Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1376316 | Bioorganic & Medicinal Chemistry Letters | 2007 | 5 Pages |
Abstract
The structure–activity relationship study focused on the polar region of the HTS hit A-80040 (1) producing several series of potent and selective ACC2 inhibitors. The SAR suggests a compact lipophilic pocket that does not tolerate polar and ionic groups. Replacement of the hydroxyurea group with isoxazoles improves ACC2 selectivity while maintaining potency. Variations at the propargylic site of 11a reduce ACC2 potency.
Graphical abstractPotent and selective ACC2 inhibitors were synthesized by modifying the polar region of a HTS hit and the SAR suggests a compact and lipophilic binding pocket.Figure optionsDownload full-size imageDownload as PowerPoint slide
Keywords
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Xiangdong Xu, Moshe Weitzberg, Robert F. Keyes, Qun Li, Rongqi Wang, Xiaojun Wang, Xiaolin Zhang, Ernst U. Frevert, Heidi S. Camp, Bruce A. Beutel, Hing L. Sham, Yu Gui Gu,