New tetrapeptide derivatives are proprotein convertase inhibitors, useful to treat e.g. viral or bacterial diseases, diabetes, arteriosclerosis, cancer, Alzheimer's disease, obesity, and respiratory tract disease

摘要

Tetrapeptide derivatives (I) are new. Tetrapeptide derivatives of formula (P5-P4-P3-P2-P1) (I) are new. P1 : arginine mimetic; P2-P4 : amino and/or imino acid radical; and P5 : N-terminal modification of amino or imino acid residue of P4. An independent claim is included for the preparation of (I). ACTIVITY : Virucide; Antibacterial; Antidiabetic; Antiarteriosclerotic; Cytostatic; Neuroprotective; Nootropic; Anorectic; Respiratory-Gen.; Antimicrobial; Nephrotropic. MECHANISM OF ACTION : Proprotein convertase inhibitor. The ability of (I) to inhibit furin was tested using a fluorescence plate reader. The result showed that (S)-6-carbamimidoyl-2-phenylacetylamino-hexanoic acid {(S)-1-[(S)-5-carbamimidoyl-1-(4-carbamimidoyl-benzylcarbamoyl)-pentylcarbamoyl]-2-methyl-propyl}-amide exhibited a inhibition constant (K i) value of 0.0014 mu M.