Substituted 1,3-benzothiazol-2(3H)-ones and [1,3]thiazolo[5,4-B]pyridin-2(1H)-ones as positive allosteric modulators of mGluR2

摘要

The present invention is directed to benzothiazol-one and thiazolo pyridine-one derivatives which are potentiators of metabotropic glutamate receptors, particularly the mGluR2 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.

主权项

1. A compound according to Formula Iwherein:
R1 is selected from the group consisting of —(CH2)pcyclopropyl, —(CH2)pcyclopentyl, —(CH2)pcyclohexyl, —(CH2)ppiperidinyl, (CH2)pphenyl, and C1-6 alkyl, wherein each said cyclopropyl, cyclopentyl, cyclohexyl and alkyl is optionally substituted with 1-3 halo, C1-6 alkyl, CF3, —C(O)OC1-6 alkyl, pyrimidinyl, 2,2-dimethylpropyl and 4,4,4-trifluorobutyl; X represents —CRb—, or —N—; each R2 is independently selected from the group consisting of: hydrogen, halo, OH, C1-4alkyl, C1-4alkoxy, CF3 and —CN; R3 is selected from the group consisting of phenyl, pyridyl, —O-phenyl, and —O-pyridyl, wherein each said phenyl, pyridyl, —O-phenyl, and —O-pyridyl are optionally substituted with 1 to 3 Ra groups; each Ra is independently selected from the group consisting of:
(1) halo,(2) C1-8alkyl,(3) C2-6alkenyl,(4) C2-6alkynyl,(5) C3-6cycloalkyl,(6) C1-6alkoxy,(7) C3-6cycloalkoxy,(8) —CN,(9) —OH,(10) —C(O)—O—R,(11) —C(O)—C1-6alkyl,(12) —N(R)2,(13) —C(O)—N(R)2,(14) —S(O)k—C1-6alkyl, wherein k is 0, 1 or 2,(15) —(CH2)pC6-10aryl,(16) —(CH2)pC5-10heterocyclyl,(17) CF3,(18) —C(O)-aryl,(19) —N(R)-aryl,(20) benzyl,(21) benzyloxy,(22) phenoxy,(23) —C(CH3)2OR,(24) —SH,(25) —SO2N(R)R,(26) —(CH2)pN(R)C(O)N(R)R,(27) —(CH2)pN(R)C(O)C1-6alkyl,(28) —(CH2)pN(R)SO2N(R)R, and(29) —B(OH)2,(30) —OR,(31) —(CH2)pNHC(O)OC1-6alkyl,(32) —OC5-10heterocyclyl, wherein groups (2) to (7), (11), (14) to (16), (18) to (23), and (32) above are optionally substituted with one up to the maximum number of substitutable positions of one or more substituents independently selected from the group consisting of: OH, CN, halo, carboxy, —C(O)—O—C1-4alkyl, C1-4alkyl, C1-4alkoxy, C1-4alkylamino, phenyl and C5-10 heterocycle, R is selected from the group consisting of: H, (CH2)pC6-10aryl and C1-6alkyl; Rb and Rk independently represent H or halo; p represents 0-1; and pharmaceutically acceptable salts thereof.