The heuristic-direct approach to theoretical quantitative structure-activity relationship analysis of α1-adrenoceptor ligands

doi:10.1016/0166-1280(94)03745-7

Journal of Molecular Structure: THEOCHEM

Volume 314, Issue 3, 20 November 1994, Pages 265-276

https://doi.org/10.1016/0166-1280(94)03745-7 Get rights and content

Abstract

The heuristic-direct quantitative structure-activity relationship approach has been applied to fifteen non-congeneric α₁-adrenergic receptor (α₁-AR) ligands interacting with the rat $α_{1AD} - AR$ subtype. The good linear correlations, which have been obtained between calculated binding energies and the pharmacological affinities, allow one to predict the pharmacological affinity of new ligands. Moreover, according to the $α_{1AD} - receptor$ model proposed, it has been possible to speculate on the amino acid residues which are mainly involved in the interaction with the ligands. This novel procedure constitutes a powerful tool for the design of new selective leads based on explicit intermolecular interactions and for suggesting site-directed mutagenesis studies, in order to give, iteractively, further support and improvement to the predictive and interpretative aspects of the model.

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¹: Permanent address: Dipartimento Farmaco-Chimico, Università di Bari, V. Orabona 4, 70125 Bari, Italy.

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The heuristic-direct approach to theoretical quantitative structure-activity relationship analysis of α1-adrenoceptor ligands

Abstract

J. Mol. Struct. (Theochem)

Bioorg. Med. Chem.

J. Biol. Chem.

Eur. J. Pharmacol.

J. Mol. Struct. (Theochem)

J. Mol. Struct. (Theochem)

J. Mol. Struct. (Theochem)

J. Mol. Struct. (Theochem)

J. Mol. Biol.

J. Biol. Chem.

J. Mol. Biol.

Trends Pharmacol. Sci.

J. Biol. Chem.

Eur. J. Biochem.

Nucleic Acids Res.

J. Biol. Chem.

Mol. Pharmacol.

Quant. Struct. -Act. Relat.

The heuristic-direct approach to theoretical quantitative structure-activity relationship analysis of α₁-adrenoceptor ligands