OPTIONALLY CONDENSED HETEROCYCLYL-SUBSTITUTED PYRIMIDINE DERIVATIVES SUITABLE FOR TREATING INFLAMMATORY, METABOLIC, ONCOLOGICAL AND AUTOIMMUNE DISEASES Russian patent published in 2020 - IPC C07D403/12 C07D401/12 C07D405/12 C07D239/49 C07D409/12 C07D487/04 C07D403/14 C07D405/14 C07D401/14 C07D413/12 A61K31/506 A61K31/519 A61P3/00 A61P37/00 A61P39/00 A61P29/00 A61P35/00 

FIELD: medicine; pharmaceuticals.

SUBSTANCE: invention relates to a novel compound of formula (I), a pharmaceutically acceptable salt or stereoisomer thereof. Compounds have properties of inhibiting the activity of the orphan receptor associated with the receptor of retinoic acid (ROR), and can be used in therapy for treating inflammatory, metabolic and autoimmune diseases. Such diseases can be rheumatoid arthritis, multiple sclerosis, asthma, chronic obstructive pulmonary disease (CORD), bronchitis, allergic diseases such as allergic rhinitis, conjunctivitis and uveitis, food allergy, atopic dermatitis, etc. In formula (I)

formula (I)

Y is NR; R is hydrogen or C_1-4-alkyl; R₁ denotes hydrogen; R₂ is halogen; or R and R₂ are combined to form condensed 5-member heteroaryl ring containing 1 nitrogen heteroatom; R_4a is selected from a group consisting of hydrogen, halogen, -OH, -CN, C_1-6-alkyl, C_1-6-alkyl substituted with a -C(=O)NR₈R₉ group or halogen, C₁-C₆-alkoxy, C₁-C₆-alkoxy substituted with halogen, C₃-C₆-cycloalkyl and 5–6-member heteroaryl containing 1–3 nitrogen heteroatoms; R_4b is selected from a group consisting of hydrogen, oxo, halogen, -OH, C_1-4-alkyl, C_1-4-alkyl substituted with halogen, C_1-4-alkoxy and C_1-4-alkoxy substituted with halogen ; R₅ is -(CR₈R₉)p-CR₁₃R₁₄R₁₅; n is an integer selected from a group consisting of 0, 1, 2, 3 and 4; p is an integer selected from 0, 1 and 2; R_6a and R_6b are independently selected from a group consisting of hydrogen, C_1-6-alkyl, C_1-6-alkyl substituted with phenyl, phenyl and C_3-8-cycloalkyl; or R_6a and R_6b are taken together to form an oxo group or ring system selected from C_3-6-cycloalkyl and C_3-6- heteroalicyclyl containing a nitrogen atom, or R_6a and R₁₃ are taken together to form a ring system selected from C_3-6-cycloalkyl, C_2-5- heteroalicyclyl containing a nitrogen atom, and C_2-5-heteroalicyclyl containing a nitrogen atom and substituted with group SO₂-alkyl; R₇, R₈ and R₉ are independently selected from a group consisting of hydrogen, C_1-6-alkyl, C_1-6-alkyl substituted with hydroxyl, a group of di-C_1-6-alkylamino, -COOH, NH₂, C_1-6-alkoxy, 5-member heteroaryl containing 1 heteroatom of oxygen, or halogen, C_3-6-cycloalkyl, C_3-6-heteroalicyclyl containing a nitrogen atom and substituted C_3-6-heteroalicyclyl containing a nitrogen atom and substituted with C_1-6-alkyl; R₁₃ is absent or is selected from a group consisting of hydrogen, -OH, fluorine, C_1-6-alkyl, C_1-6-alkyl substituted with hydroxyl, halogen, C_1-6-alkoxy or -NR₈SO₂R₇, C_3-8-cycloalkyl, 5–6-member heterocyclyl containing 1–2 nitrogen heteroatoms, -(CR₈R₉)p-C(=O)OR₇, -(CR₈R₉)p-SO₂R₇ and -(CR₈R₉)p-C(=O)NR₈R₉; R₁₄ and R₁₅ are combined to form a ring system selected from a group consisting of C_3-8-cycloalkyl, C_3-7-heteroalicyclyl containing 1–2 heteroatoms independently selected from a group consisting of oxygen, nitrogen and optionally oxidized sulfur, phenyl and 5–6-member heteroaryl containing heteroatoms, independently selected from nitrogen, oxygen and sulfur; and where said ring system is optionally substituted with one or two -(CH₂)_q(R_5a), where each R_5a is independently selected from a group consisting of -CN, C_1-6-alkyl, -OR₂₀, -OH, -COR₂₀, -CONR₂₁R₂₂, -COOR₂₀, imidazolyl-2,4-dione, methyl-substituted imidazolyl-2,4-dione, tetrazolyl, -SO₂R₂₀, -SO₂NR₂₁R₂₂, -NR₂₁SO₂R₂₀ 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_1-6-alkyl, C_1-6-alkyl substituted with halogen, C_1-6-alkoxy or -CN, and C_3-6-cycloalkyl; B represents a ring system selected from the group consisting of phenyl, naphthyl, and 5–6-membered heteroaryl containing 1–2 nitrogen atoms; R_3a is selected from a group consisting of C_1-4-alkyl, C_2-4-alkylene-C_3-6-cycloalkyl, C_1-4-alkylene-C_3-6-heteroalicyclyl containing an oxygen atom as a heteroatom, C_3-6-cycloalkyl and C_3-5-heteroalicyclyl containing an oxygen atom as a heteroatom; R_3b is hydrogen; and R_3c is selected from a group consisting of hydrogen, C_1-4-alkyl and C_3-6-cycloalkyl; or R_3b and R_3c are combined to form cyclopropyl.

EFFECT: compounds enable reducing the rate of developing such a disease as arthritis, and reducing the severity of the disease.

32 cl, 2 dwg, 9 tbl, 155 ex