In a preliminary work, we reported two NO-sartans, possessing the characteristics of an AT(1) antagonist and a "slow NO donor", obtained by adding NO-donor side chains to losartan 1. The NO release from an NO-sartan should be modulated in order to strengthen the antihypertensive activity of the native drug and to ensure additional effects, such as the antiplatelet and anti-ischemic ones. To obtain a collection of prototypical NO-sartans, showing different rates of NO release, new NO-donor moieties have been linked to 1 or its active metabolite 2 (EXP 3174). Almost all the synthesized compounds exhibited both AT(1)-antagonist and NO-mediated vasorelaxing properties, with a wide range of NO-releasing rates. Further pharmacological investigation on compound 4a showed that it possessed antihypertensive and cardiac antihypertrophic effects similar to those of the reference AT(1)-blocking or ACE-inhibiting drugs. Furthermore, the additional anti-ischemic cardio-protective properties and antiplatelet effects of 4a have been preliminarily investigated.
|Autori:||BRESCHI M.C; CALDERONE V; DIGIACOMO M; MACCHIA M; MARTELLI A; MARTINOTTI E; MINUTOLO F; RAPPOSELLI S; ROSSELLO A; TESTAI L; BALSAMO A|
|Titolo:||New NO-Releasing Pharmacodynamic Hybrids of Losartan and Its Active Metabolite: Design,Synthesis, and Biopharmacological Properties|
|Anno del prodotto:||2006|
|Digital Object Identifier (DOI):||10.1021/jm0600186|
|Appare nelle tipologie:||1.1 Articolo in rivista|