PYRIDO[2,3-d]PYRIMIDINE-2,4(1H,3H)-DIONE DERIVATIVES

摘要

This invention relates to novel Pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione derivatives of Formula (I):;;and their use as TRPC5 modulators, pharmaceutical compositions containing the same, and methods of using the same as agents for the treatment of TRPC5 receptor mediated disorders or conditions. R1, R2, R3 and R4 have meanings given in the description.

主权项

1. A compound of Formula (I):or a pharmaceutically acceptable salt thereof, wherein:
R1 is C2-C10 hydroxyalkyl, optionally substituted with 1-3 R6; R2 is H, C1-C6 alkyl, C1-C6 hydroxyalkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, or C1-C6 alkoxy; R3 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 acyl, C3-C10 cycloalkyl, C1-C6 alkoxy, C4-C10 cycloalkyloxy, halo, C1-C6haloalkyl, C1-C6haloalkoxy, hydroxyl, C1-C10 hydroxyalkyl, alkylthio, thionyl, sulfonyl, sulfonamidyl, C6-C12 aryl, 5-14-membered heteroaryl, C6-C12 aryl-C1-C6 alkyl, 5-14-membered heteroaryl-C1-C6 alkyl, C6-C12 aryloxy, —O—C6-C12 aryl-C1-C6 alkyl, —O— C1-C6 alkyl-C6-C12 aryl, —C6-C12 aryl-C1-C6 alky-O, 5-14-membered heteroaryloxy, 3-18-membered heterocycloalkyl, amino, C1-C6 alkylamino, C2-C12 dialkylamino,—C(O)NH—,—C(O)N—C1-C6 alkyl-,—NHC(O)—, —N— C1-C6 alkyl C(O)—, urea, sulfonylurea, nitro, or cyano, optionally substituted with 1-5 R5; R4 is C1-C6 alkyl, C1-C6 acyl, C3-C10 cycloalkyl, C1-C6 alkoxy, C4-C10 cycloalkyloxy, halo, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyl, alkylthio, thionyl, sulfonyl, sulfonamidyl, C6-C12 aryl, 5-14-membered heteroaryl, C6-C12 aryl-C1-C6 alkyl, 5-14-membered heteroaryl-C1-C6 alkyl, C6-C12 aryloxy, —O—C6-C12 aryl-C1-C6 alkyl, —O— C1-C6 alkyl-C6-C12 aryl, —C6-C12 aryl-C1-C6 alky-O, 5-14-membered heteroaryl-C1-C6 alkyl, 5-14-membered heteroaryloxy, 3-18-membered heterocycloalkyl, amino, C1-C6 alkylamino, C2-C12 dialkylamino, —C(O)NH—,—C(O)N—C1-C6 alkyl-,—NHC(O)—, —N—C1-C6 alkyl C(O)—, urea, sulfonylurea, nitro, or cyano, optionally substituted with 1-5 R5; each R5 is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 acyl, C1-C6 alkoxy, C4-C10 cycloalkyloxy, halo, C1-C6haloalkyl, C1-C6haloalkoxy, hydroxy, C1-C10 hydroxyalkyl, amino, C6-C12 aryl, 5-14-membered heteroaryl, C6-C12 aryl-C1-C6 alkyl, C6-C12 aryloxy, O—C6-C12 aryl-C1-C6 alkyl, —O— C1-C6 alkyl-C6-C12 aryl, —C6-C12 aryl-C1-C6 alky-O, or 5-14-membered heteroaryloxy, each of which is optionally substituted with 1-5 R6; and each R6 is independently C1-C6 alkyl, C1-C6 alkoxy, C3-C10 cycloalkyl, halo, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyl, amino, C1-C6 alkylamino, C2-C12 dialkylamino, cyano, nitro, —C(O)NH—,—C(O)N—C1-C6 alkyl-,—NHC(O)—, —N— C1-C6 alkyl C(O)—, —C(O)O—C1-C6 alkyl, —C(O)OH, —C(O)O—C1-C6 alkyl, —C(O)—C1-C6 alkyl, acyl, nitro, or cyano.