GNRH ANTAGONISTS MODIFIED AT POSITIONS 5 AND 6 Russian patent published in 2003 - IPC

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 α-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