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Benzimidazole-carboxamides as potent and bioavailable stearoyl-CoA desaturase (SCD1) inhibitors from ligand-based virtual screening and chemical optimization.

Abstract：

:The discovery of potent benzimidazole stearoyl-CoA desaturase (SCD1) inhibitors by ligand-based virtual screening is described. ROCS 3D-searching gave a favorable chemical motif that was subsequently optimized to arrive at a chemical series of potent and promising SCD1 inhibitors. In particular, compound SAR224 was selected for further pharmacological profiling based on favorable in vitro data. After oral administration to male ZDF rats, this compound significantly decreased the serum fatty acid desaturation index, thus providing conclusive evidence for SCD1 inhibition in vivo by SAR224.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Matter H,Zoller G,Herling AW,Sanchez-Arias JA,Philippo C,Namane C,Kohlmann M,Pfenninger A,Voss MD

doi

10.1016/j.bmcl.2013.01.030

subject

Has Abstract

pub_date

2013-03-15 00:00:00

pages

1817-22

issue

6

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(13)00052-8

journal_volume

23

pub_type

杂志文章

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