Bioorg Med Chem Lett. 2007 Jan 1;17(1):161-6. Epub 2006 Oct 11.

N6-Cycloalkyl-2-substituted adenosine derivatives as selective, high affinity adenosine A1 receptor agonists.

Elzein E, Kalla R, Li X, Perry T, Marquart T, Micklatcher M, Li Y, Wu Y, Zeng D, Zablocki J.

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Department of Bioorganic Chemistry, CV Therapeutics Inc., 3172 Porter Drive, Palo Alto, CA 94304, USA. elfatih.elzein@cvt.com

Abstract

A series of new selective, high affinity A(1)-AdoR agonists is reported. Compound 23 that incorporated a carboxylic acid functionality in the 4-position of the pyrazole ring displayed K(iL) value of 1 nM for the A(1)-AdoR and >5000-fold selectivity over the A(3) and A(2A)-AdoRs. In addition, compound 19 that incorporated a carboxamide functionality in the 4-position of the pyrazole ring displayed subnanomolar affinity for the A(1)-AdoR (K(iL)=0.6 nM) and >600-fold selectivity over the A(3) and A(2A)-AdoRs.

PMID:: 17045477; [PubMed - indexed for MEDLINE]

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