title: Design and synthesis of novel 2-(3-substituted propyl)-3-(2-methyl phenyl) quinazolin-4-(3H)-ones as a new class of H1-antihistaminic agents.
abstract: A series of novel 2-(3-substituted propyl)-3-(2-methyl phenyl) quinazolin-4-(3H)-ones were synthesized by the reaction of 2-(3-bromopropyl thio)-3-(2-methyl phenyl) quinazolin-4-(3H)-one with various amines. The starting material, 2-(3-bromopropyl thio)-3-(2-methyl phenyl) quinazolin-4-(3H)-one was synthesized from 2-methyl aniline. When tested for their in vivo H(1)-antihistaminic activity on conscious guinea pigs, all the test compounds protected the animals from histamine induced bronchospasm significantly. Compound 2-(3-(4-methylpiperazin-1-yl) propylthio)-3-(2-methyl phenyl) quinazolin-4(3H)-one (OT5) emerged as the most active compound (71.70% protection) of the series when compared to the reference standard chlorpheniramine maleate (70.09% protection). Compound OT5 shows negligible sedation (7%) compared to chlorpheniramine maleate (33%). Therefore, compound OT5 can serve as the leading molecule for further development into a new class of H(1)-antihistaminic agents.
authors.affiliation: Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Sangareddy, Gr. Hyderabad, Andhra Pradesh, India. drvalagarsamy@gmail.com
authors.forename: V
authors.initials: V
authors.lastname: Alagarsamy
authors.forename: P
authors.initials: P
authors.lastname: Parthiban
mesh_terms: D000818:Animals; D001986:Bronchial Spasm / Q000517:prevention & control; D060326:Chemistry Techniques, Synthetic; D002744:Chlorpheniramine / Q000494:pharmacology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011799:Quinazolines / Q000737:chemistry*; D052999:Quinazolinones / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C583492:2-(3-(4-methylpiperazin-1-yl)propylthio)-3-(2-methylphenyl)quinazolin-4(3H)-one; D006634:Histamine H1 Antagonists; D006993:Hypnotics and Sedatives; D010879:Piperazines; D011799:Quinazolines; D052999:Quinazolinones; D002744:Chlorpheniramine