title: Flat SAR of P3-methylsulphonamide based small molecule legumain inhibitors.
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.
authors.affiliation: CCRCB Drug Discovery Group, Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Rd., Belfast BT9 7BL, UK.
authors.forename: Kerry Anne
authors.initials: KA
authors.lastname: Ness
authors.affiliation: CCRCB Drug Discovery Group, Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Rd., Belfast BT9 7BL, UK.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Eddie
authors.affiliation: Almac Discovery, Almac House, 20 Seagoe Industrial Estate, Craigavon BT63 5QD, UK.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Burton
authors.affiliation: Almac Discovery, Almac House, 20 Seagoe Industrial Estate, Craigavon BT63 5QD, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Harrison
authors.affiliation: CCRCB Drug Discovery Group, Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Rd., Belfast BT9 7BL, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Mullan
authors.affiliation: 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.
authors.forename: Rich
authors.initials: R
authors.lastname: Williams
mesh_terms: D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D008745:Methylation; D051379:Mice; D009369:Neoplasms / Q000201:enzymology; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D000099240:Asparaginyl Endopeptidase
chemical_list: D003546:Cysteine Endopeptidases; D011480:Protease Inhibitors; D054852:Small Molecule Libraries; D013449:Sulfonamides; D000099240:Asparaginyl Endopeptidase
keywords: Cancer; Legumain; SAR; Small molecule protease inhibitor