| 摘要 |
There is provided a method of treating human hepatomas utilizing bombesin antagonist pseudopeptides of Formula I:
€ƒ€ƒ€ƒ€ƒ€ƒ€ƒ€ƒ€ƒ X-A 1 -A 2 -Trp-Ala-Val-Gly-His-Leu-¨-A 9 -Q€ƒ€ƒ€ƒ€ƒ€ƒ(SEQ ID NO: 32)
wherein X is hydrogen, Hca, Hna, Hpp, Mpp or Naa,
A 1 is a D-, L- or DL-amino acid residue selected from the group consisting of Phe, p-HI-Phe, pGlu, Nal, Pal, Tpi, unsubstituted Trp or Trp substituted in the benzene ring by one or more members selected from the group consisting of F, Cl, Br, NH 2 or C 1-3 alkyl; or a peptide bond linking the acyl moiety of X (where present) to the alpha amino moiety of A 2 ,
A 2 is Gin, Glu [-], Glu (Y), or His, wherein
[-] is a single bond, linking the gamma carboxyl moiety or the 3-propionyl moiety of A 2 with the alpha amino moiety of A 1 ,
Y is
a) -OR 5 wherein R 5 is hydrogen, C 3 alkyl or phenyl; or
b) R 6
wherein R 6 is hydrogen or C 1-3 alkyl; R 7 is hydrogen, C 1-3 alkyl or-NHCONH 2 . Leu-¨- is a reduced form of Leu wherein the C = O moiety of Leu is instead -CH 2 - such that the bond of this -CH 2 - moiety with the alpha amino moiety of the adjacent A 9 residue is a pseudopeptide bond. Suitably A 9 is Tac, MTac, or DMTac,
Q is NH 2 or -OQ' where Q' is hydrogen, C 1-10 alkyl, phenyl or phenyl-C 1-10 -alkyl; and the pharmaceutically acceptable acids or salts thereof.
|
