Claims
- 1. A peptide of the formula: ##STR12## wherein A is an amino acyl residue selected from the group consisting of
- N-acetyl-D-3-(2-naphthyl)alanine,
- N-acetyl-sarcosyl,
- N-acetyl-D-phenylalanyl,
- N-acetyl-D-(4-chlorophenyl)alanyl, and
- B is an amino acyl residue selected from the group consisting of
- D-3-(4-chlorophenyl)alanyl,
- D-3-(4-fluorophenyl)alanyl,
- D-phenylalanyl, and
- D-3-(2-naphthyl)alanyl;
- C is an amino acyl residue selected from the group consisting of
- D-3-(3-pyridyl)alanyl,
- D-3-(1-naphthyl)alanyl,
- D-3-(2-thiazolyl)alanyl, and
- D-3-(2-benzo[b]thienyl)alanyl,
- D is an amino acyl residue selected from the group consisting of
- L-seryl,
- N-(R.sup.0)-L-seryl,
- E is an amino acyl residue selected from the group consisting of
- N-(R.sup.0)-L-tyrosyl,
- N-(R.sup.0)-L-tyrosyl(O-methyl),
- N-(R.sup.0)-L-phenylalanyl,
- N-(R.sup.0)-L-3-cyclohexylalanyl,
- F is an amino acyl residue selected from the group consisting of
- D-trypyl,
- D-3-(3-pyridyl)alanyl,
- D-seryl,
- D-[epsilon-N-(N'-morpholinylcarbonyl)]lysyl,
- D-[epsilon-N-(2-pyrazinyl)carbonyl]lysyl,
- D-[epsilon-N-(N'-piperidinyl-N'-methyl)carbonyl]lysyl,
- D-[epsilon-N-(3-quinolinyl)carbonyl]lysyl, and
- D-(epsilon-N-nicotinoyl)lysyl;
- G is an amino acyl residue selected from the group consisting of
- L-leucyl,
- L-valyl,
- L-cyclohexylalanyl,
- N-(R.sup.0)-L-cyclohexylalanyl,
- N-(R.sup.0)-L-leucyl;
- H is an amino acyl residue selected from the group consisting of
- L-(epsilon-N-isopropyl)lysyl,
- N-(R.sup.0)-L-arginyl, and
- L-arginyl;
- I is an amino acyl residue selected from the group consisting of
- L-prolyl,
- N-(R.sup.0)-L-alanyl; and
- J is --NH(CH.sub.2 CH.sub.3) or is an amino acyl residue selected from the group consisting of
- D-alaninamide,
- N-(R.sup.0)-D-alaninamide,
- N-(R.sup.0)-L-alaninamide,
- sarcosamide,
- alpha-aza-glycinamide,
- D-serinamide, and
- wherein R.sup.0 is alkyl of from one to four carbon atoms; provided that when J is --NH(CH.sub.2 CH.sub.3), I is L-prolyl.
- 2. A peptide as defined by claim 1 wherein R.sup.0 is methyl.
- 3. A peptide of the formula: ##STR13## wherein A is an amino acyl residue selected from the group consisting of
- N-acetyl-sarcosyl,
- N-acetyl-D-3-(2-naphthyl)alanine,
- B is an amino acyl residue selected from the group consisting of
- D-3-(4-chlorophenyl)alanyl,
- D-3-(4-fluorophenyl)alanyl,
- C is an amino acyl residue selected from the group consisting of
- D-3-(3-pyridyl)alanyl,
- D-3-(1-naphthyl)alanyl,
- D-3-(2-benzo[b]thienyl)alanyl,
- D is an amino acyl residue selected from the group consisting of
- L-seryl,
- N-methyl-L-seryl,
- E is an amino acyl residue selected from the group consisting of
- N-methyl-L-tyrosyl,
- N-methyl-L-tyrosyl(O-methyl),
- N-methyl-L-3-cyclohexylalanyl,
- F is an amino acyl residue selected from the group consisting of
- D-trypyl,
- D-[epsilon-N-(N'-morpholinylcarbonyl)]lysyl,
- D-[epsilon-N-(3-quinolinyl)carbonyl]lysyl, and
- D-(epsilon-N-nicotinoyl)lysyl;
- G is an amino acyl residue selected from the group consisting of
- L-leucyl,
- N-methyl-D-leucyl, and
- N-methyl-L-leucyl;
- H is an amino acyl residue selected from the group consisting of
- L-(epsilon-N-isopropyl)lysyl,
- N-methyl-L-arginyl, and
- L-arginyl;
- I is an amino acyl residue selected from the group consisting of
- L-prolyl,
- N-methyl-L-alanyl; and
- J is --NH(CH.sub.2 CH.sub.3) or is an amino acyl residue selected from the group consisting of
- D-alaninamide,
- sarcosamide,
- alpha-aza-glycinamide,
- D-serinamide, and
- provided that when J is --NH(CH.sub.2 CH.sub.3), I is L-prolyl.
- 4. A peptide of the formula: ##STR14## wherein A is an amino acyl residue selected from the group consisting of
- N-acetyl-sarcosyl,
- N-acetyl-D-3-(2-naphthyl)alanine,
- B is an amino acyl residue selected from the group consisting of
- D-3-(4-chlorophenyl)alanyl,
- C is an amino acyl residue selected from the group consisting of
- D-3-(3-pyridyl)alanyl,
- D-3-(1-naphthyl)alanyl,
- D-3-(2-benzo[b]thienyl)alanyl,
- D is an amino acyl residue selected from the group consisting of
- L-seryl,
- N-methyl-L-seryl,
- E is an amino acyl residue selected from the group consisting of
- N-methyl-L-tyrosyl,
- N-methyl-L-tyrosyl(O-methyl),
- F is an amino acyl residue selected from the group consisting of
- D-[epsilon-N-(N'-morpholinylcarbonyl)]lysyl,
- D-(epsilon-N-nicotinoyl)lysyl;
- G is an amino acyl residue selected from the group consisting of
- L-leucyl,
- H is an amino acyl residue selected from the group consisting of
- L-(epsilon-N-isopropyl)lysyl, and
- L-arginyl;
- I is an amino acyl residue selected from the group consisting of
- L-prolyl, and
- J is --NH(CH.sub.2 CH.sub.3) or is an amino acyl residue selected from the group consisting of
- D-alaninamide,
- sarcosamide,
- D-serinamide, and
- provided that when J is --NH(CH.sub.2 CH.sub.3), I is L-prolyl.
- 5. A compound selected from the group consisting of:
- N-Ac-D-4-Cl-Phe-D-4-Cl-Phe-D-2-Thia-N-Me-Ser-Tyr-D-Lys-Leu-Arg-Pro-D-AlaNH.sub.2 ;
- N-Ac-D-4-Cl-Phe-D-4-Cl-Phe-D-2-Thia-Ser-N-Me-Tyr-D-Lys-Leu-Arg-Pro-AlaNH.sub.2 ;
- N-Ac-D-4-Cl-Phe-D-4-Cl-Phe-D-2-Thia-Ser-Tyr-D-Lys-Leu-Arg-Pro-SarNH.sub.2 ;
- N-Ac-D-4-Cl-Phe-N-Me-D-4-Cl-Phe-D-2-Thia-Ser-Tyr-D-Lys-Leu-Arg-Pro-D-AlaNH.sub.2 ;
- N-Ac-D-4-Cl-Phe-D-4-Cl-Phe-D-2-Thia-Ser-Tyr-N-Me-D-Lys-Leu-Arg-Pro-D-AlaNH.sub.2 ;
- N-Ac-D-2-Nal-N-Me-D-4-Cl-Phe-D-3-Pal-Ser-Lys(N-epsilon-nicotinyl)-D-Lys(N-epsilon-nicotinyl)-Leu-Lys(N-epsilon-isopropyl)-Pro-D-AlaNH.sub.2 ;
- N-Ac-D-4-Cl-Phe-D-4-Cl-Phe-D-2-Thia-Ser-N-Me-Tyr-D-Lys-Leu-Arg-Pro-D-AlaNH.sub.2 ;
- N-Ac-D-4-Cl-Phe-D-4-Cl-Phe-D-2-Thia-N-Me-Ser-Tyr-D-Lys-Leu-Arg-Pro-D-AlaNH.sub.2 ;
- N-Ac-D-2-Nal-D-4-Cl-Phe-D-3-Pal-N-Me-Ser-Lys(N-epsilon-nicotinyl)-D-Lys(N-epsilon-nicotinyl)-Leu-Lys(N-epsilon-isopropyl)-Pro-D-AlaNH.sub.2 ;
- pyro-Glu-His-Trp-Ser-N-Me-Tyr-D-Leu-Arg-ProNHEt;
- pyro-Glu-N-Me-Phe-Trp-Ser-Tyr-D-Trp-D-Leu-Arg-ProNHEt;
- pyro-Glu-His-Trp-Ser-N-Me-Tyr-D-Ser(O-t-butyl)-Leu-Arg-ProNHEt;
- pyro-Glu-His-Trp-N-Me-Ser-Tyr-D-2-Nal-Leu-Arg-ProGlyNH.sub.2 ;
- pyro-Glu-His-Trp-Ser-N-Me-Tyr-D-Trp-Leu-Arg-Pro-azaGlyNH.sub.2 ;
- pyro-Glu-His-Trp-Ser-N-Me-Tyr-D-Trp-N-Me-Leu-Arg-Pro-Gly-NH.sub.2 ;
- pyro-Glu-His-Trp-N-MeSer-N-Me-Tyr-D-Trp-Leu-Arg-Pro-NHEt; and
- N-Ac-D-4-Cl-Phe-D-4-Cl-Phe-D-2-Thia-Ser-Tyr-D-Lys-Leu-N-Me-Arg-Pro-D-AlaNH.sub.2.
- 6. N-Ac-D-2-Nal-D-4-Cl-Phe-D-3-Pal-Ser-N-Me-Tyr-D-Lys(N-epsilon-nicotinyl)-Leu-Lys(N-epsilon-isopropyl)-Pro-D-AlaNH.sub. 2 ; or a pharmaceutically acceptable salt thereof.
- 7. A method for suppressing levels of sex hormones in male or female mammals comprising administering to a host in need of such treatment a therapeutically effective amount of an LHRH antagonist compound of claim 1.
- 8. A pharmaceutical composition for suppressing levels of sex hormones in male and female mammals, comprising a pharmaecutical carrier and a therapeutically effective amount of an LHRH antagonist compound of claim 1.
- 9. A method for suppressing levels of sex hormones in male or female mammals comprising administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 1 in combination with a therapeutically effective amount of an antiandrogenic agent.
- 10. A method for suppressing levels of sex hormones in male or female mammals comprising administering to a host in need of such treatment a therapeutically effective amount of an LHRH compounds of claim 1 antagonist in combination with a therapeutically effective amount of an antiandrogenic agent.
Parent Case Info
This is a continuation-in-part of U.S. patent application Ser. No. 390,572, filed Aug. 7, 1989, which is a continuation in part of patent application Ser. No. PCT/US89/00528, filed Feb. 9, 1989, which is a continuation-in-part of U.S. patent application Ser. No. 154,681, filed Feb. 10, 1988.
US Referenced Citations (11)
Foreign Referenced Citations (1)
| Number |
Date |
Country |
| WO8901944 |
Mar 1989 |
WOX |
Non-Patent Literature Citations (3)
| Entry |
| Thiasrivongs et al., J. of Hypertension, 7, (suppl. 2): 521-523, 1989. |
| Stewart et al., Solid Phase Peptide Synthesis, Pierce Chem. Co., 1984. |
| Coy et al., J. Med. Chem. 19 423 (1976). |
Continuation in Parts (3)
|
Number |
Date |
Country |
| Parent |
390572 |
Aug 1989 |
|
| Parent |
528 |
Feb 1989 |
|
| Parent |
154681 |
Feb 1988 |
|
Patent Grant
5110904
