title: Design, synthesis and histamine H1-receptor antagonistic activity of some novel 4-amino-2-(substituted)-5-(substituted) aryl-6-[(substituted aryl) amino] pyrimidines.
abstract: A series of 4-amino-2-(substituted)-5-(substituted)aryl-6-[(substituted)aryl)-amino]pyrimidines was designed based on the triangular pharmacophoric requirements for histamine H1-receptor antagonists. The designed molecules were synthesized by condensation of arylacetonitriles with respective arylisothiocyanates to form corresponding acrylonitriles followed by cyclocondensation with carboxamidines to afford substituted pyrimidines. All compounds were screened for their histamine H1-receptor antagonistic activity using the model "Inhibition of the isotonic contraction induced by histamine on isolated guinea pig ileum". Target compounds were also evaluated for their sedative potential as well as their anticholinergic activities as these two are known to be the common adverse effects of histamine H1-receptor antagonists. Compounds 2h, 2i, 2j and 2k exhibited potent histamine H1-receptor antagonistic activity, which was found to be comparable with the standard drug, cetirizine (CAS 83881-51-0) and more potent than the conventional drug mepyramine (CAS 91-84-9). Some of the compounds have displayed very low sedative potential compared to diphenhydramine (CAS 58-73-1), but was found higher than cetirizine. None of them showed anticholinergic activity indicating potentialities of this series to be developed as second-generation histamine H1-receptor antagonists.
authors.affiliation: Department of Pharmaceutical Chemistry, L. M. College of Pharmacy, Navrangpura, Ahmedabad, Gujarat, India. mahesh.chhabria@rediffmail.com
authors.forename: Mahesh T
authors.initials: MT
authors.lastname: Chhabria
authors.forename: Vimal T
authors.initials: VT
authors.lastname: Patel
authors.forename: Kombu S
authors.initials: KS
authors.lastname: Rajan
authors.forename: Pathik S
authors.initials: PS
authors.lastname: Brahmkshatriya
mesh_terms: D000818:Animals; D018680:Cholinergic Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis / Q000494:pharmacology; D007202:Indicators and Reagents; D051379:Mice; D008958:Models, Molecular; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D018680:Cholinergic Antagonists; D006634:Histamine H1 Antagonists; D006993:Hypnotics and Sedatives; D007202:Indicators and Reagents; D011743:Pyrimidines