Discovery and optimization of antibacterial AccC inhibitors

…, KA Soucy, A Soriano, P Orth, L Xiao, P Mann…

Index: Cheng, Cliff C.; Shipps Jr., Gerald W.; Yang, Zhiwei; Sun, Binyuan; Kawahata, Noriyuki; Soucy, Kyle A.; Soriano, Aileen; Orth, Peter; Xiao, Li; Mann, Paul; Black, Todd Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 23 p. 6507 - 6514

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Citation Number: 33

Abstract

The biotin carboxylase (AccC) is part of the multi-component bacterial acetyl coenzyme-A carboxylase (ACCase) and is essential for pathogen survival. We describe herein the affinity optimization of an initial hit to give 2-(2-chlorobenzylamino)-1-(cyclohexylmethyl)-1H-benzo [d] imidazole-5-carboxamide (1), which was identified using our proprietary Automated Ligand Identification System (ALIS). 1 The X-ray co-crystal structure of 1 was solved and ...