Flat SAR of P3-methylsulphonamide based small molecule legumain inhibitors

Kerry Anne Ness; Sharon L Eddie; Stephanie Burton; Timothy Harrison; Paul Mullan; Rich Williams

doi:10.1016/j.bmcl.2015.11.101

Flat SAR of P3-methylsulphonamide based small molecule legumain inhibitors

Bioorg Med Chem Lett. 2016 Jan 15;26(2):413-416. doi: 10.1016/j.bmcl.2015.11.101. Epub 2015 Nov 28.

Authors

Kerry Anne Ness¹, Sharon L Eddie¹, Stephanie Burton², Timothy Harrison², Paul Mullan¹, Rich Williams³

Affiliations

¹ CCRCB Drug Discovery Group, Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Rd., Belfast BT9 7BL, UK.
² Almac Discovery, Almac House, 20 Seagoe Industrial Estate, Craigavon BT63 5QD, UK.
³ CCRCB Drug Discovery Group, Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Rd., Belfast BT9 7BL, UK. Electronic address: rich.williams@qub.ac.uk.

PMID: 26653614
DOI: 10.1016/j.bmcl.2015.11.101

Abstract

This letter describes the design, development and SAR exploration of a novel series of small legumain inhibitors. The SAR of a new small molecule legumain inhibitor chemotype was explored and found to have improved physiochemical properties compared to previously developed inhibitors within our group. However, further development of this series was found to be limited as the SAR was observed to be relatively flat.

Keywords: Cancer; Legumain; SAR; Small molecule protease inhibitor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cysteine Endopeptidases / metabolism*
Drug Design
Humans
Methylation
Mice
Neoplasms / enzymology
Protease Inhibitors / chemistry*
Protease Inhibitors / pharmacology*
Rats
Small Molecule Libraries / chemistry*
Small Molecule Libraries / pharmacology*
Structure-Activity Relationship
Sulfonamides / chemistry
Sulfonamides / pharmacology

Substances

Protease Inhibitors
Small Molecule Libraries
Sulfonamides
Cysteine Endopeptidases
asparaginylendopeptidase