9-(2-氟苄基)-6-(烷基氨基)-9H-嘌呤。一类新型抗惊厥药。

9-(2-Fluorobenzyl)-6-(alkylamino)-9H-purines. A new class of anticonvulsant agents.

作者信息

Kelley J L, Krochmal M P, Linn J A, McLean E W, Soroko F E

机构信息

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

出版信息

J Med Chem. 1988 May;31(5):1005-9. doi: 10.1021/jm00400a019.

DOI:10.1021/jm00400a019

PMID:3361569

Abstract

Several substituted aryl and 6-alkylamino analogues of the anticonvulsant purine 9-(2-fluorobenzyl)-6-(methyl-amino)-9H-purine (1) were synthesized and tested for anticonvulsant activity against maximal electroshock-induced seizures (MES) in rats. Derivatives with a second fluoro substituent in the 5- or 6-position of the aryl moiety were very active with ip ED50's that ranged from 2 to 4 mg/kg. Congeners in which the purine 6-substituent was varied among a number of alkylamino groups possessed potent activity against MES that was comparable to or several times better than phenytoin.

摘要

合成了抗惊厥嘌呤9-(2-氟苄基)-6-(甲氨基)-9H-嘌呤(1)的几种取代芳基和6-烷基氨基类似物，并在大鼠中测试了它们对最大电休克诱导惊厥(MES)的抗惊厥活性。在芳基部分的5-或6-位带有第二个氟取代基的衍生物非常活跃，腹腔注射的半数有效剂量(ED50)为2至4mg/kg。嘌呤6-取代基在多个烷基氨基之间变化的同类物对MES具有强效活性，与苯妥英相当或比苯妥英强几倍。