Cytotoxic benzodiazepine derivatives

摘要

The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VII). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

主权项

1. A cytotoxic compound represented by CM-Q, wherein CM is a cytotoxic moiety represented by the following formula: or a pharmaceutically acceptable salt thereof, wherein:
Q is —COORc, or —COE, wherein —COE represents a reactive ester selected from the group consisting of N-hydroxysuccinimide ester, N-hydroxy sulfosuccinimide ester, nitrophenyl ester, dinitrophenyl ester, sulfo-tetrafluorophenyl ester, and pentafluorophenyl ester;the double line between N and C represents a single bond or a double bond, provided that when the double line is a double bond, X is absent and Y is —H; and when the double line is a single bond, X is —H and Y is —SO3H or —OH;Rc is —H, a linear C1-C4 alkyl or a branched C1-C4 alkyl; and,m is an integer from 1 to 24.