Nonapeptide and decapeptide derivatives of luteinizing hormone releasing hormone, their preparation and pharmaceutical compositions containing them
申请人:SYNTEX (U.S.A.) INC.
公开号:EP0021234A1
公开(公告)日:1981-01-07
Nonapeptide and decapeptide analogs of LH-RH of the formula
(pyro)Glu-His-V-Ser-W-X-Y-Arg-Pro-Z (I) and the pharmaceutically acceptable salt thereof wherein:
V is tryptophyl, phenylalanyl or 3-(1-naphthyl)-L-alanyl;
W is tyrosyl, phenylalanyl or 3-(1-pentafluorophenyl)-L-alanyl;
X is a D-amino acid residue wherein R is
(a) a carbocyclic aryl-containing radical selected from the group consisting of naphthyl, anthryl, fluorenyl, phenanthryl, biphenylyl, benzhydryl and phenyl substituted with three or more straight chain lower alkyl groups; or
(b) a saturated carbocyclic radical selected from the group consisting of cyclohexyl substituted with three or more straight chain lower alkyl groups, perhydronaphthyl, perhydrobiphenylyl, perhydro-2,2-diphenylmethyl and adamantyl;
Y is leucyl, isoleucyl, nor-leucyl or N-methyl-leucyl;
Z is glycinamide or-NH-R1, wherein
R' is lower alkyl, cycloalkyl, fluoro lower alkyl or
wherein
R2 is hydrogen or lower alkyl, are disclosed. These compounds exhibit potent LH-RH agonist properties.
式中的 LH-RH 的非肽和十肽类似物
(焦)Glu-His-V-Ser-W-X-Y-Arg-Pro-Z (I)及其药学上可接受的盐 其中:
V 是色氨酰、苯丙氨酰或 3-(1-萘基)-L-丙氨酰;
W 是酪氨酰基、苯丙氨酰基或 3-(1-五氟苯基)-L-丙氨酰;
X 是 D-氨基酸残基,其中 R 是
(a) 一个含碳环芳基,选自由萘基、蒽基、芴基、菲基、联苯基、苯hydryl 和被三个或三个以上直链低级烷基取代的苯基组成的组;或
(b) 饱和碳环基,选自由三个或三个以上直链低级烷基取代的环己基、全氢萘 基、全氢联苯基、全氢-2,2-二苯基甲基和金刚烷基组成的组;
Y 是亮氨酰、异亮氨酰、去亮氨酰或 N-甲基亮氨酰;
Z 是甘氨酰胺或-NH-R1,其中
R' 是低级烷基、环烷基、氟低级烷基或
其中
R2 是氢或低级烷基。这些化合物具有强效的 LH-RH 激动剂特性。