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1. A conjugate comprising: a compound and a cell binding agent (CBA), wherein the compound comprises a linking group which covalently links the compound to the CBA, and wherein said compound is represented by any one of the following formulas: or a pharmaceutically acceptable salt thereof, wherein:
the double line between N and C represents a single bond or a double bond, provided that when it is a double bond X is absent and Y is —H, or a linear or branched alkyl having 1 to 4 carbon atoms, and when it is a single bond, X is —H, the linking group, or an amine protecting moiety;Y is —H or a leaving group selected from the group consisting of —OR, —OCOR′, —OCOOR′, —OCONR′R″, —NR′R″, —NR′COR″, —NR′NR′R″, an optionally substituted 5- or 6-membered nitrogen-containing heterocycle, —NR′(C═NH)NR′R″, an amino acid, and a peptide represented by —NRCOP′, wherein P′ is an amino acid or a polypeptide containing between 2 to 20 amino acid units, —SR, —SOR′, —SO2M, —SO3M, —OSO3M, halogen, cyano and an azido; or,Y is HSO3, HSO2 or a salt of HSO3−, SO32− or HSO2− formed with a cation, H2S2O5 or a salt of S2O52− formed with a cation, PO3SH3, PO2S2H2, POS3H2, PS4H2 or a salt of PO3S3−, PO2S23−, POS33− or PS43− formed with a cation, (RiO)2PS(ORi), RiS—, RiSO, RiSO2, RiSO3, HS2O3 or a salt of S2O32− formed with a cation, HS2O4 or a salt of S2O42− formed with a cation, P(═S)(ORk′)(S)(OH) or a salt thereof formed with a cation, Rk′(═O)NOH or a salt formed with a cation, HOCH2SO2− or a salt of HOCH2SO2− formed with a cation or a mixture thereof, wherein Ri is a linear or branched alkyl having 1 to 10 carbon atoms and is substituted with at least one substituent selected from the group consisting of —N(Rj)2, —CO2H, —SO3H, and —PO3H; Ri can be further optionally substituted with a substituent for an alkyl described herein; Rj is a linear or branched alkyl having 1 to 6 carbon atoms; Rk′ is a linear, branched or cyclic alkyl, alkenyl or alkynyl having 1 to 10 carbon atoms, aryl, heterocyclyl or heteroaryl;M is —H or a cation;R, for each occurrence, is independently selected from the group consisting of —H, an optionally substituted linear, branched or cyclic alkyl, alkenyl or alkynyl having from 1 to 10 carbon atoms, a polyethylene glycol unit —(CH2CH2O)n—Rc, an optionally substituted aryl having 6 to 18 carbon atoms, an optionally substituted 5- to 18-membered heteroaryl ring containing one or more heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur, and an optionally substituted 3- to 18-membered heterocyclic ring containing 1 to 6 heteroatoms independently selected from the group consisting of O, S, N and P;R′ and R″ are each independently selected from the group consisting of —H, —OH, —OR, —NHR, —NR2, —COR, an optionally substituted linear, branched or cyclic alkyl, alkenyl or alkynyl having from 1 to 10 carbon atoms, a polyethylene glycol unit —(CH2CH2O)n—Rc, and an optionally substituted 3- to 18-membered heterocyclic ring having 1 to 6 heteroatoms independently selected from the group consisting of O, S, N and P;Rc is —H or an optionally substituted linear or branched alkyl having 1 to 4 carbon atoms, or the linking group;n is an integer from 1 to 24;W is C═O;X′ is selected from the group consisting of —H, an amine-protecting group, the linking group, an optionally substituted linear, branched or cyclic alkyl, alkenyl or alkynyl having from 1 to 10 carbon atoms, a polyethylene glycol unit —(CH2CH2O)n—Rc, an optionally substituted aryl having 6 to 18 carbon atoms, an optionally substituted 5- to 18-membered heteroaryl ring containing one or more heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an optionally substituted 3- to 18-membered heterocyclic ring containing 1 to 6 heteroatoms independently selected from the group consisting of O, S, N and P;Y′ is selected from the group consisting of —H, an oxo group, the linking group, an optionally substituted linear, branched or cyclic alkyl, alkenyl or alkynyl having from 1 to 10 carbon atoms, an optionally substituted 6- to 18-membered aryl, an optionally substituted 5- to 18-membered heteroaryl ring containing one or more heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur, and an optionally substituted 3 to 18-membered heterocyclic ring having 1 to 6 heteroatoms;R1, R2, R3, R4, R1′, R2′, R3′ and R4′ are each independently selected from the group consisting of —H, an optionally substituted linear, branched or cyclic alkyl, alkenyl or alkynyl having from 1 to 10 carbon atoms, a polyethylene glycol unit —(OCH2CH2)n—Rc, halogen, —NH(C═NH)NH2, —OR, —NR′R″, —NO2, —NCO, —NR′COR″, —SR, —SOR′, —SO2R′, —SO3−M+, —OSO3−M+, —SO2NR′R″, cyano, azido, —COR′, —OCOR′, —OCONR′R″ and the linking group;R6 is —H, —R, —OR, —SR, —NR′R″, —NO2, halogen or the linking group;Z and Z′ are —CH2—A and A′ are the same or different, and are independently selected from the group consisting of —O—, —C(═O)—, —CRR′O—, —CRR′—, —S—, —CRR′S—, —N(R5)— and —CRR′N(R5)—,R5 for each occurrence is independently —H or an optionally substituted linear or branched alkyl having 1 to 10 carbon atoms;D and D′ are the same or different, and are independently absent or selected from the group consisting of an optionally substituted linear, branched or cyclic alkyl, alkenyl or alkynyl having 1 to 10 carbon atoms, an amino acid, a peptide bearing 2 to 6 amino acids, and a polyethylene glycol unit (—OCH2CH2)n—;L is absent, the linking group, a polyethylene glycol unit (—OCH2CH2)n—, a linear, branched or cyclic alkyl or alkenyl having 1 to 10 carbon atoms, a phenyl group, a 3- to 18-membered heterocyclic ring or a 5- to 18-membered heteroaryl ring having 1 to 6 heteroatoms independently selected from the group consisting of O, S, N and P, wherein the alkyl or alkenyl is optionally substituted with the linking group; phenyl or heterocyclic or heteroaryl ring can be optionally substituted, wherein the substituent can be the linking group; wherein the optional substituent described above is a linear, branched or cyclic alkyl, alkenyl or alkynyl having from 1 to 10 carbon atoms, aryl, heteroaryl, heterocycyclyl, halogen, —NH(C═NH)NH2, —OR100, NR101R102, —NO2, —NR101COR102, —SR100, —SOR101, —SO2R101, —SO3M, —OSO3M, —SO2NR101R102, cyano, an azido, —COR101, —OCOR101, —OCONR101R102 and a polyethylene glycol unit (—OCH2CH2)nR101 wherein M is H or a cation; R100, R101, R102, and R103 are each independently selected from the group consisting of H, linear, branched or cyclic alkyl, alkenyl or alkynyl having from 1 to 10 carbon atoms, a polyethylene glycol unit (—OCH2CH2)n—R104, an aryl having from 6 to 10 carbon atoms, a heterocyclic ring having from 3 to 10 carbon atoms and a heteroaryl having 5 to 10 carbon atoms; n is an integer from 1 to 24, and R104 is H or a linear or branched alkyl having 1 to 4 carbon atoms, wherein the alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclcyl in the groups represented by R100, R101, R102, R103 and R104 are optionally substituted with one or more substituents independently selected from the group consisting of halogen, —OH, —CN, —NO2 and unsubstituted linear or branched alkyl having 1 to 4 carbon atoms. |
