Claims
- 1. The peptides having the structure: ##STR55## wherein: X is CH.sub.2, S, ##STR56## SO.sub.2 and [X].sub.n wherein n=0; Y is CH.sub.2, S, ##STR57## SO.sub.2 and [Y].sub.n wherein n=0; R is H, NH.sub.2 and R"NH and wherein
- R" is Ala-Gly-, lower acyl containing 2 to 6 carbon atoms or aroyl containing 7 to 21 carbon atoms;
- R' is H and CO.sub.2 H; wherein X and Y are not both heteroatoms and when R' is H, X and Y are not both --CH.sub.2 --; and R'" is asparagine, alanine or .alpha.-aminobutyric acid.
- 2. The peptides having the structure: ##STR58## wherein X-Y is: ##STR59## R is H, NH.sub.2 and R"NH wherein R" is Ala-Gly-, lower acyl containing 2 to 6 carbon atoms or aroyl containing 7 to 21 carbon atoms;
- R' is H and CO.sub.2 H and when R' is H, X and Y are also --CH.sub.2 --CH.sub.2 -- and --CH.sub.2 --; and R'" is asparagine, alanine or .alpha.-aminobutyric acid.
- 3. The peptide according to claim 2 having the structure: ##STR60##
- 4. The peptide according to claim 3 having the structure: ##STR61##
- 5. The peptide according to claim 2 having the structure: ##STR62##
- 6. The peptide according to claim 2 having the structure: ##STR63##
- 7. The peptide according to claim 2 having the structure: ##STR64##
- 8. The peptide according to claim 7 having the structure: ##STR65##
- 9. The peptide according to claim 2 having the structure: ##STR66## wherein X-Y is --CH.sub.2 --S-- and --S--CH.sub.2 --.
- 10. The peptide according to claim 9 having the structure: ##STR67## wherein X-Y is --CH.sub.2 --S-- and --S--CH.sub.2 --.
- 11. The peptides having the structure: ##STR68## ##STR69## wherein: X is CH.sub.2, S and [X].sub.n wherein n=0;
- Y is CH.sub.2, S and [Y].sub.n wherein n=0;
- R is H, NH.sub.2 or R"NH wherein
- R" is Ala-Gly-, lower acyl containing 1 to 6 carbon atoms or aroyl containing 7 to 21 carbon atoms;
- R' is H or CO.sub.2 H; wherein X and Y are not both heteroatoms.
- 12. The peptide according to claim 11 having the structure: ##STR70##
- 13. The peptides having the structure: ##STR71## wherein: X is CH.sub.2, S and [X].sub.n wherein n=0;
- Y is CH.sub.2, S and [Y].sub.n wherein n=0;
- R' is H and CO.sub.2 H.
- 14. The peptides having the structure: ##STR72## wherein: X is CH.sub.2, S and [X].sub.n wherein n=0;
- Y is CH.sub.2, S and [Y].sub.n wherein n=0;
- R' is H and CO.sub.2 H; wherein X and Y are not both heteroatoms.
- 15. The peptide according to claim 14 having the structure: ##STR73##
- 16. The peptide according to claim 15 having the structure: ##STR74##
- 17. The peptides having the structure: ##STR75## wherein: X is CH.sub.2, S and [X].sub.n wherein n=0;
- Y is CH.sub.2, S and [Y].sub.n wherein n=0;
- R' is H and CO.sub.2 H; wherein X and Y are not both heteroatoms.
- 18. The peptides having the structure: ##STR76## wherein: X is CH.sub.2, S and [X].sub.n wherein n=0;
- Y is CH.sub.2, S and [Y].sub.n wherein n=0;
- R' is H or CO.sub.2 H; wherein X and Y are not both heteroatoms.
- 19. The peptide according to claim 18 having the structure: ##STR77##
- 20. The peptides having the structure: ##STR78## wherein: X is CH.sub.2, S and [X].sub.n wherein n=0;
- Y is CH.sub.2, S and [Y].sub.n wherein n=0;
- R' is a H and CO.sub.2 H; wherein X and Y are not both heteroatoms.
- 21. The peptides having the structure: ##STR79## wherein: X is CH.sub.2, S and [X].sub.n wherein n=0;
- Y is CH.sub.2, S and [Y].sub.n wherein n=0;
- R"" is H and --COOtBu; wherein X and Y are not both heteroatoms.
- 22. The peptides according to claim 21 having the structure: ##STR80##
- 23. The peptides having the structure: ##STR81## wherein: X is CH.sub.2, S and [X].sub.n wherein n=0;
- Y is CH.sub.2, S and [Y].sub.n wherein n=0;
- R"" is H and --COOtBu; wherein X and Y are not both heteroatoms.
- 24. The compound having the structure: ##STR82##
- 25. The process for preparing the peptides having the structure: ##STR83## wherein: X is CH.sub.2, S, ##STR84## SO.sub.2 and [X].sub.n wherein n=0; Y is CH.sub.2, S, ##STR85## SO.sub.2 and [Y].sub.n wherein n=0; R is H, NH.sub.2 and R"NH wherein
- R" is Ala-Gly-, lower acyl containing 2 to 6 carbon atoms or aroyl containing 7 to 21 carbon atoms;
- R' is H and CO.sub.2 H; wherein X and Y are not both heteroatoms and R"' is asparagine, alanine or .alpha.-aminobutyric acid which comprises treating the peptides having the structure: ##STR86## wherein X, Y, R, R', R" and R"' are as defined above with zinc dust in an aqueous solution of a lower alkanoic acid and wherein:
- X is ##STR87## and SO.sub.2 ; Y is ##STR88## and SO.sub.2 further oxidizing with performic acid or hydrogen peroxide, respectively.
- 26. The process according to claim 25 for preparing the peptide having the structure: ##STR89##
- 27. The process for preparing the peptides having the structure: ##STR90## wherein: X is CH.sub.2, S and [X].sub.n wherein n=0;
- Y is CH.sub.2, S and [Y].sub.n wherein n=0;
- R' is H and CO.sub.2 H; wherein X and Y are not both heteroatoms which comprises treating the peptide of structure: ##STR91## wherein X, Y and R' are as defined above; (a) with a methanolic solution of hydrazine to convert the -OMe group to a hydrazide;
- (b) removing the BOC protecting group from tryptophan by treating the undecapeptide hydrazide with anhydrous HCl in the presence of mercaptoethanol;
- (c) forming the desired cyclic peptide by converting the hydrazide group to an azide by treatment with isoamylnitrite at about -25.degree. C. at strongly acid pH; diluting the solution to a concentration of about 1 mg./ml. with a suitable organic solvent;
- (d) adjusting the pH to slightly basic to convert the .alpha.-amine group of the tryptophan amino acid to the free .alpha.-amino group and initiating the cyclization wherein the cyclization is completed by allowing the reaction to stand at about about -20.degree. C. for about four days.
- 28. The process according to claim 27 for preparing the peptide having the structure: ##STR92## from the peptide having the structure: ##STR93##
- 29. The process for preparing the peptides having the structure: ##STR94## wherein: X is CH.sub.2, S and [X].sub.n wherein n=0;
- Y is CH.sub.2, S and [Y].sub.n wherein n=0;
- R' is H and CO.sub.2 H; wherein X and Y are not both heteroatoms which comprises treating the peptide of structure: ##STR95## wherein X, Y and R' are as defined above in an inert solvent with a solution of BOC-Trp-(.epsilon.-INOC)Lys-Thr-Phe-Thr-Ser-N.sub.3 or BOC-D-Trp-(.epsilon.-INOC)Lys-Thr-Phe-Thr-Ser-N.sub.3 in an inert solvent at about -30.degree. C.
- 30. The process according to claim 29 for preparing the peptide having the structure: ##STR96## from the peptide having the structure: ##STR97##
- 31. The process for preparing the peptides having the structure: ##STR98## wherein: X is CH.sub.2, S and [X].sub.n wherein n=0;
- Y is CH.sub.2, S and [Y].sub.n wherein n=0;
- R' is H and CO.sub.2 H; wherein X and Y are not both heteroatoms which comprises treating the peptide of structure: ##STR99## wherein X and Y are as defined above and R"" is H or ##STR100## with a solution containing (.epsilon.-INOC)Lys-Asn-Phe-Phe-OMe.2HCl at a basic pH for about overnight and treating the resulting blocked pentapeptide with TFA to remove the BOC group.
- 32. The process according to claim 31 for preparing the peptide having the structure: ##STR101##
- 33. A composition comprising a therapeutically effective amount of the peptides having the structure: ##STR102## wherein X is CH.sub.2, S, ##STR103## SO.sub.2 and [X].sub.n wherein n=0; Y is CH.sub.2, S, ##STR104## SO.sub.2 and [Y].sub.n wherein n=0; R is H, NH.sub.2 and R"NH wherein
- R" is Ala-Gly-, lower acyl containing 2 to 6 carbon atoms or aroyl containing 7 to 21 carbon atoms;
- R' is H and CO.sub.2 H; wherein X and Y are not both heteroatoms and when R' is H, X and Y are not both --CH.sub.2 --; and a pharmaceutically acceptable carrier.
- 34. A therapeutic composition comprising a therapeutically effective amount of the peptides having the structure: ##STR105## and a pharmaceutically acceptable carrier.
- 35. A composition according to claim 33 wherein the composition contains from about 0.07 mg. to about 140 mg. of the peptide.
- 36. A composition according to claim 34 wherein the composition contains from about 0.07 mg. to about 140 mg. of the peptide.
- 37. A compound of the formula: ##STR106## wherein n=2 or 3 and m=2 or 3 with the proviso that n and m are not both 3.
Parent Case Info
This application is a continuation-in-part of application Ser. No. 680,005, filed Apr. 23, 1976, abandoned which in turn is a continuation-in-part of co-pending application Ser. No. 603,067, filed Aug. 8, 1975, abandoned.
US Referenced Citations (3)
Number |
Name |
Date |
Kind |
3842066 |
McKinley et al. |
Oct 1974 |
|
3904594 |
Guillemin et al. |
Sep 1975 |
|
3988304 |
Garsky |
Oct 1976 |
|
Non-Patent Literature Citations (6)
Entry |
J. Med. Chem. 18, 123 (1975). |
Endocrinology 98, 336 (1976). |
Biochem. Biophys. Res. Commun. 65, 746 (1975). |
Coll. Czech. Chem. Commun. 32, 1229 (1967). |
Experientia 20, 570 (1964). |
J.A.C.S. 98, 2367 (1967). |
Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
680005 |
Apr 1976 |
|
Parent |
603067 |
Aug 1975 |
|