Evaluation of bisbenzamidines as inhibitors for matriptase-2.
The serine protease matriptase-2 has attracted much attention as a potential target for the treatment of iron overload diseases. In this study, a series of 27 symmetric, achiral bisbenzamidines was evaluated for inhibitory activity against human matriptase-2, against the closely related enzyme human matriptase, as well as against human thrombin, bovine factor Xa and human trypsin. The conformationally restricted piperazine derivative 19 and the oxamide-derived bisbenzamidine 1 were identified as the most potent inhibitors of this series for matriptase-2 and matriptase, respectively.
Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany.
Anna-Madeleine
AM
Beckmann
Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany; Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, University of Bonn, Dahlmannstr. 2, 53113 Bonn, Germany.
Erik
E
Gilberg
Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany.
Susanne
S
Gattner
Department of Basic Pharmaceutical Science, College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
Tien L
TL
Huang
Department of Basic Pharmaceutical Science, College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
Jean Jacques
JJ
Vanden Eynde
Department of Basic Pharmaceutical Science, College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
Annie
A
Mayence
Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, University of Bonn, Dahlmannstr. 2, 53113 Bonn, Germany.
Jürgen
J
Bajorath
Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany.
Marit
M
Stirnberg
Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany.
Michael
M
Gütschow
D000818:Animals; D001550:Benzamidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D015951:Factor Xa / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D012697:Serine Endopeptidases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
D001550:Benzamidines; D008565:Membrane Proteins; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; C467801:matriptase 2; D014357:Trypsin; D013917:Thrombin; D015951:Factor Xa
Bisbenzamidines; Matriptase-2; Serine proteases