Preparation of triazolo[1,5-c]pyrimidines as potential antiasthma agents

Preparation of triazolo[1,5-c]pyrimidines as potential antiasthma agents

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. T...

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Bibliographic Details
Published in:Journal of medicinal chemistry Vol. 33; no. 4; pp. 1230 - 1241
Main Authors: Medwid, Jeffrey B, Paul, Rolf, Baker, Jannie S, Brockman, John A, Du, Mila T, Hallett, William A, Hanifin, J. William, Hardy, Robert A, Tarrant, M. Ernestine
Format: Journal Article
Language:English
Published: Washington, DC American Chemical Society 01-04-1990
Subjects:
Animals
Asthma - drug therapy
Chemical Phenomena
Chemistry
Exact sciences and technology
Female
Heterocyclic compounds
Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings
Histamine H1 Antagonists - chemical synthesis
Mice
Organic chemistry
Passive Cutaneous Anaphylaxis - drug effects
Preparations and properties
Pyrimidines - chemical synthesis
Pyrimidines - therapeutic use
Structure-Activity Relationship
Chemical conversion
Cyclization
Structure activity relation
Angular nitrogen heterocycle
Bicyclic compound
Dimroth rearrangement
Antiasthma agent
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Summary: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.
Bibliography:istex:893733955D6FC1DD183ED2B11C40B4D3334AC4DB
ark:/67375/TPS-NPMNJLT4-Z
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00166a023