Synthesis and Adenosine Receptor Affinity of a Series of Pyrazolo[3,4-d]pyrimidine Analogues of 1-Methylisoguanosine

Fiona A. Harden, Ronald J. Quinn, Peter J. Scammells

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Abstract

Pyrazolo[3,4-d]pyrimidines are pyrazolo analogues of purines. They have been shown to be a general class of compounds which exhibit A1 adenosine receptor affinity. Two series of pyrazolo[3,4-d]pyrimidine analogues of 1-methylisoguanosine have been synthesized. The first involved substitution of the N1-position while the second involved substitution of the N5-position. Both alkyl and aryl substituents were examined. All compounds were tested for A1adenosine receptor affinity by using a (R)-[3H]-N6-(phenylisopropyl)adenosine binding assay. The 3-chlorophenyl group showed the greatest activity in the N1-position and the butyl group produced the greatest activity in the N5-position. Combination of the best substituent in each of these positions enhanced the overall activity. The most potent compound was 4-amino-5-N-butyl-1-(3-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-6(5.H)-one with an IC50of 6.4 × 10-6M. Selectivity at the receptor subclasses was examined by performing an A2adenosine receptor affinity assay with [3H]CGS 21680. This series of compounds were slightly less potent at A2receptors. 4-Amino-5-N-butyl-1-(3-chloro- phenyl)-1H-pyrazolo[3,4-d]pyrimidin-6(5H)-one was the most potent compound with an IC50of 19.2 × 10-6M. © 1991, American Chemical Society. All rights reserved.
Original languageEnglish
Pages (from-to)2892-2898
Number of pages7
JournalJournal of Medicinal Chemistry
Volume34
Issue number9
DOIs
Publication statusPublished - 1 Sep 1991

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