| 摘要 |
The invention relates to novel heptapeptide and octapeptide amide derivatives of the general formula (I), wherein X1 stands for an aromatic D-amino acid residue or a derivative thereof ring-substituted by halogen or hydroxyl; or a D-phenylglycyl, p-hydroxyphenyl- glycyl, o-aminobenzoyl, m-aminobenzoyl, D-tetra- hydroisoquinolylcarbonyl, sarcosylalanyl group; or an wherein A1 means a primary or secondary aromatic or aliphatic amino group or an alkoxy, aryl- oxy or aralkyloxy group; X2 represents an aromatic amino acid residue or a derivative thereof ring-substituted by halogen or hydroxyl group; or a histidyl group; X3 means D-tryptophyl, o-aminobenzoyl, m-amino- benzoyl, aspartyl, D-aspartyl, .beta.-aspartyl, .beta.-D- -aspartyl, aminosuccinyl group; or an group, wherein A1 is as defined above; X4 stands for an amino acid residue bearing an alkyl or aralkyl side chain, or a derivative thereof substituted by a hydroxyl or methyl group in .beta.- -position; or a prolyl or .beta.-alanyl group; or a valence bond; X5 means an aromatic amino acid residue or a derivative thereof ring-substituted by halogen or hydroxyl group; or a threonyl group: R1 represents hydrogen or an A2-CO-group, wherein A2 means hydrogen or a C1-C4 alkylgroup optionally substituted by halogen; R2 means hydrogen, -S-, -S-acetamidomethyl, phenyl or p- hydroxyphenyl group; R3 stands for hydrogen or hydroxyl group: R4 means a phenyl or p-hydroxyphenyl group; or -S- or -S- acetamidomethyl group when the meaning of R2 is the same group; or a methyl group when R3 is hydroxyl group, and n is 1, 2, 3 or 4, with the proviso that, if X1 stands for D-Phe, X2 is Tyr or Phe, X3 stands for D-Trp, X5 is Trp or Thr and R2 and R4 form a disulfide bridge, then X4 is other than Val, Thr or Ser, and the acid addition salts thereof, pharmaceutical compositions containing them and a process for their preparation. The compounds of general formula (I) possess tumour- inhibiting effect and are capable to inhibit the tyrosin kinase enzyme.
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