Gonadotropin-releasing hormone (GnRH) antagonist peptide, pharmaceutical composition containing the same, the use thereof and an intermediate

摘要

Peptides are provided which have improved duration of GnRH antagonistic properties. These antagonists may be used to regulate fertility and to treat steroid-dependent tumors and for other short-term and long-term treatment indications. These antagonists have a derivative of aminoPhe or its equivalent in the 5- or the 5- and 6- positions. This derivative is modified so as to contain a carbamoyl group or heterocycle, including a urea moiety in its side chain. Particularly effective decapeptides, which continue to exhibit very substantial suppression of LH secretion at 96 hours following injection, have the formulae Ac-D-2Nal-D-4Cpa-D-3Pal-Ser-4Aph(L-hydroorotyl)-D-4Aph(acetyl)- Leu-Lys(isopropyl)-Pro-D-Ala-NH2, and Ac-D-2Nal-D-4Cpa-D-3Pal- Ser-4Aph(L-hydroorotyl)-D-4Amf(Q2)-Leu-Lys(isopropyl)-Pro-Xaa10, wherein Q2 is Cbm or MeCbm and Xaa10 is D-Ala-NH2, D-Ala-ol or Ala-ol.