Heterocyclic amides of formula (1)
wherein: X is N or CH;
R
4
and R
5
together are either —S—C(R
6
)═C(R
7
)— or —C(R
7
)═C(R
6
)—S—;
R
6
and R
7
are independently selected from, for example hydrogen, halo and C
l-4
alkyl; A is phenylene or heteroarylene; n is 0, 1 or 2;
R
1
is selected from for example halo, nitro, cyano, hydroxy, carboxy;
R
2
is hydrogen, hydroxy or carboxy;
R
3
is selected from for example hydrogen, hydroxy, aryl, heterocyclyl and C
1-4
alkyl(optionally substituted by 1 or 2 R
8
groups);
R
8
is selected from for example hydroxy, —COCOOR
9
, —C(O)N(R
9
)(R
10
), —NHC(O)R
9
, (R
9
)(R
10
)N— and —COOR
9
;
R
9
and R
10
are selected from for example hydrogen, hydroxy, C
1-4
alkyl (optionally substituted by 1 or 2 R
13
);
R
13
is selected from hydroxy, halo, trihalomethyl and C
1-4
alkoxy; or a pharmaceutically acceptable salt or pro-drug thereof; possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of said heterocyclic amide derivatives and pharmaceutical compositions containing them are described.
公式(1)的杂环酰胺,其中:X是N或CH;R4和R5一起是—S—C(R6)═C(R7)—或—C(R7)═C(R6)—S—;R6和R7独立选择自氢、卤素和Cl-4烷基;A是苯基或杂环芳基;n为0、1或2;R1选择自卤素、硝基、
氰基、羟基、羧基;R2是氢、羟基或羧基;R3选择自氢、羟基、芳基、杂环芳基和C1-4烷基(可选地取代1或2个R8基);R8选择自羟基、—COCOOR9、—C(O)N(R9)(R10)、—NHC(O)R9、(R9)(R10)N—和—COOR9;R9和R10选择自氢、羟基、C1-4烷基(可选地取代1或2个R13);R13选择自羟基、卤素、三卤甲基和C1-4烷氧基;或其药学上可接受的盐或前药;具有
糖原磷酸化酶抑制活性,因此在治疗与增加的
糖原磷酸化酶活性相关的疾病状态中具有价值。还描述了制造该杂环酰胺衍
生物的过程以及含有它们的制药组合物。