Analogs of 1,3-dipropyl-8-phenylxanthine: enhancement of selectivity at A1-adenosine receptors by aryl substituents

• Published in: Journal of medicinal chemistry Vol. 29; no. 8; pp. 1520 - 1524
• Main Authors: Daly, J. W, Padgett, W. L, Shamim, M. T
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.08.1986
• Subjects: Animals; Cerebral Cortex - metabolism; Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Organic chemistry; Preparations and properties; Rats; Receptors, Cell Surface - metabolism; Receptors, Purinergic; Structure-Activity Relationship; Xanthines - chemical synthesis; Xanthines - pharmacology; Substituent effect; Nitrogen heterocycle; Bicyclic compound; Phenols; Benzenic compound; Ureas; Selectivity
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00158a034

The effect of a variety of aryl substituents on the potency and selectivity of 19 analogues of 1,3-dipropyl-8-phenylxanthine as antagonists at A1- and A2-adenosine receptors in brain tissue was determined. The 4-sulfamoylphenyl and 4-carbamoylphenyl analogues are potent and somewhat selective for the A1 receptor. None of the dihydroxyphenyl analogues are remarkably potent, but all are selective for the A1 receptor. 1,3-Dipropyl-8-(2-hydroxy-4-methoxyphenyl)xanthine is the most selective A1 antagonist of the analogues with a A1/A2 potency ratio of about 90.