2rbe

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Revision as of 08:44, 23 January 2008

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spinqualitylabelsall models 2rbe, resolution 1.900Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors

Overview

A series of 2-anilinothiazolones were prepared as inhibitors of, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). The most potent, compounds contained a 2-chloro or 2-fluoro group on the aniline ring with, an isopropyl substituent on the 5-position of the thiazolone ring, (compounds 2 and 3, respectively). The binding mode was determined through, the X-ray co-crystal structure of the enzyme with compound 3. This, compound was also approximately 70-fold selective over 11beta-HSD2 and was, orally bioavailable in rat pharmacokinetic studies. However, compound 3, was >580-fold less active in the 11beta-HSD1 cell assay when tested in the, presence of 3% human serum albumin.

About this Structure

2RBE is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as 11-beta-hydroxysteroid dehydrogenase, with EC number 1.1.1.146 Full crystallographic information is available from OCA.

Reference

The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors., Yuan C, St Jean DJ Jr, Liu Q, Cai L, Li A, Han N, Moniz G, Askew B, Hungate RW, Johansson L, Tedenborg L, Pyring D, Williams M, Hale C, Chen M, Cupples R, Zhang J, Jordan S, Bartberger MD, Sun Y, Emery M, Wang M, Fotsch C, Bioorg Med Chem Lett. 2007 Nov 15;17(22):6056-61. Epub 2007 Sep 25. PMID:17919905

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