WO2001010425A2 - Verwendung von cgrp-antagonisten und cgrp-release-hemmern zur bekämpfung menopausaler hitzewallungen - Google Patents

Verwendung von cgrp-antagonisten und cgrp-release-hemmern zur bekämpfung menopausaler hitzewallungen Download PDF

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Publication number
WO2001010425A2
WO2001010425A2 PCT/EP2000/007613 EP0007613W WO0110425A2 WO 2001010425 A2 WO2001010425 A2 WO 2001010425A2 EP 0007613 W EP0007613 W EP 0007613W WO 0110425 A2 WO0110425 A2 WO 0110425A2
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WO
WIPO (PCT)
Prior art keywords
piperidinyl
carbonyl
dihydro
dibromo
piperidine
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.)
Ceased
Application number
PCT/EP2000/007613
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German (de)
English (en)
French (fr)
Other versions
WO2001010425A3 (de
Inventor
Henri Doods
Klaus Rudolf
Wolfgang Eberlein
Wolfhard Engel
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 Pharma GmbH and Co KG
Boehringer Ingelheim Pharmaceuticals Inc
Original Assignee
Boehringer Ingelheim Pharma GmbH and Co KG
Boehringer Ingelheim Pharmaceuticals Inc
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 UA2002031932A priority Critical patent/UA73137C2/uk
Priority to EEP200200061A priority patent/EE04928B1/xx
Priority to AU69928/00A priority patent/AU777709B2/en
Priority to CA002378428A priority patent/CA2378428C/en
Priority to NZ517367A priority patent/NZ517367A/en
Priority to EP00958385A priority patent/EP1207884B1/de
Priority to SK197-2002A priority patent/SK285587B6/sk
Priority to PL364049A priority patent/PL198483B1/pl
Priority to JP2001514945A priority patent/JP2003506403A/ja
Application filed by Boehringer Ingelheim Pharma GmbH and Co KG, Boehringer Ingelheim Pharmaceuticals Inc filed Critical Boehringer Ingelheim Pharma GmbH and Co KG
Priority to DK00958385T priority patent/DK1207884T3/da
Priority to MXPA02001373A priority patent/MXPA02001373A/es
Priority to EA200200207A priority patent/EA007531B1/ru
Priority to IL148057A priority patent/IL148057A/en
Priority to DE50008527T priority patent/DE50008527D1/de
Priority to BR0013009-5A priority patent/BR0013009A/pt
Priority to AT00958385T priority patent/ATE281168T1/de
Priority to HK02108347.1A priority patent/HK1046854B/zh
Priority to SI200030566T priority patent/SI1207884T1/xx
Publication of WO2001010425A2 publication Critical patent/WO2001010425A2/de
Priority to NO20020605A priority patent/NO20020605D0/no
Publication of WO2001010425A3 publication Critical patent/WO2001010425A3/de
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • 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
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
    • A61P5/22—Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of calcitonin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/30—Oestrogens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • Hot flashes are a common symptom of peri / post-menopausal syndrome, the physiology of which is still not fully understood. Apart from hormone replacement therapy (hormone replacement therapy), which is a complex intervention and often cannot be used permanently due to the associated side effects, there is currently no easy to carry out therapy with few side effects for this generally perceived as annoying.
  • hormone replacement therapy hormone replacement therapy
  • the present invention thus relates to the use of CGRP antagonists or / and CGRP release inhibitors for combating menopausal hot flashes, which includes both prevention and acute treatment.
  • the use according to the invention preferably relates to monotherapy with a single substance, but also includes combination therapy with several substances of the active substance groups mentioned. Furthermore, the use according to the invention can take place in addition to a hormone substitution that is usually carried out.
  • the invention furthermore relates to the use of CGRP antagonists or / and CGRP release inhibitors for the production of a medicament for combating menopausal hot flashes, and the corresponding medicaments containing one or more CGRP antagonists and / or CGRP release inhibitors as active ingredient.
  • all pharmaceutically acceptable active substances can be used which antagonize the known effects of CGRP or inhibit the release of CGRP from sensory nerve endings.
  • Possible CGRP antagonists are, for example, the amino acid derivatives described in WO 98/11128 or DE 199 11 039, and also the non-peptide active ingredients described in WO 98/56779, WO 98/09630 and WO 97/09046.
  • Possible CGRP release inhibitors are, for example, serotonin 5-HT 1D agonists such as avitriptan, eletriptan, naratriptan, rizatriptan, sumatriptan or zolmitriptan, furthermore 5-HT 1F agonists or NPY agonists.
  • serotonin 5-HT 1D agonists such as avitriptan, eletriptan, naratriptan, rizatriptan, sumatriptan or zolmitriptan, furthermore 5-HT 1F agonists or NPY agonists.
  • CGRP antagonists described in WO 98/11128 come to combat menopausal hot flashes, to produce a corresponding medicament and as a constituent part of a corresponding drug, preferably the following compounds in question:
  • BG 1- [3,5-dibromo-N- [[4- (3,4-dihydro-2 (IH) -oxoquinazolin-3-yl) -l-piperidinyl] carbonyl] -D-tyrosyl] -4 - [1- (hydroxycarbonylmethyl) -4 -piperidinyl] -piperidine,
  • the dose required to achieve a corresponding effect is expediently 0.0001 to 3 mg / kg body weight in the case of intravenous or subcutaneous administration, preferably 0.01 to 1 mg / kg body weight, and 0.01 to in the case of oral, nasal or inhalation administration 10 mg / kg body weight, preferably 0.1 to 10 mg / kg body weight, each 1 to 3 times a day.
  • the treatment with CGRP antagonists or / and CGRP release inhibitors is carried out in addition to a conventional hormone substitution, a reduction in the above-mentioned dosages is recommended, the dosage then being 1/5 of the above-mentioned lower limits up to 1 / l of the above specified upper limits can be.
  • the CGRP antagonists or / and CGRP release inhibitors can be used together with one or more inert customary carriers and / or diluents, e.g. with corn starch, milk sugar, cane sugar, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water / ethanol, water / glycerol, water / sorbitol, water / polyethylene glycol, propylene glycol, cetylstearyl alcohol, carboxymethyl cellulose substances or carboxymethyl cellulose substances or their suitable mixtures, incorporated into conventional pharmaceutical preparations such as tablets, coated tablets, capsules, powders, suspensions, solutions, metered dose aerosols or suppositories.
  • inert customary carriers and / or diluents e.g. with corn starch, milk sugar, cane sugar, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid,
  • Medicines containing one of the active ingredients are particularly suitable for combating menopausal hot flashes
  • A 1- [N 2 - [3,5-dibromo-N- [[4- (3,4-dihydro-2 (IH) -oxoquinazolin-3-yl) -l-piperidinyl] carbonyl] -D- tyrosyl] -L-lysyl] -
  • CGRP is released by sensory nerves, such as the trigeminal nerve, which is part of the facial skin. It has already been shown that the irritation of the trigeminal ganglion in humans leads to an increase in the CGRP plasma level and causes facial flushing ([4]: PJ Goadsby et al., Annais of Neurology, Vol. 23, No. 2, 1988, 193 -196,).
  • (A) 1- [N 2 - [3,5-dibromo-N- [[4- (3,4-dihydro-2 (IH) -oxoquinazolin-3-yl) -l-piperidinyl] carbonyl] -D-tyrosyl] -L-lysyl] - 4- (4-pyridinyl) -piperazine,
  • (B) 1- [4-amino-3,5-dibromo-N- [[4- (2, 3, 4, 5-tetrahydro-2 (IH) - oxo-1, 3-benzodiazepin-3-yl ) -l-piperidinyl] carbonyl] -D-phenylalanyl] -4- (l-piperidinyl) -piperidine,
  • (AC) (R, S) -1- [4- [4- (3,4-dihydro-2 (IH) -oxoquinazolin-3-yl) -1- piperidinyl] -2- [(3, 5- dibromo-4-methylphenyl) methyl] -1, 4-dioxobutyl] -4- (4-methyl-l-piperazinyl) piperidine,
  • (AM) 1- [4-amino-3,5-dibromo-N- [[4- (3,4-dihydro-2 (IH) -oxoquinazolin-3-yl) -1-piperidinyl] carbonyl] -D-phenylalanyl] -4- (l-piperidinyl) piperidine,
  • Marmosets of both sexes (300-400 g) are anesthetized with pentobarbital (induction with 30 mg / kg, i.p., infusion 6 mg / kg / h, i.m.).
  • the body temperature is kept at 37 ° C on a hot plate.
  • Pancurmium (initially 1 mg / kg, 0.5 mg after each additional hour) is administered as muscle relaxants.
  • the head of the animals is fixed in a stereotactic device. After the scalp has been opened by a longitudinal cut, a small hole is drilled in the skull and a bipolar electrode (Rhodes SNES 100) is lowered into the trigeminal organ.
  • Finding the ganglion is made easier by an x-ray that shows the bony cranial structure.
  • the petrous bone serves as an orientation for placing the electrode (X-ray device CCX-Digital).
  • the position of the The electrode in the ganglion is checked at the end of each experiment.
  • the stimulation parameters are: 10 Hz, 2 mA, 2 msec, for 30 sec.
  • the blood flow in the micro vessels of the facial skin is measured by means of laser Doppler flow measurement with a PeriFlux Laser Doppier system.
  • the animals are exposed to 2 to 3 stimulation periods at 30 min intervals.
  • the first stimulation serves as a reference value for the further stimulations.
  • the test substances are i.v. Applied 5 min before the 2nd or 3rd stimulation period.
  • 1 capsule for powder inhalation contains: Active ingredient (A) or (B) 1.0 mg
  • the active ingredient is ground to the grain size required for inhalants.
  • the ground active ingredient is mixed homogeneously with the milk sugar. The mixture is filled into hard gelatin capsules.
  • 1 hub includes:
  • 1 vial contains:
  • Active ingredient sodium chloride and benzalkonium chloride are in
  • 1 hub includes:
  • the micronized active ingredient is homogeneously suspended in the mixture of lecithin and propellant.
  • the suspension is filled into a pressure vessel with a metering valve.
  • Be is el V
  • the active ingredient and excipients are dissolved in water and filled into a suitable container.
  • VT VT
  • Acid / salt formers in the amount required to form a neutral salt q.s.
  • Polysorbate 80 Tween 80 2 mg
  • Dissolve glucose and polysorbate in water for injections Dissolve the active substance with heating or using ultrasound; fill up to volume with Wfl; Fill into ampoules while gassing with inert gas.
  • Dissolve polysorbate 80 sodium chloride, monopotassium dihydrogen phosphate and disodium hydrogen phosphate in water for injections (Wfl); Add human serum albumin; Dissolve active ingredient while heating; fill up to volume with Wfl; fill in ampoules.
  • Acid / salt formers in the amount required to form a neutral salt q.s.
  • Dissolve mannitol in water for injections Wfl
  • Add salt formers Dissolve active ingredient while heating; fill up to volume with Wfl; fill in vials; freeze-dry.
  • Polysorbate 80 Tween 80 20 mg
  • Active ingredient (A) or (B) in basic form 5 mg polar or non-polar solvent (which can be removed by freeze drying) ad 1 ml
  • Dissolve the active ingredient in a suitable solvent fill in vials; freeze-dry.
  • Polysorbate 80 Tween 80 5 mg
  • the active ingredient is dissolved in purified water; Hydrochloric acid is added until the solution becomes clear; PHB methyl and propyl esters are added; the solution is made up to the starting volume with purified water; the solution is sterile filtered and filled into an appropriate container.
  • the active ingredient is dissolved in 1,2-propanediol; a hydroxyethyl cellulose solution in purified water containing sorbic acid is prepared and added to the active ingredient solution; the solution is sterile filtered and filled into an appropriate container.
  • the active ingredient is dissolved in 1,2-propanediol; the solution is filled with Wfl to approximately batch volume; the mannitol is added and made up to volume with Wfl; the solution is sterile filtered, filled into individual containers and autoclaved.
  • the active ingredient is dissolved in a mixture of lecithin and cholesterol; the solution is added to a mixture of glycerol and Wfl and homogenized by means of high-pressure homogenization or microfluidizer technology; the liposomal formulation obtained in this way is filled into an appropriate container under aseptic conditions.
  • the active ingredient is suspended in an aqueous CMC solution; the other constituents are added to the suspension one after the other and the suspension is made up to the starting volume with purified water.
  • the active ingredient is dissolved in the phosphate buffer solution after
  • the addition of the table salt is made up to the starting volume with water. crowded.
  • the solution is sterile filtered and, after filling, autoclaved in an appropriate container.
  • Aqueous suspension for subcutaneous application with 5 mg substance (A or (B)
  • the active ingredient is suspended in the Polysorbate 80 solution and comminuted to a particle size of approx. 1 ⁇ m using suitable dispensing technology (e.g. wet grinding, high-pressure homogenization, microfluidization, etc.).
  • suitable dispensing technology e.g. wet grinding, high-pressure homogenization, microfluidization, etc.
  • the suspension is filled into an appropriate container under aseptic conditions.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Reproductive Health (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
PCT/EP2000/007613 1999-08-10 2000-08-05 Verwendung von cgrp-antagonisten und cgrp-release-hemmern zur bekämpfung menopausaler hitzewallungen Ceased WO2001010425A2 (de)

Priority Applications (19)

Application Number Priority Date Filing Date Title
UA2002031932A UA73137C2 (en) 1999-08-10 2000-05-08 Use of cgrp antagonists and cgrp release inhibitors for controlling menopausal hot flashes
MXPA02001373A MXPA02001373A (es) 1999-08-10 2000-08-05 Utilizacion de agentes antagonistas del cgrp en inhbidores de la liberacion del cgrp para combatir sofocos menopausicos..
CA002378428A CA2378428C (en) 1999-08-10 2000-08-05 Use of cgrp antagonists and cgrp release inhibitors for combating menopausal hot flushes
NZ517367A NZ517367A (en) 1999-08-10 2000-08-05 Use of CGRP antagonists and CGRP release inhibitors for combating menopausal hot flashes
EP00958385A EP1207884B1 (de) 1999-08-10 2000-08-05 Verwendung von cgrp-antagonisten und cgrp-release-hemmern zur bekämpfung menopausaler hitzewallungen
SK197-2002A SK285587B6 (sk) 1999-08-10 2000-08-05 Použitie CGRP-antagonistov a inhibítorov uvoľňovania CGRP
PL364049A PL198483B1 (pl) 1999-08-10 2000-08-05 Zastosowanie antagonistów CGRP i inhibitorów uwalniania CGRP do zwalczania menopauzalnych przypływów gorąca
IL148057A IL148057A (en) 1999-08-10 2000-08-05 Use of cgrp antagonists for preparing a pharmaceutical composition for treating menopausal hot flashes
AU69928/00A AU777709B2 (en) 1999-08-10 2000-08-05 Use of CGRP antagonists for combating menopausal hot flushes
DK00958385T DK1207884T3 (da) 2000-08-05 2000-08-05 Anvendelse af CGRP-antagonister og CGRP-releaseinhibitorer til bekæmpelse af menopausale hedestigninger
EA200200207A EA007531B1 (ru) 1999-08-10 2000-08-05 Применение антагонистов cgrp для устранения приливов в период менопаузы
EEP200200061A EE04928B1 (et) 1999-08-10 2000-08-05 CGRP antagonistide ja CGRP vabanemise inhibiitorite kasutamine menopausaalsete kuumahoogude vastu v?itlemiseks
JP2001514945A JP2003506403A (ja) 1999-08-10 2000-08-05 閉経期の顔面潮紅を治療するためのｃｇｒｐアンタゴニスト及びｃｇｒｐ放出インヒビターの使用
DE50008527T DE50008527D1 (de) 1999-08-10 2000-08-05 Verwendung von cgrp-antagonisten und cgrp-release-hemmern zur bekämpfung menopausaler hitzewallungen
BR0013009-5A BR0013009A (pt) 1999-08-10 2000-08-05 Uso de antagonistas de cgrp e de inibidores de liberação de cgrp para combate a jatos quentes menopáusicos
AT00958385T ATE281168T1 (de) 1999-08-10 2000-08-05 Verwendung von cgrp-antagonisten und cgrp-release-hemmern zur bekämpfung menopausaler hitzewallungen
HK02108347.1A HK1046854B (zh) 1999-08-10 2000-08-05 用於控制絕經熱潮紅的降鈣素基因有關肽的拮抗劑及其釋出的抑制劑
SI200030566T SI1207884T1 (sl) 1999-08-10 2000-08-05 Uporaba CGRP antagonistov in inhibitorjev sproščanja CGRP za odpravljanje menopavznih navalov vročine
NO20020605A NO20020605D0 (no) 1999-08-10 2002-02-07 Anvendelse av CGRP-antagonister og CGRP- frigjöringsinhibitorer for bekjempelse av menopause-varmetokter

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19937304A DE19937304C2 (de) 1999-08-10 1999-08-10 Verwendung von CGRP-Antagonisten zur Bekämpfung menopausaler Hitzewallungen
DE19937304.3 1999-08-10

Publications (2)

Publication Number Publication Date
WO2001010425A2 true WO2001010425A2 (de) 2001-02-15
WO2001010425A3 WO2001010425A3 (de) 2002-02-07

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PCT/EP2000/007613 Ceased WO2001010425A2 (de) 1999-08-10 2000-08-05 Verwendung von cgrp-antagonisten und cgrp-release-hemmern zur bekämpfung menopausaler hitzewallungen

Country Status (32)

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EP (1) EP1207884B1 (https=)
JP (1) JP2003506403A (https=)
KR (1) KR100713573B1 (https=)
CN (1) CN1166361C (https=)
AR (1) AR025078A1 (https=)
AT (1) ATE281168T1 (https=)
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WO2003015787A1 (en) * 2001-08-17 2003-02-27 Boehringer Ingelheim Pharma Gmbh & Co. Kg Use of bibn4096 in combination with other antimigraine drugs for the treatment of migraine
WO2003050109A1 (en) * 2001-12-12 2003-06-19 Eli Lilly And Company Alanyl-piperidine heterocyclic derivatives useful against cardiovascular diseases
WO2003070215A1 (de) * 2002-02-20 2003-08-28 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pulverinhalativum, enthaltend den cgrp-antagonisten bibn4096 und verfahren zu dessen herstellung
WO2003070753A1 (de) * 2002-02-19 2003-08-28 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verfahren zur herstellung eines pulverinhalativums enthaltend ein salz des cgrp-antagonisten bibn4096
WO2004000289A3 (de) * 2002-06-19 2004-03-25 Boehringer Ingelheim Pharma Zubereitungen zur intranasalen applikation ausgewählter, von aminosäuren abgeleiteter grp-antagonisten
WO2004037810A1 (de) * 2002-10-25 2004-05-06 Boehringer Ingelheim Pharma Gmbh & Co. Kg Ausgewählte cgrp-antagonisten, verfahren zu deren herstellung sowie deren verwendung als arzneimittel
WO2004063171A1 (de) * 2003-01-14 2004-07-29 Boehringer Ingelheim International Gmbh N- (1-benzyl-2-oxo-2- (1-piperazinyl) ethyl) -1-piperidincarboxamid-derivate und verwandte verbindungen als cgrp-antagonisten zur behandlung von kopfschmerzen
WO2005004869A1 (en) * 2003-07-07 2005-01-20 Boehringer Ingelheim International Gmbh Use of cgrp antagonists in treatment and prevention of hot flushes in prostate cancer patients
WO2005018609A1 (de) * 2003-08-18 2005-03-03 Boehringer Ingelheim International Gmbh Mikropartikel, enthaltend den cgrp-antagonisten 1- [n2-[3,5-dibrom-n-[[4-(3,4-dihydro-2(1h)-oxochinazolin-3-yl)-1-piperidinyl]carbonyl]-d-tyrosyl]-l-lysyl]-4-(4-pyridinyl)-piperazin, verfahren zu deren herstellung sowie deren verwendung als inhalationspulver
US6900317B2 (en) 2002-02-19 2005-05-31 Boehringer Ingelheim Pharma Gmbh & Co. Kg Salts of the CGRP antagonist BIBN4096 and inhalable powdered medicaments containing them
WO2005103037A3 (de) * 2004-04-22 2006-01-12 Boehringer Ingelheim Int Ausgewählte cgrp-antagonisten, verfahren zu deren herstellung sowie deren verwendung als arzneimittel
WO2006069754A1 (en) * 2004-12-29 2006-07-06 Boehringer Ingelheim International Gmbh Use of cgrp antagonists in treatment and prevention of hot flushes in prostate cancer patients
WO2006072415A1 (de) * 2004-12-29 2006-07-13 Boehringer Ingelheim International Gmbh Verwendung ausgewählter cgrp-antagonisten zur bekämpfung menopausaler hitzewallungen
US7407963B2 (en) 1999-10-29 2008-08-05 Boehringer Ingelheim Pharma Gmbh & Co. Kg Cyclopropane CGRP antagonists, medicaments containing these compounds, and method for the production thereof
US7439237B2 (en) 2005-04-15 2008-10-21 Boehringer Ingelheim International Gmbh Selected CGRP-antagonists, process for preparing them and their use as pharmaceutical compositions
US7479488B2 (en) 2004-03-29 2009-01-20 Boehringer Ingelheim International Gmbh Selected CGRP—antagonists, process for preparing them and their use as pharmaceutical compositions
US7528129B2 (en) 2005-03-23 2009-05-05 Boehringer Ingelheim International Gmbh CGRP-antagonists, process for preparing them and their use as pharmaceutical compositions
US7595312B2 (en) 2002-10-25 2009-09-29 Boehringer Ingelheim Pharma Gmbh & Co. Kg Selected CGRP antagonists, processes for preparing them and their use as pharmaceutical compositions
US7696195B2 (en) 2004-04-22 2010-04-13 Boehringer Ingelheim International Gmbh Selected CGRP-antagonists, process for preparing them and their use as pharmaceutical compositions

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CN100418948C (zh) * 2003-07-15 2008-09-17 麦克公司 羟基吡啶cgrp受体抗拮抗剂
US7491717B2 (en) 2005-03-23 2009-02-17 Boehringer Ingelheim International Gmbh Selected CGRP-antagonists, process for preparing them and their use as pharmaceutical compositions

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ES2132855T3 (es) * 1995-09-07 1999-08-16 Oreal Extracto de iridaceas y composiciones que lo contienen.
US5910482A (en) * 1996-03-19 1999-06-08 Board Of Regents, The University Of Texas System Treatment or prevention of preeclampsia, eclampsia with calcitonin gene related peptide, CGRP analog, progestational agent, nitric oxide source, and cyclooxygenase inhibitor
US5710024A (en) * 1996-07-23 1998-01-20 Smithkline Beecham Corporation Polynucleotides that encode the calcitonin gene-related peptide receptor coponent factor (HOUNDC44)
DE59711622D1 (de) * 1996-09-10 2004-06-17 Boehringer Ingelheim Pharma Abgewandelte aminosäuren, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
DE19911039A1 (de) * 1999-03-12 2000-09-14 Boehringer Ingelheim Pharma Abgewandelte Aminosäureamide, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung

Cited By (24)

* Cited by examiner, † Cited by third party
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US7407963B2 (en) 1999-10-29 2008-08-05 Boehringer Ingelheim Pharma Gmbh & Co. Kg Cyclopropane CGRP antagonists, medicaments containing these compounds, and method for the production thereof
WO2003015787A1 (en) * 2001-08-17 2003-02-27 Boehringer Ingelheim Pharma Gmbh & Co. Kg Use of bibn4096 in combination with other antimigraine drugs for the treatment of migraine
WO2003050109A1 (en) * 2001-12-12 2003-06-19 Eli Lilly And Company Alanyl-piperidine heterocyclic derivatives useful against cardiovascular diseases
US7115609B2 (en) 2001-12-12 2006-10-03 Eli Lilly And Company Alanyl-piperidine heterocyclic derivatives useful against cardiovascular diseases
US6900317B2 (en) 2002-02-19 2005-05-31 Boehringer Ingelheim Pharma Gmbh & Co. Kg Salts of the CGRP antagonist BIBN4096 and inhalable powdered medicaments containing them
WO2003070753A1 (de) * 2002-02-19 2003-08-28 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verfahren zur herstellung eines pulverinhalativums enthaltend ein salz des cgrp-antagonisten bibn4096
WO2003070215A1 (de) * 2002-02-20 2003-08-28 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pulverinhalativum, enthaltend den cgrp-antagonisten bibn4096 und verfahren zu dessen herstellung
WO2004000289A3 (de) * 2002-06-19 2004-03-25 Boehringer Ingelheim Pharma Zubereitungen zur intranasalen applikation ausgewählter, von aminosäuren abgeleiteter grp-antagonisten
EP1769790A1 (de) * 2002-06-19 2007-04-04 Boehringer Ingelheim Pharma GmbH & Co. KG Zubereitungen zur intranasalen Applikation ausgewählter, von Aminosäuren abgeleiteter CGRP-Antagonisten
WO2004037810A1 (de) * 2002-10-25 2004-05-06 Boehringer Ingelheim Pharma Gmbh & Co. Kg Ausgewählte cgrp-antagonisten, verfahren zu deren herstellung sowie deren verwendung als arzneimittel
EA009219B1 (ru) * 2002-10-25 2007-12-28 Бёрингер Ингельхайм Фарма Гмбх Унд Ко. Кг Селективные cgrp-антагонисты, способ их получения, их физиологически совместимые соли, а также их применение в качестве лекарственных средств
US7595312B2 (en) 2002-10-25 2009-09-29 Boehringer Ingelheim Pharma Gmbh & Co. Kg Selected CGRP antagonists, processes for preparing them and their use as pharmaceutical compositions
WO2004063171A1 (de) * 2003-01-14 2004-07-29 Boehringer Ingelheim International Gmbh N- (1-benzyl-2-oxo-2- (1-piperazinyl) ethyl) -1-piperidincarboxamid-derivate und verwandte verbindungen als cgrp-antagonisten zur behandlung von kopfschmerzen
WO2005004869A1 (en) * 2003-07-07 2005-01-20 Boehringer Ingelheim International Gmbh Use of cgrp antagonists in treatment and prevention of hot flushes in prostate cancer patients
WO2005018609A1 (de) * 2003-08-18 2005-03-03 Boehringer Ingelheim International Gmbh Mikropartikel, enthaltend den cgrp-antagonisten 1- [n2-[3,5-dibrom-n-[[4-(3,4-dihydro-2(1h)-oxochinazolin-3-yl)-1-piperidinyl]carbonyl]-d-tyrosyl]-l-lysyl]-4-(4-pyridinyl)-piperazin, verfahren zu deren herstellung sowie deren verwendung als inhalationspulver
US7479488B2 (en) 2004-03-29 2009-01-20 Boehringer Ingelheim International Gmbh Selected CGRP—antagonists, process for preparing them and their use as pharmaceutical compositions
US7700598B2 (en) 2004-03-29 2010-04-20 Boehringer Ingelheim International Gmbh Selected CGRP-antagonists, process for preparing them and their use as pharmaceutical compositions
WO2005103037A3 (de) * 2004-04-22 2006-01-12 Boehringer Ingelheim Int Ausgewählte cgrp-antagonisten, verfahren zu deren herstellung sowie deren verwendung als arzneimittel
US7696195B2 (en) 2004-04-22 2010-04-13 Boehringer Ingelheim International Gmbh Selected CGRP-antagonists, process for preparing them and their use as pharmaceutical compositions
WO2006072415A1 (de) * 2004-12-29 2006-07-13 Boehringer Ingelheim International Gmbh Verwendung ausgewählter cgrp-antagonisten zur bekämpfung menopausaler hitzewallungen
WO2006069754A1 (en) * 2004-12-29 2006-07-06 Boehringer Ingelheim International Gmbh Use of cgrp antagonists in treatment and prevention of hot flushes in prostate cancer patients
US7528129B2 (en) 2005-03-23 2009-05-05 Boehringer Ingelheim International Gmbh CGRP-antagonists, process for preparing them and their use as pharmaceutical compositions
US7696209B2 (en) 2005-03-23 2010-04-13 Boehringer Ingelheim International Gmbh CGRP-antagonists, process for preparing them and their use as pharmaceutical compositions
US7439237B2 (en) 2005-04-15 2008-10-21 Boehringer Ingelheim International Gmbh Selected CGRP-antagonists, process for preparing them and their use as pharmaceutical compositions

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AR025078A1 (es) 2002-11-06
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