New phosphonamide-contg. polypeptide derivs. - useful as bacterial collagenase inhibitors to treat gangrene and periodontal disease

摘要

Peptide derivatives of formula R1-P(=O)(OR'5)-NH-CH2- CO-R2-N(R3)-CH(R4)-COOR5 (I) are new. Where R1 = aryl or aralkyl, opt. aryl-substd. by one or more halo, CF3, 1-4C alkoxy, 1-4C alkyl, 1-4C alkanoyloxy, 2-5C carbonyloxyalkyl, NO2, CO2H or CN groups. R1 can also be -CH(R6)-NH-R7-R8. R6 = an alpha-aminoacid. R7 = a bond, an alpha-aminoacid residue or a peptide of formula (CO-CH(R9)-NH)n. R9 = an alpha-aminoacid; n = 1 or 2 and when n is 2, R9 can be the same or different. R8 = a blocking group or an aralkyl group that is opt. substd. by one or more halo, CF3, 1-4C alkoxy, 1-4C alkyl, 1-4C alkanoyloxy, 2-5C carbonyloxy, NO2, CO2H or CN groups. R2 = proline, hydroxyproline, thiazolidine or dehydroproline. R3 = H or 1-4C alkyl. R4 = 1-5C alkyl or an alpha-aminoacid. R5,R'5 = independently H, a metal atom, 1-5C alkyl or benzyl. When R1 = unsubstd. aryl or aralkyl, R3 = H and R4 = N-butyl. The daily dose is 1-5 mg/kg. USE/ADVANTAGE - As bacterial collagenase inhibitors in the treatment of gangrene or periodontal disease.