A2B Adenosine Receptor Agonists: Synthesis and Biological Evaluation of 2‐Phenylhydroxypropynyl Adenosine and NECA Derivatives
- 1 January 2004
- journal article
- Published by Taylor & Francis in Nucleosides, Nucleotides and Nucleic Acids
- Vol. 23 (1-2) , 471-481
- https://doi.org/10.1081/ncn-120028340
Abstract
In the search for agonists for the elusive A2B adenosine receptor subtypes, 2‐phenylhydroxypropynyl‐5′‐N‐methylcarboxamido adenosine (PHPMECA, 14), 2‐phenylhydroxypropynyl‐5′‐N‐propylcarboxamido adenosine (PHPPECA, 15), and N 6‐ethyl‐2‐phenylhydroxypropynyl‐5′‐N‐ethylcarboxamidoadenosine (19) were synthesized on the basis that introduction of alkynyl chains in 2‐position of adenosine derivatives resulted in reasonably good A2B potency compared to NECA [see N 6‐ethyl‐2‐phenylhydroxypropynyl adenosine (5) EC50 = 1,700 nM and 2‐phenylhydroxypropynyl‐5′‐N‐ethylcarboxamido adenosine (PHPNECA, 8) EC50 = 1,100 nM, respectively]. Radioligand binding studies and adenylyl cyclase assays, performed with recently cloned human A1, A2A, A2B, and A3 adenosine receptors, showed that these modifications produced a decrease in potency at A2B receptor, as well as a general reduction in affinity at the other receptor subtypes. On the other hand, the contemporary presence of an ethyl substituent in N 6‐position and of a 4′‐et...Keywords
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