Non-xanthine heterocycles: Activity as antagonists of A1 and A2-adenosine receptors

doi:10.1016/0006-2952(88)90139-6

Biochemical Pharmacology

Volume 37, Issue 4, 15 February 1988, Pages 655-664

https://doi.org/10.1016/0006-2952(88)90139-6 Get rights and content

Abstract

A variety of non-xanthine heterocycles were found to be antagonists of binding of [³H]phenylisopropyladenosine to rat brain A₁-adenosine receptors and of activation of adenylate cyclase via interaction of N-ethylcarboxamidoadenosine with A₂-adenosine receptors in human platelet and rat pheochromocytoma cell membranes. The pyrazolopyridines tracazolate, cartazolate and etazolate were several fold more potent than theophylline at both A₁ and A₂-adenosine receptors. The pyrazolopyridines, however, were still many fold less potent than 8-phenyltheophylline and other 8-phenyl-1,3-dialkylxanthines. A structurally related N⁶-substituted 9-methyladenine was also a potent adenosine antagonist with selectivity for A₁ receptors. None of several aryl-substituted heterocycles, including a thiazolopyrimidine, imidazopyridines, benzimidazoles, a pyrazoloquinoline, a mesoionic xanthine analog and a triazolopyridazine exhibited the high potency typical of 8-phenyl-1,3-dialkylxanthines. A furyl-substituted triazoloquinazoline was very potent at both A₁ and A₂ receptors. A pteridin-2,4-dione, 1,3-dipropyllumazine, was somewhat less potent than theophylline at A₁- and A₂-adenosine receptors, whereas 1,3-dimethyllumazine was much less potent. A benzopteridin-2,4-dione, alloxazine, was somewhat more potent than theophylline. Other heterocycles with antagonist activity were the dibenzazepine carbamazepine and β-carboline-3-ethyl carboxylate. The phenylimidazoline clonidine had no activity, whereas a related dihydroxyphenylimidazoline was a weak non-competitive adenosine antagonist.

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Non-xanthine heterocycles: Activity as antagonists of A1 and A2-adenosine receptors

Abstract

Life Sci.

Life Sci.

Biochem. Pharmac.

Fedn Ew. Biochem. Soc. Lett.

Life Sci.

Fedn Eur. Biochem. Soc. Lett.

Life Sci.

Biochem. Pharmac.

Neurosci. Lett.

Life Sci.

Biochem. Pharmac.

Life Sci.

Neuropharmacology

Eur. J. Pharmac.

Eur. J. Pharmac.

Eur. J. Pharmac.

Pharmac. Biochem. Behau.

Life Sci.

Brain Res.

Life Sci.

Eur. J. Pharmac.

J. med. Chem.

Non-xanthine heterocycles: Activity as antagonists of A₁ and A₂-adenosine receptors