title: A quantitative analysis of binding affinities of ligands active at adenosine receptors.
abstract: Binding affinities, pKi's, of 1,3-dipropyl-8-phenylxanthines and 8-substituted xanthines as selective antagonists at A(1)- and A(2)- adenosine receptors, were quantitatively analysed in terms of hydrophobic parameter, pi, and van der Waals volume, Vw. For ligands of the first series, the hydrophobicity of para-substituents and the bulk of meta-substituents are shown to be the deciding factors. Similarly, for the other series, the binary substitutions at X-, Y- and R-positions, highlighted by respective dummy variables, and the bulk rendered by groups at R(1)-position, are found to be significantly correlated with A(1)- and A(2)-receptor affinities. Additionally, the Free-Wilson study of this series resulting into individual substituent contribution, provides similar inferences to these, but in a more exact manner. This study also hints at the possibility of a different accommodation site at the receptor for the R(1)-substituents of the congeners on account of conformational dissimilarity of A(1)- and A(2)-receptors.
authors.affiliation: Department of Chemistry, S. K. Government College, India.
authors.forename: R C
authors.initials: RC
authors.lastname: Sharma
authors.forename: P
authors.initials: P
authors.lastname: Singh
authors.forename: T N
authors.initials: TN
authors.lastname: Ojha
authors.forename: S
authors.initials: S
authors.lastname: Tiwari
mesh_terms: D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007700:Kinetics; D008024:Ligands; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000737:chemistry / Q000378:metabolism*; D014970:Xanthines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D008024:Ligands; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines