Amura Therapeutics Limited

Synapse B.v.

Manoj Kumar Ramjee

Martin Quibell

Hendrik Coenraad Hemker

Robert Wagenvoord

Compounds of general formula (I):wherein R, Y, (X), (W), (V), Z and U are as defined in the specification, are inhibitors of cruzipain and other cysteine protease inhibitors and are useful as therapeutic agents, for example in Chagas' disease, or for validating therapeutic target compounds.

Inhibitors of cruzipain and other cysteine proteases

A process is provided for the assessment of an active proteolytic enzyme in a blood or another biological fluid sample possibly comprising a complex of said proteolytic enzyme and &agr; -macroglobulin, wherein said sample is contacted with a substrate comprising a molecule of sufficient size coupled to a signal-substrate, said signal-substrate comprising a detectable leaving group, wherein said substrate is hydrolysed by said proteolytic enzyme but not by said complex. The proteolytic enzyme is preferably selected from the group consisting of thrombin, activated clotting factor, activated fibrinolytic factor, and activated component of the complement system. Of these, thrombin is most preferred. The molecules of sufficient size are preferably water soluble and selected from the group consisting of inert protein, preferably ovalbumin, polysaccharide, and synthetic polymer. The size of these molecules is such that they will not fit into the cavity of the &agr; M molecules.

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Cambridge, United Kingdom

Manoj Kumar Ramjee