title: Pharmacophore elucidation for a new series of 2-aryl-pyrazolo-triazolo-pyrimidines as potent human A3 adenosine receptor antagonists.
abstract: A ligand-based pharmacophore was obtained for a new series of 2-unsubstituted and 2-(para-substituted)phenyl-pyrazolo-triazolo-pyrimidines as potent human A(3) adenosine receptor antagonists. Through comparative molecular field analysis-based quantitative structure-activity relationship studies, structural features at the N(5)-, N(8)- and C(2)-positions of the tricyclic nucleus were deeply investigated, with emphasis given to the unprecedentedly explored C(2)-position. The resulting model showed good correlation and predictability (r(2)=0.936; q(2)=0.703; r(pred)(2)=0.663). Overall, the contribution of steric effect was found relatively more predominant for the optimal interaction of these antagonists to the human A(3) receptor.
authors.affiliation: Department of Pharmacy, National University of Singapore, 3 Science Drive 2, Block S15, #05-PI-03, Singapore 117543, Singapore.
authors.forename: Siew Lee
authors.initials: SL
authors.lastname: Cheong
authors.forename: Stephanie
authors.initials: S
authors.lastname: Federico
authors.forename: Gopalakrishnan
authors.initials: G
authors.lastname: Venkatesan
authors.forename: Priyankar
authors.initials: P
authors.lastname: Paira
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Shao
authors.forename: Giampiero
authors.initials: G
authors.lastname: Spalluto
authors.forename: Chun Wei
authors.initials: CW
authors.lastname: Yap
authors.forename: Giorgia
authors.initials: G
authors.lastname: Pastorin
mesh_terms: D058918:Adenosine A3 Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D011720:Pyrazoles / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*
chemical_list: D058918:Adenosine A3 Receptor Antagonists; D011720:Pyrazoles; D011743:Pyrimidines; D014230:Triazoles; C031280:pyrazole