Nonapeptide ethylamide inhibitors of the luteinizing hormone-releasing hormone (LH-RH) having a D-alanyl residue in position 6 and variations at positions 2 and 3

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Abstract
A series of 10 analogues, of structure des-Gly10-[amino acid2,amino acid3,D-Ala6]-LH-RH ethylamide, was synthesized by solid-phase methods. L-Aromatic and alkylamino acids were substituted into position 2 and alkylamino acids into position 3. Highest in vitro inhibition of LH-RH action was obtained with analogues having aromatic residues in position 2. Des-Gly10-[Trp2,Leu3,D-Ala6]-LH-RH ethylamide inhibited the action of 0.6 ng/ml of LH-RH in an isolated pituitary [rat] assay at a dosage as low as 1 .mu.g/ml, and the corresponding Phe2 analogue inhibited the effect of 0.3 ng of LH-RH at 0.1 .mu.g/ml. The Trp2 analogue inhbited ovulation in rats at the dosage of 1.5 mg/rat.