具有抗鼻病毒活性的2-取代-6-(二甲基氨基)-9-(4-甲基苄基)-9H-嘌呤的合成及其构效关系

Synthesis and structure-activity relationships of 2-substituted-6-(dimethylamino)-9-(4-methylbenzyl)-9H-purines with antirhinovirus activity.

作者信息

Kelley J L, Linn J A, Selway J W

机构信息

Division of Organic Chemistry, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709.

出版信息

J Med Chem. 1989 Jan;32(1):218-24. doi: 10.1021/jm00121a039.

DOI:10.1021/jm00121a039

PMID:2535875

Abstract

A series of 2-substituted-6-(dimethylamino)-9-(4-methylbenzyl)-9H-purines where the 2-substituent was H, F, Cl, CF3, CH3, CH2CH3, NH2, NHCH3, N(CH3)2, SCH3, or SO2CH3 was synthesized and tested for antirhinovirus activity to evaluate the effect of 2-substituents on antiviral activity. Intuitive and quantitative structure-activity relationship (QSAR) analysis showed that optimum antirhinovirus serotype 1B activity was associated with 9-benzylpurines that contained a C-2 lipophilic, electron-withdrawing substituent. The most active compound, 6-(dimethylamino)-9-(4-methylbenzyl)-2-(trifluoromethyl)-9H-purine (14), had an IC50 = 0.03 microM against serotype 1B, but its activity against 18 other serotypes was not uniform; the IC50s ranged over 260-fold.

摘要

合成了一系列2-取代-6-(二甲氨基)-9-(4-甲基苄基)-9H-嘌呤，其中2-取代基为H、F、Cl、CF3、CH3、CH2CH3、NH2、NHCH3、N(CH3)2、SCH3或SO2CH3，并测试了其抗鼻病毒活性，以评估2-取代基对抗病毒活性的影响。直观的定量构效关系(QSAR)分析表明，最佳的抗1B型鼻病毒活性与含有C-2亲脂性吸电子取代基的9-苄基嘌呤有关。活性最高的化合物6-(二甲氨基)-9-(4-甲基苄基)-2-(三氟甲基)-9H-嘌呤(14)对1B型的IC50 = 0.03 microM，但它对其他18种血清型的活性并不一致；IC50范围超过260倍。