PRODRUG CONTAINING SELF-CLEAVABLE LINKER Russian patent published in 2018 - IPC A61K47/50 

FIELD: medicine; pharmaceuticals.

SUBSTANCE: present invention relates to a prodrug containing a drug conjugate-linker D-L, where D is a nitrogen-containing monoclonal or polyclonal antibody, or its fragment, or the product of its merger; L is a biologically inactive linker fragment L¹, represented by the structural formula (I)

,

where the dotted line shows the attachment to the nitrogen of a monoclonal or polyclonal antibody, or its fragment, or its fusion product through the formation of an amide bond; X is C (R⁴R^4a), C(R⁴R^4a)-C(R⁵R^5a) or C(R⁵R^5a)-C(R⁴R^4a); X¹ represents C; X² represents C(R⁷, R^7a) or C(R⁷, R^7a)-C(R⁸, R^8a); X³ represents O; R¹, R^1a, R², R^2a, R³, R^3a, R⁴, R^4a, R⁵, R^5a, R⁷, R^7a, R⁸, R^8a is independently selected from the group consisting of H and C_1-4 alkyl; if necessary, one or more pairs of R¹/R⁴ or R²/R³ together with the atoms to which they are attached, combine to form ring A; if necessary R³/R^3a together with the nitrogen atom to which they are attached, combine to form a 5- or 6-membered heterocycle; A is a C₆ cycloalkyl and where L¹ substituted by one group L²-Z under the condition that the hydrogen indicated by the symbol * in the formula (I) cannot be replaced by a substituent, where is l² represents a single chemical bond or an alkyl chain having from 1 to 20 carbon atoms, which is optionally interrupted by one or more groups independently selected from -O- and C (O)N(R^3aa); optionally substituted with one or more groups independently selected from OH and C(O)N(R^3aaR^3aaa), and in which r^3aa, R^3aaa independently selected from the group consisting of H and C_1-4 alkyl; and where L² attached to Z through an end group selected from

and

and Z is a hydrogel.

EFFECT: invention relates to a prodrug comprising a drug-linker conjugate D-L.

9 cl, 3 dwg, 52 ex