Interest of cluster significance analysis in structure-affinity relationships for non-xanthine heterocyclic antagonists of adenosine

Autor:	M Adenot, Veronique Benezech, Pierre-Antoine Bonnet, Jean-Pierre Chapat, Gérard Grassy, J. Bompart
Rok vydání:	1997
Předmět:	Pharmacology Quantitative structure–activity relationship Stereochemistry Organic Chemistry Enthalpy General Medicine Xanthine Receptor binding site Adenosine chemistry.chemical_compound chemistry Drug Discovery medicine Binding site Cluster analysis Quantum medicine.drug
Zdroj:	European Journal of Medicinal Chemistry. 32:493-504
ISSN:	0223-5234
Popis:	Summary In order to define some predictive rules for the discrimination of adenosine antagonists by their A1-receptor affinity, we performed a systematic QSAR analysis. As no significant descriptors of affinity were found, we then proposed to introduce a calculated enthalpy or entropy change for the interaction as a first approximation of the affinity descriptors. Since the structural details of the common receptor binding site remain to be determined, we utilized an indirect strategy involving the simulation of amino acid residues that are thought to interact with the ligand. Estimating enthalpic and entropic components by means of a semi-empirical quantum mechanical AM1 force calculation, we found a significant clustering of enthalpy change values. This method provides a good descriptor of interaction and also a simple tool for testing hypotheses on the nature of putative binding sites.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::cccacfd4d1b975a7d204a1e1226c171e https://doi.org/10.1016/s0223-5234(97)84012-3 Zobrazit plný text záznamu Full Text from ScienceDirect