Fluorescent nitrile-based inhibitors of cysteine cathepsins

Maxim Frizler; Matthias D Mertens; Michael Gütschow

doi:10.1016/j.bmcl.2012.09.086

Fluorescent nitrile-based inhibitors of cysteine cathepsins

Bioorg Med Chem Lett. 2012 Dec 15;22(24):7715-8. doi: 10.1016/j.bmcl.2012.09.086. Epub 2012 Oct 3.

Authors

Maxim Frizler¹, Matthias D Mertens, Michael Gütschow

Affiliation

¹ Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.

PMID: 23122525
DOI: 10.1016/j.bmcl.2012.09.086

Abstract

Cysteine cathepsins play an important role in many (patho)physiological conditions. Among them, cathepsins L, S, K and B are subjects of several drug discovery programs. Besides their role as drug targets, cysteine cathepsins are additionally considered to be possible biomarkers for inflammation and cancer. Herein, we describe the design, synthesis, biological evaluation and spectral properties of fluorescently labeled dipeptide- and azadipeptide nitriles.

MeSH terms

Cathepsins / antagonists & inhibitors*
Cathepsins / metabolism
Cysteine Proteinase Inhibitors / chemical synthesis
Cysteine Proteinase Inhibitors / chemistry
Cysteine Proteinase Inhibitors / pharmacology*
Dipeptides / chemistry*
Dose-Response Relationship, Drug
Drug Design
Fluorescence*
Molecular Structure
Nitriles / chemical synthesis
Nitriles / chemistry
Nitriles / pharmacology*
Structure-Activity Relationship

Substances

Cysteine Proteinase Inhibitors
Dipeptides
Nitriles
Cathepsins