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Discovery and structure-activity relationships of pentanedioic acid diamides as potent inhibitors of 11beta-hydroxysteroid dehydrogenase type I.

Abstract：

:Benzylamides of pentanedioic acid were identified as inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) by high-throughput screening. Optimisation to 2-adamantyl amides yielded inhibitors with single digit nanomolar IC(50)s on the 11beta-HSD1 human isoform. The hydroxy adamantyl amide lead compound was selective against 11beta-hydroxysteroid dehydrogenase type 2 (selectivity ratio >1000) and displayed good inhibition of 11beta-HSD1 (IC(50)<0.1microM) in a cellular model (3T3L1 adipocytes).

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Roche D,Carniato D,Leriche C,Lepifre F,Christmann-Franck S,Graedler U,Charon C,Bozec S,Doare L,Schmidlin F,Lecomte M,Valeur E

doi

10.1016/j.bmcl.2009.03.140

subject

Has Abstract

pub_date

2009-05-15 00:00:00

pages

2674-8

issue

10

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(09)00465-X

journal_volume

19

pub_type

杂志文章

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