Design and Synthesis of Novel 3-(4-Chlorophenyl)-2-(3-Substituted Propyl Thio) Quinazolin-4-(3H)-ones as a New Class of H1-Antihistaminic Agents

V. Alagarsamy; P. Parthiban

doi:10.1055/s-0032-1321778

Arzneimittelforschung, Table of Contents

Arzneimittelforschung 2012; 62(09): 433-438
DOI: 10.1055/s-0032-1321778

Original Article

Design and Synthesis of Novel 3-(4-Chlorophenyl)-2-(3-Substituted Propyl Thio) Quinazolin-4-(3H)-ones as a New Class of H₁-Antihistaminic Agents

V. Alagarsamy

¹Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Sangareddy, Hyderabad, Andhra Pradesh, India

,

P. Parthiban

¹Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Sangareddy, Hyderabad, Andhra Pradesh, India

› Author Affiliations

Abstract

A series of novel 3-(4-chlorophenyl)-2-(3-substituted propyl) quinazolin-4-(3H)-ones have been synthesized and tested for their in vivo H₁-antihistaminic activity on conscious guinea pigs. All the test compounds have protected the animals from histamine induced bronchospasm significantly. Compound 3-(4-chlorophenyl)-2-(3-(4-methylpiperazin-1-yl) propylthio) quinazolin-4(3H)-one (PC5) emerged as the most active compound (77.53% protection) of the series when compared to the reference standard chlorpheniramine maleate (70.09% protection). Compound PC5 shows negligible sedation (6.16%) compared to chlorpheniramine maleate (29.58%). Therefore, compound PC5 can serve as the lead molecule for further development into a new class of H₁-antihistaminic agents.

Key words

quinazolin-4-ones - sedation - H₁-antihistaminic activity

Full Text

References

References
1 Simons FE, Simons KJ. The pharmacology and use of H1-receptor-antagonist drugs. N Engl J Med 1994; 330: 1663-1670
2 Ellis EF, Adkinson NF, Yungingen JW. (eds.). Allergy Principles and Practice In Histamine H1-receptor antagonists. Mosby-Year Book, Inc; St. Louis: 1985. p 856-891
3 Carr AA, Meyer DR. Synthesis of terfenadine. Arzneimittelforschung 1982; 32: 1157-1159
4 Hopp RJ, Bewtra A, Nair NM et al. The effect of age on methacholine response. J Allergy Clin Immunol 1985; 76: 609-613
5 Chairungsrilerd N, Furukawa K, Ohta T et al. Pharmacological properties of alpha-mangostin, a novel histamine H1 receptor antagonist. Eur J Pharmacol 1996; 314: 351-356
6 Rao AR, Reddy VM. Synthesis and H₁-antihistaminic activity of beta-alkoxyethyl and beta-(N,N-dialkylamino)ethyl-(3-aryl-3,4-dihydro-4-oxoquinazolin- 2-yl)m ethyl ethers. Pharmazie 1992; 47: 794-796
7 Buyuktimkin SB, Buyuktimkin N, Ozdemir O et al. Synthesis of 3-[2-(2,3-dihydro-5-phenyl-4-substituted-3H-1,2,4-triazole-3-thione-2-yl)-acetylamino]-2-methyl-4(3H)-quinazolinones and their pharmacological activities. Arch Pharm 1989; 322: 49-51
8 Rao AR, Reddy VM. Synthesis of N-heteryl-beta-[(2-alkoxyethyl)oxy]/beta-[[2-(N,N-dialkylamino)ethyl]oxy]acetamides as possible H1-antihistaminics. J Pharm Sci 1994; 83: 953-955
9 Alagarsamy V, Venkatesaperumal R, Vijayakumar S et al. Synthesis and pharmacological investigation of some novel 2-phenyl-3-(substituted methyl amino) quinazolin-4(3H)-ones as H1-receptor blockers. Pharmazie 2002; 57: 306-307
10 Alagarsamy V. Synthesis and pharmacological investigation of some novel 2-methyl-3-(substituted methylamino)-(3H)-quinazolin-4-ones as histamine H1-receptor blockers. Pharmazie 2004; 59: 753-755
11 Alagarsamy V, Solomon VR, Murugan M. Synthesis and pharmacological investigation of novel 4-benzyl-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones as new class of H₁-antihistaminic agents. Bioorg Med Chem 2007; 15: 4009-4015
12 Van Arman CG, Miller LM, O'Malley MP. SC-10049: a catecholamine bronchodilator and hyperglycemic agent. J Pharmacol Exp Ther 1961; 133: 90-97
13 Dews PB. The measurement of the influence of drugs on voluntary activity in mice. Br J Pharmacol 1953; 8: 46-48
14 Kuhn WL, Van Maanen EF. Central nervous system effects of thalidomide. J Pharmacol Exp Ther 1961; 134: 60-68