DGAT-1 inhibitor compounds of formula (1), 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 ═0;
Ring B is optionally substituted 1,4-phenylene;
Y
1
is a direct bond or —O—;
Y
2
is —(CH
2
)
r
— wherein r is 2 or 3;
n is 0 or n is 1 when Y
1
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.
描述了公式(1)的DGAT-1
抑制剂化合物,其药学上可接受的盐和前药,以及药物组成物、制备它们的过程以及它们在治疗肥胖等方面的用途,其中,例如,环A是可选的取代2,6-
吡唑二基;X是═0;环B是可选的取代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是环B和环C之间的直接键时,n为1,并且当环B是1,4-苯基且环C是(4-6C)环烷基时;环C是可选的取代(4-6C)环烷基,(7-10C)双环烷基,(8-12C)
三环烷基,苯基或
吡啶二基;L是直接键或—O—;p为0、1或2,当p为1或2时,RA1和RA2各自独立地为氢或(1-4C)烷基;Z是羧基或其模拟物或
生物同位素。