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Details for Patent: 4,851,386

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Details for Patent: 4,851,386

Title: Method of treating precocious puberty
Abstract:A novel method of treating prostate adenocarcinoma, prostate benign hypertrophia, endometriosis, dysmenorrhea, hirsuitism, hormono-dependent 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, E-lauryl -D Lys, E-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), Cy.sub.3 (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 (Paris, FR)
Filing Date:Nov 13, 1987
Application Number:07/120,408
Claims:1. A method of treating or preventing precocious puberty in male mammals consisting essentially of administering to male mammals an 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, 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, .epsilon.-lauryl-D Lys, e-dextran-D Lys, (c) Z is NH-cyclopropyl or NH-cycloproyl 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 (Otbu), 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, 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' wherein Alk' is alkyl of 1 to 3 carbon atoms, Y is Ser (but), Cys (but), Asp (Obut), Glu (Obut), Orn (boc) and X is Gly in association with an antiandrogen sufficient for the treatment or prevention of precocious puberty.

2. The method of claim 1 wherein 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 and Ala.

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