Date of Award

Fall 1986

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry & Biochemistry

Program/Concentration

Chemistry

Committee Director

Roy L. Williams

Committee Member

Patricia B. Williams

Committee Member

Patricia A. Pleban

Committee Member

Billy T. Upchurch

Call Number for Print

Special Collections LD4331.C45 D445

Abstract

An investigation was undertaken to synthesize and evaluate the cardiovascular activity of two imidazole ring systems. Imidazoles with hypotensive activity would provide novel potential antihypertensive drugs. These novel structures may also find use as chemical probes in the study of the cardiovascular system and as prototypes for other potential cardiovascular agents.

The histamine derivative, 7,7-dipyridyl-4,5,6,7-tetrahydroimidazo-[4,5-c]pyridine (ligand l), was demonstrated to possess significant hypotensive activity in laboratory rats. A 15 mg/Kg dose of ligand 1 produces a statistically significant decrease in blood pressure when injected IP. This hypotensive effect is also associated with marked increase in heart rate. Although compound 1 is structurally distinct from known antagonists of adrenoceptors, inquiries into the possible mode of action suggest possible antagonism of α-adrenoceptors. Structure-activity relationships indicate that the dipyridyl rings are absolutely essential for producing cardiovascular activity.

In addition, the novel 4(5)-methylimidazo-2-imidazoline, 4, was synthesized and evaluated for cardiovascular activity. The dihydrochloride salt of 4 was shown to significantly reduce heart rate, while having little or no effect on blood pressure.

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DOI

10.25777/23ft-g259

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