| 摘要 |
Disclosed herein are analogues of the luteinizing hormone-releasing hormone (LH-RH), which are potent antagonists of LH-RH. These peptides inhibit the release of gonadrotropins from the pituitary in mammals, including humans and possess antitumor activity. Formula (I): X-R<1>-R<2>-R<3>-Ser-R<5>-R<6>(AY2)-Leu-Arg-Pro-D-Ala-NH2 represents peptides which are within the scope of this invention and the pharmaceutically acceptable salts thereof, wherein R<1> is D-Phe, D-Phe(4Cl), D-Nal(1) or D-Nal(2), R<2> is D-Phe or D-Phe(4Hl), R<3> is D-Trp, D-Phe, D-Phe(4Hl), D-Nal(1), D-Nal(2) or D-Pal(3), R<5> is Tyr or Arg, R<6> is D-Lys or D-Orn, Hl is fluoro, chloro or bromo, X is a lower alkanoyl group of 2-5 carbon atoms, A is a diaminoacyl residue having formula (II), where m is 0 or 1, n is 0 or 1, Y is hydrogen or Y<1> or Y<2>, wherein Y<1> is an acyl group derived from straight or branched chain aliphatic, alicyclic carboxylic acids having from 3 to 12 carbon atoms or aromatic carboxylic acid of 6 or 10 ring carbon atoms, Y<2> is carbamoyl or alkyl-substituted carbamoyl group having formula (III): H-(CH2)n-NH-CO-, where n is 0-3. |
