Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Bioorg Med Chem Lett. 2012 Jan 1;22(1):327-33. doi: 10.1016/j.bmcl.2011.11.007. Epub 2011 Nov 16.
A new series of 2,3,8-trisubstituted-4(3H)-quinazoline derivatives were synthesized, evaluated for their anticonvulsant activity against electrically (MES) and chemically (PTZ, picrotoxin and Strychnine) induced seizures and compared with the standard drugs methaqualone and sodium valproate. Compounds 3, 17 and 22 proved to be the most potent compounds of this series with relatively low neurotoxicity and low toxicity in the median lethal dose test as compared with the reference drugs. The obtained results showed that the most active compounds could be useful as a template for future design, modification and investigation to produce more active analogs.
合成了一系列新的 2,3,8-三取代-4(3H)-喹唑啉衍生物,评估了它们对电(MES)和化学(PTZ、picrotoxin 和士的宁)诱导的癫痫发作的抗惊厥活性,并与标准药物美沙酮和丙戊酸钠进行了比较。与参比药物相比,化合物 3、17 和 22 被证明是该系列中最有效的化合物,具有相对较低的神经毒性和较低的半数致死剂量试验毒性。所得结果表明,最有效的化合物可作为模板,用于进一步设计、修饰和研究,以产生更有效的类似物。