| 摘要 |
FIELD: organic chemistry, peptides, pharmacy. SUBSTANCE: invention relates to peptide-antagonists of GnRH of the formula: X-D-Nal-(A)D-Phe-D-Pal-Ser-Xaa5-Xaa6-Leu-Xaa8-Pro-Xaa10 and their pharmaceutically acceptable salts where X means acyl group with more 7 carbon atoms; A means 4-Cl or Br; Xaa5 means Aph(Q1) or Amf(Q1) where Q1 means Q or or (D- or L-Hor), (D- or L-Imz) where Q means and where R means H or lower alkyl; Xaa6 means D-Aph(Q2), D-Amf(Q2), D-Cit or D-Pal where Q2 means Ac or Q1; Xaa8 means Lys(ipr); and Xaa10 means D-Ala-NH2, D-Ala-ol, Ala-ol, NHCH2CH3, Gly-NH2 or Ala-NH2 under condition that if Xaa5 involves Q then Xaa6 means Q also. Invention relates also to pharmaceutical composition for inhibition of gonadotropin secretion in mammals comprising effective antagonist of GnRH as active component. Invention relates also to method of inhibition of gonadotropin secretion in mammals and to compounds of the formula: X1-D-Nal-(A)D-Phe-D-Pal-Ser(X2)-Xaa5-Xaa6-Leu-Lyx(ipr)(X4)-Pro-X5 where X1 is alpha-amino-protective group; A is 4-Cl or 4-Br; X2 is H or hydroxy-protective group; Xaa5 means Aph(Q1) or Amf(Q1) where Q1 means structures (I) and (II) or carbamoyl or methyl-carbamoyl; Xaa6 means D-Amf(Q2), D-Amf(Q2) or D-Pal where Q2 is Ac; X4 means amino-protective group sensitive to acid effect; X5 means D-Ala-, Gly-, Ala-[polymeric carrier] , N(Et)-[polymeric carrier], D-Ala, Gly or Ala amide; or ethylamide as intermediate compound for synthesis of peptide-antagonist of GnRH receptors. EFFECT: valuable medicinal properties of compounds. 16 cl, 8 ex |
