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Electrophilic derivatives of purines as irreversible inhibitors of A sub(1) adenosine receptors

Functionalized congeners derived from 1,3-dipropyl-8-phenylxanthine and from N super(6)-phenyladenosine were derivatized to contain electrophilic groups (isothiocyanate, N-hydroxysuccinimide ester, maleimide, sulfonyl chloride, or alpha -haloacyl group) capable of reaction with nucleophiles on biopo...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1989-01, Vol.32 (5), p.1043-1051
Main Authors: Jacobson, KA, Barone, S, Kammula, U, Stiles, G L
Format: Article
Language:English
Online Access:Get full text
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Summary:Functionalized congeners derived from 1,3-dipropyl-8-phenylxanthine and from N super(6)-phenyladenosine were derivatized to contain electrophilic groups (isothiocyanate, N-hydroxysuccinimide ester, maleimide, sulfonyl chloride, or alpha -haloacyl group) capable of reaction with nucleophiles on biopolymers. The goal was to inhibit chemically the A sub(1) adenosine receptor by using reactive agonist and antagonist ligands. Some of the electrophilic derivatives were synthesized through acylation of amine-functionalized congeners using hetero- or homobifunctional reagents available for protein cross-linking. The affinity for A sub(1) adenosine receptors was evaluated in competitive binding assays by using rat and bovine brain membranes. Several xanthine and adenosine thiourea derivatives prepared from 1,3- and 1,4-phenylene diisothiocyanate (DITC) were potent irreversible inhibitors of adenosine receptors.
ISSN:0022-2623