Trypsin-like serine protease factor

In addition to the use in the synthesis of potential hepatitis C drugs, microwave-assisted chemistry has also been used in the synthesis of mast cell tryptase inhibitors, thrombin inhibitors, and Factor Xa inhibitors. The trypsin-like serine protease tryptase is the major secretory product of human mast cells and has been implicated as an inflammatory mediator in a number of conditions, especially asthma. Once released upon mast cell activation, the tryptase cleaves substrates that otherwise cause smooth muscle relaxation and thereby bronchi- and vasodilation. It is therefore not surprising that numerous reports on low molecular weight tryptase inhibitors have appeared. 

Tetrahydro-lH-pyrazolo[3,4-c]pyridine derivatives, (II), and other 5-6 to 5-7 heterobicycles prepared by Pinto (3) were effective as trypsin-like serine protease inhibitors, especially for factor Xa. 

The coagulation and anticoagulation proteases, factors VII, IX, and X, and protein C, have a common domain structure with an N-terminal gamma-carboxyglutamic acid (Gla)-containing domain that is followed by two EGF-like modules, whereas the C-terminal half of each protein is occupied by a trypsin-like serine protease domain. Prothrombin also has an N-terminal Gla domain and a C-terminal serine protease... 

Gadad et al. [69] reported a series of indole/benzoimidazole-5-carboxami-dines which inhibited various trypsin-like serine proteases such as uPA, tPA, Factor Xa, thrombin, plasmin, and trypsin. 3D-QSAR models were gener-... 

Protease nexin 2 is identical to the secreted form of the amyloid precursor protein containing the Kunitz-type serine protease inhibitor domain (128,129), Protease nexin 2 circulates in blood stored as a platelet a-granule protein, which is secreted upon platelet activation (127). Protease nexin 2 inhibits trypsin- and chymotrypsin-like serine proteases and is also a potent inhibitor of factor Xla (126,127,128). Its location in platelets and its ability to inhibit factor Xla suggests a role in regulating blood coagulation for protease nexin 2. 

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