AMINOPYRIMIDINE DERIVATIVES AS LEUCINE-RICH REPEAT KINASE 2 (LRRK2) MODULATORS

摘要

FIELD: chemistry.;SUBSTANCE: in the general formula I I, A is a five-, six- or seven-membered saturated or unsaturated ring, that includes one or two heteroatoms selected from O and N, which is substituted once with R⁵ and which is optionally substituted one, two or three times with R⁶ groups; X is -NR^a-, wherein R^a is hydrogen; R¹ is C_1-6alkyl; R² is halogen, C_1-6alkoxy, cyano or halo-C_1-6alkyl; one of the groups R³ and R⁴ is halogen, C_1-6alkyl or C_1-6alkoxy, and the other group is hydrogen; R⁵ is oxo, C_1-6alkyl, C_3-6cycloalkyl or -C (O) -NR^bR^c, where each of the R^b and R^c is independently hydrogen or C_1-6alkyl, or R^b and R^c together with atoms, to which they are attached, can form a 4-6-membered saturated heterocyclyl, which optionally comprises an additional heteroatom selected from O and N, and which is optionally substituted once with R⁶; or R^b and R^c together with the atoms to which they are attached, can form 2-oxa-5-azabicyclo [2.2.1] heptanyl; and each group R⁶ is independently C_1-6alkyl, C_3-6cycloalkyl, halogen, hydroxy-C_1-6alkyl, C_1-6alkoxy-C_1-6alkyl or 4-6-membered saturated heterocyclyl with oxygen as a heteroatom. Preferable compound is a compound corresponding the formula IIa or IIb ; where m is 0; 1 or 2; Z is -C (R⁷)₂-; -NR⁸- or -O-; each group R⁷ is independently hydrogen or C_1-6alkyl; and each group R⁸ is independently hydrogen, C_1-6alkyl, C_3-6cycloalkyl, halogen, hydroxy-C_1-6alkyl, C_1-6alkoxy-C_1-6alkyl or 4-6-membered saturated heterocyclyl with oxygen as a heteroatom.;EFFECT: invention relates to a novel compound of formula I or a pharmaceutically acceptable salt thereof, which possess the properties of the LRRK2 inhibitor and can be used to prevent or treat Parkinson's disease.;22 cl, 3 tbl, 13 ex