title: N6-Cycloalkyl-2-substituted adenosine derivatives as selective, high affinity adenosine A1 receptor agonists.
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.
authors.affiliation: Department of Bioorganic Chemistry, CV Therapeutics Inc., 3172 Porter Drive, Palo Alto, CA 94304, USA. elfatih.elzein@cvt.com
authors.forename: Elfatih
authors.initials: E
authors.lastname: Elzein
authors.forename: Rao
authors.initials: R
authors.lastname: Kalla
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Li
authors.forename: Thao
authors.initials: T
authors.lastname: Perry
authors.forename: Tim
authors.initials: T
authors.lastname: Marquart
authors.forename: Mark
authors.initials: M
authors.lastname: Micklatcher
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Wu
authors.forename: Dewan
authors.initials: D
authors.lastname: Zeng
authors.forename: Jeff
authors.initials: J
authors.lastname: Zablocki
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D000889:Anti-Arrhythmia Agents / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D000960:Hypolipidemic Agents / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D058907:Adenosine A1 Receptor Agonists; D000889:Anti-Arrhythmia Agents; D000960:Hypolipidemic Agents; C519005:N-cyclopentyl-2-(4-carbamoylpyrazol-1-yl)adenosine; C519004:N-norbornyl-2-(4-carboxypyrazol-1-yl)adenosine; D011720:Pyrazoles; D000241:Adenosine