BICYCLIC HETEROCYCLIC COMPOUNDS AND THEIR APPLICATIONS Russian patent published in 2024 - IPC C07D235/24 C07D403/04 C07D487/04 C07D471/04 A61K31/519 A61K31/5377 A61P35/00 

FIELD: chemistry; pharmaceuticals.

SUBSTANCE: invention is related to compounds of formula (I) having the properties of SOS1 inhibitors and their use. Compounds of formula (I), their pharmaceutically acceptable salts, solvates, hydrates, stereoisomers and tautomers having the properties of SOS1 inhibitors, as well as pharmaceutical compositions based on them, a method for inhibiting SOS1, a method for inhibiting the interaction of SOS1 and a protein of the RAS family in a cell or inhibiting the interaction SOS1 and RAC1 in a cell, a method for treating or preventing a disease, wherein the treatment or prevention of a disease is characterized by inhibition of the interaction of SOS1 and a RAS family protein or inhibition of the interaction of SOS1 and RAC1, and a method of treating or preventing cancer using them are disclosed. In the general formula (I), Q¹ represents N; Q² represents N; Q⁴ represents N; each of Q³ and Q⁵ are independently C(R^QC)₂, NR^QN, O, S or SO₂, where each R^QC is independently H, F, Cl, Br or 6-10 membered aryl, and each R^QN is independently H, C_1-6 alkyl or 6-10 membered aryl; m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; moreover, if m is equal to 0, then n is not equal to 0; R¹ is selected from the group consisting of H, C_1-6 alkyl, halogen, –CONHR^1a, -NHR^1a, –OR^1a, cyclopropyl, azetidinyl and –CN; wherein each C_1-6 alkyl and azetidinyl are optionally substituted with halogen, R^1a, -NHR^1a or –OR^1a ; where R^1a represents H, C _1-6 alkyl, cyclopropyl, 3-6 membered heterocyclyl containing 1-3 ring heteroatoms selected from the group consisting of oxygen, nitrogen, phosphorus and sulfur, or C_1-6 haloalkyl; L² is selected from the group consisting of connected –C(O)–, –C(O)O–, –C(O)NH(CH₂)_o –, –S(O)₂ –, –C(O)(CH₂) _p–, –(CH₂)_p– and –O–; where o is 0, 1 or 2; and where p is a number from 1 to 6; R² is selected from the group consisting of H, C_1-6 alkyl, -NR^2bR^2c, -OR^2a, 3-14 membered cycloalkyl, 3-14 membered cycloalkenyl, 3-14 membered heterocyclyl, including 1-3 ring heteroatoms selected from the group consisting of oxygen, nitrogen, phosphorus and sulfur, 6-10 membered aryl and 5-10 membered heteroaryl including 1-5 ring heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur ; where each C_1-6 alkyl is 3-14 membered cycloalkyl, 3-14 membered cycloalkenyl, 3-14 membered heterocyclyl containing 1-3 ring heteroatoms selected from the group consisting of oxygen, nitrogen, phosphorus and sulfur, 6-10 membered aryl and 5-10 membered heteroaryl containing 1-5 ring heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur independently optionally substituted with C_1-6 alkyl, C_1-6 haloalkyl, C_{1- 6} hydroxyalkyl, C_1-6 methoxyalkyl, –OH, –OR^2a, oxo, =N, halogen, –C(O)R^2a, –C(O)OR^2a, –C(O)NR^2bR^2c, - SO₂R^2a, –CN, -NR^2bR^2c, 3-6-membered cycloalkyl, 3-7-membered heterocyclyl, including 1-3 ring heteroatoms selected from the group consisting of oxygen, nitrogen, phosphorus and sulfur, 6-10-membered aryl or 5-10-membered heteroaryl, including 1-5 ring heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur; R⁵, R⁶, R⁷, R⁸ and R⁹ are independently selected from the group consisting of H, D, C_1-6 alkyl, C_2-6 alkenyl, 4-8 membered cycloalkenyl, C_2-6 alkynyl, 3-8 membered cycloalkyl, 3-14 membered heterocyclyl containing from 1 to 3 ring heteroatoms selected from the group consisting of oxygen, nitrogen, phosphorus and sulfur, -OH, halogen, -NO₂, -CN, -NR¹¹R¹², -SR¹⁰, -S(O)₂NR¹¹R¹², -S(O)₂R¹⁰, -NR¹⁰S(O)₂NR¹¹ R¹², -NR¹⁰S(O)₂R¹¹, -S(O)NR¹¹R¹², -S(O)R¹⁰, -NR¹⁰S(O)NR¹¹R¹², -NR¹⁰S(O)R¹¹, -C(O)R¹⁰ and -CO ₂ R ¹⁰, where each C _1-6 alkyl is C _2-6 alkenyl, 4-8 membered cycloalkenyl, C _2-6 alkynyl, 3-8 membered cycloalkyl and 3-14 membered heterocyclyl, including 1-3 ring heteroatoms selected from the group consisting of oxygen, nitrogen, phosphorus and sulfur, independently optionally substituted with -OH, halogen, -NO₂, oxo, -CN, -R¹⁰, -OR¹⁰, -NR¹¹R¹², -SR¹⁰, -S(O)₂NR¹¹R¹², -S(O)₂R¹⁰, -NR¹⁰S(O)₂NR¹¹R¹², -NR¹⁰S(O)2R¹¹, -S(O)NR¹¹R¹², -S(O)R¹⁰, -NR¹⁰S(O)NR¹¹R¹², -NR¹⁰S(O)R¹¹, 3-8 membered cycloalkyl, 3-14 membered heterocyclyl containing 1-3 ring heteroatoms selected from the group consisting of oxygen, nitrogen, phosphorus and sulfur, 6-10 membered aryl or 5-10 membered heteroaryl containing 1-5 ring heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, or any two adjacent R⁵, R⁶, R⁷, R⁸ и R⁹ form a 3-14 membered fused ring.

EFFECT: bicyclic heterocyclic compounds and their applications are proposed.

23 cl, 3 dwg, 2 tbl, 540 ex

(I)