Thieno- and furo[2,3-d]pyrimidine-2,4[1H,3H]-dione derivatives

摘要

This invention relates to novel Thieno- and Furo[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. A, 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:
A is S or O; R1 is C2-C10 hydroxyalkyl, wherein one or more carbon atom of the alkyl portion of the hydroxylalkyl group is optionally substituted with 1-3 R5; R2 is C1-C4 alkyl or C1-C4 hydroxyalkyl; R3 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 acyl, C3-C10 cycloalkyl, C1-C6 alkoxy, C4-C10 cycloalkyloxy, halo, 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, 5-14-membered heteroaryloxy, 3-18-membered heterocycloalkyl, amino, C1-C6 alkylamino, C2-C12 dialkylamino, —C(O)NH—R5, —C(O)N—(C1-C6 alkyl)-R5, —NHC(O)—R5, —N—(C1-C6 alkyl)-C(O)—R5, urea, sulfonylurea, nitro, or cyano, wherein each alkyl, alkenyl, alkynyl, acyl, cycloalkyl, alkoxy, cycloalkyloxy, alkylthio, aryl, heteroaryl, aryloxy, heteroaryloxy, and heterocycloalkyl represented by R3 is optionally and independently substituted with 1-4 R5; R4 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 acyl, C3-C10 cycloalkyl, C1-C6 alkoxy, C4-C10 cycloalkyloxy, halo, 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, 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—R5, —C(O)N—(C1-C6 alkyl)-R5, —NHC(O)—R5, —N—(C1-C6 alkyl)C(O)—R5, urea, sulfonylurea, nitro, or cyano, wherein each alkyl, alkenyl, alkynyl, acyl, cycloalkyl, alkoxy, cycloalkyloxy, alkylthio, aryl, heteroaryl, aryloxy, heteroaryloxy, and heterocycloalkyl represented by R4 is optionally and independently substituted with 1-4 R5; each R5 is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 acyl, C3-C10 cycloalkyl, C1-C6 alkoxy, C4-C10 cycloalkyloxy, halo, hydroxyl, alkylthio, thionyl, sulfonyl, sulfonamidyl, amino, C1-C6 alkylamino, C2-C12 dialkylamino, —C(O)NH—R6, —C(O)N—(C1-C6 alkyl)-R6, —NHC(O)—R6, —N—(C1-C6 alkyl)C(O)—R6, urea, sulfonylurea, nitro, or cyano, wherein each alkyl, alkenyl, alkynyl, acyl, cycloalkyl, alkoxy, cycloalkoxy, and alkylthio represented by R5 is optionally and independently substituted with 1-5 R6; and each R6 is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 acyl, C1-C6 alkoxy, halo, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyl, amino, —C(O)NH2, —C(O)NHC1-C6 alkyl, —NHC(O)(C1-C6 alkyl), —N—(C1-C6 alkyl)C(O)(C1-C6 alkyl), nitro, or cyano.