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Studies on antidiabetic agents. 11. Novel thiazolidinedione derivatives as potent hypoglycemic and hypolipidemic agents.

Abstract：

:In the course of further chemical modification of the novel antidiabetic pioglitazone (AD-4833, U-72,107), a series of 5-[4-(2- or 4-azolylalkoxy)benzyl- or -benzylidene]-2,4-thiazolidinediones was prepared and evaluated for hypoglycemic and hypolipidemic activities in insulin-resistant, genetically obese, and diabetic KKA(y) mice. Replacement of the 2-pyridyl moiety of pioglitazone by a 2- or 4-oxazolyl or a 2- or 4-thiazolyl moiety greatly enhanced in vivo potency. The corresponding 5-benzylidene-type compounds, in which a methine was used as a linker between the benzene ring and the thiazolidinedione ring, also had potent biological activity. Among the compounds synthesized, 5-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]-2,4- thiazolidinedione (18) exhibited the most potent activity, more than 100 times that of pioglitazone. The synthesis and structure-activity relationships for this novel series of derivatives are detailed.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Sohda T,Mizuno K,Momose Y,Ikeda H,Fujita T,Meguro K

doi

10.1021/jm00092a012

keywords:

subject

Has Abstract

pub_date

1992-07-10 00:00:00

pages

2617-26

issue

14

eissn

0022-2623

issn

1520-4804

journal_volume

35

pub_type

杂志文章

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