4EO6

HCV NS5B polymerase inhibitors: Tri-substituted acylhydrazines as tertiary amide bioisosteres

4EO6 の概要

• エントリーDOI: 10.2210/pdb4eo6/pdb
• 関連するPDBエントリー: 4EO8
• 分子名称: RNA-directed RNA polymerase, 5-(3,3-dimethylbut-1-yn-1-yl)-3-{[(trans-4-methylcyclohexyl)carbonyl](propan-2-yl)amino}thiophene-2-carboxylic acid (3 entities in total)
• 機能のキーワード: hcv, ns5b, rna, rna polymerase, polymerase inhibitor, thumb site 2 inhibitor, rna-dependent rna polymerase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Hepatitis C virus (isolate BK) (HCV)
• 細胞内の位置: Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein. Core protein p19: Virion (By similarity). Envelope glycoprotein E1: Virion membrane; Single-pass type I membrane protein (Potential). Envelope glycoprotein E2: Virion membrane; Single-pass type I membrane protein (Potential). p7: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Protease NS2-3: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). Non-structural protein 4A: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential). Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Non-structural protein 5A: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). RNA-directed RNA polymerase: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential): P26663
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 129068.14

構造登録者

Appleby, T.C.,Canales, E.,Watkins, W.J. (登録日: 2012-04-13, 公開日: 2012-06-27, 最終更新日: 2024-10-30)

主引用文献

Canales, E.,Carlson, J.S.,Appleby, T.,Fenaux, M.,Lee, J.,Tian, Y.,Tirunagari, N.,Wong, M.,Watkins, W.J.
Tri-substituted acylhydrazines as tertiary amide bioisosteres: HCV NS5B polymerase inhibitors.
Bioorg.Med.Chem.Lett., 22:4288-4292, 2012

PubMed Abstract: The use of a tri-substituted acylhydrazine as an isostere of a tertiary amide was explored in a series of HCV NS5B thumb site II inhibitors. Direct replacement generated an analog with similar conformational and physicochemical properties. The series was extended to produce compounds with potent binding affinities and encouraging levels of cellular potency.

PubMed: 22664130
DOI: 10.1016/j.bmcl.2012.05.025

実験手法

X-RAY DIFFRACTION (1.791 Å)