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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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Published in: | Journal of medicinal chemistry 1989-01, Vol.32 (5), p.1043-1051 |
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Main Authors: | , , , |
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. |
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ISSN: | 0022-2623 |