Kelley J L, Krochmal M P, Linn J A, McLean E W, Soroko F E
Organic Chemistry Department, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709.
J Med Chem. 1988 Mar;31(3):606-12. doi: 10.1021/jm00398a019.
Several 9-alkyl-6-substituted-purines were synthesized and tested for anticonvulsant activity against maximal electroshock-induced seizures (MES) in rats. Most compounds were prepared in three steps from 5-amino-4,6-dichloropyrimidine or in two steps via alkylation of 6-chloropurine. Potent anticonvulsant activity against MES resided in compounds that contain a benzyl substituent at the 9-position of 6-(methylamino)- or 6-(dimethyl-amino)purine. Among commonly used agents for control of seizures, this type of structure represents a new class of potent anticonvulsant agents.
合成了几种9-烷基-6-取代嘌呤,并对其在大鼠中针对最大电休克诱发惊厥(MES)的抗惊厥活性进行了测试。大多数化合物由5-氨基-4,6-二氯嘧啶分三步制备,或通过6-氯嘌呤的烷基化分两步制备。对MES具有强效抗惊厥活性的化合物是在6-(甲氨基)-或6-(二甲氨基)嘌呤的9位含有苄基取代基的那些化合物。在常用的控制癫痫发作的药物中,这种类型的结构代表了一类新的强效抗惊厥药物。