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• W2074964923 abstract "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 Ki 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." @default.
• W2074964923 created "2016-06-24" @default.
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• W2074964923 date "2009-11-09" @default.
• W2074964923 modified "2023-09-30" @default.
• W2074964923 title "Phosphinic Tripeptides as Dual Angiotensin-Converting Enzyme C-Domain and Endothelin-Converting Enzyme-1 Inhibitors" @default.
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• W2074964923 doi "https://doi.org/10.1021/jm9010803" @default.
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