Geometry, topology, and atom-weights assembly descriptors to predicting A1 adenosine receptors agonists

• Published in: Bioorganic & medicinal chemistry letters Vol. 15; no. 10; pp. 2641 - 2645
• Main Authors: González, Maykel Pérez, Terán, Carmen, Teijeira, Marta, Besada, Pedro
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 16-05-2005; Elsevier
• Subjects: A1 adenosine receptors agonists; Biological and medical sciences; GETAWAY descriptors; Medical sciences; Models, Molecular; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Purinergic P1 Receptor Agonists; QSAR; Quantitative Structure-Activity Relationship; QSAR; A1 adenosine receptors agonists; GETAWAY descriptors; Agonist; Purine nucleoside; Acetylenic compound; Prediction; A1 Adenosine receptor; Topology; Modeling; Structure activity relation; Topological index; Molecular model; Uronic acid; Organic amide; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.03.028

The GETAWAY approach has been applied to the study of the A1 adenosine receptor agonist effect with excellent results. Five different approaches failed to give satisfactory models for this property.
The GEometry, Topology, and Atom-Weights AssemblY (GETAWAY) approach has been applied to the study of the A1 adenosine receptors agonist effect of 32 adenosine analogues: N6-arylcarbamoyl, 2-arylalkynyl-N6-arylcarbamoyl, and N6-carboxamido derivatives. A model, able to describe more than 77% of the variance in the experimental activity, was developed with the use of the above mentioned approach. Five different approaches (Topological, Galvez Topological Charges indexes, Randić Molecular Profiles, Geometrical, and WHIM descriptors) failed to give satisfactory models (R2=0.70) for this property with the same number of variables in the equation. Although statistically significant models were derived containing descriptors other than GETAWAY, the best fitted out model was still found with these descriptors.