Claims
- 1. A compound of the formula
- A--B--C--Ser--Tyr--X--Leu--Arg--Pro--E ( I)
- and the pharmaceutically acceptable salts thereof, wherein:
- X is a D-alanyl residue wherein one hydrogen on C-3 is replaced by:
- (a) a carbocyclic aryl-containing radical selected from the group consisting of phenyl substituted with three or more straight chain lower alkyl groups, naphthyl, anthryl, fluorenyl, phenanthryl, biphenylyl and benzhydryl; or
- (b) a saturated carbocyclic radical selected from the group consisting of cyclohexyl sustituted with three or more straight chain lower alkyl groups, perhydronaphthyl, perhydrobiphenylyl, perhydro-2, 2-diphenylmethyl, and adamantyl; or
- (c) a heterocyclic aryl containing radical selected from the group consisting of radicals represented by the following structural formulas: ##STR15## wherein A" and A' are independently selected from the group consisting of hydrogen, lower alkyl, chlorine, and bromine, and G is selected from the group consisting of oxygen, nitrogen, and sulfur;
- A is an aminoacyl residue selected from the group consisting of L-pyroglutamyl, D-pyroglutamyl, N-acyl-L-prolyl, N-acyl-D-prolyl, N-acyl-D-tryptophanyl, N-acyl-D-phenylalanyl, N-acyl-D-p-halophenylalanyl, and N-acyl-X, wherein X is as defined previously;
- B is a D-p-halophenylalanyl residue;
- C is an amino acyl residue selected from the group consisting of L-tryptophanyl, D-tryptophanyl, D-phenylalanyl and X wherein X is as defined above;
- E is glycinamide or --NH-R.sup.1, wherein R.sup.1 is lower alkyl, cycloalkyl, fluoro lower alkyl or ##STR16## wherein R.sup.2 is hydrogen or lower alkyl.
- 2. The compound of claim 1, and the pharmaceutically acceptable salts thereof, wherein
- A is selected from the group consisting of L-( pyro)Glu, D-( pyro)Glu, NAc-D-Phe, NAc-D-Nal(1), NAc-D-Nal(2), NAc-D-p-halo-Phe, NAc-D-Me5Phe, NAc-D-TMP, NAc-D-BIA, NAc-D-TBA, and NAc-L-Pro;
- B is D-p-F-Phe;
- C is selected from the group consisting of L-Trp, D-Trp, D-Phe, D-Nal(1), D-Nal(2), D-p-halo-Phe, D-Me5Phe, D-TMP, D-BIA and D-TBA;
- X is selected from the group consisting of D-Nal(1), D-Nal(2), D-p-halo-Phe, D-Me5Phe, D-TMP, D-BIA and D-TBA; and
- E is glycinamide or --NH-R, wherein R.sup.1 is lower alkyl, cycloalkyl, fluoro lower alkyl or ##STR17## wherein R.sup.2 is hydrogen or lower alkyl.
- 3. The compound of claim 2 and the pharmaceutically acceptable acid addition salts thereof, wherein:
- X is D-Nal(2).
- 4. The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof, wherein:
- A is NAc-Pro, C is D-Nal(2), and E is Gly-NH.sub.2, i.e. NAc-Pro-D-p-F-Phe-D-Nal(2)-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-GlyNH.sub.2.
- 5. The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof, wherein:
- A is NAc-Pro, C is D-Nal(2), and E is ProNHEt, i.e. NAc-Pro-D-p-F-Phe-D-Nal(2)-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-ProNHEt.
- 6. The compount of claim 3 and the pharmaceutically acceptable acid addition salts thereof, wherein:
- A is NAc-Pro, C is D-Nal(2) and E is AzaGlyNH.sub.2, i.e. NAc-Pro-D-p-F-Phe-D-Nal(2)-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-AzaGlyNH.sub.2.
- 7. The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof, wherein:
- A is NAc-D-Nal(2), C is D-Nal(2) and E is GlyNH.sub.2, i.e. NAc-D-Nal(2)-D-p-F-Phe-D-Nal(2)-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-GlyNH.sub.2.
- 8. The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof, wherein:
- A is NAc-D-Nal(2), C is D-Nal(2) and E is ProNHEt, i.e. NAc-D-Nal(2)-D-p-F-Phe-D-Nal(2)-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-ProNHEt.
- 9. The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof, wherein:
- A is NAc-D-Nal(2), C is D-Nal(2) and E is AzaGlyNH.sub.2, i.e., NAc-D-Nal(2)-D-p-F-Phe-D-Nal(2)-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-AzaGlyNH.sub.
- 10. The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof, wherein:
- A is NAc-Pro, C is L-Trp and E is GlyNH.sub.2, i.e., NAc-Pro-D-p-F-Phe-L-Trp-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-GlyNH.sub.2.
- 11. The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof, wherein:
- A is NAc- Pro, C is L-Trp and E is AzaGlyNH.sub.2, i.e., NAc-Pro-D-p-F-Phe-L-Trp-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-AzaGlyNH.sub.2.
- 12. The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof, wherein:
- A is NAc-D-Nal(2), C is L-Trp and E is GlyNH.sub.2, i.e., NAc-D-Nal(2)-D-p-F-Phe-L-Trp-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-GlyNH.sub.2.
- 13. The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof, wherein:
- A is NAc-D-Nal(2), C is L-Trp and E is AzaGlyNH.sub.2, i.e., NAc-D-Nal(2)-D-p-F-Phe-L-Trp-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-AzaGlyNH.
- 14. The compound of claim 1 and the pharmaceutically acceptable salts thereof, wherein A is NAc-L-Pro, B is D-p-Cl-Phe, C is D-Trp, and E is AzaGlyNH.sub.2, i.e., NAc-L-Pro-D-p-Cl-Phe-D-Trp-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-AzaGlyNH.sub.2.
- 15. The compound of claim 1 and the pharmaceuticaly acceptable salts thereof, wherein A is NAc-L-Pro, B is D-p-Cl-Phe, C is D-Trp, and E is GlyNH.sub.2, i.e., NAc-L-Pro-D-p-Cl-Phe-D-Trp-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-GlyNH.sub.2.
- 16. The compound of claim 1 and the pharmaceutically acceptable addition salts thereof wherein A is NAc-L-Pro, B is D-p-Cl-Phe, C is D-Trp and E is PronNHEt, i.e., NAc-L-Pro-D-p-Cl-Phe-Pro-D-Trp-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-ProNHEt.
- 17. The compound of claim 1 and the pharmaceutically acceptable salts thereof, wherein A is NAc-L-Pro, B is D-p-Cl-Phe, C is D-Trp, and E is AzaGlyNH.sub.2, i.e., NAc-L-Pro-D-p-Cl-Phe-D-Trp-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-AzaGlyNH.sub.2.
- 18. The compound of claim 2 and the pharmaceutically acceptable salts thereof wherein A is NAc-Pro, B is D-p-F-Phe, C is D-Phe, X is Nal(2) and E is GlyNH.sub.2, i.e. NAc-Pro-D-p-F-Phe-D-Phe-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-GlyNH.sub.2.
- 19. The compound of claim 2 and the pharmaceutically acceptable salts thereof wherein A is NAc-Pro, B is D-p-F-Phe, C is D-Phe, X is Nal(2) and E is AzaGlyNH.sub.2, i.e. NAc-Pro-D-p-F-Phe-D-Phe-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-AzaGlyNH.sub.2.
- 20. The compound of claim 2 and the pharmaceutically acceptable salts thereof wherein A is NAc-Pro, B is D-p-F-Phe, C is D-Phe, X is Nal(2) and E is ProNHEt, i.e., NAc-Pro-D-p-F-Phe-D-Phe-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-ProNHEt.
- 21. The compound of claim 1 and the pharmaceutically acceptable salts thereof wherein A is NAc-Pro, B is D-p-Cl-Phe, C is D-Phe, X is Nal(2) and E is GlyNH.sub.2, i.e. NAc-Pro-D-p-Cl-Phe-D-Phe-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-GlyNH.sub.2.
- 22. The compound of claim 1 and the pharmaceutically acceptable salts thereof wherein A is NAc-Pro, B is D-p-Cl-Phe, C is D-Phe, X is Nal(2) and E is AzaGlyNH.sub.2, i.e. NAc-Pro-D-p-Cl-Phe-D-Phe-Ser-Tyr-D-Nal(2)-Leu-ArgPro-AzaGlyNH.sub.2.
- 23. The compound of claim 1 and the pharmaceutically acceptable salts thereof wherein A is NAc-Pro, B is D-p-Cl-Phe, C is D-Phe, X is Nal(2) and E is ProNHEt, i.e., NAc-Pro-D-p-Cl-Phe-D-Phe-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-ProNHEt.
- 24. A method of inhibiting ovulation in a female mammalian subject, which method comprises administering to said subject an effective amount of the compound of claim 2 or a pharmaceutical composition containing same.
- 25. A method of treating endometriosis in a female mammalian subject, which method comprises administering to said subject an effective amount of the compound of claim 1 or a pharmaceutical composition containing same.
- 26. A method of treating prostatic hypertrophy in a male mammalian subject, which method comprises administering to said subject an effective amount of the compound of claim 1 or a pharmaceutical composition containing same.
- 27. A method of inhibiting spermatogenesis in a male mammalian subject, which method comprises administering to said subject an effective amount of the compound of claim 1 or a pharmaceutical composition containing same.
- 28. A pharmaceutical composition for inhibiting of ovulation or for treating endometriosis in a female mammalian subject and for treating prostatic hypertrophy or inhibiting spermatogenesis in a male mammalian subject comprising an effective amount of the compound of claim 1 in admixture with at least one pharmaceutically acceptable excipient.
Parent Case Info
This is a continuation, of application Ser. No. 194,180, filed Oct. 6, 1980, now U.S. Pat. No. 4,341,767 issued 7/27/82.
US Referenced Citations (3)
Number |
Name |
Date |
Kind |
4234571 |
Nestor et al. |
Nov 1980 |
|
4318905 |
Nestor et al. |
Mar 1982 |
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4341767 |
Nestor et al. |
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Continuations (1)
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Number |
Date |
Country |
Parent |
194180 |
Oct 1980 |
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