6-氮尿嘧啶的抗球虫衍生物。2. N1-苯基结构的高效能和长血浆半衰期。

Anticoccidial derivatives of 6-azauracil. 2. High potency and long plasma life of N1-phenyl structures.

作者信息

Miller M W, Mylari B L, Howes H L, Lynch J E, Lynch M J, Koch R C

出版信息

J Med Chem. 1979 Dec;22(12):1483-7. doi: 10.1021/jm00198a010.

Abstract

Attachment of substituted phenyl side chains at N1 of 6-azauracil caused striking increases in plasma life and anticoccidial potency. The increases were related in part to the acidity of the imide hydrogen. Maximum effects were shown by phenyl rings substituted in both meta positions by compact, electron-withdrawing, lipophilic substituents, as in 1-(3',5'-dichlorophenyl)-6-azauracil, which had plasma half-life of 160 h and a potency 250-fold greater than that of 6-azauracil.

摘要

在6-氮杂尿嘧啶的N1位连接取代的苯基侧链，可显著延长血浆半衰期并提高抗球虫效力。这种提高部分与酰亚胺氢的酸度有关。当苯环的间位被紧密的吸电子亲脂性取代基取代时效果最佳，如1-(3',5'-二氯苯基)-6-氮杂尿嘧啶，其血浆半衰期为160小时，效力比6-氮杂尿嘧啶高250倍。