title: 3-(1H-tetrazol-5-yl)-4(3H)-quinazolinone sodium salt (MDL 427): a new antiallergic agent.
abstract: 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.
mesh_terms: D000818:Animals; D001393:Azoles / Q000138:chemical synthesis*; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D006967:Hypersensitivity / Q000188:drug therapy*; D008297:Male; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D052999:Quinazolinones; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D001393:Azoles; D006634:Histamine H1 Antagonists; D011799:Quinazolines; D052999:Quinazolinones; D013777:Tetrazoles; C050656:3-(1H-tetrazol-5-yl)-4(3H)-quinazolinone