Design and synthesis of 3-(4-chlorophenyl)-2-(2-(4-substituted)-2-oxoethylthio)quinazolin-4(3H)-one as antihistamine agents

被引:3
作者
Alagarsamy, V. [1 ]
Narendhar, B. [1 ]
Sulthana, M. T. [1 ]
Solomon, V. Raja [1 ]
机构
[1] MNR Coll Pharm, Med Chem Res Lab, Hyderabad 502294, Andhra Pradesh, India
关键词
Quinazolinones; Antihistaminic agents; Bronchospasm; Sedation;
D O I
10.1007/s00044-014-1034-9
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of novel 3-(4-chlorophenyl)-2-(2-(4substituted)-2-oxoethylthio) quinazolin-4(3H)-one was synthesized by the reaction of 2-(3-(4-chlorophenyl)-4oxo-3,4-dihydroquinazolin-2-ylthio) acetyl chloride with various amines. The starting material, (3-(4-chlorophenyl)4-oxo-3,4-dihydroquinazolin-2-ylthio) acetyl chloride was synthesized from 4-chloroaniline by a multistep synthesis. All the title compounds were tested for their in vivo H-1-antihistaminic activity on conscious guinea pigs at the dose level of 10 mg/kg using chlorpheniramine maleate as the reference standard. The results of the biological activity indicate that the test compounds protected the animals from histamine-induced bronchospasm significantly. Compound 3-(4-chlorophenyl)-2-(2-(4-methylpiperazin-1-yl)-2-oxoethylthio) quinazolin-4(3H)-one (1) emerged as the most potent compound of the series (71.13 % protection) when compared to the reference standard chlorpheniramine maleate (70.09 % protection). Interestingly, compound A1 shows negligible sedation (12 %) compared to chlorpheniramine maleate (32 %). Therefore, compound A1 can serve as the lead molecule for further development.
引用
收藏
页码:4692 / 4699
页数:8
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