申请人:AstraZeneca AB
公开号:US07994179B2
公开(公告)日:2011-08-09
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 RA1 and RA2 are each independently hydrogen or (1-4C)alkyl;
Z is carboxy or a mimic or bioisostere thereof.
本发明涉及一种公式(I)的DGAT-1抑制剂化合物、药学上可接受的盐和前药,以及制备它们的制药组合物、制备过程及其在治疗肥胖等方面的用途,其中,例如,环A是可选取代的2,6-吡唑基;X是═O;环B是可选取代的1,4-苯基;Y1是直接键或—O—;Y2是—(CH2)r—,其中r为2或3;n为0或当Y1为环B和环C之间的直接键且环B为1,4-苯基且环C为(4-6C)环烷时,n为1;环C是可选取代的(4-6C)环烷、(7-10C)双环烷、(8-12C)三环烷、苯基或吡啶二基基团;L是直接键或—O—;p为0、1或2,当p为1或2时,RA1和RA2各自独立地是氢或(1-4C)烷基;Z是羧基或其类似物或生物同位素。