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.
A series of ten 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 assay, at a dosage as low as 1 microgram/mL, and the corresponding Phe2 analogue inhibited the effect of 0.3 ng of LH-RH at 0.1 microgram/mL. The Trp2 analogue inhibited ovulation in rats at the dosage of 1.5 mg per rat.
D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D010060:Ovulation / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
D000577:Amides; D007987:Gonadotropin-Releasing Hormone