Document Report Card

ID: ALA1122621

Journal: J Med Chem

Title: Antihypertensive activities of phenyl aminoethyl sulfides, a class of synthetic substrates for dopamine beta-hydroxylase.

Authors: Padgette SR, Herman HH, Han JH, Pollock SH, May SW.

Abstract: Four sulfur-containing analogues of phenylpropylamine were synthesized and evaluated as substrates for dopamine beta-hydroxylase (DBH) and monoamine oxidase (MAO). All four phenyl aminoethyl sulfides were shown to be good substrates for DBH whereas only the two analogues not possessing a methyl group alpha to the terminal amino group were substrates for MAO. All four analogues were tested for acute antihypertensive activity in an animal model for hypertension, the spontaneously hypertensive rat (SHR). Two of the analogues, both of which should partition readily across the blood-brain barrier, did not appreciably reduce systemic blood pressure in the 6-h testing period. However, the two analogues that were designed to be relatively restricted to peripheral sites of action caused a dramatic drop in blood pressure in SHR of 25% within 1-1.5-h postinjection, with the analogue designed to be both restricted to the periphery and MAO inactive, causing a more prolonged antihypertensive activity.

CiteXplore: 6481771

DOI: 10.1021/jm00376a024