| 摘要 |
The invention comprises the hexapeptide L - lysyl - L - phenylalanyl - L - isoleucyl-glycyl - L - leucyl - L - methioninamide and its derivatives wherein the two amino groups of lysine are each blocked by an amino protective group and acid addition salts thereof and the preparation thereof by condensing L-leucylmethioninamide with L-lysyl-L-phenylalanyl-L-isoleucyl-glycine, having the two lysyl amino groups protected by amino protecting agents, in the presence of a carbodiimide condensing agent, and where appropriate, eliminating the amino protecting groups and so liberating the free hexapeptide. Suitable protecting groups include triphenylmethyl, paratoluenesulphonyl, phthalyl, carbobenzoxy, carbo-t-butoxy, trifluoroacetyl and formyl. L - Leucyl - L - methioninamide is prepared from carbo-t-butoxy-L-leucine and L-methioninamide to form the protected dipeptide and removing the protecting groups. Na ,Ne -dicarbo - t - butoxy - L - lysyl - L - phenylalanyl - L - isoleucyl - glycine is prepared from glycine ethyl ester and N-carbobenzoxy-L-isoleucine dicyclohexylammonium salt through N - carbobenzoxy - L - isoleucyl - glycine ethyl ester, L - isoleucyl - glycine ethel ester hydrobromide, N - carbobenzoxy - L - phenylalanyl-L - isoleucyl - glycine ethyl ester, L - phenylalanyl - L - isoleucyl - glycine ethyl ester hydrobromide and Na ,Ne - dicarbo - t - butoxy - L-lysyl - L - phenylalanyl - L - isoleucyl - glycine ethyl ester by stepwise condensation and removal of protecting groups where appropriate. Na ,Ne - Dicarbo - t - butoxy - lipine p - nitrophenyl ester is prepared from the protected amino acid and the phenol. Pharmaceutical compositions comprise the hexapeptide of the invention together with a suitable pharmaceutical carrier. The compositions, which are preferably administered by the parenteral route, are hypotensive agents. Specifications 872,332 and 984,810 are referred to. |
