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Ligand design for alpha(1) adrenoceptor subtype selective antagonists


Bremner, JB and Coban, B and Griffith, R and Groenewoud, KM and Yates, BF, Ligand design for alpha(1) adrenoceptor subtype selective antagonists, Bioorganic & Medicinal Chemistry , 8, (1) pp. 201-214. ISSN 0968-0896 (2000) [Refereed Article]

DOI: doi:10.1016/S0968-0896(99)00263-1


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.

Item Details

Item Type:Refereed Article
Research Division:Chemical Sciences
Research Group:Medicinal and biomolecular chemistry
Research Field:Medicinal and biomolecular chemistry not elsewhere classified
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Groenewoud, KM (Ms Karina Groenewoud)
UTAS Author:Yates, BF (Professor Brian Yates)
ID Code:19757
Year Published:2000
Web of Science® Times Cited:65
Deposited By:Chemistry
Deposited On:2000-08-01
Last Modified:2011-08-04

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