HGH-RH(1-29)NH2 analogues having antagonistic activity

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

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514 9, 514 12, 530317, 530324, A61K 3816, A61K 3812, C07K 764, C07K 700

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active

059424893

ABSTRACT:
A peptide selected from the group having the formulae:
.alpha.) X-R.sup.1 -R.sup.2 -R.sup.3 -R.sup.4 -R.sup.5 -R.sup.6 -Thr-R.sup.8 -R.sup.9 -R.sup.10 -R.sup.11 -R.sup.12 -Val-Leu-R.sup.15 -Gln-Leu-Ser-R.sup.19 -R.sup.20 -R.sup.21 -Leu-Leu-Gln-Asp-Ile-R.sup.27 -R.sup.28 -R.sup.29, wherein X is H, Ac, Aqc, IAc, BrProp, For, Ibu, Nac, 2-Nac, 1- or 2-Npt, 1- or 2-Npr, PhAc, Fpr, or any other aromatic or nonpolar acyl group, R.sup.1 is Tyr, His or Phe(Y), in which Y=H, F, Cl, Br, NO.sub.2, CH.sub.3 or OCH.sub.3, R.sup.2 is D-Arg, D-Cit, D-Har, D-Lys, D-Tic or D-Orn, R.sup.3 is Asp, D-Asp, Ala, D-Ala or Gly, R.sup.4 is Ala, Abu or Gly, R.sup.5 is Ile, Ala or Gly, R.sup.6 is Phe, Tic, Ala, Pro, Tpi, Nal or Phe(Y), in which Y=H, F, Cl, Br, NO.sub.2, NH.sub.2, CH.sub.3 or OCH.sub.3, R.sup.8 is Asn, Gln, Ser, Thr, Val, Leu, Ile, Ala, D-Ala, D-Asn, D-Gln, D-Thr, D-Leu, Abu, D-Abu, Nle, or Alb, R.sup.9 is Ser, R.sup.10 is Tyr or Phe(Y), in which Y=H, F, Cl, Br, NO.sub.2, CH.sub.3 or OCH.sub.3, R.sup.11 is Arg, D-Arg, or Cit, R.sup.12 is Lys, D-Lys, Cit, D-Cit, Orn, D-Orn, Nle 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, Orn or Cit, R.sup.27 is Met, Nle or Abu, R.sup.28 is Ser, Asn, Ala 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, and
.beta.) X-A.sup.1 -B.sup.2 -A.sup.3 -R.sup.4 -R.sup.5 -R.sup.6 -Thr-A.sup.8 Ser-R.sup.10 -R.sup.11 -B.sup.12 -Val-Leu-R.sup.15 -A.sup.16 -A.sup.17 -Ser-R.sup.19 -B.sup.20 -B.sup.21 -Leu-Leu-Gln-A.sup.26 -Ile-R.sup.27 -R.sup.28 -R.sup.29, wherein a lactam bridge is formed between any one of the pairs of positions 1,2; 2,3; 8,12; 16,20; 17-21; 21,25; 25,29 or both 8,12 and 21,25 positions, and X is H, Ac, Aqc, IAc, BrProp, For, Ibu, Nac, 2-Nac, 1- or 2-Npt, 1- or 2-Npr, PhAc, Fpr, or any other aromatic or nonpolar acyl group, A is Glu, D-Glu, Gln, Asp, D-Asp, Asn, Abu, Leu, Tyr, His, Phe(Y), in which Y=H, F, cl, Br, NO.sub.2, NH.sub.2, CH.sub.3 or OCH.sub.3, Ser, Thr, Val, Ile, Ala, D-Ala, D-Asn, D-Gln, D-Thr, D-Leu, Abu, D-Abu, Nle, or Aib, B is Lys, D-Lys, Arg, D-Arg,Orn, D-Orn, or Agm; R.sup.4 is Ala, Abu or Gly, R.sup.5 is Ile, Ala or Gly, R.sup.6 is Phe, Tic, Tpi, Nal or Phe(Y), in which Y=H, F, Cl, Br, NO.sub.2, NH.sub.2 CH.sub.3 or OCH.sub.3, R.sup.10 is Tyr or Phe(Y), in which Y=H, F, Cl, Br, NO.sub.2, NH.sub.2 CH.sub.3 or OCH.sub.3, R.sup.15 is Gly, Ala, Abu or Gin, R.sup.27 is Met, Nle or Abu, R.sup.28 is Ser, Asn, Asp, Ala or Abu, and pharmaceutically acceptable salts thereof.

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