OPTIONALLY CONDENSED HETEROCYCLYL-SUBSTITUTED PYRIMIDINE DERIVATIVES SUITABLE FOR TREATING INFLAMMATORY, METABOLIC, ONCOLOGICAL AND AUTOIMMUNE DISEASES Russian patent published in 2020 - IPC C07D403/12 C07D401/14 C07D405/14 C07D413/14 C07D403/04 C07D409/12 C07D409/14 C07D413/04 C07D417/14 C07D471/04 C07D407/04 A61K31/506 A61K31/519 A61K31/5377 A61P3/00 A61P37/00 

FIELD: pharmaceuticals.

SUBSTANCE: invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, where Y is NR; R is hydrogen or C_1-4alkyl; R₁ denotes hydrogen, C_1-4alkyl or C_1-4alkyl substituted with halogen; R₂ is halogen; or R and R₂ are combined to form condensed 5-member heteroaryl ring, containing 1 nitrogen heteroatom; R₃ is selected from a group consisting of hydrogen, halogen, C_1-4alkyl, C_1-4alkyl substituted with halogen, C_1-4alkoxy, C_1-4alkoxy substituted with halogen, and oxo; R_4a is selected from a group consisting of hydrogen, halogen, -OH, -CN, C_1-6alkyl, C_1-6alkyl substituted with -C(=O)NR₈R₉, C_1-6alkyl substituted by halogen, C₁-C₆alkoxy, C₁-C₆alkoxy substituted with halogen, and 5–6-member heteroaryl containing 1–3 nitrogen heteroatoms; R_4b is selected from a group, consisting of hydrogen, halogen, oxo, -OH, C_1-4alkyl substituted with halogen, C_1-4alkyl, C_1-4alkoxy and C_1-4alkoxy substituted with halogen; R₅ is -(CR₈R₉)p-CR₁₃R₁₄R₁₅; n, m and p are integers, independently selected from a group consisting of 0, 1 and 2; R_6a is selected from a group consisting of hydrogen, C_1-6alkyl and C_1-6alkyl substituted with hydroxyl; R_6b is hydrogen; each R₇ independently represents hydrogen or C_1-6alkyl; R₈ and R₉ are independently selected from a group consisting of hydrogen, C_1-6alkyl and C_1-6alkyl substituted with hydroxyl, a group of di-C_1-6alkylamino, -COOH, NH₂, C_1-6 alkoxy or halogen; R₁₃ is absent or selected from the group consisting of hydrogen, -OH, -CN, halogen, C_1-6alkyl, C_1-6alkyl substituted with hydroxy, halogen, C_1-6alkoxy or -NR₈SO₂R₇, C_1-6alkoxy, -(CR₈R₉)pC(=O)OR₇, -(CR₈R₉)p-SO₂R₇ and -(CR₈R₉)pC(=O)NR₈R₉; R₁₄ and R₁₅ are combined to form a ring system selected from a group consisting of substituted or unsubstituted C_3-8cycloalkyl, substituted or unsubstituted C_3-7heteroalicylic, containing 1–2 heteroatoms, independently selected from a group consisting of oxygen, nitrogen and optionally oxidised sulfur, substituted or unsubstituted phenyl and substituted or unsubstituted 5–6 membered heteroaryl containing 1–4 heteroatoms, independently selected from nitrogen, oxygen and sulfur; where, when the ring system is substituted, the substituent is present once or twice and is -(CH₂)_q(R_5a), where R_5a is independently selected from a group, consisting of -CH₂COOR₂₀, -COOR₂₀, -CH₂CONR₂₁R₂₂, -CN, -CH₂-CN, C_1-6alkyl, -C(=O)-C_1-6alkyl, -OR₂₀ , -OH, -COR₂₀, morpholinyl, -C(=O)-morpholinyl, -OCH₂-tetrahydrofuryl, piperazinonyl, piperidinyl-CONR₂₁R₂₂, -CONR₂₁R₂₂, -CH₂-triazolyl, -CF₃, imidazolyl-2,4-dione, methyl-substituted imidazolyl-2,4-dione, tetrazolyl, CH₂-tetrazolyl, piperidyl-CH₂OR₂₀, possibly methyl substituted pyrrolidonyl, -NR₂₁SO₂R₂₀, -CH₂OR₂₀, -SO₃R₂₀, -SO₂R₂₀, -CH₂-SO₂R₂₀, -CH₂C(CH₃)₂(OR₂₀), -CH₂CH(CH₃)(OR₂₀), -CH(OR₂₀)CH₃, -SO₂NR₂₁R₂₂, -CH₂-SO₂NR₂₁R₂₂, -NR₂₁SO₂R₂₀, optionally methyl substituted C_3-6cycloalkyl and halogen, and q is an integer selected from 0, 1 and 2; R₂₀, R₂₁ and R₂₂ are independently selected from a group consisting of hydrogen, C_1-6alkyl, C_1-6alkyl, substituted with one to three halogens or C_1-6alkoxy, -CN, and C_3-6cycloalkyl; B is a ring system selected from a group, consisting of phenyl, naphthyl and 5–6-member heteroaryl containing 1–2 nitrogen atoms; C is a ring system selected from C_3-5heteroalicyclyl, containing nitrogen heteroatom and optionally containing additional heteroatom nitrogen or oxygen, and 5-member heteroaryl, containing nitrogen heteroatom and optionally containing 1–2 additional heteroatoms independently selected from nitrogen and oxygen; where B is bonded to carbon atom adjacent to atom N of ring system C. Invention also relates to pharmaceutical composition, having the property of an inhibitor of activity of an orphan receptor, associated with a receptor of retinoic acid (ROR), based on said compounds.

formula (I)

EFFECT: technical result is obtaining novel compounds and a pharmaceutical composition based thereon, which can be used in medicine for treating inflammatory, metabolic, oncological and autoimmune diseases.

39 cl, 3 dwg, 5 tbl, 205 ex