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Claims for Patent: 5,389,613

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Claims for Patent: 5,389,613

Title: Method of treating prostate adenocarcinoma, prostate benign hypertrophia and endometriosis
Abstract:A novel method of treating prostate adenocarcinoma, prostate benign hypertrophia, endometriosis, dysmenorrhea, hirsuitism, hormono-dependant mammary tumors, treatment and prevention of precocious puberty, induction of a retardation of the appearance of puberty and treatment of acne of mammals comprising administering to warm-blooded animals an effective amount of a peptide of the formula wherein (a) Z is Gly--NH.sub.2, Y is Leu and X is Gly, (b) Z is Gly--NH.sub.2, Y is Leu, X is DN Leu, DN Val, D Abu (.alpha.-aminobutyric acid), D Phe, D Ser, D Thr, D Met, D Pgl, D Lys, Leu, Ile, Nle, Val, N Val, Met, Phe, D Leu, D Arg, D Ser (tbu), D Thr (tbu), D Cys (tbu), D Asp (O tbu), D Glu (Otbu), D Orn (boc), D Lys (boc), D Trp, Trp, 2-methyl Ala, D Tyr, D Met .epsilon.-lauryl D Lys, .epsilon.-dextran-D Lys, (c) Z is NH-cyclopropyl or NH-Alk wherein Alk is alkyl of 1 to 3 carbon atoms, Y is Leu and X is D Ser (tbu), D Thr (tbu), D Asp (Othu), D Glu (Otbu), D Orn (boc), D Lys (boc), (d) Z is --NH--CH.sub.3, --NH--CH.sub.2 --CH.sub.3, NH--CH.sub.2 --CH.sub.2 --CH.sub.3, --NH--CH.sub.2 --CH.sub.2 --OH, ##STR1## Y is Leu and X is Gly, (e) Z is --NH--CH.sub.2 --CH.sub.3, Y is Leu and X is D Trp, D Leu, D Ala, D Ser (tbu), D Tyr, D Lys, Ala, (f) Z is Gly--NH.sub.2 or --NH--CH.sub.2 --CH.sub.3, Y is N.alpha.Me Leu and X is Gly, (g) Z is --NH-cyclopropyl, Y is Leu and X is D Leu or (h) Z is Gly--NH.sub.2, --NH-cyclopropyl or --NHAlk' where Alk' is alkyl of 1 to 3 carbon atoms, Y is Ser (but), Cys (but), Asp (Obut), Glu (Obut), Orn (boc), Lys (boc) and X is Gly.
Inventor(s): Labrie; Fernand (Quebec, CA), Raynaud; Jean-Pierre (Paris, FR)
Assignee: Roussel Uclaf (both of, DE) Shering Corporation (both of, DE)
Application Number:08/019,232
Patent Claims: 1. A method of treating prostate adenocarcinoma, prostate begnin hypertrophia and endometriosis in warm blooded animals comprising administering to warm-blooded animals an effective amount of at least one peptide of the formula

wherein (a) Z is Gly--NH.sub.2, Y is Leu and X is Gly, (b) Z is Gly--NH.sub.2, Y is Leu, X is DL Leu, DL Val, D Abu (.alpha.-aminobutyric acid), D Phe, D Ser, D Thr, D Met, D Pgl, D Lys, Leu, Ile, Nle, Val, Met, Phe, D Leu, D Arg, D Ser (tbu), D Thr (tbu), D Cys (tbu), D Asp (O tbu), D Glu (O tbu), D Orn (boc), D Lys (boc), D Trp, Trp, 2-methyl Ala, D Tyr, lauryl-D Lys, dextran-D Lys, (c) Z is NH-cyclopropyl or NH--Alk- wherein Alk is alkyl of 1 to 3 carbon atoms, Y is Leu and X is D Ser (tbu), D Thr (tbu), D Asp (O tbu), D Glu (Otbu), D ORn (boc), D Lys (boc), (d) Z is --NH--CH.sub.3, --NH--CH.sub.2 --CH.sub.3 --NH--CH.sub.2 --CH.sub.2 --CH.sub.3 --NH--CH.sub.2 --CH.sub.2 --OH, ##STR3## Y is Leu and X is Gly, (e) Z is --NH--CH.sub.2 --CH.sub.3, Y is Leu and X is D Trp, D Leu, D Ala, D Ser (tbu), D Tyr, D Lys, Ala (f) Z is Gly--NH.sub.2 or --N--CH.sub.2 --CH.sub.3, Y is N Me Leu and X is Gly, (g) Z is --NH-cyclopropyl, Y is Leu and X is D Leu or (h) Z is Gly--NH.sub.2, NH-cyclopropyl or --NHAlk' wherein Alk' is alkyl of 1 to 3 carbon atoms, Y is Ser (but), Cys (but), Asp (Obut), Glu (Obut), Orn (boc), Lys (boc) and X is Gly sufficient to treat said conditions.

2. The method of claim 1 wherein the peptide is administered in association with an antiandrogen.

3. The method of claim 1 wherein the peptide is [D Ser (Tbu).sup.6 des Gly NH.sub.2.sup.10 ] LH-RH ethylamine.

4. The method of claim 2 wherein the antiandrogen is 5,5'-dimethyl-3-[4-nitro-3-trifluoromethyl-phenyl]-2,4-imidazolidinedione.

5. The method of claim 3 wherein the antiandrogen is 5,5-dimethyl-3-[4-nitro-3-trifluoromethyl-phenyl]-2,4-imidazolidinedione.

6. The method of claim 2 wherein the antiandrogen is 2-methyl-N-[4-nitro-3-trifluoromethyl-phenyl]-propanamide.
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