| 摘要 |
The present invention provides novel imidazo[4,5-c]quinoline and imidazo[4,5-c][1,5]naphthyridine derivatives of Formula (I), and the pharmaceutically acceptable salts thereof;;wherein R1, R1a, R1b, R2, R4, R5, R6, X and Z are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of Formula (I) and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy. |
| 主权项 |
1. A compound of Formula (I) or a pharmaceutically acceptable salt thereof; wherein X is CR7 or N; Z is CR3 or N; R1 is selected from the group consisting of hydrogen, cyano and a 5- to 10-membered heteroaryl which contains 1 to 5 heteroatoms independently selected from N, O and S; wherein the 5- to 10-membered heteroaryl is optionally substituted with 1 to 3 R8; R1a and R1b are each independently hydrogen, halo, hydroxy or C1-C3alkyl; or R1a and R1b taken together with the carbon to which they are attached are a C3-C6cycloalkyl or C(O); R2 is a C1-C6alkyl, C3-C7cycloalkyl or a 4- to 7-membered heterocycloalkyl which contains 1 to 3 heteroatoms independently selected from NR, O and S; wherein the C3-C7cycloalkyl and 4- to 7-membered heterocycloalkyl are each optionally substituted with 1 to 3 R9; and wherein the C1-C6alkyl is optionally substituted with 1 to 3 R10; R is hydrogen, C1-C6alkyl or absent; R3, R4, R5, R6 and R7 are each independently selected from the group consisting of hydrogen, deutero, amino, halo, hydroxy, cyano, C1-C6alkyl, C3-C6cycloalkyl and C1-C6alkoxy; wherein the C1-C6alkyl, C3-C6cycloalkyl and C1-C6alkoxy are each optionally substituted with 1 to 3 halo or C1-C3alkoxy; R8 at each occurrence is independently selected from the group consisting of halo, —C(O)NH2, —C(O)NH(C1-C3alkyl), —C(O)N(C1-C3alkyl)2, C1-C6alkyl, C1-C6alkoxy and C3-C6cycloalkyl; wherein the C1-C6alkyl, C1-C6alkoxy and C3-C6cycloalkyl are each optionally substituted with 1 to 3 halo, cyano, hydroxy or C1-C3alkoxy; R9 at each occurrence is independently selected from the group consisting of halo, hydroxy, C1-C6alkyl, C1-C6alkoxy, and C1-C6alkoxyC1-C6alkyl, wherein the C1-C6alkyl, C1-C6alkoxy, and C1-C6alkoxyC1-C6alkyl are optionally substituted with one to three halo or a cyano; and R10 at each occurrence is independently selected from the group consisting of halo, C1-C6alkoxy, C1-C6thioalkoxy, amino, C1-C6alkylamino and di(C1-C6alkyl)amino. |
