| abstract |
Synthetic analogues of hGH-RH(1-29)NH2 having substitutions of various amino acids and acylated at the N-terminus, and exhibiting prolonged antagonistic duration. Embodiments include analogues of the formula: X-R?1-R2-R3-R4-R5-R6-Thr-R8¿-Ser-Tyr-R11-R12-Val-Leu-R15-Gln-Leu-Ser-R?19-R20-R21¿-Leu-Leu-Gln-Asp-Ile-R?27-R28-R29¿, wherein X is nil, H, Ac, IAc, BrProp, For, Ibu, Nac, 2-Nac, 1- or 2-Npt, 1- or 2-Npr or Aqc; R1 is Tyr, His, Glu or Glt; R2 is D-Arg, D-Cit, D-Har, D-Lys or D-Orn; R3 is Asp, Ala or Gly; R4 is Ala or Gly; R5 is Ile, Ala or Gly; R6 is Phe, Ala, Pro, Tpi, Nal or Phe(Y), in which Y is F, Cl, Br, NO¿2?, CH3 or OCH3; R?8¿ is Asn, Ser, Val, Ile, Ala, Abu, Nle or Aib; R11 is Arg, D-Arg or Cit; R12 is Lys, D-Lys Cit or Ala; R15 is Gly, Ala, Abu or Gln; R19 is Ala or Abu; R20 is Arg, D-Arg or Cit; R21 is Lys, D-Lys or Cit; R27 is Met, Nle or Abu; R28 is Ser, Asn, Asp or Abu; R29 is Agm, Arg-NH¿2?, Arg-OH, Cit-NH2, Cit-OH, Har-NH2 or Har-OH; provided that when R?1¿ is Glt, X is nil and when X is H, R15 is other than Gly, and pharmaceutically acceptable acid addition salts thereof. |