ANTAGONISTIC ANALOGUES OF GROWTH HORMONE RELEASING-HORMONE (GH-RH) INHIBITING INSULIN-LIKE GROWTH FACTORS (IGF-I AND -II)

摘要

FIELD: medicine, oncology, chemistry of peptides.;SUBSTANCE: invention relates to peptide taken among the group of the formula: X-R¹-R²-Asp-Ala-R-Thr-R⁸-R-R¹⁰-Arg-R¹²-R¹³-R¹⁴-R¹⁵-R¹⁶-Leu-R¹⁸-R¹⁹-Arg-R²¹-R²²-Leu-Gln-Asp-Ile-R²⁷-R²⁸-R²⁹-NH₂ wherein X means PhAc, IndAc or Nac; R¹ means Tyr or His; R² means D-Arg; R⁵ means Ile or Val; R⁶ means Phe or Phe(Cl); R⁸ means Asn, Gln, Ala or D-Asn; R⁹ means Arg, Har, Lys, Orn, D-Arg, D-Har, D-Lys, D-Orn, Cit, Nle, Tyr(Me), Ser, Ala or Aib; R¹⁰ means Tyr or Tyr(Me); R¹² means Lys; R¹³ means Val or Nle; R¹⁴ means Leu or Nle; R¹⁵ means Gly, Ala, Abu, Nle or Gln; R¹⁶ means Gln or Arg; R¹⁸ means Ser or Nle; R¹⁹ means Ala; R²¹ means Lys; R²² means Leu, Ala or Aib; R²⁷ means Met, Leu, Nle, Abu or D-Arg; R²⁸ means Arg, D-Arg or Ser; R²⁹ means Arg, D-Arg, Har or D-Har under condition that if R⁹ and R²⁸ mean Ser then R²⁹ is not Arg or Har, and its pharmaceutically acceptable salts. Compounds are antagonists of the growth hormone releasing hormone and elicit the enhanced affinity for receptor. Invention describes also a method for suppression of excessive levels of the growth hormone in a patient, method for treatment of malignant tumor and method for inhibition of levels of IGF-II in tumors.;EFFECT: valuable medicinal properties of analogues.;11 cl, 9 tbl, 5 dwg, 4 ex