N-formyl hydroxylamine containing dipeptides: generation of a new class of vasopeptidase inhibitors.

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Robl JA, Simpkins LM, Asaad MM

N-formyl hydroxylamine containing dipeptides: generation of a new class of vasopeptidase inhibitors.

Bioorg Med Chem Lett. 2000 Feb 7;10(3):257-60.

PubMed ID

10698448 [ View in PubMed

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Abstract

Four primary zinc-binding pharmacophores (thiols, carboxylates, phosphorus acids, and hydroxamates) have been utilized in generating inhibitors of zinc metalloproteases such as ACE, NEP, the MMPs, and ECE. Although compounds which inhibit the activity of both ACE and NEP (vasopeptidase inhibitors, VPIs) have been reported which incorporate a thiol, carboxylate, or phosphorus acid pharmacophore, the generation of hydroxamate based vasopeptidase inhibitors has remained elusive. Herein we report the first potent vasopeptidase inhibitors which were generated from the incorporation of conformationally restricted dipeptide mimetics to an N-formyl hydroxylamine zinc-binding group. Compounds such as 13c and 13d are among the most potent in this series, exhibiting in vitro activity comparable to other classes of inhibitors.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Omapatrilat	Angiotensin-converting enzyme	IC 50 (nM)	6	N/A	N/A	Details