2,2-DIFLUORODIOXOLO A2A RECEPTOR ANTAGONISTS

摘要

The present invention is directed to 2,2-difluorodioxolo compounds that are antagonists of A2A receptor. The present invention is also directed to uses of the 2,2-difluorodioxolo compounds described herein in the potential treatment or prevention of neurological disorders and diseases in which A2A receptor are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds and to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which A2A receptors are involved.

主权项

1. A compound of formula I: wherein: R1a and R1b are independently selected from the group consisting of:
(1) hydrogen,(2) halogen,(3) hydroxyl,(4) C1-6alkyl, unsubstituted or substituted with one or more halogen,(5) C3-6cycloalkyl, and(6) carbonyl; X is selected from hydrogen or  wherein:
Y is CH or N; and,R2 and R3 are independently selected from the group consisting of:
(1) hydrogen,(2) C1-6alkyl, unsubstituted or substituted with one or more halogen, hydroxy, phenyl (optionally substituted with C1-6alkyl, halogen or CF3), C3-6cycloalkyl, or a mono- or bicyclic heterocyclic moiety comprising up to 8 carbon atoms and one or more heteroatoms selected from N, S, or O (optionally substituted with C1-6alkyl),(3) C3-6cycloalkyl, unsubstituted or substituted with one or more halogen or C1-6alkyl (optionally substituted with one or more halogen),(4) —(C═O)O—C1-6alkyl, and(5) a mono- or bicyclic heterocyclic moiety comprising up to 8 carbon atoms and one or more heteroatoms selected from N, S, or O (optionally substituted with C1-6alkyl);or R2 and R3 are joined to form a cyclic moiety selected from:
(1) C3-6cycloalkyl, unsubstituted or substituted with one or more substituents selected from R4, or(2) a mono- or bicyclic heterocyclic moiety comprising up to 10 carbon atoms and one or more heteroatoms selected from N, S, or O, unsubstituted or substituted on either a carbon or a heteroatom with one or more substituents selected from R4; R4 is selected from the group consisting of:
(1) hydroxyl,(2) halogen,(3) C1-6alkyl, optionally substituted with one or more halogen or C3-6cycloalkyl,(4) —C3-6cycloalkyl,(5) —O—C1-6alkyl,(6) —(O)m—(CH2)pO—C1-3alkyl,(7) oxo,(8) —Om-phenyl, where the phenyl is optionally substituted with halogen, C1-6alkyl or —O—C1-6alkyl (wherein the C1-6alkyl or —O—C1-6alkyl are substituted with —O—C1-6alkyl), and(9) heterocycle, which is optionally substituted with one or more halogen, C1-6alkyl, or phenyl (optionally substituted with halogen or CF3); wherein if two R4 substituents are attached to the same carbon atom, they may optionally be joined to form a spirocyclic moiety; m is 0 or 1 (wherein if m is 0, a bond is present); n is 0, 1, 2 or 3 (wherein if n is 0, a bond is present); and, p is 1, 2 or 3; or a pharmaceutically acceptable salt thereof.