BIVALENT BROMODOMAIN INHIBITORS AND ROUTES OF USE THEREOF Russian patent published in 2021 - IPC A61K31/551 A61K47/60 A61P11/00 A61P17/00 A61P19/02 A61P25/00 A61P29/00 A61P3/00 A61P3/10 A61P31/00 A61P35/00 A61P37/06 A61P39/02 A61P9/00 A61P5/00 C07D495/14 

FIELD: medicine; pharmaceuticals.

SUBSTANCE: present invention provides bivalent bromodomain BET inhibitors. In particular, the invention relates to a compound of formula (I-a) or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof, where L¹ is C_1-36 heteroalkylene containing heteroatoms independently selected from N and O, optionally containing C_3-6 heterocyclyl containing one or more heteroatoms N, and in which each carbon atom is optionally substituted with a carbonyl group (=O); L¹ is bonded to a thiophenyl ring through a group selected from a group consisting of -CH₂- and -C(=O)-; in each case, R¹, R², R³ and R⁴ is independently halogen, -CN or C_1-10 alkyl; R⁵ is -OR^5a or -N(R^5b)₂; R^5a is independently C_1-10 alkyl; in each case R^5b is independently hydrogen, C_1-10 alkyl, optionally substituted with -OH or C 3-6 heterocyclyl containing one or more heteroatoms N, where C_3-6 heterocyclyl is optionally substituted with one copy of C_1-6 alkyl; and in each case m equals 1. Certain bromodomain-containing proteins (for example, BRD4) are characterized by a primary structure of a tandem bromodomain, containing more than one bromodomain binding site (for example, BRD4 contains BD1 and BD2). Present invention also provides pharmaceutical compositions and kits containing compounds of the present invention, as well as methods of using the disclosed compounds.

Formula (I-a).

EFFECT: bivalent BET bromodomains inhibitors disclosed herein can be targeted to bromodomains through preferred polyvalent interactions and can therefore be used for treating diseases or conditions associated with bromodomain-containing proteins.

120 cl, 54 dwg