Peptides comprising opioid receptor agonist and nk1 receptor antagonist activities
AssigneeArizona Board of Regents on Behalf of the University of Arizona
InventorsVictor J. Hruby, Aswini K. Giri
Life of this patent
Estimating the term…
Abstract
The present invention relates generally to a compound having both agonist activity at opioid receptor(s) and antagonist activity at NK1 receptor, and methods for producing and using the same. This combination of activities provides several synergistic and/or beneficial effects such as enhanced potency in analgesic effect and reduction or inhibition of tolerance.
Claims13
An oligopeptide of the formula:
- AA1-Q-Pro-AA2-AA3
- where
- AA1 is Tyr or Dmt;
- AA2 is Leu or methylate Leu;
- AA3 is Trp or methylated Trp each of which is covalently linked to optionally substituted benzyl amine or (optionally substituted phenyl)ethan-1-amine;
- and
- Q is a moiety of the formula:
- -(D)-NRAla-Phe′-NRGly-Tyr′-Pro-Ser-, or
- -Pro-[Z]b-Phe′-Pro-;
- -AA4-AA5-AA6-AA7-Pro-Ser- (i)
- AA4 is (D)-Ala or methylated (D)-Ala;
- AA5 is Phe, Phe(4-F), methylated Phe, or methylated Phe(4-F);
- AA6 is Gly or methylated Gly;
- and
- AA7 is Tyr or Dmt;
- or
- -Pro-(AA8)a-AA9-Pro- (ii)
- a is 0 or 1;
- AA8 is Phe or Trp;
- and
- AA9 is Phe, Phe(4-F), methylated Phe, or methylated Phe(4-F), provided at least one of AA2, AA3, AA5, or AA9 is methylated.
A method for treating pain comprising administering a subject in need of such a treatment a therapeutically effective amount of a compound of an oligopeptide of the formula:
- AA1-Q-Pro-AA2-AA3
- where
- AA1 is Tyr or Dmt;
- AA2 is Leu or methylate Leu;
- AA3 is Trp or methylated Trp each of which is covalently linked to optionally substituted benzyl amine or (optionally substituted phenyl)ethan-1-amine;
- and
- Q is a moiety of the formula:
- -(D)-NRAla-Phe′-NRGly-Tyr′-Pro-Ser-, or
- -Pro-[Z]b-Phe′-Pro-;
- -AA4-AA5-AA6-AA7-Pro-Ser- (i)
- AA4 is (D)-Ala or methylated (D)-Ala;
- AA5 is Phe, Phe(4-F), methylated Phe, or methylated Phe(4-F);
- AA6 is Gly or methylated Gly;
- and
- AA7 is Tyr or Dmt;
- or
- -Pro-(AA8)a-AA9-Pro- (ii)
- a is 0 or 1;
- AA8 is Phe or Trp;
- and
- AA9 is Phe, Phe(4-F), methylated Phe, or methylated Phe(4-F), provided at least one of AA2, AA3, AA5, or AA9 is methylated.
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and an oligopeptide of the formula:
- AA1-Q-Pro-AA2-AA3
- where
- AA1 is Tyr or Dmt;
- AA2 is Leu or methylate Leu;
- AA3 is Trp or methylated Trp each of which is covalently linked to optionally substituted benzyl amine or (optionally substituted phenyl)ethan-1-amine;
- and
- Q is a moiety of the formula:
- -(D)-NRAla-Phe′-NRGly-Tyr′-Pro-Ser-, or
- -Pro-[Z]b-Phe′-Pro-;
- -AA4-AA5-AA6-AA7-Pro-Ser- (i)
- AA4 is (D)-Ala or methylated (D)-Ala;
- AA5 is Phe, Phe(4-F), methylated Phe, or methylated Phe(4-F);
- AA6 is Gly or methylated Gly;
- and
- AA7 is Tyr or Dmt;
- or
- -Pro-(AA8)a-AA9-Pro- (ii)
- a is 0 or 1;
- AA8 is Phe or Trp;
- and
- AA9 is Phe, Phe(4-F), methylated Phe, or methylated Phe(4-F), provided at least one of AA2, AA3, AA5, or AA9 is methylated.
Dependencies are inferred from the claim text.