Nonpeptide Inhibitors of Measles Virus Entry
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- 作者：Aiming Sun ; Andrew Prussia ; Weiqiang Zhan ; Ernest E. Murray ; Joshua Doyle ; Li-Ting Cheng ; Jeong-Joong Yoon ; Eugene V. Radchenko ; Vladimir A. Palyulin ; Richard W. Compans ; Dennis C. Liotta ; Richard K.
- 刊名：Journal of Medicinal Chemistry
- 出版年：2006
- 出版时间：August 24, 2006
- 年：2006
- 卷：49
- 期：17
- 页码：5080 - 5092
- 全文大小：389K
- 年卷期：v.49,no.17(August 24, 2006)
- ISSN：1520-4804
文摘
Measles virus (MV) is one of the most infectious pathogens known. Despite the existence of a vaccine,over 500 000 deaths/year result from MV or associated complications. Anti-measles compounds couldconceivably reverse these statistics. Previously, we described a homology model of the MV fusion proteintrimer and a putative binding site near the head-neck region. The resulting model permitted the identificationof two nonpeptidic entry inhibitors. Here, we present the design, synthesis, and bioevaluation of severalseries of fusion inhibitors and describe their structure-activity relationships (SAR). Five simply substitutedanilides show low-
M blockade of the MV, one of which (AS-48) exhibits IC50 = 0.6-3.0 M across apanel of wild-type MV strains found in the field. Molecular field topology analysis (MFTA), a 2D QSARapproach based on local molecular properties (atomic charges, hydrogen-bonding capacity and locallipophilicity), applied to the anilide series suggests structural modifications to improve potency.
M blockade of the MV, one of which (AS-48) exhibits IC50 = 0.6-3.0 M across apanel of wild-type MV strains found in the field. Molecular field topology analysis (MFTA), a 2D QSARapproach based on local molecular properties (atomic charges, hydrogen-bonding capacity and locallipophilicity), applied to the anilide series suggests structural modifications to improve potency.