908607-44-3Relevant academic research and scientific papers
Phosphinic tripeptides as dual angiotensin-converting enzyme C-domain and endothelin-converting enzyme-1 inhibitors
Jullien, Nicolas,Makritis, Anastasios,Georgiadis, Dimitris,Beau, Fabrice,Yiotakis, Athanasios,Dive, Vincent
experimental part, p. 208 - 220 (2010/05/02)
A new series of phosphinic inhibitors able to interact with both angiotensin-converting enzyme (ACE) C-domain and endothelin-converting enzyme-1 (ECE-1), while sparing neprilysin (NEP), has been developed. The most potent and selective inhibitor in this series (compound 8F2) displays K i values of 0.65 nM, 150 nM, 14 nM and 6.7 μM toward somatic ACE C-domain, ACE N-domain, ECE-1, and NEP, respectively. Remarkably, in this series, the inhibitor's ability to discriminate between ECE-1 and NEP was observed to depend on the stereochemistry of the residue present in the inhibitor's P1′ position. After iv administration, compound 8F2 (10 mg/kg) lowered mean arterial blood pressure by 24 ± 2 mmHg in spontaneously hypertensive rats, as compared with controls. Mixed ACE/ECE-1 inhibitor may lead to a new generation of vasopeptide inhibitors that should reduce the levels of angiotensin-II and endothelin-1, without interfering with bradykinin cleavage.
