title: Preparation of triazolo[1,5-c]pyrimidines as potential antiasthma agents.
abstract: With the use of the human basophil histamine release assay, 5-aryl-2-amino[1,2,4]triazolo[1,5-c]pyrimidines were found to be active as mediator release inhibitors. These compounds were prepared by reacting arylamidines with sodium ethyl formylacetate or with ethyl propiolate to give pyrimidinones. Treatment with phosphorus oxychloride gave a chloropyrimidine, which was converted to a hydrazinopyrimidine with hydrazine. Cyclization, using cyanogen bromide, gave the triazolo[1,5-c]pyrimidines, after a Dimroth rearrangement. Following a structure-activity evaluation, the 5-[3-(trifluoromethyl)phenyl]-2-amino (8-10), 5-(3-bromophenyl)-2-amino (8-13), 5-[3-(difluoromethoxy)-phenyl]-2-amino (8-11), and 5-(4-pyridinyl)-2-amino (6-7) compounds were found to have the best activity. They were chosen for further pharmacological and toxicological study.
authors.affiliation: Medical Research Division, American Cyanamid Company, Lederle Laboratories, Pearl River, New York 10965.
authors.forename: J B
authors.initials: JB
authors.lastname: Medwid
authors.forename: R
authors.initials: R
authors.lastname: Paul
authors.forename: J S
authors.initials: JS
authors.lastname: Baker
authors.forename: J A
authors.initials: JA
authors.lastname: Brockman
authors.forename: M T
authors.initials: MT
authors.lastname: Du
authors.forename: W A
authors.initials: WA
authors.lastname: Hallett
authors.forename: J W
authors.initials: JW
authors.lastname: Hanifin
authors.forename: R A
authors.initials: RA
authors.lastname: Hardy
authors.forename: M E
authors.initials: ME
authors.lastname: Tarrant
authors.forename: L W
authors.initials: LW
authors.lastname: Torley
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis*; D051379:Mice; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D006634:Histamine H1 Antagonists; D011743:Pyrimidines