NOVEL CONJUGATES OF CC-1065 ANALOGUES AND BIFUNCTIONAL LINKERS Russian patent published in 2016 - IPC C07D471/04 A61K31/437 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to the conjugate of formula (III) or to a pharmaceutically acceptable salt thereof, where the group V² is selected from an anti-CD19 antibody, an anti-CD22 antibody, an anti-CD30 antibody, an anti-CD33 antibody, an anti-CD56 antibody, an anti-CD70 antibody, an anti-CD74 antibody, an anti-CD138 antibody, an anti-CLL-1 antibody, an anti-5T4 antibody, an anti-CD303 antibody, an anti-Tag 72 antibody, an anti-Lewis A like carbohydrate antibody, an anti-EphB3 antibody, an anti-HMW- MAA antibody, an anti-CD38 antibody, an anti-Cripto antibody, an anti-EphA2 antibody, an anti-GPNMB antibody, an anti-integrin antibody, an anti-MN antibody, an anti-Her2 antibody and an anti-PSMA antibody, or from an epitope-binding fragment; each L² is independently a linker group: ; each L is selected from structures indicated in claim 1; each V¹ is selected from valylcitrulline, valyllysine, phenylalanyllysine, alanylphenylalanyllysine, and D-alanylphenylalanyllysine; each Y is the self-eliminating spacer system which consists of 1 or more self-elimination spacers and is linked to V¹, optionally L and Z; p equals 1, z equals q; q ranges from 1 to 4; z equals a positive integer equal to or less than the total number of binding sites for Z; each Z is independently a compound selected from a group consisting of the structures given in claim 1; each Z is linked to Y by an OH group through an ω-amino amino carbonyl cyclisation spacer which is part of Y; where the spacer Y is , and where the ω-amino amino carbonyl cyclisation spacer A is selected from the structures indicated in claim 1. The invention also relates to the intermediate compound of formula (IV) and use of the conjugate of formula (III).

EFFECT: obtaining the conjugate of a DNA-alkylating agent and the system of bifunctional linkers, having anti-tumour activity.

12 cl, 7 dwg, 16 ex