Adenosine receptor prodrugs: synthesis and biological activity of derivatives of potent, A1-selective agonists

Détails

ID Serval
serval:BIB_909D8DECFD70
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Adenosine receptor prodrugs: synthesis and biological activity of derivatives of potent, A1-selective agonists
Périodique
Journal of Pharmaceutical Sciences
Auteur(s)
Maillard  M. C., Nikodijevic  O., LaNoue  K. F., Berkich  D., Ji  X. D., Bartus  R., Jacobson  K. A.
ISSN
0022-3549 (Print)
Statut éditorial
Publié
Date de publication
01/1994
Volume
83
Numéro
1
Pages
46-53
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan
Résumé
5'-Ester derivatives of the potent adenosine agonists N6-[4-[[[[4-[[[(2-acetylaminoethyl)amino]carbonyl]methyl] anilino]carbonyl]methyl]phenyl]adenosine (N-AcADAC; 1) and N6-cyclopentyladenosine (CPA; 2) were prepared as prodrugs. Both alkyl esters or carbonates (designed to enter the brain by virtue of increased lipophilicity) and 1,4-dihydro-1-methyl-3-[(pyridinylcarbonyl)oxy]esters designed to concentrate in the brain by virtue of a redox delivery system were synthesized. In the 5'-blocked form, the adenosine agonists displayed highly diminished affinity for rat brain A1-adenosine receptors in binding assays. The dihydropyridine prodrug 29 was active in an assay of locomotor depression in mice, in which adenosine agonists are highly depressant. The behavior depression was not reversible by peripheral administration of a non-central nervous system active adenosine antagonist. In an assay of the peripheral action of adenosine (i.e., the inhibition of lipolysis in rats), the parent compounds were highly potent and the dihydropyridine prodrug was much less potent.
Mots-clé
Adenosine/analogs & derivatives/*chemical synthesis/pharmacology Animals Glycerol/blood Male Mice Motor Activity/drug effects Prodrugs/*chemical synthesis/pharmacology Rats Rats, Sprague-Dawley Receptors, Purinergic P1/*drug effects Structure-Activity Relationship
Pubmed
Web of science
Création de la notice
25/01/2008 13:59
Dernière modification de la notice
20/08/2019 15:54
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