EP1648466A1 - Utilisation d'antagonistes du cgrp dans le traitement et la prevention de bouffees de chaleur chez les patients atteints du cancer de la prostate - Google Patents

Utilisation d'antagonistes du cgrp dans le traitement et la prevention de bouffees de chaleur chez les patients atteints du cancer de la prostate

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Publication number
EP1648466A1
EP1648466A1 EP04763078A EP04763078A EP1648466A1 EP 1648466 A1 EP1648466 A1 EP 1648466A1 EP 04763078 A EP04763078 A EP 04763078A EP 04763078 A EP04763078 A EP 04763078A EP 1648466 A1 EP1648466 A1 EP 1648466A1
Authority
EP
European Patent Office
Prior art keywords
piperidinyl
dihydro
dibromo
carbonyl
amino
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP04763078A
Other languages
German (de)
English (en)
Inventor
Henri Doods
Klaus Rudolf
Wolfgang Eberlein
Wolfhard Engel
Mats Hammar
Anna-Clara Spetz
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boehringer Ingelheim International GmbH
Original Assignee
Boehringer Ingelheim International 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
Application filed by Boehringer Ingelheim International GmbH filed Critical Boehringer Ingelheim International GmbH
Priority to EP04763078A priority Critical patent/EP1648466A1/fr
Publication of EP1648466A1 publication Critical patent/EP1648466A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system

Definitions

  • the present invention relates to a method of treatment or prevention of hot flushes in men who underwent castration, e.g. due to androgen ablation treatment in prostate cancer therapy (orchiectomy), comprising administration of an effective amount of a CGRP antagonist and/or of a CGRP release inhibitor to a person in need of such treatment.
  • the method according to the invention preferably comprises monotherapy with a single substance, but also includes combined therapy with a number of substances from the specified groups of active substances.
  • the invention relates to the use of a CGRP antagonist and/or of a CGRP release inhibitor for manufacture of a pharmaceutical composition for prevention or treatment of hot flushes in men who underwent castration.
  • Hot flushes and sweating that is vasomotor symptoms, are reported by 43 to 77% of prostate cancer patients after medical or surgical castration, usually persisting for many years, possibly impairing quality of life (Arch. Surg. 43: 209, 1941 ; J. Urol. 152: 1170, 1994). Furthermore, hot flushes occur in 75% of women after menopause.
  • CGRP antagonists CGRP antagonists
  • CGRP release inhibitors CGRP release inhibitors
  • a second object of the invention is the use of a CGRP antagonist and/or of a CGRP release inhibitor for manufacture of a pharmaceutical composition for prevention or treatment of hot flushes in men who underwent castration.
  • the present invention thus relates to the use of CGRP antagonists and/or CGRP release inhibitors for combating hot flushes in men who underwent castration, including both prevention and acute treatment.
  • the use according to the invention preferably comprises monotherapy with a single substance, but also includes combined therapy with a number of substances from the specified groups of active substances.
  • the treatment according to the invention may be carried out in addition to conventional therapy, thus any aspect of the invention includes combination with conventional therapy or those drugs used in conventional therapy.
  • hormonal therapies comprising oral and topical administration (although especially oral hormonal therapies are known to cause side effects), e.g. oral diethylstilbestrol, topical estrogens such as estrogen patches, oral medroxyprogesterone acetate, megestrol acetate and cyproterone acetate,
  • oral central ⁇ 2-agonists e.g. oral clonidine
  • selective 5-hydroxytryptamine (5-HT) reuptake inhibitors e.g. sertraline (Zoloft ® ) and venlafaxine (Effexor ® ), and
  • acupuncture preferably electrostimulated acupuncture.
  • First-line treatments estrogen patches 0.05 mg/24 hours or 0.10 mg/24 hours (e.g. twice weekly for 4 weeks), transdermal estradiol 0.05 mg/24 hours or oral diethylstilboestrol (DES) 1 mg/day.
  • estrogen patches 0.05 mg/24 hours or 0.10 mg/24 hours (e.g. twice weekly for 4 weeks), transdermal estradiol 0.05 mg/24 hours or oral diethylstilboestrol (DES) 1 mg/day.
  • DES diethylstilboestrol
  • Oral progestagens e.g. megestrol acetate 40 mg/day or oral cyproterone acetate 50 to 300 mg/day, e.g. 50 mg orally twice a day or 300 mg intramuscularly once every 2 weeks, preferably 150 mg/day.
  • the invention also includes the use of an active substance selected from CGRP antagonists and CGRP release inhibitors for the preparation of a pharmaceutical composition for treatment or prevention of hot flushes jn men who underwent castration wherein the pharmaceutical composition comprises an active compound used in conventional therapy selected from the group consisting of
  • hormonal drugs e.g. oral diethylstilbestrol, an estrogen, medroxyprogesterone acetate, megestrol acetate and cyproterone acetate, including other salt forms of these drugs,
  • oral central 2-agonists e.g. oral clonidine
  • selective 5-hydroxytryptamine (5-HT) reuptake inhibitors e.g. sertraline (Zoloft .® ) ⁇ and venlafaxine (Effexor ® ).
  • Any pharmaceutically acceptable active substances which antagonise the known effects of CGRP or inhibit the release of CGRP from sensory nerve endings may be used for the purposes of the present invention.
  • CGRP antagonists include the amino acid derivatives described in WO 98/11128, WO 00/55154, WO 01/32648, WO 01/32649 and WO 01/49676 as well as the non-peptidic active substances described in WO 98/56779, WO 98/09630 aand WO 97/09046.
  • CGRP release inhibitors include serotonin 5-HT-i B/ i D -agonists such as almotriptan, avitnptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan or zolmitriptan, as well as 5-HTi F -agonists or NPY-agonists.
  • 5-HTi F -agonists or NPY-agonists 5-HTi F -agonists or NPY-agonists.
  • (AM) 1-[4-amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1 H)-oxoquinazolin-3-yl)-1- piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
  • (AN) 1-[N 2 -[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperi- dinyl]carbonyl]-D-tyrosyl]-N 6 ,N 6 -dimethyl-L-lysyl]-4-(4-pyridinyl)-piperazine,
  • (AV) 1-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1 H)-oxoquinazolin-3-yl)-1-piperidinyi]car- bonyl]-D-tyrosyl]-4-[1-(methylsulphonyl)-4-piperidinyl]-piperidine
  • (AW) 1-[4-amino-3,5-dibromo-N-[[4-(1 ,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)- 1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine,
  • the tautomers, the diastereomers, the enantiomers, the mixtures thereof and the physiologically acceptable salts thereof are particularly preferred.
  • the dosage required to produce the desired effect is appropriately 0.0001 to 3 mg/kg of body weight, preferably 0.01 to 1 mg/kg of body weight for intravenous or subcutaneous administration and 0.01 to 10 mg/kg of body weight, preferably 0.1 to 10 mg/kg of body weight for administration by oral or nasal route or by inhalation, 1 to 3 times a day in each case.
  • the dosage may range from 1/5 of the lower limits specified above up to 1/1 of the upper limits specified above.
  • the CGRP antagonists and/or CGRP release inhibitors may be formulated with one or more conventional inert carriers and/or diluents, e.g. with com starch, lactose, glucose, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water/ethanol, water/glycerol, water/sorbitol, water/polyethyleneglycol, propylene glycol, cetylstearyl alcohol, carboxymethylcellulose or fatty substances such as hard fat or suitable mixtures thereof in conventional galenic preparations such as plain or coated tablets, capsules, powders, suspensions, solutions, metering aerosols or suppositories.
  • conventional inert carriers and/or diluents e.g. with com starch, lactose, glucose, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water/ethanol
  • capsules for powder inhalation containing 1 mg of active substance, preferably active substance (A) or (B),
  • inhalable solution for nebulisers containing 1 mg of active substance, preferably active substance (A) or (B),
  • propellant gas-operated metering aerosol containing 1 mg of active substance, preferably active substance (A) or (B),
  • aqueous solution for nasal application containing 10 mg of active substance, preferably active substance (A) or (B),
  • aqueous solution for nasal application containing 5 mg of active substance, preferably active substance (A) or (B), or
  • suspension for nasal application containing 20 mg of active substance, preferably active substance (A) or (B).
  • active substance (A) may also be used in form of a physiologically acceptable salt, preferably in form of the hydrochloride salt which is available by reaction of the free base with hydrochloric acid by conventional methods. Amounts are given based on the free base.
  • CGRP is released by sensory nerves, e.g. the trigeminal nerve which innervates part of the skin of the face. It has already been shown that stimulation of the trigeminal ganglion in humans leads to an increase in the CGRP plasma level and causes reddening of the face ([4]: P.J. Goadsby et al., Annals of Neurology, Vol. 23, No. 2, 1988, 193-196,).
  • (A) 1-[N 2 -[3,5-dibromo-N-[[4-(3,4-dihydro-2(1 H)-oxoquinazolin-3-yl)-1-piperidi- nyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine,
  • (B) 1-[4-amino-3,5-dibromo-N-[[4-(2,3,4,5-tetrahydro-2(1 H)-oxo-1 ,3-benzodiaze- pin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine,
  • (AC) (R,S)-1-[4-[4-(3,4-dihydro-2(1 H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,5-di- bromo-4-methylphenyl)methyl]-1 ,4-dioxobutyl]-4-(4-methyl-1-piperazinyl)-piperidine,
  • (AM) 1-[4-amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1 H)-oxoquinazolin-3-yl)-1-pi- peridinyl]carbonyl]-D-phenylalanyI]-4-(1-piperidinyl)-piperidine,
  • Marmosets of both sexes are anaesthetised with pentobarbital (initially with 30 mg/kg, i.p., followed by infusion of 6mg/kg/h, i.m.).
  • pentobarbital initially with 30 mg/kg, i.p., followed by infusion of 6mg/kg/h, i.m.
  • the body temperature is maintained at 37°C using a heating plate.
  • Pancurmium is administered as a muscle relaxant (initially 1 mg/kg, 0.5 mg after each hour thereafter).
  • the animal's head is secured in a stereotactical apparatus. After the skin on the head has been opened using a lengthwise incision, a small hole is drilled in the skull and a bipolar electrode (Rhodes SNES 100) is lowered into the trigeminal ganglion.
  • Rhodes SNES 100 bipolar electrode
  • Locating the ganglion is made easier by the use of an X-ray which shows up the bone structure of the skull.
  • the petrous bone serves as a guide for placing the electrode (CCX-Digital X-ray apparatus).
  • the position of the electrode in the ganglion is monitored at the end of each experiment.
  • the stimulation parameters are:
  • the blood flow in the micro-vessels of the facial skin is determined by laser Doppler flow measurement using a PeriFlux Laser Doppler System.
  • the animals are exposed to 2 to 3 stimulation periods at intervals of 30 min in each case.
  • the first stimulation serves as a reference value for the other stimulations.
  • the test substances are administered i.v. 5 min before the 2nd and 3rd stimulation periods.
  • CGRP antagonist or CGRP release inhibitor for use according to the invention, preferably one of the amino acid derivatives described in WO 98/11128, WO 00/55154, WO 01/32648, WO 01/32649 or WO 01/49676 , for example one of the abovementioned active substances (A) or (B), most preferred is substance (A) hydrochloride.
  • 1 capsule for powder inhalation contains: active substance (A) or (B) 01.0 mg lactose 20.0 mg hard gelatine capsules 50.0 mg 71.0 mg
  • the active substance is ground to the particle size needed for inhalation.
  • the ground active substance is homogeneously mixed with the lactose.
  • the mixture is packed into hard gelatine capsules.
  • composition 1 spray contains: active substance (A) or (B) 1.0 mg benzalkonium chloride 0.002 mg disodium edetate 0.0075 mg purified water ad 15.0 ⁇ l
  • the active substance and benzalkonium chloride are dissolved in water and packed in Respimat ® cartridges.
  • 1 vial contains: active substance (A) or (B) 0.1 g sodium chloride 0.18 g benzalkonium chloride 0.002 g purified water ad 20.0 ml
  • Active substance sodium chloride and benzalkonium chloride are dissolved in water.
  • Composition 1 spray contains: active substance (A) or (B) 1.0 mg lecithin 0.1 % propellant gas ad 50.0 ⁇ l
  • micronised active substance is homogeneously suspended in the mixture of lecithin and propellant gas.
  • the suspension is transferred into a pressurised container with a metering valve.
  • 1 spray jet contains active substance (A) or (B) 1.0 mg mannitol 5.0 mg disodium edetate 0.05 mg ascorbic acid 1.0 mg purified water ad 0.1 ml
  • the active substance and the excipients are dissolved in water and transferred into a suitable container.
  • composition active substance (A) or (B) in basic form 5 mg acid/salt-forming agent in the amount needed to form a neutral salt q.s. glucose 250 mg human serum albumin 10 mg glycofurol 250 mg water for injections ad 5 ml
  • Preparation Dissolve the glycofurol and glucose in water for injections (Wfl); add human serum albumin; add salt-forming agent; dissolve active substance with heating; make up to specified volume with Wfl; transfer into ampoules under nitrogen gas.
  • Injectable solution for subcutaneous administration containing 5 mg of active substance (A) or (B) per 1 ml
  • active substance (A) or (B) 5 mg glucose 50 mg polysorbate 80 Tween 80 2 mg water for injections ad 1 ml
  • Dissolve glucose and polysorbate in water for injections dissolve active substance with heating or using ultrasound; make up to specified volume with Wfl; transfer into ampoules under inert gas.
  • composition active substance (A) or (B) in basic form 10 mg acid/salt-forming agent in the amount needed to form a neutral salt q.s. mannitol 300 mg water for injections ad 2 ml
  • Dissolve mannitol in water for injections (Wfl); add salt-forming agent; dissolve active substance with heating; make up to specified volume with Wfl; transfer into viais; freeze-dry.
  • composition active substance (A) or (B) in basic form 5 mg polar or nonpolar solvent (which can be removed by freeze-drying) ad 1 ml
  • composition active substance (A) or (B) 20 mg lactose 120 mg maize starch 40 mg magnesium stearate 2 mg Povidone K 25 18 mg
  • Example XII Capsules containing 20 mg of active substance (A) or (B)
  • composition active substance (A) or (B) 20 mg maize starch 80 mg highly dispersed silica 5 mg magnesium stearate 2.5 mg
  • composition active substance (A) or (B) 50 mg hard fat (Adeps solidus) q.s. ad 1700 mg
  • the active substance is dissolved in purified water; hydrochloric acid is added until the solution is clear; methyl and propyl PHB are added; the solution is made up to the specified volume with purified water; the solution is filtered sterile and transferred into a suitable container.
  • composition active substance (A) or (B) 5 mg
  • the active substance is dissolved in 1 ,2-propanediol; a hydroxyethyl-cellulose solution in purified water containing sorbic acid is prepared and added to the solution of active substance; the solution is filtered sterile and transferred into a suitable container.
  • Example XVI Agueous solution for intravenous administration containing 5 mg of active substance (A) or (B)
  • composition active substance (A) or (B) 5 mg
  • the active substance is dissolved in 1 ,2-propanediol; the solution is made up to approximately the specified volume with Wfl; the mannitol is added and made up to approximately the specified volume with Wfl; the solution is filtered sterile, transferred into individual containers and autoclaved.
  • Liposomal formulation for intravenous injection containing 7.5 mg of active substance (A) or (B)
  • composition active substance (A) or (B) 7.5 mg egg lecithin, e.g. Lipoid E 80 100.0 mg cholesterol 50.0 mg glycerol 50.0 mg water for injections ad 1.0 ml
  • the active substance is dissolved in a mixture of lecithin and cholesterol; the solution is added to a mixture of glycerol and Wfl and homogenised by high pressure homogenisation or by the Microfluidizer technique; the liposomal formulation obtained is transferred into a suitable container under aseptic conditions.
  • composition active substance (A) or (B) 20.0 mg carboxymethylcellulose (CMC) 20.0 mg sodium monohydrogen phosphate/sodium dihydrogen phosphate buffer pH 6.8 q.s. sodium chloride 8.0 mg methyl parahydroxybenzoate 0.01 mg propyl parahydroxybenzoate 0.003 mg purified water ad 1.0 ml
  • the active substance is suspended in an aqueous CMC solution; the other ingredients are added successively to the suspension and the suspension is topped up to the specified volume with purified water.
  • composition active substance (A) or (B) 10.0 mg sodium monohydrogen phosphate/sodium dihydrogen phosphate buffer q.s. ad pH 7.0 sodium chloride 4.0 mg water for injections ad 0.5 ml
  • the active substance is dissolved in the phosphate buffer solution, after the addition of the common salt the solution is made up to the specified volume with water.
  • the solution is filtered sterile, transferred into a suitable container and autoclaved.
  • composition active substance (A) or (B) 5.0 mg polysorbate 80 0.5 mg water for injections 0.5 ml
  • the active substance is suspended in the polysorbate 80 solution and comminuted to a particle size of about 1 ⁇ m using a suitable dispersing technique (e.g. wet grinding, high pressure homogenisation, microfluidisation, etc.).
  • a suitable dispersing technique e.g. wet grinding, high pressure homogenisation, microfluidisation, etc.
  • the suspension is transferred into a corresponding container under aseptic conditions.

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Urology & Nephrology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne un procédé de traitement ou de prévention de bouffées de chaleur chez les hommes ayant subi une stérilisation, par exemple à cause du traitement par ablation des androgènes en thérapie du cancer de la prostate, qui consiste à administrer au patient une dose efficace d'un antagoniste du CGRP et/ou d'un inhibiteur de libération du CGRP ; elle concerne également l'utilisation desdits composés actifs pour fabriquer une composition pharmaceutique destinée à servir dans ce procédé.
EP04763078A 2003-07-07 2004-07-02 Utilisation d'antagonistes du cgrp dans le traitement et la prevention de bouffees de chaleur chez les patients atteints du cancer de la prostate Withdrawn EP1648466A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP04763078A EP1648466A1 (fr) 2003-07-07 2004-07-02 Utilisation d'antagonistes du cgrp dans le traitement et la prevention de bouffees de chaleur chez les patients atteints du cancer de la prostate

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP03015335 2003-07-07
EP03021802 2003-09-26
EP04763078A EP1648466A1 (fr) 2003-07-07 2004-07-02 Utilisation d'antagonistes du cgrp dans le traitement et la prevention de bouffees de chaleur chez les patients atteints du cancer de la prostate
PCT/EP2004/007228 WO2005004869A1 (fr) 2003-07-07 2004-07-02 Utilisation d'antagonistes du cgrp dans le traitement et la prevention de bouffees de chaleur chez les patients atteints du cancer de la prostate

Publications (1)

Publication Number Publication Date
EP1648466A1 true EP1648466A1 (fr) 2006-04-26

Family

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Application Number Title Priority Date Filing Date
EP04763078A Withdrawn EP1648466A1 (fr) 2003-07-07 2004-07-02 Utilisation d'antagonistes du cgrp dans le traitement et la prevention de bouffees de chaleur chez les patients atteints du cancer de la prostate

Country Status (3)

Country Link
EP (1) EP1648466A1 (fr)
CA (1) CA2531407A1 (fr)
WO (1) WO2005004869A1 (fr)

Families Citing this family (1)

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Publication number Priority date Publication date Assignee Title
CN101203491A (zh) * 2005-06-24 2008-06-18 伊莱利利公司 可用作雄激素受体调节剂的四氢咔唑衍生物（sarm）

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19937304C2 (de) * 1999-08-10 2003-08-21 Boehringer Ingelheim Pharma Verwendung von CGRP-Antagonisten zur Bekämpfung menopausaler Hitzewallungen
DE10211770A1 (de) * 2002-03-14 2003-10-02 Boehringer Ingelheim Pharma Neue substituierte Piperidine, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
DE10250080A1 (de) * 2002-10-25 2004-05-13 Boehringer Ingelheim Pharma Gmbh & Co. Kg Ausgewählte CGRP-Antagonisten, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2005004869A1 *

Also Published As

Publication number Publication date
CA2531407A1 (fr) 2005-01-20
WO2005004869A1 (fr) 2005-01-20

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