Oxazole phosphonic acids as fructose 1,6-bisphosphatase inhibitors with potent glucose-lowering activity

被引：18

作者：

Dang, Qun

Kasibthatla, Srinivas Rao

Jiang, Tao

Taplin, Frank

Gibson, Tony

Potter, Scott C.

van Poelje, Paul D.

Erion, Mark D.

机构：

[1] Metabasis Therapeut Inc, Dept Chem, La Jolla, CA 92037 USA

[2] Metabasis Therapeut Inc, Dept Biochem, La Jolla, CA 92037 USA

来源：

MEDCHEMCOMM | 2011年 / 2卷 / 04期

关键词：

AMP MIMICS; BENZOXAZOLE BENZENESULFONAMIDES; ALLOSTERIC INHIBITORS; FRUCTOSE-1,6-BISPHOSPHATASE; DESIGN; SERIES; HYPERGLYCEMIA; DISCOVERY; PRODRUGS; CS-917;

D O I：

10.1039/c0md00269k

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

To discover an alternative heterocyclic scaffold to the thiazole series of FBPase inhibitors such as thiazole 1, oxazoles were investigated to see if replacing the sulfur of the thiazole scaffold with an oxygen is tolerated. Numerous oxazoles with a phosphonic group linked by both 2,5-furandiyl and -COOCH(2)- groups were prepared and several oxazoles were discovered to have similar potency as thiazole 1. For example, oxazole 3.10 has an IC(50) of 70 nM and lowered blood glucose in normal fasted rats by 61%.

引用

收藏

页码：287 / 290

页数：4

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