2. Academic Validation
  3. Optimization of O3-acyl kojic acid derivatives as potent and selective human neutrophil elastase inhibitors

Optimization of O3-acyl kojic acid derivatives as potent and selective human neutrophil elastase inhibitors

  • J Med Chem. 2013 Dec 12;56(23):9802-6. doi: 10.1021/jm4011725.
Susana D Lucas 1,  Lídia M Gonçalves,  Luís A R Carvalho,  Henrique F Correia,  Eduardo M R Da Costa,  Romina A Guedes,  Rui Moreira,  Rita C Guedes
Affiliations

Affiliation

  • 1 Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa , Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
PMID: 24224573 DOI: 10.1021/jm4011725
Abstract

Human neutrophil Elastase (HNE) is an attractive target for treating chronic and acute inflammatory lung diseases. An optimization campaign of the kojic acid scaffold to develop new potent HNE inhibitors is reported. O3-Pivaloyl derivatives were shown to be the most potent inhibitors with IC5o values down to 80 nM. These compounds presented excellent selectivity and cytotoxicity profiles with suitable ligand efficiency.

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