GLUCOSE TRANSPORT-ENHANCING AND HYPOGLYCEMIC ACTIVITY OF 2-METHYL-2-PHENOXY-3-PHENYLPROPANOIC ACIDS

Citation
R. Sarges et al., GLUCOSE TRANSPORT-ENHANCING AND HYPOGLYCEMIC ACTIVITY OF 2-METHYL-2-PHENOXY-3-PHENYLPROPANOIC ACIDS, Journal of medicinal chemistry, 39(24), 1996, pp. 4783-4803
Citations number
33
Categorie Soggetti
Chemistry Medicinal
ISSN journal
00222623
Volume
39
Issue
24
Year of publication
1996
Pages
4783 - 4803
Database
ISI
SICI code
0022-2623(1996)39:24<4783:GTAHAO>2.0.ZU;2-P
Abstract
A series of 2-phenoxy-3-phenylpropanoic acids has been prepared which contains many potent hypoglycemic agents as demonstrated by assessing glucose lowering in ob/ob mice. Some compounds (32, 33, 59) normalize plasma glucose in this diabetic model at doses of approximately 1 mg/k g. The mechanism of action of these drugs may involve enhanced glucose transport, especially in fat cells, but the compounds do not stimulat e GLUT4 translocation and do not increase the levels of GLUT1 or GLUT4 in vivo. Thus, these compounds may enhance the intrinsic activity of the glucose transporter GLUT1 or GLUT4. Some compounds also modestly d ecrease hepatocyte gluconeogenesis in vitro, but this is not likely to be a major contributor to the hypoglycemic effect observed in vivo. L ikewise, a modest decrease in food consumption observed with some of t hese compounds was shown by a pair-feeding experiment not to be the pr imary cause of the hypoglycemia observed.