Synthetic vasoactive intestinal peptide analogs
AssigneeHoffmann-La Roche Inc.
InventorsDavid R. Bolin, Johannes A. Meienhofer, Iou-Iou Sytwu
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Abstract
Novel vasoactive intestinal peptide analogs containing substitutions of appropriately selected amino acids at specific positions of the VIP molecule, with potent sustained bronchodilatory activity without cardiovascular side effects.
Claims17
A peptide of the formula ##STR8## R is Asn or Ala;
- R.sub.2 is Thr or Ser;
- R.sub.3 is Arg, Lys or Orn;
- R.sub.4 is Leu or Phe;
- R.sub.5 is Arg or Lys;
- R.sub.6 is Nle, Ile or Leu;
- R.sub.7 is Asn or Thr;
- R.sub.8 is Ser or Thr;
- R.sub.9 is Ile or Val;
- R.sub.10 is Asn or Thr;
- X is hydrogen, ##STR9## R.sub.11 is C.sub.1-3 alkyl;
- Y is --OR.sub.12 or NHR.sub.12 ;
- R.sub.12 is hydrogen or C.sub.1-3 alkyl;
- or with the proviso that (Nle).sup.17 -VIP is excluded from the scope of Formula I;
- and the pharmaceutically acceptable acid or base addition salts thereof.
A peptide which is
- Ac-(Lys.sup.12, Nle.sup.17, Val.sup.26, Thr.sup.28)-VIP.
A peptide which is
- Ac-(Orn.sup.12, Nle.sup.17, Val.sup.26, Thr.sup.28)-VIP.
A peptide which is
- Ac-(Lys.sup.12, Lys.sup.14, Nle.sup.17, Val.sup.26, Thr.sup.28)-VIP.
A peptide which is
- Ac-(Lys.sup.12, Nle.sup.17, Thr.sup.25, Val.sup.26, Thr.sup.28)-VIP.
A pharmaceutical composition comprising an active agent which is a peptide having bronchotracheal smooth muscle relaxant activity and a pharmaceutically acceptable carrier, wherein said peptide has the formula:
- ##STR11## R is Asn or Ala;
- R.sub.2 is Thr or Ser;
- R.sub.3 is Arg, Lys or Orn;
- R.sub.4 is Leu or Phe;
- R.sub.5 is Arg or Lys;
- R.sub.6 is, Ile or Leu;
- R.sub.7 is Asn or Thr;
- R.sub.8 is Ser or Thr;
- R.sub.9 is Ile or Val;
- R.sub.10 is Asn or Thr;
- X is hydrogen, ##STR12## R.sub.11 is C.sub.1-3 alkyl;
- Y is --OR.sub.12 or NHR.sub.12 ;
- R.sub.12 is hydrogen or C.sub.1-3 alkyl;
- with the proviso that (Nle).sup.17 -VIP is excluded from the scope of Formula I;
- and the pharmaceutically acceptable acid or base addition salts thereof.
A method of treating bronchotraceal constriction disorders which comprises administering a bronchotracheal smooth muscle relaxing effective amount of a peptide having the formula:
- ##STR13## R is Asn or Ala;
- R.sub.2 is Thr or Ser;
- R.sub.3 is Arg, Lys or Orn;
- R.sub.4 is Leu or Phe;
- R.sub.5 is Arg or Lys;
- R.sub.6 is Nle, Ile or Leu;
- R.sub.7 is Asn or Thr;
- R.sub.8 is Ser or Thr;
- R.sub.9 is Ile or Val;
- R.sub.10 is Asn or Thr;
- X is hydrogen, ##STR14## R.sub.11 is C.sub.1-3 alkyl;
- Y is --OR.sub.12 or NHR.sub.12 ;
- R.sub.12 is hydrogen or C.sub.1-3 alkyl;
- with the proviso that (Nle).sup.17 -VIP is excluded from the scope of Formula I;
- and the pharmaceutically acceptable acid or base addition salts thereof.
Dependencies are inferred from the claim text.