Monoacylglycerol lipase inhibitors for the treatment of metabolic diseases and related disorders

1. A method for treating a patient suffering from obesity, said method comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of formula (I)

or an enantiomer, diastereomer, solvate, or pharmaceutically acceptable salt thereof;

wherein:

Y is a heteroaryl selected from the group consisting of thienyl, furanyl, thiazolyl, isothiazolyl, oxazolyl, pyridinyl, isoxazolyl, imidazolyl, furazan-3-yl, pyrazolyl, triazolyl, tetrazolyl, and [1,2,3]thiadiazolyl;

wherein Y is optionally independently substituted with one to two substituents selected from the group consisting of fluoro, chloro, bromo, C 1-4 alkyl, cyano, and trifluoromethyl;

Z is a heteroaryl selected from the group consisting of indolyl, indazolyl, benzoxazolyl, benzothiazolyl, benzothienyl, benzofuranyl, imidazo[1,2-a]pyridin-2-yl, pyrrolo[2,3-b]pyridinyl, pyrrolo[3,2-b]pyridinyl, thieno[2,3-b]pyridinyl, quinolinyl, quinazolinyl, and benzimidazolyl;

wherein said Z is optionally independently substituted with one to two substituents selected from the group consisting of C 1-4 alkyl, trifluoromethyl, 2,2,2-trifluoroethoxy-methyl, 2,2,2-trifluoroethoxy, trifluoromethylthio, chloro, fluoro, bromo, and iodo;

with the proviso that a compound of formula (I) is other than

a compound wherein Y is thiazol-4-yl and Z is 5-fluoro-3H-benzimidazol-2-yl; a compound wherein Y is thiazol-2-yl and Z is 5-fluoro-1H-benzimidazol-2-yl;

a compound wherein Y is thiazol-4-yl and Z is 5-chloro-benzofuran-2-yl; a compound wherein Y is isothiazol-5-yl and Z is 6-trifluoromethyl-1H-indol-2-yl; a compound wherein Y is thiazol-4-yl and Z is 5-trifluoromethyl-1H-pyrrolo[3,2-b]pyridin-2-yl; a compound wherein Y is thiazol-2-yl and Z is 8-bromo-6-chloro-imidazo[1,2-a]pyridin-2-yl; or a compound wherein Y is thiazol-2-yl and Z is 6-trifluoromethyl-imidazo[1,2-a]pyridin-2-yl.

2. A method of treating obesity comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of formula (I)

or an enantiomer, diastereomer, solvate, or pharmaceutically acceptable salt thereof;

wherein:

Y is a heteroaryl selected from the group consisting of thienyl, furanyl, thiazolyl, and isothiazolyl;

wherein Y is optionally substituted with one to two substituents independently selected from the group consisting of fluoro, chloro, bromo, and trifluoromethyl;

Z is a heteroaryl selected from the group consisting of indolyl, benzothiazolyl, benzothienyl, pyrrolo[2,3-b]pyridinyl, and thieno[2,3-b]pyridinyl;

wherein Z is optionally independently substituted with one to two substituents selected from the group consisting of C 1-4 alkyl, trifluoromethyl, 2,2,2-trifluoroethoxy-methyl, 2,2,2-trifluoroethoxy, chloro, fluoro, bromo, and iodo;

with the proviso that a compound of formula (I) is other than a compound wherein Y is isothiazol-5-yl and Z is 6-trifluoromethyl-1H-indol-2-yl.

3. A method of treating obesity comprising administering to a subject in need thereof, a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of formula (I)

or an enantiomer, diastereomer, solvate, or pharmaceutically acceptable salt thereof;

wherein:

Y is a heteroaryl selected from the group consisting of thienyl, furanyl, thiazolyl, and isothiazolyl;

wherein Y is optionally substituted with one to two substituents independently selected from the group consisting of fluoro, chloro, bromo, and trifluoromethyl;

Z is a heteroaryl selected from the group consisting of indolyl, benzothiazolyl, benzothienyl, pyrrolo[2,3-b]pyridinyl, and thieno[2,3-b]pyridinyl;

wherein Z is optionally independently substituted with one to two substituents selected from the group consisting of C 1-4 alkyl, trifluoromethyl, 2,2,2-trifluoroethoxy-methyl, 2,2,2-trifluoroethoxy, chloro, fluoro, bromo, and iodo;

with the proviso that a compound of formula (I) is other than a compound wherein Y is isothiazol-5-yl and Z is 6-trifluoromethyl-1H-indol-2-yl.

4. A method of treating obesity comprising administering to a subject in need thereof, a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of 1-(1-{[3-chloro-6-(trifluoromethyl)-1-benzothiophen-2-yl]carbonyl}azetidin-3-yl)-4-(1,3-thiazol-4-ylcarbonyl)piperazine

or a solvate or pharmaceutically acceptable salt thereof.