Molecular design and synthesis of HCV inhibitors based on thiazolone scaffold

被引：32

作者：

Al-Ansary, Ghada H. ^{[1
]}

Ismail, Mohamed A. H. ^{[1
]}

Abou El Ella, Dalal A. ^{[1
]}

Eid, Sameh ^{[2
]}

Abouzid, Khaled A. M. ^{[1
]}

机构：

[1] Ain Shams Univ, Dept Pharmaceut Chem, Fac Pharm, Cairo 11566, Egypt

[2] Univ Basel, Inst Mol Pharm, Pharmactr, CH-4003 Basel, Switzerland

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 68卷

关键词：

HCV; Thiazole; Glide docking; HCV NS5B inhibitor; Sulfonamide derivatives; POLYMERASE ALLOSTERIC INHIBITORS; ACUTE HEPATITIS-C; HCVNS5B POLYMERASE; RNA-POLYMERASE; REPLICATION; ASSOCIATION;

D O I：

10.1016/j.ejmech.2013.07.006

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of thiazolone derivatives was designed and synthesized as potential HCV NS5B allosteric polymerase inhibitors at the allosteric site thumb II. Their antiviral activity was evaluated and molecular modeling was utilized to give further envision on their probable binding modes in the allosteric binding site. Among the tested molecules, compound 9b displayed sub-micromolar inhibitory activity with an EC50 of 0.79 mu M indicating excellent potency profile. It also showed good safety profile (CC50 >= 75 mu M and SI >= 94.3). (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：19 / 32

页数：14

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