CYTOTOXIC BENZODIASEPINE DERIVATIVES Russian patent published in 2017 - IPC A61K47/50 C07D487/04 C07D519/00 A61P35/00 

FIELD: pharmacology.

SUBSTANCE: invention relates to a cytotoxic compound of formula

or pharmaceutically acceptable salts thereof. In the formula (IA), the double line between N and C is a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H, and when it is a single bond, X is -H and Y is -SO₃M; M is -H, Na⁺ or K⁺, A and A' are both -O-, R₆ is -OR, wherein R is a linear alkyl having from 1 to 6 carbon atoms; X' is -H, Y' is -H, L' is -W'-R^X-V-R^Y-J, wherein W' and V are the same or different and each is independently absent or selected from -O-_, -S-, -CH₂-S-, -N(R^e)-, -N(R^e)-C(=O)- and -SS-; R^x and R^y are the same or different and each is independently absent or is optionally substituted by a linear or branched alkyl having from 1 to 10 carbon atoms, optionally substituted by -SO₃H; R^e is selected from -H, linear, branched alkyl having from 1 to 10 carbon atoms, or -(CH₂-CH₂-O)_n-R^k, wherein R^k is -H, a linear, branched alkyl having from 1 to 6 carbon atoms; n is an integer from 1 to 3; and J includes a reactive group bonded thereto and is selected from -SH, -COOH and -COE, wherein -COE is an N-hydroxysuccinimide ester; L" and L"' are -H, and G is -CH-. The invention also relates to a conjugate comprising a cytotoxic compound and an antibody, to methods for cancer treatment in a mammal.

EFFECT: new compounds have been obtained that can be used as antiproliferative agents.

37 cl, 60 dwg, 10 tbl, 32 ex