Selective and potent antagonists for the A(2A) adenosine receptors have been described recently. The most potent compounds have a triazolo-pyrimidine structure, whereas 8-styryl-xanthines usually possess lower affinity at the A(2A) receptor. We have examined the quantitative structure activity relationships of 34 triazolo-pyrimidines using the Comparative Molecular Field Analysis (CoMFA). The model developed accounts in a satisfactory manner for the structure-activity relationships within this series of A(2A) receptor antagonists (q2 = 0.840, r2 = 0.970) and, consequently, it can be used as a guide in the design of novel analogs with optimized antagonistic activity. The overall predictivity of this model was tested on the published data of a set of external molecules giving acceptable results. The validity of the CoMFA approach as an effective tool for studying the 3D-QSAR of series of biologically active compounds is confirmed, even if additional efforts clearly are needed for trying to extend the models to structurally more varied series of derivatives.
Comparative molecular field analysis (CoMFA) of a series of selective adenosine receptor A(2A) antagonists / Baraldi P.G.; Borea P.A.; Bergonzoni M.; Cacciari B.; Ongini E.; Recanatini M.; Spalluto G.. - In: DRUG DEVELOPMENT RESEARCH. - ISSN 0272-4391. - STAMPA. - 46:2(1999), pp. 126-133. [10.1002/(SICI)1098-2299(199902)46:2<126::AID-DDR5>3.0.CO;2-7]
Comparative molecular field analysis (CoMFA) of a series of selective adenosine receptor A(2A) antagonists
Recanatini M.;
1999
Abstract
Selective and potent antagonists for the A(2A) adenosine receptors have been described recently. The most potent compounds have a triazolo-pyrimidine structure, whereas 8-styryl-xanthines usually possess lower affinity at the A(2A) receptor. We have examined the quantitative structure activity relationships of 34 triazolo-pyrimidines using the Comparative Molecular Field Analysis (CoMFA). The model developed accounts in a satisfactory manner for the structure-activity relationships within this series of A(2A) receptor antagonists (q2 = 0.840, r2 = 0.970) and, consequently, it can be used as a guide in the design of novel analogs with optimized antagonistic activity. The overall predictivity of this model was tested on the published data of a set of external molecules giving acceptable results. The validity of the CoMFA approach as an effective tool for studying the 3D-QSAR of series of biologically active compounds is confirmed, even if additional efforts clearly are needed for trying to extend the models to structurally more varied series of derivatives.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
