method for determining whether a compound is neurotrypsin inhibitor, method for measuring neurotripsin catalytic activity, neurotrypsin inhibitor compound, its use and pharmaceutical composition

摘要

METHOD FOR DETERMINING IF A COMPOUND IS A NEUROTRIPSIN INHIBITOR, METHOD FOR MEASURING NEUROTRIPSIN CATALYTIC ACTIVITY, NEUROTRIPSIN INHIBITOR, ITS USE AND PHARMACEUTICAL COMPOSITION. The invention relates to a method for determining whether a compound is a neurotrypsin inhibitor, wherein the compound is incubated together with neurotrypsin, a variant thereof, or a fragment comprising the protease domain, and with a protein or peptide comprising agrin, a variant thereof, or a fragment comprising the agrin cleavage α- or β-site in an aqueous buffer solution, and the amount of agrin cleavage is measured. Additionally, the invention relates to neurotrypsin inhibitors found by this method, in particular to the compounds of formula (1) wherein Hal¹ and Hal² are fluorine, chlorine or bromine, and the use of such inhibitors for the treatment and / or prophylaxis of diseases caused by synapse deficiency, for example, skeletal muscle atrophy, schizophrenia, and cognitive impairment.