5-[[4-(4,5-二氢-2-恶唑基)苯氧基]烷基]-3-甲基异恶唑的构效关系研究：微小核糖核酸病毒脱壳抑制剂

Structure-activity studies of 5-[[4-(4,5-dihydro-2-oxazolyl) phenoxy]alkyl]-3-methylisoxazoles: inhibitors of picornavirus uncoating.

作者信息

Diana G D, Oglesby R C, Akullian V, Carabateas P M, Cutcliffe D, Mallamo J P, Otto M J, McKinlay M A, Maliski E G, Michalec S J

出版信息

J Med Chem. 1987 Feb;30(2):383-8. doi: 10.1021/jm00385a021.

DOI:10.1021/jm00385a021

PMID:3027340

Abstract

A series of substituted phenyl analogues of 5-[[4-(4,5-dihydro-2-oxazolyl) phenoxy]alkyl]-3-methylisoxazoles has been synthesized and evaluated in vitro against several human rhinovirus (HRV) serotypes. Substituents in the 2-position greatly enhanced activity when compared to the unsubstituted compound. Many of these compounds exhibited mean MICs (MIC) against five serotypes as low as 0.40 microM. The mean MIC correlated well (r = 0.83) with the MIC80 (the concentration that inhibited 80% of the serotypes tested). A quantitative structure-activity relationship study indicated a strong dependency of MIC on lipophilicity (log P) in combination with inductive effects (sigma m) and bulk factors (MW).

摘要

合成了一系列5-[[4-(4,5-二氢-2-恶唑基)苯氧基]烷基]-3-甲基异恶唑的取代苯基类似物，并在体外针对几种人鼻病毒（HRV）血清型进行了评估。与未取代的化合物相比，2-位的取代基极大地增强了活性。这些化合物中的许多对五种血清型的平均最低抑菌浓度（MIC）低至0.40微摩尔。平均MIC与MIC80（抑制80%测试血清型的浓度）相关性良好（r = 0.83）。定量构效关系研究表明，MIC强烈依赖于亲脂性（log P），并结合诱导效应（σm）和体积因子（MW）。