GnRh antagonists being modified in positions 5 and 6

Abstract

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. Decapeptides having the formula:wherein Q2 is Cbm or MeCbm and Xaa10 is D-Ala-ol or Ala-ol are particularly effective and continue to exhibit very substantial suppression of LH secretion at 96 hours following injection.

Description

[0001] The present invention generally relates to a class of peptides which are antagonists of human gonadotropin releasing hormone (GnRH) and possess advantageous physical, chemical and biological properties. More specifically, the present invention relates to decapeptides, which inhibit gonadal function and the long-term release of the steroid hormones progesterone and testosterone, and to the administration for this purpose of pharmaceutical compositions containing the decapeptides, in particular for the inhibition of gonadal steroid Hypersecretion. Background of the invention

[0002] Follicle-stimulating hormone (FSH) and luteinizing hormone (LH), sometimes called gonadotropins or gonadotropins, are released by the pituitary gland, which is connected to the hypothalamus through a stalk.

[0003] The release of hormones from the anterior pituitary usually requires the release of hormones produced by the hypothalamus first, such as GnRH decapeptide.

[0004] Inhibition of ...