Abstract
This article describes recent developments in the synthesis and biological activity of α- aminoboronic acids, amine-carboxyboranes and their derivatives as potential therapeutic agents. α-Amino acid analogues are of considerable interest as inhibitors of enzymes involved in amino acid and peptide metabolism. In particular, α-amino alkylphosphonic acids and α-amino alkylboronic acids, in which the carboxyl group of amino acids is replaced by a phosphonic acid or boronic acid function, respectively, constitute a unique class of amino acid mimics from which a number of potent enzyme inhibitors have been synthesized. The inhibitory activity mainly stems from the fact that the tetrahedral phosphonic moiety or the tetrahedral adduct of electrophilic boronic acid is a good mimic of the putative tetrahedral transition state or intermediate encountered in the enzymatic hydrolysis or formation of peptides. Since the peptide hydrolysis and formation invariably involves the tetrahedral high energy species in the course of the reaction, these amino acid mimics serve as a general key element for inhibitors of a broad spectrum of proteases and peptide ligases. Serine protease inhibitors provide promising compounds having a P site binding moiety and a boronic acid chelating moiety. The compounds have been shown to have high inhibitory activity.
Keywords: boron-containing compounds, serine protease, enzymes, thrombin inhibitor, anticoagulant, x-ray crystal structure
Mini-Reviews in Medicinal Chemistry
Title: Recent Advances in the Medicinal Chemistry of α-Aminoboronic Acids, Amine-Carboxyboranes and Their Derivatives
Volume: 4 Issue: 9
Author(s): Valery M. Dembitsky, Abed Al Aziz Quntar and Morris Srebnik
Affiliation:
Keywords: boron-containing compounds, serine protease, enzymes, thrombin inhibitor, anticoagulant, x-ray crystal structure
Abstract: This article describes recent developments in the synthesis and biological activity of α- aminoboronic acids, amine-carboxyboranes and their derivatives as potential therapeutic agents. α-Amino acid analogues are of considerable interest as inhibitors of enzymes involved in amino acid and peptide metabolism. In particular, α-amino alkylphosphonic acids and α-amino alkylboronic acids, in which the carboxyl group of amino acids is replaced by a phosphonic acid or boronic acid function, respectively, constitute a unique class of amino acid mimics from which a number of potent enzyme inhibitors have been synthesized. The inhibitory activity mainly stems from the fact that the tetrahedral phosphonic moiety or the tetrahedral adduct of electrophilic boronic acid is a good mimic of the putative tetrahedral transition state or intermediate encountered in the enzymatic hydrolysis or formation of peptides. Since the peptide hydrolysis and formation invariably involves the tetrahedral high energy species in the course of the reaction, these amino acid mimics serve as a general key element for inhibitors of a broad spectrum of proteases and peptide ligases. Serine protease inhibitors provide promising compounds having a P site binding moiety and a boronic acid chelating moiety. The compounds have been shown to have high inhibitory activity.
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Cite this article as:
Dembitsky M. Valery, Quntar Al Aziz Abed and Srebnik Morris, Recent Advances in the Medicinal Chemistry of α-Aminoboronic Acids, Amine-Carboxyboranes and Their Derivatives, Mini-Reviews in Medicinal Chemistry 2004; 4 (9) . https://dx.doi.org/10.2174/1389557043403125
DOI https://dx.doi.org/10.2174/1389557043403125 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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