Synthesis and evaluation of 9-deoxy analogues of (-)-thysanone, an inhibitor of HRV 3C protease

Joo Young Jeong; Jonathan Sperry; John A Taylor; Margaret A Brimble

doi:10.1016/j.ejmech.2014.09.063

Synthesis and evaluation of 9-deoxy analogues of (-)-thysanone, an inhibitor of HRV 3C protease

Eur J Med Chem. 2014 Nov 24:87:220-7. doi: 10.1016/j.ejmech.2014.09.063. Epub 2014 Sep 22.

Authors

Joo Young Jeong¹, Jonathan Sperry², John A Taylor³, Margaret A Brimble⁴

Affiliations

¹ School of Chemical Sciences, The University of Auckland, 23 Symonds St., Auckland 1142, New Zealand; School of Biological Sciences, The University of Auckland, 3A Symonds St., Auckland 1010, New Zealand.
² School of Chemical Sciences, The University of Auckland, 23 Symonds St., Auckland 1142, New Zealand.
³ School of Biological Sciences, The University of Auckland, 3A Symonds St., Auckland 1010, New Zealand. Electronic address: ja.taylor@auckland.ac.nz.
⁴ School of Chemical Sciences, The University of Auckland, 23 Symonds St., Auckland 1142, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand. Electronic address: m.brimble@auckland.ac.nz.

PMID: 25259514
DOI: 10.1016/j.ejmech.2014.09.063

Abstract

9-Deoxy analogues of the HRV 3C protease inhibitor (-)-thysanone display better inhibitory properties than the natural product, inferring the C9-OH hinders binding to the enzyme.

Keywords: C–H activation; HRV 3C protease; Inhibitor; Pyranonaphthoquinone; Thysanone.

MeSH terms

3C Viral Proteases
Benzopyrans / chemical synthesis*
Benzopyrans / chemistry
Benzopyrans / pharmacology*
Chemistry Techniques, Synthetic
Cysteine Endopeptidases / metabolism
Drug Design*
Naphthoquinones / chemical synthesis*
Naphthoquinones / chemistry
Naphthoquinones / pharmacology*
Protease Inhibitors / chemical synthesis*
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology*
Rhinovirus / enzymology*
Viral Proteins / antagonists & inhibitors*
Viral Proteins / metabolism

Substances

Benzopyrans
Naphthoquinones
Protease Inhibitors
Viral Proteins
thysanone
Cysteine Endopeptidases
3C Viral Proteases