Modification of the N-terminal sulfonyl residue in 3-amidinophenylalanine-based matriptase inhibitors.
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.
Steinmetzer
Torsten
T
Curacyte Discovery GmbH, Leipzig, Germany. steinmetzer@staff.uni-marburg.de
Dönnecke
Daniel
D
Korsonewski
Martin
M
Neuwirth
Claudia
C
Steinmetzer
Peter
P
Schulze
Alexander
A
Saupe
Sebastian Martin
SM
Schweinitz
Andrea
A
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
D000578:Amidines; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; C485595:matriptase; D013917:Thrombin