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(RQC)2, NRQN, O, S or SO2, where each RQC is independently H, F, Cl, Br or 6-10 membered aryl, and each RQN is independently H, C1-6 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, C1-6 alkyl, halogen, –CONHR1a, -NHR1a, –OR1a, cyclopropyl, azetidinyl and –CN; wherein each C1-6 alkyl and azetidinyl are optionally substituted with halogen, R1a, -NHR1a or –OR1a ; where R1a 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 C1-6 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, C1-6 alkyl, -NR2bR2c, -OR2a, 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 C1-6 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 C1-6 alkyl, C1-6 haloalkyl, C1- 6 hydroxyalkyl, C1-6 methoxyalkyl, –OH, –OR2a, oxo, =N, halogen, –C(O)R2a, –C(O)OR2a, –C(O)NR2bR2c, - SO2R2a, –CN, -NR2bR2c, 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, C1-6 alkyl, C2-6 alkenyl, 4-8 membered cycloalkenyl, C2-6 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)
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Authors
Dates
2024-01-15—Published
2020-03-02—Filed