Aminopyrimidine derivatives as LRRK2 modulators

摘要

Compounds of the formula I:;
or pharmaceutically acceptable salts thereof,

wherein m, n. X, R1, R2, R3, R4 and R5 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

主权项

1. A compound of formula I:or a pharmaceutically acceptable salt thereof,wherein:
m is from 0 to 3; X is: —NRa—; —O—; or —S(O)r— wherein r is from 0 to 2 and Ra is hydrogen or C1-6alkyl; R1 is: C1-6alkyl; R2 is: halo; C1-6 alkoxy; cyano; halo-C 1-6 alkyl; halo-C1-6alkoxy; C3-6cycloalkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; tetrahydrofuranyl; tetrahydrofuranyl-C1-6alkyl; acetyl; oxetanyl; or oxetan-C1-6 alkyl; R3 and R4 each independently is: halo; C1-6alkyl; C1-6alkoxy; C3-6cycloalkyloxy; halo-C1-6 alkyl; or halo-C1-6alkoxy; or R3 and R4 together with the atoms to which they are attached may form a five-or six-membered ring that optionally includes one or two heteroatoms each independently selected from O, N and S, the ring being optionally substituted one or more times with R6; R5 is: C1-6alkyl-sulfonyl; C3-6cycloalkylsulfonyl; C3-6cycloalkyl-C1-6alkylsulfonyl; cyano; cyano-C1-6alkyl; heterocyclyl optionally substituted one or more times with R6; heterocyclyl-C1-6alkyl wherein the heterocyclyl moiety is optionally substituted one or more times with R6; halo-C1-6alkyl; heterocyclyl-sulfonyl wherein the heterocyclyl moiety is optionally substituted one or more times with R6; or carboxy; and R6 is: C1-6alkyl; halo; halo-C1-6alkyl; or oxo.