A new class of AT1 antagonists has been synthesized, replacing the imidazole of Losartan with an imidazo[1,2-a]pyridine moiety, the tetrazole ring with a carboxylic group, while the biphenyl group is linked by an amidic bond. The effects of the new synthesized angiotensin AT1 antagonists have been evaluated in vivo on the hypertensive response, caused by intravenous (i.v.) administration of ANGII , and compared with Losartan. Synthesized compounds have also been tested in vitro for the antagonism of ANGII-induced contraction of rat aortic ring, to demonstrate the ability to counteract the effects of the agonist in a physiologically relevant system. Affinity for AT1 receptor has been evaluated with an Angiotensin II Receptor binding assay calculating the compounds’ percentage inhibition values.
Synthesis and Antihypertensive Action of New Imidazo[1,2-a]pyridine Derivatives , non Peptidic Angiotensin II Receptor Antagonists
OSTACOLO, CARMINE;
2011-01-01
Abstract
A new class of AT1 antagonists has been synthesized, replacing the imidazole of Losartan with an imidazo[1,2-a]pyridine moiety, the tetrazole ring with a carboxylic group, while the biphenyl group is linked by an amidic bond. The effects of the new synthesized angiotensin AT1 antagonists have been evaluated in vivo on the hypertensive response, caused by intravenous (i.v.) administration of ANGII , and compared with Losartan. Synthesized compounds have also been tested in vitro for the antagonism of ANGII-induced contraction of rat aortic ring, to demonstrate the ability to counteract the effects of the agonist in a physiologically relevant system. Affinity for AT1 receptor has been evaluated with an Angiotensin II Receptor binding assay calculating the compounds’ percentage inhibition values.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
