Synthesis and pharmacological investigation of some novel 2-methyl-3-(substituted methylamino)-(3H)-quinazolin-4-ones as histamine H1-receptor blockers.

A series of 2-methyl-3-(substituted methylamino)-(3H)-quinazolin-4-ones were synthesized from 3-amino-2-methyl-(3H)-quinazolin-4-one. Their structures were confirmed by spectral data (IR, NMR and MS) and the purity was ascertained by microanalysis. When tested for H1-receptor blocking activity on isolated guinea pig ileum all the test compounds inhibited histamine induced contraction whereas compound 5 (IC50 0.22 x 10(3) ng/ml) was found to be four times more potent than chlorpheniramine maleate (IC50 1 x 10(3) ng/ml) and it showed lesser sedation (8%) than the standard (32%).