH 2 ) 2-5 X 2 , 3- to 7-membered cycloalkyl or heterocycloalkyl unsubstituted or substituted with (CH 2 ) 0-5 X 2 or O(CH 2 ) 2-5 X 2 , 5- to 6-membered aryl or heteroaryl unsubstituted or substituted with (CH 2 ) 0-5 X 2 or O(CH 2 ) 2-5 X 2 ; R 11 is absent if a C1-C2, C2-C3, or C2-R 11 double bond is present and otherwise is H; each X 2 is independently H, F, Cl, Br, OH, O(C 1 -C 3 alkyl), O(C 1 -C 3 alkylene), CO 2 H, N 3 , CN, NO 2 , CO 2 (C 1 -C 3 alkyl), NH 2 , NH(C 1 -C 5 alkyl), N(C 1 -C 5 alkyl) 2 , SH, CHO, N(CH 2 CH 2 ) 2 N(C 1 -C 3 alkyl), NHNH 2 , or C(═O)NHNH 2 ; X 3 is H, OH, OMe, Me, or CH 2 OH; each R 50 is independently H, O(C 1 -C 3 alkyl), O(C 2 -C 3 alkylene), O(C 2 -C 3 alkynyl), F, Cl, Br, or CN; each Y is independently CH 2 , C═O, or CHR 12 ; wherein each R 12 is independently F, Cl, Br, or C 1 -C 3 alkyl; and Y′ and Y″ are independently CH 2 , C═O, or CHR 12 ; wherein each R 12 is independently F, Cl, Br, or C 1 -C 3 alkyl, with the proviso that at least one of Y′ and Y″ is present; wherein a heterocycloalkyl group has 1 to 2 carbons replaced with a heteroatom independently selected from N, O, or S, where the N and S optionally may be oxidized and the N optionally may be quaternized; and wherein a heteroaryl group has 1 to 4 heteroatoms independently selected from N, O, or S, where the N and S optionally may be oxidized and the N optionally may be quaternized.
wherein each R 9 is independently H, C 1 -C 3 alkyl, O(CH 2 CH 2 O) 1-4 H, (CH 2 CH 2 O) 1-4 (C1-C 3 alkyl), OH, Cl, F, or Br; R 5 is H if the double line to the N to which it is bonded is a single bond and absent if the double line is a double bond; and R 6 is H if the double line to the C to which it is bonded is a single bond and absent if the double line is a double bond.
wherein each R 9 is independently H, C 1 -C 3 alkyl, O(CH 2 CH 2 O) 1-4 H, (CH 2 CH 2 O) 1-4 (C1-C 3 alkyl), OH, Cl, F, or Br; X 3 is H, OH, OMe, Me, CH 2 OH, O(allyl), Cl, or CO 2 Me; R 5 is H if the double line to the N to which it is bonded is a single bond and absent if the double line is a double bond; and R 6 is H if the double line to the C to which it is bonded is a single bond and absent if the double line is a double bond.
wherein X 3 is H, OH, OMe, Me, CH 2 OH, O(allyl), Cl, or CO 2 Me; at least one of the double lines in a diazepine ring system is a double bond; R 5 is H if the double line to the N to which it is attached is a single bond and absent if the double line is a double bond; R 6 is H if the double line to the C to which it is attached is a single bond and absent if the double line is a double bond; and R 9 is H, O(CH 2 CH 2 O) 1-4 H, (CH 2 CH 2 O) 1-4 (C1-C 3 alkyl), OH, Cl, F, or Br.
or where a R 7 , R 8 , R 9 , or R 10 is attached to a G or G′ that is N, such R 7 , R 8 , R 9 , or R 10 is absent; the dotted lines in ring C of formula (Ib) indicate the optional presence of a C1-C2, C2-C3, or C2-R 11 double bond; R 11 is H, ═O, ═CH 2 , ═CH(C 1 -C 5 alkyl), CH═CH(CH 2 ) 1-5 X 2 , C≡C(CH 2 ) 1-5 X 2 , C 1 -C 5 alkyl, OH, O(C 1 -C 5 alkyl), cyano, NO 2 , F, Cl, Br, O(CH 2 CH 2 O) 1-8 (C 1-3 alkyl), (CH 2 ) 0-5 X 2 , 4- to 7-membered cycloalkyl, or heterocycloalkyl unsubstituted or substituted with (CH 2 ) 0-5 X 2 , O(CH 2 ) 2-5 X 2 , 3- to 7-membered cycloalkyl or heterocycloalkyl unsubstituted or substituted with (CH 2 ) 0-5 X 2 or O(CH 2 ) 2-5 X 2 , 5- to 6-membered aryl or heteroaryl unsubstituted or substituted with (CH 2 ) 0-5 X 2 or O(CH 2 ) 2-5 X 2 ; R 11′ is absent if a C1-C2, C2-C3, or C2-R 11 double bond is present and otherwise is H; each R 50 is independently H, O(C 1 -C 3 alkyl), O(C 2 -C 3 alkylene), O(C 2 -C 3 alkynyl), F, Cl, Br, or CN; each X 2 is independently H, F, Cl, Br, OH, O(C 1 -C 3 alkyl), O(C 1 -C 3 alkylene), CO 2 H, N 3 , CN, NO 2 , CO 2 (C 1 -C 3 alkyl), NH 2 , NH(C 1 -C 5 alkyl), N(C 1 -C 5 alkyl) 2 , SH, CHO, N(CH 2 CH 2 ) 2 N(C 1 -C 3 alkyl), NHNH 2 , or C(═O)NHNH 2 ; each Y is independently CH 2 , C═O, or CHR 12 ; wherein each R 12 is independently F, Cl, Br, or C 1 -C 3 alkyl; and Y′ and Y″ are independently CH 2 , C═O, or CHR 12 ; wherein each R 12 is independently F, Cl, Br, or C 1 -C 3 alkyl, with the proviso that at least one of Y′ and Y″ is present; wherein a heterocycloalkyl group has 1 to 2 carbons replaced with a heteroatom independently selected from N, O, or S, where the N and S optionally may be oxidized and the N optionally may be quatemized; and wherein a heteroaryl group has 1 to 4 heteroatoms independently selected from from N, O, or S, where the N and S optionally may be oxidized and the N optionally may be quaternized.
wherein X 3 is H, OH, OMe, Me, CH 2 OH, O(allyl), Cl, or CO 2 Me; at least one of the double lines in a diazepine ring system is a double bond; R 5 is H if the double line to the N to which it is attached is a single bond and absent if the double line is a double bond; R 6 is H if the double line to the C to which it is attached is a single bond and absent if the double line is a double bond; and R 9 is H, OH, OMe, C 1 -C 3 alkyl, O(CH 2 CH 2 O) 1-8 Me, F, Cl, or Br.
26. A conjugate according to claim 20 , wherein the antibody is an anti-fucosyl GM1 or anti-mesothelin antibody.
27. A pharmaceutical formulation comprising a conjugate according to claim 20 and a pharmaceutically acceptable excipient.
28. A method of treating a cancer in a subject suffering from such cancer, comprising administering to the subject a therapeutically effective amount of a conjugate according to claim 20 , wherein the cancer is lung or gastric cancer.
29. A compound according to claim 1 , wherein each R 2 is Me and each R 3 , R 4 , R 7 , R 8 , and R 10 is H.
32. A compound according to claim 12 , wherein each R 2 is Me and each R 3 , R 4 , R 7 , R 8 , and R 10 is H.
35. A compound according to claim 12 , wherein the self-immolating group T is a p-aminobenzyl oxycarbonyl group.
38. A conjugate according to claim 20 , wherein each R 2 is Me and each R 3 , R 4 , R 7 , R 8 , and R 10 is H.
41. A conjugate according to claim 20 , wherein the self-immolating group T is ap-aminobenzyl oxycarbonyl group.