Stillings M R, Welbourn A P, Walter D S
J Med Chem. 1986 Nov;29(11):2280-4. doi: 10.1021/jm00161a025.
This paper describes the synthesis and pharmacological evaluation of a number evaluation of a number of substituted 1,3,4-thiadiazoles. The first member of the series, 2-(aminomethyl)-5-(2-biphenylyl)-1,3,4-thiadiazole (7) was found to possess potent anticonvulsant properties in rats and mice and compared favorably with the standard anticonvulsant drugs phenytoin, phenobarbital, and carbamazepine in a number of test situations. The potency of compound 7 was maintained on alkylation of the side-chain nitrogen atom; however, aryl substitution or chain lengthening caused a drop in potency. Replacement of the 2-biphenylyl group by phenyl or benzyl also lead to inactive compounds.
本文描述了多种取代的1,3,4 - 噻二唑的合成及药理学评价。该系列的首个成员，2 -（氨甲基）-5 -（2 - 联苯基）-1,3,4 - 噻二唑（7）在大鼠和小鼠中表现出强效抗惊厥特性，并且在多种测试情况下与标准抗惊厥药物苯妥英、苯巴比妥和卡马西平相比具有优势。化合物7的效力在侧链氮原子烷基化后得以保持；然而，芳基取代或链延长会导致效力下降。用苯基或苄基取代2 - 联苯基也会产生无活性的化合物。
