一种新型抗病毒化合物（±）-α-5-[1-（吲哚-3-基）乙基]-2-甲氨基-δ2-噻唑啉-4-酮的易水解、水溶性衍生物。

Easily hydrolyzable, water-soluble derivatives of (+/-)-alpha-5-[1-(indol-3-yl)ethyl]-2-methylamino-delta2-thiazoline-4-one, a novel antiviral compound.

作者信息

Harnden M R, Bailey S, Boyd M R, Wilkinson J B, Wright N D

出版信息

J Med Chem. 1979 Feb;22(2):191-5. doi: 10.1021/jm00188a013.

Abstract

The preparation of a series of indole N-acyl and N-carbamic esters of (+/-)-alpha-5-[1-(indol-3-yl)ethyl]-2-methylamino-delta2-thiazolin-4-one (1) is reported. These derivatives were synthesized as potential water-soluble precursors of the antiviral thiazolinone 1, for evaluation by intranasal administration against influenza and other respiratory infections caused by viruses. Salts of the basic carbamic esters (16--19) possess the required water solubility, undergo rapid hydrolysis and decarboxylation at pH values greater than 6, and have high activity against influenza A2 and Coxsackie B1 viruses in vitro. In influenza A2 infected ferrets a representative ester (16) reduced the severity and duration of disease symptoms and reduced nasal wash virus titres but caused local irritancy.

摘要

报道了一系列（±）-α-5-[1-（吲哚-3-基）乙基]-2-甲氨基-δ2-噻唑啉-4-酮（1）的吲哚N-酰基酯和N-氨基甲酸酯的制备。这些衍生物被合成为抗病毒噻唑啉酮1的潜在水溶性前体，用于通过鼻内给药评估其对流感和其他由病毒引起的呼吸道感染的作用。碱性氨基甲酸酯（16 - 19）的盐具有所需的水溶性，在pH值大于6时会快速水解和脱羧，并且在体外对甲型流感病毒2型和柯萨奇病毒B1具有高活性。在感染甲型流感病毒2型的雪貂中，一种代表性的酯（16）减轻了疾病症状的严重程度和持续时间，降低了鼻洗液中的病毒滴度，但引起了局部刺激。