The invention provides novel compounds of the Formula (I) that stimulate rates of glucose oxidation in myocardial cells. The invention also relates to pharmaceutical compositions comprising compounds capable of stimulation of glucose oxidation, methods for increasing glucose oxidation rates in myocardial cells, and methods of treatment of myocardial ischemia
1
wherein
W is C
1
-C
6
alkyl, halogen, or argyl;
Cyc is C
3
or C
4
cycloalkyl;
p is 0-3 for Cyc being C
4
cycloalkyl and p=0-2 for Cyc being C
3
cycloalkyl;
Y is O, S, or NR, where R═H, alkyl or aryl;
X is O, S, NR, or CR
3
R
4
;
Z is H, alkyl, cycloalkyl, aryl or (cyclo)alkylcarbonyl;
R
1
is H, alkyl, aryl or O;
R
2
is H, alkyl or aryl;
R
3
and R
4
are, independently, H, alkyl or aryl; and
n is an integer from 1 to 10; or a pharmaceutically acceptable salt, ester or prodrug thereof.
本发明提供了式(I)的新化合物,其能够刺激心肌细胞中
葡萄糖氧化的速率。本发明还涉及包括能够刺激
葡萄糖氧化的化合物的制药组合物,增加心肌细胞
葡萄糖氧化速率的方法,以及治疗心肌缺血的方法。其中,W为C1-C6烷基,卤素或芳基;Cyc为C3或C4环烷基;对于Cyc为C4环烷基,p为0-3,对于Cyc为C3环烷基,p为0-2;Y为O、S或NR(其中R为H、烷基或芳基);X为O、S、NR或CR3R4;Z为H、烷基、环烷基、芳基或(环)烷基羰基;R1为H、烷基、芳基或O;R2为H、烷基或芳基;R3和R4独立地为H、烷基或芳基;n为1至10的整数;或其药学上可接受的盐、酯或前药。