3-(1H-tetrazol-5-yl)-4(3H)-quinazolinone sodium salt (MDL 427): a new antiallergic agent

• Published in: Journal of medicinal chemistry Vol. 29; no. 11; pp. 2403 - 2409
• Main Authors: Peet, N P, Baugh, L E, Sunder, S, Lewis, J E, Matthews, E H, Olberding, E L, Shah, D N
• Format: Journal Article
• Language: English
• Published: United States 01.11.1986
• Subjects: Animals; Azoles - chemical synthesis; Histamine H1 Antagonists - chemical synthesis; Histamine H1 Antagonists - pharmacology; Histamine Release - drug effects; Hydrogen-Ion Concentration; Hypersensitivity - drug therapy; Male; Passive Cutaneous Anaphylaxis - drug effects; Quinazolines - chemical synthesis; Quinazolines - pharmacology; Quinazolinones; Rats; Rats, Inbred Strains; Structure-Activity Relationship; Tetrazoles - chemical synthesis; Tetrazoles - pharmacology
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00161a045

Syntheses for 3-(1H-tetrazol-5-yl)-4(3H)-quinazolinone sodium salt monohydrate (9; MDL 427) and the related formamido compound, 2-(formylamino)-N-1H-tetrazol-5-ylbenzamide (10), are described. Both compounds are active in the rat passive cutaneous anaphylaxis and passive peritoneal anaphylaxis tests. A 94:6 equilibrium mixture of 9 and ionized 10, respectively, forms in aqueous buffer systems at a pH-dependent rate. In addition, analogues of 3-(1H-tetrazol-5-yl)-4(3H)-quinazolinone (8) bearing substituents on the benzene ring, substituents at the 2-position, and heteroaryl groups at the 3-position other than tetrazole were prepared. These analogue sets demonstrated that an accessible electrophilic center and an acidic functionality were requirements for good antiallergic activity.