title: Modification of the N-terminal sulfonyl residue in 3-amidinophenylalanine-based matriptase inhibitors.
abstract: Replacement of the N-terminal beta-alanyl-amide moiety in previously identified matriptase inhibitors by non-charged aryl groups caused a slightly decreased potency and partially reduced selectivity, especially towards thrombin. However, some of these analogues are still potent matriptase inhibitors with K(i)-values <10nM. In contrast, improved activity was observed for newly designed tribasic analogues, especially for compound 21, which inhibits matriptase with an K(i)-value of 80pM.
authors.affiliation: Curacyte Discovery GmbH, Leipzig, Germany. steinmetzer@staff.uni-marburg.de
authors.forename: Torsten
authors.initials: T
authors.lastname: Steinmetzer
authors.forename: Daniel
authors.initials: D
authors.lastname: Dönnecke
authors.forename: Martin
authors.initials: M
authors.lastname: Korsonewski
authors.forename: Claudia
authors.initials: C
authors.lastname: Neuwirth
authors.forename: Peter
authors.initials: P
authors.lastname: Steinmetzer
authors.forename: Alexander
authors.initials: A
authors.lastname: Schulze
authors.forename: Sebastian Martin
authors.initials: SM
authors.lastname: Saupe
authors.forename: Andrea
authors.initials: A
authors.lastname: Schweinitz
mesh_terms: D000578:Amidines / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D012697:Serine Endopeptidases / Q000187:drug effects*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors
chemical_list: D000578:Amidines; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; C485595:matriptase; D013917:Thrombin