4TLR

NS5b in complex with lactam-thiophene carboxylic acids

4TLR の概要

• エントリーDOI: 10.2210/pdb4tlr/pdb
• 分子名称: NS5b, 3-{(2R,5R)-5-cyclohexyl-2-[(2R)-2-hydroxypropyl]-3-oxomorpholin-4-yl}-5-(3,3-dimethylbut-1-yn-1-yl)thiophene-2-carboxylic acid, 5-cyclopropyl-2-(4-fluorophenyl)-6-[(2-hydroxyethyl)(methylsulfonyl)amino]-N-methyl-1-benzofuran-3-carboxamide, ... (4 entities in total)
• 機能のキーワード: complex polymerase inhbitor, hydrolase
• 由来する生物種: Hepatitis C virus (isolate 1)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 65330.99

構造登録者

Chopra, R. (登録日: 2014-05-30, 公開日: 2014-12-10, 最終更新日: 2024-11-13)

主引用文献

Barnes-Seeman, D.,Boiselle, C.,Capacci-Daniel, C.,Chopra, R.,Hoffmaster, K.,Jones, C.T.,Kato, M.,Lin, K.,Ma, S.,Pan, G.,Shu, L.,Wang, J.,Whiteman, L.,Xu, M.,Zheng, R.,Fu, J.
Design and synthesis of lactam-thiophene carboxylic acids as potent hepatitis C virus polymerase inhibitors.
Bioorg.Med.Chem.Lett., 24:3979-3985, 2014

PubMed Abstract: Herein we report the successful incorporation of a lactam as an amide replacement in the design of hepatitis C virus NS5B Site II thiophene carboxylic acid inhibitors. Optimizing potency in a replicon assay and minimizing potential risk for CYP3A4 induction led to the discovery of inhibitor 22a. This lead compound has a favorable pharmacokinetic profile in rats and dogs.

PubMed: 24986660
DOI: 10.1016/j.bmcl.2014.06.031

実験手法

X-RAY DIFFRACTION (1.86 Å)