727989-53-9Relevant academic research and scientific papers
Acylated 4-amidino- and -4-guanidinobenzylamines for inhibition of plasma kallikrein
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Page/Page column 33; 34, (2016/09/26)
The invention relates to the use of acylated 4-amidino- or 4-guanidinobenzylamine in accordance with the general formula I P4-P3-P2-P1??(I), where P4 is a monosubstituted or polysubstituted or unsubstituted benzylsulfonyl group, P3 is a monosubstituted or polysubstituted or unsubstituted, natural or unnatural α-amino acid or α-imino acid in the D configuration, P2 is a monosubstituted or polysubstituted or unsubstituted, natural or unnatural α-amino acid or α-imino acid in the L configuration, and P1 is a monosubstituted or polysubstituted or unsubstituted 4-amidino- or 4-guanidinobenzylamine group, for inhibiting plasma kallikrein (PK), factor XIa and factor XIIa, in particular for preventing the activation of coagulation at synthetic surfaces and for systemic administration as anticoagulants/antithrombotic agents, in particular for preventing the activation of coagulation at synthetic surfaces for the purpose of averting thromboembolic events.
Identification of the first low-molecular-weight inhibitors of matriptase-2
Sisay, Mihiret Tekeste,Steinmetzer, Torsten,Stirnberg, Marit,Maurer, Eva,Hammami, Maya,Bajorath, Jürgen,Gütschow, Michael
experimental part, p. 5523 - 5535 (2010/11/04)
As recently discovered, matriptase-2, a type II transmembrane serine protease, plays a crucial role in body iron homeostasis by down-regulating hepcidin expression, which results in increased iron levels. Thus, matriptase-2 represents a novel target for the development of enzyme inhibitors potentially useful for the treatment of systemic iron overload (hemochromatosis). A comparative three-dimensional model of the catalytic domain of matriptase-2 was generated and utilized for structure-based virtual screening in combination with similarity searching and knowledge-based compound design. Two N-protected dipeptide amides containing a 4-amidinobenzylamide as P1 residue (compounds 1 and 3) were identified as the first small molecule inhibitors of matriptase-2 with Ki values of 170 and 460 nM, respectively. An inhibitor of the closely related protease matriptase (compound 2, Ki = 220 nM), with more than 50-fold selectivity over matriptase-2, was also identified.
