Inspired by Nature : The 3-Halo-4,5-dihydroisoxazole Moiety as a Novel Molecular Warhead for the Design of Covalent Inhibitors
Articolo
Data di Pubblicazione:
2016
Citazione:
Inspired by Nature : The 3-Halo-4,5-dihydroisoxazole Moiety as a Novel Molecular Warhead for the Design of Covalent Inhibitors / A. Pinto, L. Tamborini, G. Cullia, P. Conti, C. De Micheli. - In: CHEMMEDCHEM. - ISSN 1860-7179. - 11:1(2016 Jan 05), pp. 10-14.
Abstract:
Over the past few decades, there has been an increasing interest in the development of covalent enzyme inhibitors. As it was recently re-emphasized, the selective, covalent binding of a drug to the desired target can increase efficiency and lower the inhibitor concentration required to achieve a therapeutic effect. In this context, the naturally occurring antibiotic acivicin, and in particular its 3-chloro-4,5-dihydroisoxazole scaffold, has provided a wealth of inspiration to medicinal chemists and chemical biologists alike. In this Concept, to underline the great potentiality that the 3-halo-4,5-dihydroisoxazole warhead has in drug discovery, we present a number of examples, grouped by their potential biological activity and targets, in which this scaffold has been fruitfully used to develop novel biologically active compounds. Through these examples, we show that the 3-halo-4,5-dihydroisoxazole moiety represents an outstanding warhead with high potential for the design of novel covalent enzyme inhibitors.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
4,5-dihydroisoxazoles; covalent inhibitors; drug warheads; electrophiles; natural products; carbon-nitrogen ligases; cysteine proteases; enzyme inhibitors; glyceraldehyde-3-phosphate dehydrogenases; humans; isoxazoles; molecular conformation; drug design; pharmacology, toxicology and pharmaceutics (all); organic chemistry; molecular medicine
Elenco autori:
A. Pinto, L. Tamborini, G. Cullia, P. Conti, C. De Micheli
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