Bronchospasmolytic activity and adenosine receptor binding of some newer 1, 3‐dipropyl‐8‐phenyl substituted xanthine derivatives. (13th March 2020)

• Record Type: Journal Article
• Authors: Gumber, Divya; Yadav, Divya; Yadav, Rakesh; Kachler, Sonja; Klotz, Karl Norbert
• Is Part Of: Chemical biology & drug design. Volume 95:Number 6(2020)
• Page Start: 600
• Page End: 609
• Publication Date: 2020-03-13
• Subjects: adenosine -- antiasthmatics -- bronchospasmolytic -- radioligand binding -- xanthines; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.13673
• Languages: English
• ISSNs: 1747-0277

Abstract

Abstract: The aldehyde derivatives of 1, 3‐dipropyl xanthines as described in this paper, constitutes a new series of selective adenosine ligands displaying bronchospasmolytic activity. The effect of substitution at third‐ and fourth‐position of 8‐phenyl xanthine has also been taken into consideration. The synthesized compounds showed varying binding affinities at different adenosine receptor subtypes (A1, A2A, A2B, and A3 ) and also good in vivo bronchospasmolytic activity against histamine aerosol‐induced asthma in guinea pigs. Most of the compounds showed maximum affinity toward the A2A receptor subtype. The monosubstituted 3‐aminoalkoxyl 8‐phenyl xanthine with a aminodiethyl moiety (compound 12e ) was found to be most potent A2A adenosine receptor ligand ( K i = 0.036 µM) followed by disubstituted 4‐aminoalkoxyl‐3‐methoxy‐8‐phenyl xanthine ( K i = 0.050 µM) (compound 10a ). Abstract : The affinity for adenosine receptors is increased when various substitutions in the xanthine moiety are introduced. Most of the A2A agonists are directly related to adenosine itself so various synthetic modifications were done to the naturally occurring xanthines to produce selective A2A receptor ligands.