NEW SUBSTITUTED AZAINDOLINE DERIVATIVES AS NIK INHIBITORS Russian patent published in 2022 - IPC C07D471/04 C07D519/00 A61K31/506 A61K31/5377 A61K31/55 A61P3/00 A61P29/00 A61P35/00 A61P37/00 

FIELD: biotechnology.

SUBSTANCE: invention relates to a compound of the formula (I), its tautomers or stereoisomeric forms, which have inhibitory activity to a nuclear factor kappa B of NF-κB-inducing kinase (hereinafter – NIK). In the formula (I), R¹ is C_1-4alkyl; R² is C_1-6alkyl optionally substituted with R⁵; Y is CR⁴; R⁴ is hydrogen or halogen; R⁵ is cyano or -OR⁷; R⁷ is hydrogen; R³ is phenyl substituted with one, two, or three substitutes selected from halogen; cyano; C_1-6alkyl; -O-C_1-; -S(=O)₂-C_1-4alkyl, etc., substituted with halogen; -O-C_1-4alkyl-R¹²; Het^1a; -O-Het^1b; R¹⁸; -NH-C(=O)-C_1-4alkyl, etc.; R¹⁰ is -OH, -NR^11aR^11b, or Het²; R¹⁸ is 5-element aromatic ring containing one, two or three N atoms; optionally substituted with one C_1-4 alkyl; each of Het^1a, Het^1c, and Het^1d is 4-7-element monocyclic saturated heterocyclyl containing one or two heteroatoms selected from O, S, S(=O)_p, and N; or 6-11-element bicyclic saturated heterocyclyl including condensed, spiro- and bridging cycles, containing one, two, or three heteroatoms selected from O and N; optionally substituted by one, two, or three atoms of N ring by a substitute selected from C_1-4alkyl, etc.; and at the same time, the specified 4-7-element monocyclic saturated heterocyclyl can be substituted by one atom of C ring by one or two substitutes selected from a group consisting of C_1-4alkyl, -O-C_1-4alkyl, and -N(C_1-4alkyl)₂; each of Het^1b, Het^1e, Het^1g is 4-7-element monocyclic saturated heterocyclyl attached to the rest of the molecule of the formula (I) by any available carbon atom of the ring, while Het^1b, Het^1e, Het^1g contain one heteroatom selected from O and N; in this case, 4-7-element monocyclic saturated heterocyclyl can be substituted by one or two atoms of N ring with a substitute selected from C_1-4alkyl; Het² is heterocyclyl of the formula (b-1): (b-1) is 4-7-element monocyclic saturated heterocyclyl bound by N, optionally containing one additional heteroatom selected from O, S, and S(=O)_p; where (b-1) is optionally substituted by one atom of C ring with one or two substitutes selected from halogen, -OH, cyano, C_1-4alkyl, and C_1-4alkyl-OH; R^11b is Het^1e; R¹³ is -NR^19aR^19b, or Het^1d; R¹² is -NR^14aR^14b, -C(=O)NR^14cR^14d, or Het^1c; R^11a, R^14a, R^14c, R^17a, and R^19a are hydrogen or C_1-4alkyl; each of R^14b, R^14d, R^17b, and R^19b is hydrogen; C_1-6alkyl; -C(=O)-C_1-4alkyl, etc., and p is 1 or 2.

EFFECT: obtaining new azaindoline derivatives as NIK inhibitors.

6 cl, 19 tbl, 9 ex