POLYPEPTIDE BOMBESIN ANTAGONISTS

摘要

Pseudopeptides comprising a peptide of formula (I): X-A<1>-A<2>-Trp-Ala-Val-Gly-His-Leu-p &cir& _s &cir& _i &cir& _-A<9>-Q wherein X is hydrogen, a single bond linking the alpha amino group of A<1> to the gamma carboxyl moiety on the 3-priopionyl moiety of A<2> when A<2> is Glu, or a group of formula R<1>CO- wherein R<1> is selected from the groups consisting of: a) hydrogen, C1-10alkyl, phenyl or phenyl-C1-10-alkyl, p-Hl-phenyl, p-Hl-phenyl-C1-10-alkyl, naphthyl, naphthyl-C1-10-alkyl, indolyl, indolyl-C1-10-alkyl, pyridyl, pyridyl-C1-10-alkyl, thienyl, thienyl-C1-10-alkyl, cyclohexyl or cyclohexyl-C1-10-alkyl, where Hl = F, Cl, Br, OH, CH3 or OCH3; b) N(R<2>)(R<3>)-, wherein R<2> is hydrogen, C1-10alkyl, phenyl or phenyl-C1-10-alkyl, R<3> is hydrogen or C1-10alkyl; c) R<4>O-, wherein R<4> is C1-10alkyl, phenyl or phenyl-C1-10-alkyl; A<1> is a D- or L-amino acid residue selected from the group consisting of Phe, p-Hl-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, NH2 or C1-3alkyl; or A<1> is a peptide bond linking the acyl moiety of R<1>CO- to the alpha amino moiety of A<2>; A<2> is Gln, Glu[-], Glu(Y) or His, wherein [-] is a single bond linking the gamma carboxyl group of A<2> when A<2> is Glu with the alpha amino group of A<1> where X is a single bond, Y is -OR<5> or -N(R<5>)(R<6>) wherein R<5> is hydrogen, C1-3alkyl or phenyl; R<6> is hydrogen or C1-3alkyl; and R<7> is hydrogen, C1-3alkyl or -NHCONH2; Leu-p &cir& _s &cir& _i &cir& _- is a reduced form of Leu wherein the C = O moiety of Leu is instead -CH2- such that the bond of this -CH2- moiety with the alpha amino moiety of the adjacent A<9> residue is a pseudopeptide bond; A<9> is Tac, MTac, or DMTac; and Q is NH2 or OQ<1> where Q<1> is hydrogen, C1-10alkyl, phenyl or phenyl-C1-10-alkyl; and the pharmaceutically acceptable acids or salts thereof.