WO2002102401A1 - Treatment of dementia and neurodegenerative diseases with intermediate doses of lhrh antagonists - Google Patents

Treatment of dementia and neurodegenerative diseases with intermediate doses of lhrh antagonists Download PDF

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Publication number
WO2002102401A1
WO2002102401A1 PCT/EP2002/004677 EP0204677W WO02102401A1 WO 2002102401 A1 WO2002102401 A1 WO 2002102401A1 EP 0204677 W EP0204677 W EP 0204677W WO 02102401 A1 WO02102401 A1 WO 02102401A1
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WO
WIPO (PCT)
Prior art keywords
use according
lhrh antagonist
methyl
treatment
monthly
Prior art date
Application number
PCT/EP2002/004677
Other languages
French (fr)
Inventor
Jürgen Engel
Rainer Voegeli
Original Assignee
Zentaris Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to AU2002310788A priority Critical patent/AU2002310788B2/en
Priority to BR0209290-5A priority patent/BR0209290A/en
Application filed by Zentaris Gmbh filed Critical Zentaris Gmbh
Priority to PL36231902A priority patent/PL362319A1/en
Priority to CA002444876A priority patent/CA2444876A1/en
Priority to SI200230730T priority patent/SI1392348T1/en
Priority to DE60227507T priority patent/DE60227507D1/en
Priority to IL15677702A priority patent/IL156777A0/en
Priority to DK02735312T priority patent/DK1392348T3/en
Priority to SK1451-2003A priority patent/SK14512003A3/en
Priority to JP2003504987A priority patent/JP2004529207A/en
Priority to HU0400067A priority patent/HUP0400067A2/en
Priority to MXPA03008666A priority patent/MXPA03008666A/en
Priority to EP02735312A priority patent/EP1392348B1/en
Priority to UA2003109180A priority patent/UA80679C2/en
Priority to KR10-2003-7014128A priority patent/KR20040000446A/en
Publication of WO2002102401A1 publication Critical patent/WO2002102401A1/en
Priority to NO20034322A priority patent/NO20034322L/en
Priority to HK05104803A priority patent/HK1072000A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/10—Peptides having 12 to 20 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/08—Peptides having 5 to 11 amino acids
    • A61K38/09—Luteinising hormone-releasing hormone [LHRH], i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Definitions

  • the present invention relates to the treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists which do not cause a castration.
  • FURUYA, Shuichi et al. in WO 01/78780 teach preventives and remedies for Alzheimer's disesase containing a compound having GnRH antagonism have effects of preventing and treating Alzheimer's disease with little toxicity.
  • This treatment would be accompanied by highly undesirable side effects as lowering sex hormone levels to castration levels would result in loss or reduction of libido, sexual desire and sexual potency. In men and pre-menopausal women this treatment would also result in the typical symptoms of drop of sex hormones like hot flushes, etc. Women would additionally suffer from loss of bone minerals that would limit the treatment. These side effects could be reduced by hormone replacement therapy.
  • the present invention relates to the treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists, wherein the antagonist is preferably cetrorelix, teverelix, antide or abarelix.
  • the antagonist can also be the LHRH antagonist D-63 153 (Ac-D-Nal-D-pCI-Phe-D-Pal-Ser-N-Me-Tyr-D-Hci-Nle- Arg-Pro-D-Ala-NH2) as described in the PCT application WO 00/55190 A1.
  • LHRH antagonists can also exhibit a heterocyclic skeletal structure.
  • Such peptidomimetics can be for example
  • the LHRH antagonist is given in a monthly dose of 10 to 100 mg per month and the treatment is repeated monthly, two-monthly or lasting several months.
  • the LHRH antagonist is given in a monthly dose of 30 to 60 mg per month and the treatment is repeated monthly, two-monthly or lasting several months.
  • compositions of the LHRH antagonist suitable for the therapeutic management of dementia and neurodegenerative diseases may be for example a) acetate salt formulations of the active compounds in the concentration of 1 mg/1 ml or lower where the lyophilisate powder may be dissolved in water for injection or in gluconic acid;
  • acetate salt formulations of the active compounds in the concentration of 1.5 mg/1 ml to 5.0 mg/1 ml, preferably 2.5 mg/1 ml where the lyophilisate powder may be dissolved in water for injection or in gluconic acid;
  • excipients and dosage forms are for example described by K.H. Bauer, K.-H. Fr ⁇ mming and C. F ⁇ hrer, Lehrbuch der Pharmazeutica Technologie, 6 th edition, Stuttgart 1999, pages 163-186 (excipients) and pages 227-386 (dosage forms), including the references as cited therein.
  • the LHRH antagonist can be administered for example subcutaneous, oral, intramuscular or inhalative.
  • the disease as mentioned, for example can be treated in accordance with the following scheme.
  • a single dose of 30-60 mg of cetrorelix is administered by injection per month.
  • the treatment is continued monthly.
  • the treatment is continued two-mothly or lasting several months after the administration of the single dose.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Peptides Or Proteins (AREA)

Abstract

The present invention relates to the treatment of dementia and neurodegenerative diseases like Alzheimer's disease with intermediate doses of LHRH antagonists which do not cause a castration. A preferred LHRH antagonist is cetrorelix.

Description

Treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists
The present invention relates to the treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists which do not cause a castration.
FURUYA, Shuichi et al. in WO 01/78780 teach preventives and remedies for Alzheimer's disesase containing a compound having GnRH antagonism have effects of preventing and treating Alzheimer's disease with little toxicity.
It has been shown in a study by Bowen R.L et al. that serum concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were significantly higher in individuals suffering of dementia , e.g. Alzheimer's disease. Bowen R.L. et al. propose in their patent application CA 2,309,395 (US priority June 4, 1999, 09/326,180) to lower FSH and LH to minimal levels by the use of castrating doses of analogues of the LH-releasing hormone (LHRH), either super-agonists or antagonists.
This treatment would be accompanied by highly undesirable side effects as lowering sex hormone levels to castration levels would result in loss or reduction of libido, sexual desire and sexual potency. In men and pre-menopausal women this treatment would also result in the typical symptoms of drop of sex hormones like hot flushes, etc. Women would additionally suffer from loss of bone minerals that would limit the treatment. These side effects could be reduced by hormone replacement therapy.
It has been found now that the treatment with intermediate doses of LHRH antagonists results in a sub-maximal lowering of FSH and LH to normal levels that leaves sex hormone levels above the castration treshold. This treatment is highly advantageous as it gives the desired results of normalising FSH and LH levels without the undesirable side-effects of sex hormone blockade. Thus the additional treatment of sex hormone replacement becomes superfluous. The present invention relates to the treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists, wherein the antagonist is preferably cetrorelix, teverelix, antide or abarelix. The antagonist can also be the LHRH antagonist D-63 153 (Ac-D-Nal-D-pCI-Phe-D-Pal-Ser-N-Me-Tyr-D-Hci-Nle- Arg-Pro-D-Ala-NH2) as described in the PCT application WO 00/55190 A1.
The mentioned LHRH antagonists can also exhibit a heterocyclic skeletal structure. Such peptidomimetics can be for example
- 1 -[7-Chloro-3-(3,5-dimethyl-phenyl)-2-oxo-4-(2-piperidin-2-yl-ethoxy)-1 ,2- dihydro-quinolin-6-yl]-3-pyridin-2-yl-urea (described in WO 97/44339),
- 3-[Benzyl-methyl-amino)-methyl]-2-tørf-butyl-8-(2-fluoro-benzyl)-6-(3-methoxy- phenyl)-7-methyl-8H-imidazo[1 ,2-a]pyrimidin-5-one (described in WO 01/29044),
- 2-(2,5-Dimethyl-furan-3-yl)-8-(2-fluoro-benzyl)-3-([methyl-(2-pyridin-2-yl-ethyl)- amino]-methyl)-5-oxo-5,8-dihydro-imidazo[1 ,2-a]pyrimidine-6-carboxylic acid 1- ethyl-propylester (described in WO 00/69859),
- 3-((2-[2-(3,5-Difluoro-phenyl)-1-(2-methoxy-benzoyl)-2-oxo-ethylidene]-2,3- dihydro-1/7-benzoimidazol-5-yl-amino)-methyl)-benzonitrile (described in WO 02/02533).
The LHRH antagonist is given in a monthly dose of 10 to 100 mg per month and the treatment is repeated monthly, two-monthly or lasting several months.
In a preferred embodiment the LHRH antagonist is given in a monthly dose of 30 to 60 mg per month and the treatment is repeated monthly, two-monthly or lasting several months.
Pharmaceutical formulations of the LHRH antagonist suitable for the therapeutic management of dementia and neurodegenerative diseases may be for example a) acetate salt formulations of the active compounds in the concentration of 1 mg/1 ml or lower where the lyophilisate powder may be dissolved in water for injection or in gluconic acid;
b) acetate salt formulations of the active compounds in the concentration of 1.5 mg/1 ml to 5.0 mg/1 ml, preferably 2.5 mg/1 ml where the lyophilisate powder may be dissolved in water for injection or in gluconic acid;
c) pamoate salt formulations of the active compounds in the concentration of 10 mg/1 ml to 30 mg/1 ml, preferably 15 mg/1 ml where the lyophilisate powder may be dissolved in gluconic acid or in water for injection.
Suitable excipients and dosage forms are for example described by K.H. Bauer, K.-H. Frδmming and C. Fϋhrer, Lehrbuch der Pharmazeutischen Technologie, 6th edition, Stuttgart 1999, pages 163-186 (excipients) and pages 227-386 (dosage forms), including the references as cited therein.
The LHRH antagonist can be administered for example subcutaneous, oral, intramuscular or inhalative.
The disease as mentioned, for example can be treated in accordance with the following scheme.
Example
In one embodiment of the invention a single dose of 30-60 mg of cetrorelix is administered by injection per month. The treatment is continued monthly. In another embodiment the treatment is continued two-mothly or lasting several months after the administration of the single dose.

Claims

Claims
1. Use of a LHRH antagonist for the preparation of a medicament for the treatment of dementia and neurodegenerative diseases in humans by administration of intermediate doses, which do not cause a castration.
2. Use according to claim 1 , characterized in that the monthly single dose is in the range of 10 - 100 mg LHRH antagonist.
3. Use according to claims 1 and 2, characterized in that the monthly single dose is about 30 to about 60 mg LHRH antagonist.
4. Use according to one of claims 1 to 3, characterized in that the administration is continued on a monthly or two-monthly or lasting several months base.
5. Use according to one of claims 1 to 4, characterized in that the treated disease is Alzheimer's disease.
6. Use according to one of claims 1 to 5, characterized in that the LHRH antagonist is cetrorelix.
7. Use according to one of claims 1 to 5, characterized in that the LHRH antagonist is teverelix.
8. Use according to one of claims 1 to 5, characterized in that the LHRH antagonist is antide.
9. Use according to one of claims 1 to 5, characterized in that the LHRH antagonist is abarelix.
10. Use according to one of claims 1 to 5, characterized in that the LHRH antagonist is D-63 153 (Ac-D-Nal-D-pCI-Phe-D-Pal-Ser-N-Me-Tyr-D-Hci-Nle- Arg-Pro-D-Ala-NH2).
11. Use according to one of claims 1 to 5, characterized in that the LHRH antagonist is a peptidomimetic.
12. Use according to claim 11 in which the peptidomimetic is a compound
- 1 -[7-Chloro-3-(3,5-dimethyl-phenyl)-2-oxo-4-(2-piperidin-2-yl-ethoxy)-1 ,2- dihydro-quinolin-6-yl]-3-pyridin-2-yl-urea
- 3-[Benzyl-methyl-amino)-methyl]-2-te/ϊ-butyl-8-(2-fluoro-benzyl)-6-(3- methoxy-phenyl)-7-methyl-8H-imidazo[1,2-a]pyrimidin-5-one
- 2-(2,5-Dimethyl-furan-3-yl)-8-(2-fluoro-benzyl)-3-([methyl-(2-pyridin-2-yl- ethyl)-amino]-methyl)-5-oxo-5,8-dihydro-imidazo[1(2-a]pyrimidine-6- carboxylic acid 1-ethyl-propylester or
- 3-((2-[2-(3,5-Difluoro-phenyl)-1-(2-methoxy-benzoyl)-2-oxo-ethylidene]-2,3- dihydro-1H-benzoimidazol-5-yl-amino)-methyl)-benzonitrile.
PCT/EP2002/004677 2001-04-30 2002-04-27 Treatment of dementia and neurodegenerative diseases with intermediate doses of lhrh antagonists WO2002102401A1 (en)

Priority Applications (17)

Application Number Priority Date Filing Date Title
EP02735312A EP1392348B1 (en) 2001-04-30 2002-04-27 Treatment of dementia and neurodegenerative diseases with intermediate doses of lhrh antagonists
DK02735312T DK1392348T3 (en) 2001-04-30 2002-04-27 Treatment of dementia and neurodegenerative diseases with moderate doses of LHRH antagonists
PL36231902A PL362319A1 (en) 2001-04-30 2002-04-27 Treatment of dementia and neurodegenerative diseases with intermediate doses of lhrh antagonists
CA002444876A CA2444876A1 (en) 2001-04-30 2002-04-27 Treatment of dementia and neurodegenerative diseases with intermediate doses of lhrh antagonists
SI200230730T SI1392348T1 (en) 2001-04-30 2002-04-27 Treatment of dementia and neurodegenerative diseases with intermediate doses of lhrh antagonists
DE60227507T DE60227507D1 (en) 2001-04-30 2002-04-27 LOW-DOSED LHRH ANTAGONISTS FOR THE TREATMENT OF NEURODEEGENERATIVE DISEASES, IN PARTICULAR ALZHEIMER DISEASE
IL15677702A IL156777A0 (en) 2001-04-30 2002-04-27 Treatment of dementia and neurodegenerative diseases with intermediate doses of lhrh antagonists
AU2002310788A AU2002310788B2 (en) 2001-04-30 2002-04-27 Treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists
SK1451-2003A SK14512003A3 (en) 2001-04-30 2002-04-27 Treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists
HU0400067A HUP0400067A2 (en) 2001-04-30 2002-04-27 Treatment of dementia and neurodegenerative diseases with intermediate doses of lhrh antagonists
JP2003504987A JP2004529207A (en) 2001-04-30 2002-04-27 Treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists
MXPA03008666A MXPA03008666A (en) 2001-04-30 2002-04-27 Treatment of dementia and neurodegenerative diseases with intermediate doses of lhrh antagonists.
BR0209290-5A BR0209290A (en) 2001-04-30 2002-04-27 Treatment of dementia and neurodegenerative diseases with intermediate doses of lhrh antagonists
UA2003109180A UA80679C2 (en) 2001-04-30 2002-04-27 Treatment of dementia and neurodegenerative diseases with intermediate doses of lhrh antagonists
KR10-2003-7014128A KR20040000446A (en) 2001-04-30 2002-04-27 Treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists
NO20034322A NO20034322L (en) 2001-04-30 2003-09-26 Treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists
HK05104803A HK1072000A1 (en) 2001-04-30 2005-06-08 Treatment of alzheimer's diseases with intemediatedoses of lhrh antagonists

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US28743401P 2001-04-30 2001-04-30
US60/287,434 2001-04-30

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WO2002102401A1 true WO2002102401A1 (en) 2002-12-27

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US (1) US7288517B2 (en)
EP (1) EP1392348B1 (en)
JP (1) JP2004529207A (en)
KR (1) KR20040000446A (en)
CN (1) CN1317030C (en)
AT (1) ATE400287T1 (en)
AU (1) AU2002310788B2 (en)
BG (1) BG108339A (en)
BR (1) BR0209290A (en)
CA (1) CA2444876A1 (en)
CZ (1) CZ20033167A3 (en)
DE (1) DE60227507D1 (en)
DK (1) DK1392348T3 (en)
ES (1) ES2307760T3 (en)
HK (1) HK1072000A1 (en)
HU (1) HUP0400067A2 (en)
IL (1) IL156777A0 (en)
MX (1) MXPA03008666A (en)
NO (1) NO20034322L (en)
NZ (1) NZ544417A (en)
PL (1) PL362319A1 (en)
PT (1) PT1392348E (en)
RU (1) RU2319501C2 (en)
SI (1) SI1392348T1 (en)
SK (1) SK14512003A3 (en)
UA (1) UA80679C2 (en)
WO (1) WO2002102401A1 (en)
ZA (1) ZA200305326B (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003011314A2 (en) * 2001-07-31 2003-02-13 Zentaris Gmbh Use of lhrh-antagonists for the improvement of t-cell mediated immunity
EP1300398A1 (en) * 2000-07-05 2003-04-09 Yamanouchi Pharmaceutical Co. Ltd. Propane-1,3-dione derivatives
WO2009033801A2 (en) * 2007-09-11 2009-03-19 Mondobiotech Laboratories Ag Syndyphalin alone or in combination with antide as a therapeutic agent
WO2009033802A2 (en) * 2007-09-11 2009-03-19 Mondobiotech Laboratories Ag Antide as a therapeutic agent
EP2095818A1 (en) * 2008-02-29 2009-09-02 AEterna Zentaris GmbH Use of LHRH antagonists at non-castrating doses
WO2009145690A1 (en) * 2008-05-29 2009-12-03 Isr Immune System Regulation Ab Method and means for treating viral disease, in particular hiv/aids
US7709519B2 (en) 2004-06-04 2010-05-04 Astellas Pharma Inc. Benzimidazolylidene propane-1,3 dione derivative or salt thereof
US7960562B2 (en) 2005-03-31 2011-06-14 Astellas Pharma Inc. Propane-1,3-dione derivative or salt thereof

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6828415B2 (en) * 1993-02-19 2004-12-07 Zentaris Gmbh Oligopeptide lyophilisate, their preparation and use
US20020077327A1 (en) * 1999-09-23 2002-06-20 Neurocrine Biosciences, Inc. Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
US20080171736A1 (en) * 2004-12-23 2008-07-17 Gregory Christopher W Treatment of Alzheimer's Disease and Mild Cognitive impairment using GnRH-I analogs and one or more of acetylcholinesterase inhibitors and NMDA receptor antagonists
WO2006071274A2 (en) * 2004-12-23 2006-07-06 Voyager Pharmaceutical Corporation Leuprolide acetate and acetylcholinesterase inhibitors or nmda receptor antagonists for the treatment of alzheimer’s disease
EP2091943B1 (en) * 2006-10-21 2013-11-20 AbbVie Deutschland GmbH & Co KG Heterocyclic compounds and their use as glycogen synthase kinase 3 inhibitors
JP5998142B2 (en) 2010-09-27 2016-09-28 アボット ゲーエムベーハー ウント カンパニー カーゲー Heterocyclic compounds and their use as glycogen synthase kinase-3 inhibitors
US9090592B2 (en) 2010-12-30 2015-07-28 AbbVie Deutschland GmbH & Co. KG Heterocyclic compounds and their use as glycogen synthase kinase-3 inhibitors
EP3560555A1 (en) * 2018-04-26 2019-10-30 LifeArc A composition for treating one or more estrogen related diseases

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997044339A1 (en) * 1996-05-20 1997-11-27 Merck & Co., Inc. Antagonists of gonadotropin releasing hormone
WO2000055190A1 (en) * 1999-03-17 2000-09-21 Zentaris Ag Novel lhrh antagonists with improved solubility characteristics
WO2000069859A1 (en) * 1999-05-14 2000-11-23 Neurocrine Biosciences, Inc. Imidazo- and pyrrolo[1,2-a]pyrimid-4-ones as gonadotropin-releasing hormone receptor antagonists
CA2309395A1 (en) * 1999-06-04 2000-12-04 Richard Lloyd Bowen Methods for preventing and treating alzheimer's disease
WO2001029044A1 (en) * 1999-10-15 2001-04-26 Neurocrine Biosciences, Inc. Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
WO2002002533A1 (en) * 2000-07-05 2002-01-10 Yamanouchi Pharmaceutical Co., Ltd. Propane-1,3-dione derivatives

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3135743A (en) 1960-06-29 1964-06-02 Sterling Drug Inc Steroido[2. 3-d]isoxazoles and preparation thereof
AU2001248760A1 (en) 2000-04-13 2001-10-30 Takeda Chemical Industries Ltd. Preventives/remedies for alzheimer's disease

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997044339A1 (en) * 1996-05-20 1997-11-27 Merck & Co., Inc. Antagonists of gonadotropin releasing hormone
WO2000055190A1 (en) * 1999-03-17 2000-09-21 Zentaris Ag Novel lhrh antagonists with improved solubility characteristics
WO2000069859A1 (en) * 1999-05-14 2000-11-23 Neurocrine Biosciences, Inc. Imidazo- and pyrrolo[1,2-a]pyrimid-4-ones as gonadotropin-releasing hormone receptor antagonists
CA2309395A1 (en) * 1999-06-04 2000-12-04 Richard Lloyd Bowen Methods for preventing and treating alzheimer's disease
WO2001029044A1 (en) * 1999-10-15 2001-04-26 Neurocrine Biosciences, Inc. Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
WO2002002533A1 (en) * 2000-07-05 2002-01-10 Yamanouchi Pharmaceutical Co., Ltd. Propane-1,3-dione derivatives

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1300398A1 (en) * 2000-07-05 2003-04-09 Yamanouchi Pharmaceutical Co. Ltd. Propane-1,3-dione derivatives
EP1300398A4 (en) * 2000-07-05 2004-03-31 Yamanouchi Pharma Co Ltd Propane-1,3-dione derivatives
US6960591B2 (en) 2000-07-05 2005-11-01 Yamanouchi Pharmaceutical Co., Ltd. Propane-1,3-dione derivative
US7569688B2 (en) 2000-07-05 2009-08-04 Astellas Pharma Inc. Propane-1, 3-dione derivative
WO2003011314A3 (en) * 2001-07-31 2003-10-16 Zentaris Gmbh Use of lhrh-antagonists for the improvement of t-cell mediated immunity
WO2003011314A2 (en) * 2001-07-31 2003-02-13 Zentaris Gmbh Use of lhrh-antagonists for the improvement of t-cell mediated immunity
US7709519B2 (en) 2004-06-04 2010-05-04 Astellas Pharma Inc. Benzimidazolylidene propane-1,3 dione derivative or salt thereof
US7960562B2 (en) 2005-03-31 2011-06-14 Astellas Pharma Inc. Propane-1,3-dione derivative or salt thereof
WO2009033801A2 (en) * 2007-09-11 2009-03-19 Mondobiotech Laboratories Ag Syndyphalin alone or in combination with antide as a therapeutic agent
WO2009033802A2 (en) * 2007-09-11 2009-03-19 Mondobiotech Laboratories Ag Antide as a therapeutic agent
WO2009033802A3 (en) * 2007-09-11 2009-09-03 Mondobiotech Laboratories Ag Antide as a therapeutic agent
WO2009033801A3 (en) * 2007-09-11 2009-09-03 Mondobiotech Laboratories Ag Syndyphalin alone or in combination with antide as a therapeutic agent
EP2095818A1 (en) * 2008-02-29 2009-09-02 AEterna Zentaris GmbH Use of LHRH antagonists at non-castrating doses
WO2009106597A1 (en) * 2008-02-29 2009-09-03 Æterna Zentaris Gmbh Use of lhrh antagonists at non-castrating doses
US8273716B2 (en) 2008-02-29 2012-09-25 Spectrum Pharmaceuticals, Inc. Use of LHRH antagonists for intermittent treatments
WO2009145690A1 (en) * 2008-05-29 2009-12-03 Isr Immune System Regulation Ab Method and means for treating viral disease, in particular hiv/aids

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CN1317030C (en) 2007-05-23
PT1392348E (en) 2008-09-09
NO20034322D0 (en) 2003-09-26
SI1392348T1 (en) 2008-12-31
AU2002310788B2 (en) 2007-04-05
KR20040000446A (en) 2004-01-03
NO20034322L (en) 2003-09-26
US20020177556A1 (en) 2002-11-28
EP1392348A1 (en) 2004-03-03
DK1392348T3 (en) 2008-09-29
IL156777A0 (en) 2004-02-08
MXPA03008666A (en) 2004-10-15
PL362319A1 (en) 2004-10-18
RU2319501C2 (en) 2008-03-20
HK1072000A1 (en) 2005-08-12
RU2003134949A (en) 2005-02-10
CZ20033167A3 (en) 2004-08-18
ZA200305326B (en) 2003-07-30
CN1575185A (en) 2005-02-02
NZ544417A (en) 2008-03-28
EP1392348B1 (en) 2008-07-09
BG108339A (en) 2004-11-30
CA2444876A1 (en) 2002-12-27
JP2004529207A (en) 2004-09-24
ATE400287T1 (en) 2008-07-15
ES2307760T3 (en) 2008-12-01
BR0209290A (en) 2004-07-13
SK14512003A3 (en) 2004-08-03
US7288517B2 (en) 2007-10-30
UA80679C2 (en) 2007-10-25
DE60227507D1 (en) 2008-08-21
HUP0400067A2 (en) 2004-04-28

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