These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: 7-Deaza-9-phenyladenines. A new class of adenosine receptor antagonists.
    Author: Daly JW, Padgett WL, Eger K.
    Journal: Biochem Pharmacol; 1988 Oct 01; 37(19):3749-53. PubMed ID: 3178888.
    Abstract:
    A series of twelve 7-deaza-9-phenyladenines and of related 9-aralkyl-, 9-alkyl-, and 9-alkenyl-analogs and of 7-deaza-9-phenylhypoxanthines inhibited binding of [3H]phenylisopropyladenosine to rat brain A1-adenosine receptors and antagonized activation of adenylate cyclase elicited by interaction of N-ethylcarboxamidoadenosine with A2-adenosine receptors in rat pheochromocytoma PC12 cell membranes. A subset of seven compounds, encompassing the range of major structural variations, antagonized inhibition of adenylate cyclase elicited by interaction of R-phenylisopropyladenosine with A1-adenosine receptors in rat fat cell membranes. 7-Deaza-9-phenyladenine had a Ki value of 3 microM at the brain A1-receptor and a KB value of 17 microM at the PC12 A2-receptor and was thus about 5-fold more potent than theophylline at the former and nearly equipotent with theophylline at the latter. It had a KB value of 4.6 microM at the fat cell A1-receptor. The presence of methyl groups at the 7- and 8-positions reduced activity at all receptors several fold. Aryl substituents in a series of 7-deaza-7,8-dimethyl-9-phenyladenines did not have major effects on affinities for the brain A1- or the PC12 cell A2-adenosine receptors. The absence of the 9-phenyl substituent in the 7,8-dimethyl series reduced activity several fold, while replacement with arylalkyl (-CH2C6H4F), alkyl (-(CH2)5CH3) or alkenyl (-CH2CH = CH2) substituents had only modest effects on potency at the brain A1-receptor and the PC12 cell A2-receptor. 7-Deaza-7,8-dimethylhypoxanthine was nearly equipotent to the analogous 7-deazaadenine at the brain and fat cell A1-receptors, but was several fold more potent than the analogous 7-deazaadenine at the A2-receptor. 7-Deaza-7,8-dimethyl-9-(2,4-dibromophenyl)hypoxanthine was less potent than the analogous 7-deazaadenine at both the brain A1- and the PC12 cell A2-adenosine receptors. 7-Deaza-9-phenyl-7,8-benzohypoxanthine was the most potent of the present series of antagonists and was somewhat selective for the A2-adenosine receptor with a Ki of 0.9 microM at the brain A1-receptor, a KB of 1.4 microM at the fat cell A1-receptor, and a KB of 0.2 microM at the A2-receptor.
    [Abstract] [Full Text] [Related] [New Search]