Inhibitors of blood platelet aggregation. Effects of some 1,2-benzisothiazol-3-ones on platelet responsiveness to adenosine diphosphate and collagen

A series of substituted 1,2-benzisothiazol-3-ones was synthesized, and the compounds were tested for ability to inhibit platelet aggregation induced by adenosine diphosphate and collagen in rats and guinea pigs ex vivo. Alkyl substituents at the 2-position bearing a basic group were necessary for ex...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1985-11, Vol.28 (11), p.1661-1667
Main Authors: Baggaley, Keith H, English, Peter D, Jennings, L. John A, Morgan, Brian, Nunn, Barbara, Tyrrell, A. William R
Format: Article
Language:English
Subjects:
Adenosine Diphosphate - pharmacology
Animals
Chemical Phenomena
Chemistry
Collagen - pharmacology
Exact sciences and technology
Guinea Pigs
Heterocyclic compounds
Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms
Humans
Male
Organic chemistry
Platelet Aggregation - drug effects
Preparations and properties
Rats
Structure-Activity Relationship
Thiazoles - chemical synthesis
Thiazoles - pharmacology
Thiazoles - toxicity
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Summary:A series of substituted 1,2-benzisothiazol-3-ones was synthesized, and the compounds were tested for ability to inhibit platelet aggregation induced by adenosine diphosphate and collagen in rats and guinea pigs ex vivo. Alkyl substituents at the 2-position bearing a basic group were necessary for ex vivo activity. Several of the compounds were potent inhibitors of adenosine diphosphate induced first-phase aggregation, but adverse toxicological findings terminated their further development. Preliminary studies suggested that inhibition of aggregation was not attributable to inhibition of prostanoid synthesis or to raised levels of cyclic 3',5'-adenosine monophosphate.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00149a021