PYRIDO[3,4-D]PYRIMIDINE DERIVATIVE AND PHARMACEUTICALLY ACCEPTABLE SALT THEREOF Russian patent published in 2019 - IPC C07D471/04 C07D519/00 A61K31/5386 A61K31/553 A61K31/541 A61K31/5377 A61K31/519 A61P35/04 A61P19/02 A61P9/10 A61P25/28 A61P29/00 A61P43/00 

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound of formula (I) or a pharmaceutically acceptable salt thereof, having CDK4/6 inhibitory activity. In general formula (I)

L is -NR⁵-, -O- or -S-; R⁵ is a hydrogen atom or C_1–6 an alkyl group; R¹ is: C_1–8 alkyl; C_3–12 cycloalkyl; (C_3–12 cycloalkyl) -C_1–6 alkyl; 4–7-member heterocyclyl containing one or two heteroatoms, each selected from a nitrogen atom, an oxygen atom and SO₂; (4–7 membered heterocyclyl) -C_1–6 alkyl, where heterocyclyl contains one or two heteroatoms, each of which is selected from a nitrogen atom, an oxygen atom and SO₂; C₆ aryl; (C_6–10 aryl) -C_1–6 alkyl; 5–10-member heteroaryl containing two nitrogen atoms; or (5–10-member heteroaryl) -C_1–6 alkyl; R¹ optionally has from one to three substitutes selected from a group consisting of halogen atoms, =O, -OH, -CN, -COOH, -COOR⁶ and -R⁷; R⁶ and R⁷ each independently represents C_1–6 an alkyl group having, as substitutes, zero or one -OH group, zero or one C_1–8 alkoxy group and from zero to three fluorine atoms; R² is C_1–4 alkyl, C_3–8 cycloalkyl, 4–6 membered heterocyclyl or C_1–4 an acyl group or -CONR⁹R¹⁰; each of C_1–4 alkyl and C_3–8 cycloalkyl groups represented by R², has, as substitutes, zero or one -OH group, zero or one C_1–6 an alkoxy group having, as substitutes, zero or one -OH group, zero or one C_1–4 alkoxy group and from zero to three fluorine atoms; and from zero to five fluorine atoms; R² is not unsubstituted C_1–8 alkyl, unsubstituted C_3–8 cycloalkyl and trifluoromethyl group; R⁸, R⁹ and R¹⁰ each independently represents a hydrogen atom or C_1–6 an alkyl group; 4–6-member heterocyclyl group represented by R², optionally carries from one to four C_1–4 alkyl groups; R³ is a hydrogen atom, C_1–8 an alkyl group or a halogen atom; X is CR¹¹ or nitrogen atom; Y is CR¹² or nitrogen atom; Z is CR¹³ or nitrogen atom; where only one of X, Y and Z can simultaneously represent a nitrogen atom; R¹¹-R¹³ each independently represents a hydrogen atom, a fluorine atom or a chlorine atom, or C_1–6 alkyl R⁴ is -A¹-A²-A³; A¹ is a single bond or C_1–8 alkylene group; one or two sp³ carbon atoms in any position in A¹ optionally each is replaced with a moiety selected from the group consisting of -O-, -NR¹⁴-, -C(=O)-, -C(=O)-O-, -C(=O)-NR¹⁵-, -NR¹⁷-C(=O) -, -NR¹⁹-C(=O) -NR²⁰-, -S(=O)_p-, -NR²²-S(=O)₂- and -NR²³-S(=O)₂-NR²⁴-, such that -OO-, -O-NR¹⁴- fragments are not formed, -NR¹⁴-O-, -O-CH₂-O-, -O-CH₂-NR¹⁴- or -NR¹⁴-CH₂-O- in case of replacement of two sp³ carbon atoms; A² is a single bond or C_1–7 alkylene, C_3–10 cycloalkylene, C_3–12 cycloalkylidene, 4–10-member heterocyclylene, phenylene or 5–10-member heteroerylene group; A³ is a halogen atom, -R²⁵, -OR²⁶, -NR²⁷R²⁸, -C(=O)R²⁹, -C(=O)-OR³⁰, -OC(=O)R³¹, -C(=O)-NR³⁴R³⁵, -NR³⁶-C(=O)R³⁷, -S(=O)₂-R⁴⁰, -S(=O)₂-NR⁴¹R⁴² or -NR⁴³-S(=O)₂R⁴⁴; A³ is -R²⁵, if A¹ end from side A² has a structure selected from a group consisting of -O-, -NR¹⁴-, -C (=O)-, -C(=O)-O-, -C(=O) -NR¹⁵-, -NR¹⁷-C(=O)-, -NR¹⁹-C(=O)-NR²⁰-, -S(=O)_p-, -NR²²-S(=O)₂- and -NR²³-S(=O)₂-NR²⁴-, and A² is a single bond; R¹⁴, R³², R³⁴ and R³⁶ each independently represents a hydrogen atom or C_1–8 alkyl, or C_1–8 alkylsulphonyl group; R¹⁵-R³¹, R³³, R³⁵ and R³⁷ each independently represents a hydrogen atom or C_1–8 alkyl, or 4–12 membered heterocyclyl group; A² and R¹⁴-R³⁷ in A¹, A² and A³ each independently can have substitutes for from one to four substitutes selected from a group consisting of -OH, = O, -COOH, -CN, a halogen atom and C_1–4 alkyl group having zero or one -OH group as substitutes, zero to two -OR⁴⁵ groups and from zero to three fluorine atoms; R¹⁴-R³⁷ are not necessarily connected in A¹, A² or A³ or between A¹ and A², between A¹ and A³, or between A² and A³ by single bond, -O-, -NR⁵⁰- or -S(=O)_p- to form a cycle; R¹¹ or R¹³ optionally associated with A¹, A² or A³ by single bond, -O-, -NR⁵¹- or -S (= O)_p- to form a cycle; R⁴⁵-R⁵¹ each represents a hydrogen atom or C_1-4 an alkyl group having, as substitutes, zero or one -OH group and zero to three fluorine atoms; p is integer from 0 to 2; and each of heteroatom-containing groups presented by A¹, A² and A³, contains from one to four heteroatoms selected from oxygen, sulphur or its oxide, or nitrogen atoms.

EFFECT: compounds can be used for preparing a drug for preventing or treating rheumatoid arthritis, arteriosclerosis, pulmonary fibrosis, ischemic stroke or malignant growth.

25 cl, 1 dwg, 4 tbl, 26 ex