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Ligand design for alpha(1) adrenoceptor subtype selective antagonists

journal contribution
posted on 2023-05-16, 12:20 authored by Bremner, JB, Coban, B, Griffith, R, Karina GroenewoudKarina Groenewoud, Brian YatesBrian Yates
α1 Adrenoceptors have three subtypes and drugs interacting selectively with these subtypes could be useful in the treatment of a variety of diseases. In order to gain an insight into the structural principles governing subtype selectivity, ligand based drug design (pharmacophore development) methods have been used to design a novel 1,2,3-thiadiazole ring D analogue of the aporphine system. Synthesis and testing of this compound as a ligand on cloned and expressed human α1 adrenoceptors is described. Low binding affinity was found, possibly due to an unfavourable electrostatic potential distribution. Pharmacophore models for antagonists at the three adrenoceptor sites (α(1A), α(1B), α(1D)) were generated from a number of different training sets and their value for the design of new selective antagonists discussed. The first preliminary antagonist pharmacophore model for the α(1D) adrenoceptor subtype is also reported. (C) 2000 Elsevier Science Ltd.

History

Publication title

Bioorganic & Medicinal Chemistry

Volume

8

Pagination

201-214

ISSN

0968-0896

Department/School

School of Natural Sciences

Publisher

Pergamon-Elsevier

Place of publication

Oxford, UK

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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    University Of Tasmania

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