Carbamoyl compounds as dgat1 inhibitors 190

Details Carbamoyl compounds as dgat1 inhibitors 190 Carbamoyl compounds as dgat1 inhibitors 190

C - Chemistry, Metallurgy

07

D

C07D 213/81 (2006.01) A61K 31/4418 (2006.01) A61K 31/4965 (2006.01) A61K 31/497 (2006.01) A61P 3/00 (2006.01) C07D 213/82 (2006.01) C07D 241/24 (2006.01) C07D 401/04 (2006.01) C07D 401/10 (2006.01) C07D 403/10 (2006.01)

Patent

CA 2707660

DGAT-1 inhibitor compounds of formula (I), pharmaceutically-acceptable salts and pro- drugs thereof are described, together with pharmaceutical compositions, processes for making them and their use in treating, for example, obesity wherein, for example, Ring A is optionally substituted 2,6-pyrazindiyl; X is =O; Ring B is optionally substituted 1,4-phenylene; Y1 is a direct bond or -O-; Y2 is -(CH2)r- wherein r is 2 or 3; n is 0 or n is 1 when Y1 is a direct bond between Ring B and Ring C and when Ring B is 1,4-phenylene and Ring C is (4-6C)cycloalkane; Ring C is optionally substituted (4-6C)cycloalkane, (7-10C)bicycloalkane, (8-12C)tricycloalkane, phenylene or pryidindiyl; L is a direct bond or -O-; p is 0, 1 or 2 and when p is 1 or 2 R A1 and R A2 are each independently hydrogen or (1-4C)alkyl; Z is carboxy or a mimic or bioisostere thereof.

L'invention porte sur des composés inhibiteurs de DGAT-1 de formule (I), sur des sels pharmaceutiquement acceptables et des promédicaments de ceux-ci, conjointement avec des compositions pharmaceutiques, des procédés permettant de les fabriquer et leur utilisation dans le traitement, par exemple, de l'obésité, selon lesquels, par exemple, le noyau A est le 2,6-pyrazinediyle facultativement substitué; X = 0; le noyau B est le 1,4-phénylène facultativement substitué; Y1 est une liaison directe ou -O-; Y2 est (CH2)r- où r vaut 2 ou 3; n est 0 ou n est 1 lorsque Y1 est une liaison directe entre le noyau B et le noyau C et lorsque le noyau B est le 1,4-phénylène et le noyau C est un cycloalcane en C4-6; le noyau C est un cycloalcane en C4-6, bicycloalcane en C7-10, tricycloalcane en C8-12, phénylène ou pryidinediyle facultativement substitué; L est une liaison directe ou -O-; p est 0, 1 ou 2 et lorsque p est 1 ou 2 RA1 et RA2 représentent chacun indépendamment hydrogène ou alkyle en C1-4; Z représente carboxy ou un mimique ou bioisostère de celui-ci.

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