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Your search keyword '"Douglas A. Thomason"' showing total 2 results
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2 results on '"Douglas A. Thomason"'

1. The synthesis and biological activity of tetrahydroquinoline angiotensin II antagonists containing a substituted biphenyltetrazole group

Author

David Anthony Roberts, Andrew Peter Thomas, and Douglas A. Thomason

Subjects
Chemistry, Stereochemistry, Organic Chemistry, Clinical Biochemistry, Pharmaceutical Science, Angiotensin ii antagonist, Biological activity, Biochemistry, Angiotensin II, In vitro, Pressor response, Drug Discovery, Molecular Medicine, Molecular Biology
Abstract

The synthesis of analogues of tetrahydroquinoline angiotensin II antagonist, ZENECA ZD6888, bearing substituents on the biphenyl ring system is reported. Several of these compounds show comparable or superior activity to ZD6888 in an in vitro beinding assay and in inhibition of the AII-induced pressor response in normotensive rats.

Published
1994

2. New nonpeptide angiotensin II receptor antagonists. 1. Synthesis, biological properties and structure-activity relationships of 2-alkylbenzimidazole derivatives

Author

Arnold Harry Ratcliffe, J. S. Major, Keith Hopkinson Gibson, Christopher P. Allott, Simon Thomas Russell, Brian B. Masek, Andrew Peter Thomas, A. A. Oldham, David A. Roberts, and Douglas A. Thomason

Subjects
Male, Models, Molecular, Angiotensin receptor, Benzimidazole, Stereochemistry, Guinea Pigs, Molecular Conformation, Blood Pressure, Binding, Competitive, Molecular mechanics, Angiotensin Receptor Antagonists, Structure-Activity Relationship, chemistry.chemical_compound, In vivo, Drug Discovery, Animals, Structure–activity relationship, Molecular Structure, Angiotensin II, Rats, Inbred Strains, In vitro, Rats, chemistry, Hypertension, Molecular Medicine, Benzimidazoles, Rabbits, hormones, hormone substitutes, and hormone antagonists
Abstract

On the basis of an extension of the literature lead 1, a series of benzimidazoles have been synthesized and shown to be angiotensin II (AII) receptor antagonists. The structure-activity relationships of these new antagonists have been explored and the key binding interactions defined. Molecular mechanics calculations were carried out on analogues of imidazole AII antagonists and conformationally restricted analogues were synthesized. The benzimidazole antagonists displaced AII in binding studies in vitro with IC50 values in the range 10(-5)-10(-7) M and antagonized the hypertensive effects of AII in vivo (rats) following intravenous administration with ED50 values in the range of 5-20 mg/kg.

Published
1992

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