CALICHEAMICIN DERIVATIVES AND THEIR ANTIBODY-DRUG CONJUGATES Russian patent published in 2020 - IPC C07H15/00 A61K47/64 

FIELD: chemistry; medicine; pharmaceuticals.

SUBSTANCE: present invention relates to novel calicheamicin derivatives (IIA), (IIIA) and (IVA), pharmaceutical derivatives containing them, pharmaceutical compositions and combinations applicable in medicine, methods of using them in treating leukaemia and inhibiting proliferation of leukaemia cells:

or pharmaceutically acceptable salts thereof, where R³ is -CH₂CH₃; X is selected from -C₂-C₈ alkyl, optionally substituted with one R¹⁰; -(C₀-C₆ alkyl)-C₃-C₁₀ carbocyclyl; -(C₀-C₆ alkyl)-6-member heterocyclyl, wherein said 6-member heterocyclyl is optionally substituted with one R¹⁰ and said 6-member heterocyclyl contains one nitrogen heteroatom; -(C₀-C₆ alkyl)-phenyl, where said phenyl is optionally substituted with one R¹⁰; and -(C₀-C₆ alkyl)-6-member heteroaryl, wherein said 6-member heteroaryl is optionally substituted with one R¹⁰ and where said 6-member heteroaryl contains one nitrogen heteroatom; where X is optionally further substituted with 1 G; R¹⁰ is -R^10a-R^10b, wherein R^10a is absent; R^10b is selected from -CO₂H; -CO₂C₁-C₄ alkyl; -NH-R¹¹; -CONH-R¹¹; -CON(C₁-C₄ alkyl)-R¹¹; -CONHNH-R¹¹; R¹¹ is -R^11a-R^11b-R^11c, where R^11a and R^11b are absent; R^11c is selected from a group consisting of -H and -C₁-C₄ alkyl; G is selected, independently for each case, from a group consisting of -NH₂, -CO₂H, -C₁-C₄ alkyl, = O and -CO₂C₁-C ₄ alkyl; L and L^R are linker fragments, AB is an antibody which binds immunospecifically to one or more antigens of the malignant cell, b equals 1–20.

EFFECT: novel calicheamicin derivatives, a pharmaceutical composition and based combinations thereof, effective for treating leukaemia.

28 cl, 50 ex, 14 tbl, 9 dwg