Analogues of hGH-RH(1-29)NH.sub.2 having antagonistic activity

Details Analogues of hGH-RH(1-29)NH.sub.2 having antagonistic activity Analogues of hGH-RH(1-29)NH.sub.2 having antagonistic activity

1993-12-17

1996-08-27

Weimar, Elizabeth C.

Chemistry: natural resins or derivatives; peptides or proteins;

Peptides of 3 to 100 amino acid residues

25 or more amino acid residues in defined sequence

A61K 3800, C07K 710, C07K 700

Patent

active

055502121

ABSTRACT:
Synthetic analogues of hGH-RH(1-29)NH.sub.2 having substitutions of various amino acids and acylated at the N-terminus, and exhibiting prolonged antagonistic duration. Embodiments include analogues of the formula: ##STR1## wherein X is nil, H, Ac, IAc, BrProp, Ibu, Nac, 2-Nac, 1- or 2-Npt, 1- or 2-Npr or Aqc; R.sup.1 is Tyr, His, Glu or Glt; R.sup.2 is D-Arg, D-Cit, D-Har, D-Lys or D-Orn; R.sup.3 is Asp, Ala or Gly; R.sup.4 is Ala or Gly; R.sup.5 is Ile, Ala or Gly; R.sup.6 is Phe, Ala, Pro, Tpi, Nal or Phe(Y), in which Y is F, Cl, Br, NO.sub.2, CH.sub.3 or OCH.sub.3 ; R.sup.8 is Asn, Ser, Val, Ile, Ala, Abu, Nle, or Aib; R.sup.11 is Arg, D-Arg or Cit; R.sup.12 is Lys, D-Lys, Cit or Ala; R.sup.15 is Gly, Ala, Abu or Gln; R.sup.19 is Ala or Abu; R.sup.20 is Arg, D-Arg or Cit; R.sup.21 is Lys, D-Lys or Cit; R.sup.27 is Met, Nle or Abu; R.sup.28 is Ser, Asn, Asp or Abu; R.sup.29 is Agm, Arg-NH.sub.2, Arg-OH, Cit-NH.sub.2, Cit-OH, Har-NH.sub.2 or Har-OH; provided that when R.sup.1 is Glt, X is nil and when X is H, R.sup.15 is other than Gly, and pharmaceutically acceptable acid addition salts thereof.

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