EP1778691A1 - Nouveaux hydrates et polymorphes du 4-[[(7r)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-4-6-oxo-2-piperidinyl]amino]-3-methoxy-n-(1-methyl-4-piperidinyl)-benzamide, son procede de production et son utilisation comme medicament - Google Patents

Nouveaux hydrates et polymorphes du 4-[[(7r)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-4-6-oxo-2-piperidinyl]amino]-3-methoxy-n-(1-methyl-4-piperidinyl)-benzamide, son procede de production et son utilisation comme medicament

Info

Publication number
EP1778691A1
EP1778691A1 EP05772062A EP05772062A EP1778691A1 EP 1778691 A1 EP1778691 A1 EP 1778691A1 EP 05772062 A EP05772062 A EP 05772062A EP 05772062 A EP05772062 A EP 05772062A EP 1778691 A1 EP1778691 A1 EP 1778691A1
Authority
EP
European Patent Office
Prior art keywords
compound
formula
anhydrate
preparation
methyl
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Withdrawn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
EP05772062A
Other languages
German (de)
English (en)
Inventor
Guenter Linz
Peter Sieger
Gerd F. Kraemer
Werner Rall
Rolf Herter
Matthias Hoffmann
Rolf Schmid
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
Boehringer Ingelheim Pharma GmbH and Co KG
Original Assignee
Boehringer Ingelheim International GmbH
Boehringer Ingelheim Pharma GmbH and Co KG
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=35311878&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP1778691(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Boehringer Ingelheim International GmbH, Boehringer Ingelheim Pharma GmbH and Co KG filed Critical Boehringer Ingelheim International GmbH
Priority to EP05772062A priority Critical patent/EP1778691A1/fr
Publication of EP1778691A1 publication Critical patent/EP1778691A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/56—Nitrogen atoms
    • C07D211/58—Nitrogen atoms attached in position 4
    • 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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D475/00—Heterocyclic compounds containing pteridine ring systems

Definitions

  • the present invention relates to new hydrates and new polymorphs of 4 - [[(7i?) - 8-cyclopentyl-T-S-ethyl ⁇ j ⁇ J -tetrahydro-S-methyl- ⁇ -oxo-l-pteridinyllaminoJ-S-methoxy- N- (1-methyl-4-piperidmyl) benzamide, process for their preparation and their use as pharmaceuticals.
  • the compound 4 - [[(7i) - 8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-6-oxo-2-olpteridyl] amino] -3-methoxy-N - (1-methyl-4-piperidinyl) benzamide has the structure of the following formula (I).
  • the present invention provides novel hydrates and novel polymorphic forms of the compound of formula (I) having antiproliferative activity.
  • Another object of the invention is the anhydrate of the compound of formula (I).
  • Another object of the invention is a pharmaceutical composition which contains a therapeutically effective amount of one of the above-described hydrates and polymorphic forms of the compound of formula (I) and one or more pharmaceutically acceptable excipients. Boehringer Ingelheim - 3 - 1-1758-out
  • the invention furthermore relates to the hydrates and polymorphic forms of the compound of the formula (I) according to the invention for use as medicaments having an antiproliferative action.
  • Another object of the invention is the use of hydrates and polymorphic forms of the compound of formula (I) according to the invention for the manufacture of a medicament for the treatment and / or prevention of cancer, infections, inflammatory and autoimmune diseases.
  • Another object of the invention is the use of the erfmdungshielen
  • Another object of the invention is a process for the preparation of the compound of formula (I), characterized in that a compound of formula 4
  • Another object of the invention is a process for the preparation of a compound of formula 9,
  • Another object of the invention is a compound of formula 3
  • the invention further provides a process for preparing the monohydrate of the compound of the formula (I), which comprises the following process steps:
  • Another object of the invention is a process for preparing the trihydrate of the compound of formula (I), wherein the monohydrate of the compound of formula (I) is exposed to a relative humidity of at least 70%.
  • Another object of the invention is a process for the preparation of the anhydrate form III of the compound of formula (I), wherein:
  • the monohydrate of the compound of formula (I) is exposed to a temperature of about 70 ° C, preferably 70 to 120 ° C, more preferably 70 to 90 ° C.
  • Another object of the invention is a process for the preparation of the anhydrate Form I of the compound of formula (I), wherein the anhydrate Form III of the compound of formula (I) is melted and then the melt at a temperature of at least 140 ° C, preferably from 140 ° C to 160 0 C, is crystallized.
  • the invention further provides a process for preparing the anhydrate Form I of the compound of the formula (I) comprising the following process steps: a) Preparation of a solution of the compound of the formula (I) in a solvent mixture of ethyl acetate and methyl tert-butyl ether , preferably in the ratio of ethyl acetate / methyl tert-butyl ether of 3: 5 (v / v) or from a
  • the invention further provides a process for preparing the anhydrate Form II of the compound of the formula (I) comprising the following process steps: a) preparation of a solution of the compound of the formula (I) in ethyl acetate, b) crystallization of the anhydrate Form II of the compound of the formula (I) from ethyl acetate with subsequent addition of diethyl ether and c) isolation of the anhydrate Form II of the compound of the formula (I).
  • the invention further provides a process for preparing the anhydrate Form I of the compound of the formula (I) comprising the following process steps: a) melting the anhydrate Form II of the compound of the formula (I), b) crystallizing the melt at a temperature of at least 185 0 C, preferably at a temperature of 185 to 200 ° C.
  • the organic phase is separated off and the product-containing water phase is transferred back into the reactor. It is rinsed with 4 L of water. Under reduced pressure, 3.2 L of water are distilled off at 50 ° C. To the remaining solution is allowed at 4O 0 C 4.87 kg (60.9 mol) sodium hydroxide sol. Accrue (50%). It is rinsed with 4 L of water. The product suspension is allowed to cool to 22 ° C and stirred for 30 min. At this temperature. The suspension is filtered off with suction and the filter cake is washed with 40 L of water. The product is dried in a vacuum drying cabinet at 4O 0 C. This gives 5.65 kg of product.
  • the filtrate is transferred to a reactor and rinsed the transport vessel with 5 L demineralized water.
  • the reactor contents are heated to 5O 0 C.
  • a mixture of 5.45 kg (68.2 mol) of sodium hydroxide solution is added. (50%, techn.) And 7 L of demineralised water too.
  • the mixture is stirred for 10 minutes at 45-50 ° C.
  • the suspension is cooled to 20 ° C and stirred for 1-1.5 hours at this temperature.
  • the product is filtered off, washed with 30 L demineralized water and dried at 45 ° C in a vacuum oven. 4.13 kg of product 4 are obtained.
  • the preparation of the methyl ester 6a, the ethyl ester 6b and the 2-propyl ester 6c is carried out according to literature known regulations, for example according to WO 03/020722.
  • the tert-butyl ester 6d is prepared by transesterification with tert-butyl acetate in the presence of perchloric acid (J. Med. Chem., Vol. 37, No. 20, 1994, 3294-3302).
  • the amino acids can be used in the form of the bases or as hydrochlorides in the subsequent nucleophilic substitution reaction.
  • Amino acid amide 6e is prepared by aminolysis of methyl ester 6a with 40% aqueous methylamine solution at room temperature.
  • Amino acid amide 6f is prepared by amidation of the free amino acid with a five-fold excess of 2 molar dimethylamine solution in tetrahydrofuran in the presence of O- (benzotriazol-1-yl) -N, N, N ', N'-
  • lipophilic solvents such as cyclohexane, methylcyclohexane, toluene and mixtures thereof are particularly suitable
  • the compounds 7b-f are prepared.
  • a more polar solvent e.g. Ethyl acetate or dichloromethane.
  • the catalyst was filtered off and the hydrogenation solution was evaporated under reduced pressure.
  • To the residue are added 4 L of demineralized water and 4 L of ethyl acetate. Between the phases, a precipitate forms, which contains product.
  • the aqueous phase is separated off. 2 liters of ethyl acetate are added to the organic phase and the precipitate is filtered off with suction.
  • the precipitate is suspended in 600 mL of demineralized water, stirred for 1 hour at room temperature, suction filtered and washed with demineralised water. This gives HO g of moist product A.
  • Dimethylacetamide is added at 4-1O 0 C in portions within one hour 38 g (0.95 mol) of sodium hydride (60 percent dispersion in mineral oil). Remove the cooling bath Boehringer Ingelheim - 14 - 1-1758-out
  • a suspension of 100 g (356 mmol) of 8 and 73.8 g (534 mmol) of potassium carbonate in 400 ml of dimethyl carbonate is heated to 130 ° C. in an autoclave for 6 hours. It is allowed to cool and 300 ml of demineralized water and 200 ml of ethyl acetate are added with stirring. The aqueous phase is separated together with undissolved salts. Are mbar at a pressure of 180 from the organic phase and a bath temperature of 70 0 C distilled off 500 ml of solvent. To the residue is added 600 mL of demineralized water and distilled at a pressure of 150 mbar and a heating bath temperature of 80 0 C 100 mL of solvent.
  • a suspension of 201 g (1.06 mol) of para-toluenesulfonic acid hydrate, 209 g (706 mmol) of 9 and 183 g (695 mmol) of 4 in 800 mL of 2-methyl-4-pentanol is heated to reflux. 100 ml of solvent are distilled off. The mixture is refluxed for 3 hours, 200 ml of 2-methyl-4-pentanol are added and distilled off 120 ml of solvent. After heating for 2 hours under reflux, a further 280 ml of solvent are distilled off. It is allowed to cool to 100 ° C and to the reaction solution 1 L demineralized water and then 0.5 L ethyl acetate.
  • the organic phase is separated and the aqueous phase washed again with 0.5 L ethyl acetate.
  • aqueous phase are added 1.5 L dichloromethane and 0.5 L ethyl acetate.
  • the pH of the aqueous phase is brought to pH 9.2 with 260 ml of 6N sodium hydroxide solution.
  • the aqueous phase is separated off and the organic phase is washed three times with 1 l each of normal aqueous sodium bicarbonate solution.
  • the organic phase is over
  • the crude product is dissolved in 1.5 L of ethyl acetate. At a temperature of 50-55 ° C, 2.5 L of methyl tert-butyl ether are added. At 45 ° C is inoculated and stirred with cooling to room temperature for 16 hours. The suspension is stirred for 3.5 hours at 0-5 ° C and the precipitate is filtered off with suction. The filter cake is washed with methyl tert-butyl ether / ethyl acetate (2: 1) and methyl tert-butyl ether. The product is dried in a vacuum oven at 50 ° C. This gives 236 g of crystalline product of the compound of formula (I) as anhydrate Form I.
  • the crude product of the reaction described above can also be crystallized directly as crystalline monohydrate from 1-propanol / demineralized water.
  • the hydrates and anhydrates according to the invention are characterized by DSC / TG (Differential Scanning Calorimetry / Thermogravimetry) and XRD (X-ray powder diffractograms) (Table 1-5, Figures Ia to 5a).
  • the DSC / TG measurements were carried out using devices from Mettler Toledo (DSC 821 and TGA 851). The sample amount was between 2 and 10 mg for DSC measurements and 10 to 30 mg for TG measurements. The heating rates were 10 K / min, the measurements were carried out under inert atmosphere (nitrogen purge).
  • anhydrate I, anhydrate II and monohydrate of the compound of the formula (I) according to the invention can be used alone or in combination with other active compounds according to the invention, if appropriate also in combination with other pharmacologically active substances.
  • Suitable application forms are, for example, tablets, capsules, suppositories, solutions, in particular solutions for injection (s.c., i.V., i.m.) and infusion, juices, emulsions or dispersible powders.
  • the proportion of the pharmaceutically active compound (s) in each case in the range of 0.01 to 90 wt .-%, preferably 0.1 to 50 wt .-% of the total composition, i. in amounts sufficient to reach the dosage range given below.
  • the said doses may, if necessary, be given several times a day.
  • Corresponding tablets can be prepared, for example, by mixing the active substance (s) with known excipients, for example inert diluents such as calcium carbonate, calcium phosphate or lactose, disintegrants such as corn starch or alginic acid, binders such as starch or gelatin, lubricants such as magnesium stearate or talc, and / or agents to obtain the depot effect, such as carboxymethyl cellulose, cellulose acetate phthalate, or polyvinyl acetate.
  • excipients for example inert diluents such as calcium carbonate, calcium phosphate or lactose, disintegrants such as corn starch or alginic acid, binders such as starch or gelatin, lubricants such as magnesium stearate or talc, and / or agents to obtain the depot effect, such as carboxymethyl cellulose, cellulose acetate phthalate, or polyvinyl acetate.
  • excipients for example iner
  • Coated tablets can accordingly be produced by coating cores produced analogously to the tablets with agents customarily used in tablet coatings, for example collidone or shellac, gum arabic, talc, titanium dioxide or sugar.
  • the core can also consist of several layers.
  • the dragee sheath to achieve a depot effect of several layers may consist of the above mentioned in the tablets excipients can be used.
  • Juices of the active compounds or active compound combinations according to the invention may additionally contain a sweetener, such as saccharin, cyclamate, glycerol or sugar, and a taste-improving agent, for example flavorings, such as vanillin or orange extract. They may also contain suspending aids or thickening agents, such as sodium carboxymethylcellulose, wetting agents, for example Boehringer Ingelheim - 24 - 1-1758-out
  • Injection and infusion solutions are in the usual way, eg. with the addition of isotonic agents, preservatives, such as p-hydroxybenzoates, or stabilizers, such as alkali metal salts of ethylenediaminetetraacetic acid, if appropriate using emulsifiers and / or dispersants, wherein, for example, when using water as a diluent organic solvents may optionally be used as solubilizers or auxiliary solvents , manufactured and filled into injection vials or ampoules or infusion bottles.
  • preservatives such as p-hydroxybenzoates
  • stabilizers such as alkali metal salts of ethylenediaminetetraacetic acid
  • the capsules containing one or more active ingredients or combinations of active substances can be prepared, for example, by mixing the active ingredients with inert carriers, such as lactose or sorbitol, and encapsulating them in gelatine capsules.
  • suitable suppositories can be prepared, for example, by mixing with suitable carriers, such as neutral fats or polyethylene glycol or its derivatives.
  • water pharmaceutically acceptable organic solvents such as paraffins (e.g., petroleum fractions), oils of vegetable origin (e.g., peanut or sesame oil), mono- or polyfunctional alcohols (e.g., ethanol or glycerin), carriers such as e.g.
  • paraffins e.g., petroleum fractions
  • oils of vegetable origin e.g., peanut or sesame oil
  • mono- or polyfunctional alcohols e.g., ethanol or glycerin
  • carriers such as e.g.
  • ground natural minerals eg kaolins, clays, talc, chalk
  • ground synthetic minerals eg fumed silica and silicates
  • sugars eg pipe, milk and dextrose
  • emulsifiers eg lignin, liquors, methylcellulose, starch and polyvinylpyrrolidone
  • lubricants eg Magnesium stearate, talc, stearic acid and sodium lauryl sulfate.
  • the application is carried out in a customary manner, preferably orally, via injection or transdermally.
  • the tablets may of course also contain additives such as, for example, sodium citrate, calcium carbonate and dicalcium phosphate together with various additives, such as starch, Boehringer Ingelheim - 25 - 1-1758-out
  • aqueous suspensions the active ingredients may be added to the abovementioned excipients with various flavor enhancers or dyes.
  • solutions of the active ingredients may be employed using suitable liquid carrier materials.
  • the dosage for intravenous use is 1 - 1000 mg per hour, preferably between 5 - 500 mg per hour.
  • the finely ground active substance, lactose and part of the corn starch are mixed together.
  • the mixture is sieved, then moistened with a solution of polyvinylpyrrolidone in water, kneaded, wet granulated and dried.
  • the granules, the remainder of the corn starch and the magnesium stearate are sieved and mixed together.
  • the mixture is compressed into tablets of suitable shape and size.
  • the finely ground active ingredient, a portion of the corn starch, lactose, microcrystalline cellulose and polyvinylpyrrolidone are mixed together, the mixture is sieved and processed with the remainder of the corn starch and water to a granulate which is dried and sieved.
  • the active ingredient is dissolved in water at its own pH or optionally at pH 3.5-6.5 and treated with sodium chloride as isotonan.
  • the resulting solution is filtered pyrogen-free and the filtrate filled under aseptic conditions in ampoules, which are then sterilized and sealed.
  • the vials contain 5 mg, 25 mg and 50 mg active ingredient.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)

Abstract

La présente invention concerne de nouveaux hydrates et de nouveaux polymorphes du 4-[[(7R)-8-cyclopentyl-7-éthyl-5,6,7,8-tétrahydro-5-méthyl-6-oxo-2-ptéridinyl]amino]-3-méthoxy-N-(1-méthyl-4-pipéridinyl)-benzamide. L'invention concerne également son procédé de production et son utilisation comme médicament.
EP05772062A 2004-08-14 2005-08-11 Nouveaux hydrates et polymorphes du 4-[[(7r)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-4-6-oxo-2-piperidinyl]amino]-3-methoxy-n-(1-methyl-4-piperidinyl)-benzamide, son procede de production et son utilisation comme medicament Withdrawn EP1778691A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP05772062A EP1778691A1 (fr) 2004-08-14 2005-08-11 Nouveaux hydrates et polymorphes du 4-[[(7r)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-4-6-oxo-2-piperidinyl]amino]-3-methoxy-n-(1-methyl-4-piperidinyl)-benzamide, son procede de production et son utilisation comme medicament

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP04019366 2004-08-14
PCT/EP2005/008736 WO2006018222A1 (fr) 2004-08-14 2005-08-11 Nouveaux hydrates et polymorphes du 4-[[(7r)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-4-6-oxo-2-piperidinyl]amino]-3-methoxy-n-(1-methyl-4-piperidinyl)-benzamide, son procede de production et son utilisation comme medicament
EP05772062A EP1778691A1 (fr) 2004-08-14 2005-08-11 Nouveaux hydrates et polymorphes du 4-[[(7r)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-4-6-oxo-2-piperidinyl]amino]-3-methoxy-n-(1-methyl-4-piperidinyl)-benzamide, son procede de production et son utilisation comme medicament

Publications (1)

Publication Number Publication Date
EP1778691A1 true EP1778691A1 (fr) 2007-05-02

Family

ID=35311878

Family Applications (1)

Application Number Title Priority Date Filing Date
EP05772062A Withdrawn EP1778691A1 (fr) 2004-08-14 2005-08-11 Nouveaux hydrates et polymorphes du 4-[[(7r)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-4-6-oxo-2-piperidinyl]amino]-3-methoxy-n-(1-methyl-4-piperidinyl)-benzamide, son procede de production et son utilisation comme medicament

Country Status (19)

Country Link
US (3) US7728134B2 (fr)
EP (1) EP1778691A1 (fr)
JP (1) JP2008509953A (fr)
KR (1) KR101221864B1 (fr)
CN (1) CN101006090A (fr)
AR (1) AR052404A1 (fr)
AU (1) AU2005274340B2 (fr)
BR (1) BRPI0514351A2 (fr)
CA (1) CA2578098A1 (fr)
EA (1) EA011407B1 (fr)
EC (1) ECSP077249A (fr)
IL (1) IL181302A0 (fr)
MX (1) MX2007001854A (fr)
NO (1) NO20070752L (fr)
NZ (1) NZ553649A (fr)
PE (1) PE20060424A1 (fr)
TW (1) TWI370131B (fr)
UA (1) UA87865C2 (fr)
WO (1) WO2006018222A1 (fr)

Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6861422B2 (en) * 2003-02-26 2005-03-01 Boehringer Ingelheim Pharma Gmbh & Co. Kg Dihydropteridinones, processes for preparing them and their use as pharmaceutical compositions
US20040219338A1 (en) * 2003-05-01 2004-11-04 Hebrink Timothy J. Materials, configurations, and methods for reducing warpage in optical films
DE102004029784A1 (de) * 2004-06-21 2006-01-05 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue 2-Benzylaminodihydropteridinone, Verfahren zur deren Herstellung und deren Verwendung als Arzneimittel
DE102004033670A1 (de) * 2004-07-09 2006-02-02 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Pyridodihydropyrazinone, Verfahren zu Ihrer Herstellung und Ihre Verwendung als Arzneimittel
US7759485B2 (en) * 2004-08-14 2010-07-20 Boehringer Ingelheim International Gmbh Process for the manufacture of dihydropteridinones
US7728134B2 (en) 2004-08-14 2010-06-01 Boehringer Ingelheim International Gmbh Hydrates and polymorphs of 4[[(7R)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-6-oxo-2-pteridinyl]amino]-3-methoxy-N-(1-methyl-4-piperidinyl)-benzamide, process for their manufacture and their use as medicament
US20060074088A1 (en) 2004-08-14 2006-04-06 Boehringer Ingelheim International Gmbh Dihydropteridinones for the treatment of cancer diseases
US20060058311A1 (en) 2004-08-14 2006-03-16 Boehringer Ingelheim International Gmbh Combinations for the treatment of diseases involving cell proliferation
US20060035903A1 (en) * 2004-08-14 2006-02-16 Boehringer Ingelheim International Gmbh Storage stable perfusion solution for dihydropteridinones
EP1632493A1 (fr) * 2004-08-25 2006-03-08 Boehringer Ingelheim Pharma GmbH & Co.KG Dérivés de dihydropteridine, méthodes de préparation et utilisation en tant que médicament
EP1630163A1 (fr) * 2004-08-25 2006-03-01 Boehringer Ingelheim Pharma GmbH & Co.KG Dihydropteridinones, procédés de préparation et leur utilisation en tant que médicaments
DE102004058337A1 (de) * 2004-12-02 2006-06-14 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verfahren zur Herstellung von annelierten Piperazin-2-on Derivaten
US7439358B2 (en) * 2006-02-08 2008-10-21 Boehringer Ingelheim International Gmbh Specific salt, anhydrous and crystalline form of a dihydropteridione derivative
TW200808325A (en) * 2006-07-06 2008-02-16 Astrazeneca Ab Novel compounds
WO2008009909A1 (fr) * 2006-07-17 2008-01-24 Astrazeneca Ab Ptéridimones en tant que modulateurs de la kinase de type polo
EP2073807A1 (fr) 2006-10-12 2009-07-01 Astex Therapeutics Limited Combinaisons pharmaceutiques
JP5528806B2 (ja) 2006-10-12 2014-06-25 アステックス、セラピューティックス、リミテッド 複合薬剤
EP2102210B1 (fr) 2006-12-14 2011-02-09 Vertex Pharmceuticals Incorporated Composés utilisables en tant qu'inhibiteurs de protéines kinases
JP5261487B2 (ja) * 2007-08-03 2013-08-14 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング ジヒドロプテリジノン誘導体の結晶形
CA2695753A1 (fr) * 2007-08-15 2009-02-19 Vertex Pharmaceuticals Incorporated Composes utilises comme inhibiteurs de proteines kinases
EP2100894A1 (fr) 2008-03-12 2009-09-16 4Sc Ag Pyridopyrimidinones utilisés comme inhibiteurs de la kinase de type Plk1 (polo-like kinase)
AU2009271658B2 (en) * 2008-06-23 2014-04-10 Vertex Pharmaceuticals Incorporated Protein kinase inhibitors
CN102020643A (zh) 2009-09-22 2011-04-20 上海恒瑞医药有限公司 二氢喋啶酮类衍生物、其制备方法及其在医药上的应用
JP2013515734A (ja) * 2009-12-23 2013-05-09 エラン ファーマシューティカルズ，インコーポレイテッド ポロ様キナーゼの阻害薬としてのプテリジノン
US8546566B2 (en) 2010-10-12 2013-10-01 Boehringer Ingelheim International Gmbh Process for manufacturing dihydropteridinones and intermediates thereof
US9358233B2 (en) 2010-11-29 2016-06-07 Boehringer Ingelheim International Gmbh Method for treating acute myeloid leukemia
US9370535B2 (en) 2011-05-17 2016-06-21 Boehringer Ingelheim International Gmbh Method for treatment of advanced solid tumors
RU2016105108A (ru) 2013-07-25 2017-08-30 Дана-Фарбер Кэнсер Инститьют, Инк. Ингибиторы факторов транскрипции и их применение
JP2016525532A (ja) 2013-07-26 2016-08-25 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 骨髄異形成症候群の処置
JP2017504651A (ja) 2014-01-31 2017-02-09 ダナ−ファーバー キャンサー インスティテュート， インコーポレイテッド ジアゼパン誘導体の使用
CN105939607A (zh) * 2014-01-31 2016-09-14 达纳-法伯癌症研究所股份有限公司 二氢蝶啶酮衍生物及其用途
KR20160115953A (ko) 2014-01-31 2016-10-06 다나-파버 캔서 인스티튜트 인크. 디아미노피리미딘 벤젠술폰 유도체 및 그의 용도
CA2955074A1 (fr) 2014-08-08 2016-02-11 Dana-Farber Cancer Institute, Inc. Derives de diazepane et leurs utilisations
US9867831B2 (en) 2014-10-01 2018-01-16 Boehringer Ingelheim International Gmbh Combination treatment of acute myeloid leukemia and myelodysplastic syndrome
EP3307728A4 (fr) 2015-06-12 2019-07-17 Dana Farber Cancer Institute, Inc. Thérapie d'association utilisant des inhibiteurs de transcription et des inhibiteurs de kinases
CA2996974A1 (fr) 2015-09-11 2017-03-16 Dana-Farber Cancer Institute, Inc. Cyano-thienotriazoloazepines et leurs utilisations
PE20181086A1 (es) 2015-09-11 2018-07-05 Dana Farber Cancer Inst Inc Acetamida tienotrizolodiazepinas y usos de las mismas
EP3380100A4 (fr) 2015-11-25 2019-10-02 Dana-Farber Cancer Institute, Inc. Inhibiteurs de bromodomaines bivalents et leurs utilisations

Family Cites Families (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL8303657A (nl) 1983-10-24 1985-05-17 Pharmachemie Bv Voor injectie geschikte, stabiele, waterige, zoutzuur bevattende oplossing van cisplatine, alsmede werkwijze ter bereiding daarvan.
DE3537761A1 (de) * 1985-10-24 1987-04-30 Bayer Ag Infusionsloesungen der 1-cyclopropyl-6-fluor-1,4-dihydro-4-oxo-7- (1-piperazinyl)-chinolin-3-carbonsaeure
EP0347146B1 (fr) 1988-06-16 1993-09-01 Smith Kline & French Laboratories Limited Dérivés de pyrimidine condensés, procédé et intermédiaires pour leur préparation et compositions pharmaceutiques les contenant
FR2645152B1 (fr) * 1989-03-30 1991-05-31 Lipha 3h-pteridinones-4, procedes de preparation et medicaments les contenant
US5043270A (en) 1989-03-31 1991-08-27 The Board Of Trustees Of The Leland Stanford Junior University Intronic overexpression vectors
CA2029651C (fr) 1989-11-17 2000-06-06 David D. Davey Pteridinones tricycliques et procede pour leur preparation
US5198547A (en) 1992-03-16 1993-03-30 South Alabama Medical Science Foundation, Usa Process for N5-formylating tetrahydropteridines
TW274550B (fr) * 1992-09-26 1996-04-21 Hoechst Ag
EP1195372A1 (fr) 1994-04-18 2002-04-10 Mitsubishi Pharma Corporation Dérivés benzamide substitués avec un N-hétérocycle présentant des propriétés antihypertensives
GB9418499D0 (en) * 1994-09-14 1994-11-02 Ciba Geigy Ag Process for producing n-methylated organic pigments
CO4410191A1 (es) 1994-09-19 1997-01-09 Lilly Co Eli SINTESIS DE 3-[4-(2-AMINOETOXI)BENZOIL]-2-ARIL-6- HIDROXIBENZO [b] TIOFENOS
IL117923A (en) 1995-05-03 2000-06-01 Warner Lambert Co Anti-cancer pharmaceutical compositions containing polysubstituted pyrido¬2,3-d¾pyrimidine derivatives and certain such novel compounds
BR9609083A (pt) 1995-05-19 1999-02-02 Novartis Ag Processo para a hidrogenação catalítica de compostos nitro aromáticos
US5698556A (en) * 1995-06-07 1997-12-16 Chan; Carcy L. Methotrexate analogs and methods of using same
JP3887836B2 (ja) * 1995-12-21 2007-02-28 東ソー株式会社 Ｎ−メチルイミダゾール類の製造法
ID21924A (id) 1996-09-23 1999-08-12 Lilly Co Eli Olanzapin dihidrat d
IL140868A0 (en) * 1998-08-11 2002-02-10 Pfizer Prod Inc Substituted 1,8-naphthyridin-4(1h)-ones as phosphodiesterase 4 inhibitors
BR0013952A (pt) 1999-09-15 2002-05-14 Warner Lambert Co Pteridinonas como inibidores de cinase
GB2359551A (en) 2000-02-23 2001-08-29 Astrazeneca Uk Ltd Pharmaceutically active pyrimidine derivatives
HUP0300136A2 (en) 2000-03-06 2003-05-28 Warner Lambert Co 5-alkylpyrido [2,3-d]pyrimidines tyrosine kinase inhibitors, pharmaceutical compositions containing them and their use
DE10018783A1 (de) 2000-04-15 2001-10-25 Fresenius Kabi De Gmbh Lagerstabile Infusionslösung des Ciprofloxacins mit verringertem Säuregehalt
US20020183292A1 (en) * 2000-10-31 2002-12-05 Michel Pairet Pharmaceutical compositions based on anticholinergics and corticosteroids
DE10058119A1 (de) * 2000-11-22 2002-05-23 Bayer Ag Pepinotan-Kit
US6756374B2 (en) 2001-01-22 2004-06-29 Hoffmann-La Roche Inc. Diaminothiazoles having antiproliferative activity
WO2002076954A1 (fr) 2001-03-23 2002-10-03 Smithkline Beecham Corporation Composes utiles en tant qu'inhibiteurs de kinase pour le traitement de maladies hyperproliferantes
WO2002076985A1 (fr) 2001-03-23 2002-10-03 Smithkline Beecham Corporation Composes utiles en tant qu'inhibiteurs de kinases pour le traitement des maladies hyperproliferatives
US20030055026A1 (en) * 2001-04-17 2003-03-20 Dey L.P. Formoterol/steroid bronchodilating compositions and methods of use thereof
US6806272B2 (en) * 2001-09-04 2004-10-19 Boehringer Ingelheim Pharma Kg Dihydropteridinones, processes for preparing them and their use as pharmaceutical compositions
JP3876254B2 (ja) * 2001-09-04 2007-01-31 ベーリンガー インゲルハイム ファルマ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト 新規なジヒドロプテリジノン、その製造方法及びその医薬組成物としての使用
EP1908463B1 (fr) * 2001-12-14 2011-09-28 Merck Serono SA Procédés d'induction d'ovulation utilisant un modulateur de niveau CAMP sans polypeptide
RU2004135533A (ru) * 2002-05-03 2005-07-20 Шеринг Акциенгезельшафт (De) Тиазолидиноны и их применение в качестве ингибиторов polo- подобной киназы
FR2843114B1 (fr) * 2002-08-01 2004-09-10 Poudres & Explosifs Ste Nale Procede de monomethylation d'heterocycles azotes
PL375532A1 (en) 2002-08-08 2005-11-28 Smithkline Beecham Corporation Benzimidazol-1-yl-thiophene compounds for the treatment of cancer
US6861422B2 (en) * 2003-02-26 2005-03-01 Boehringer Ingelheim Pharma Gmbh & Co. Kg Dihydropteridinones, processes for preparing them and their use as pharmaceutical compositions
CA2517020C (fr) 2003-02-26 2012-06-26 Boehringer Ingelheim Pharma Gmbh & Co. Kg Dihydropteridinones, prodede de production et utilisation de ces dernieres comme medicaments
BRPI0408779A (pt) 2003-03-26 2006-04-04 Wyeth Corp uso de composições, composição imunogênica e kit
EP1617820B1 (fr) 2003-04-14 2018-03-21 Vectura Limited Inhalateurs a poudre seche et formulations de poudres seches destinees a augmenter l'efficacite de dosage
DE102004002557A1 (de) * 2004-01-17 2005-08-04 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verwendung von substituierten Pyrimido(5,4-d)pyrimidinen zur Behandlung von Atemwegserkrankungen
JP2007517828A (ja) * 2004-01-17 2007-07-05 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 気道の疾患を治療するための置換プテリジンの使用
DE102004029784A1 (de) * 2004-06-21 2006-01-05 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue 2-Benzylaminodihydropteridinone, Verfahren zur deren Herstellung und deren Verwendung als Arzneimittel
DE102004033670A1 (de) 2004-07-09 2006-02-02 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Pyridodihydropyrazinone, Verfahren zu Ihrer Herstellung und Ihre Verwendung als Arzneimittel
DE102004034623A1 (de) * 2004-07-16 2006-02-02 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue 6-Formyl-tetrahydropteridine, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
US20060058311A1 (en) * 2004-08-14 2006-03-16 Boehringer Ingelheim International Gmbh Combinations for the treatment of diseases involving cell proliferation
US7759485B2 (en) * 2004-08-14 2010-07-20 Boehringer Ingelheim International Gmbh Process for the manufacture of dihydropteridinones
US7728134B2 (en) 2004-08-14 2010-06-01 Boehringer Ingelheim International Gmbh Hydrates and polymorphs of 4[[(7R)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-6-oxo-2-pteridinyl]amino]-3-methoxy-N-(1-methyl-4-piperidinyl)-benzamide, process for their manufacture and their use as medicament
US20060035903A1 (en) * 2004-08-14 2006-02-16 Boehringer Ingelheim International Gmbh Storage stable perfusion solution for dihydropteridinones
US20060074088A1 (en) 2004-08-14 2006-04-06 Boehringer Ingelheim International Gmbh Dihydropteridinones for the treatment of cancer diseases
EP1632493A1 (fr) * 2004-08-25 2006-03-08 Boehringer Ingelheim Pharma GmbH & Co.KG Dérivés de dihydropteridine, méthodes de préparation et utilisation en tant que médicament
EP1630163A1 (fr) * 2004-08-25 2006-03-01 Boehringer Ingelheim Pharma GmbH & Co.KG Dihydropteridinones, procédés de préparation et leur utilisation en tant que médicaments
EP1786817A1 (fr) * 2004-08-26 2007-05-23 Boehringer Ingelheim International GmbH Pteridinones en tant que inhibiteurs de plk (polo like kinase)
WO2006021548A1 (fr) * 2004-08-27 2006-03-02 Boehringer Ingelheim International Gmbh Dihydropteridinones, leur procede de production, et leur utilisation en tant que medicaments
DE102004058337A1 (de) 2004-12-02 2006-06-14 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verfahren zur Herstellung von annelierten Piperazin-2-on Derivaten
CA2617589A1 (fr) 2005-08-03 2007-02-08 Boehringer Ingelheim International Gmbh Dihydropteridinones utilisees pour le traitement de maladies respiratoires
US7439358B2 (en) 2006-02-08 2008-10-21 Boehringer Ingelheim International Gmbh Specific salt, anhydrous and crystalline form of a dihydropteridione derivative
EP1994002A1 (fr) 2006-03-07 2008-11-26 AstraZeneca AB Dérivés de pipéridine, leur procédé de synthèse, leur emploi en tant qu'agents thérapeutiques et les compositions pharmaceutiques les incluant
JP5261487B2 (ja) 2007-08-03 2013-08-14 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング ジヒドロプテリジノン誘導体の結晶形

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2006018222A1 *

Also Published As

Publication number Publication date
AU2005274340A1 (en) 2006-02-23
PE20060424A1 (es) 2006-06-09
CA2578098A1 (fr) 2006-02-23
AU2005274340B2 (en) 2012-04-05
JP2008509953A (ja) 2008-04-03
UA87865C2 (en) 2009-08-25
US20060035902A1 (en) 2006-02-16
US7728134B2 (en) 2010-06-01
IL181302A0 (en) 2007-07-04
US20090318457A1 (en) 2009-12-24
EA200700387A1 (ru) 2007-08-31
BRPI0514351A2 (pt) 2012-10-30
WO2006018222A8 (fr) 2006-06-15
NO20070752L (no) 2007-05-10
EA011407B1 (ru) 2009-02-27
US8034816B2 (en) 2011-10-11
TWI370131B (en) 2012-08-11
TW200619220A (en) 2006-06-16
AR052404A1 (es) 2007-03-21
CN101006090A (zh) 2007-07-25
MX2007001854A (es) 2007-03-28
US8202867B2 (en) 2012-06-19
US20090298840A1 (en) 2009-12-03
WO2006018222A1 (fr) 2006-02-23
NZ553649A (en) 2010-11-26
KR20070050967A (ko) 2007-05-16
KR101221864B1 (ko) 2013-01-14
ECSP077249A (es) 2007-03-29

Similar Documents

Publication Publication Date Title
EP1778691A1 (fr) Nouveaux hydrates et polymorphes du 4-[[(7r)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-4-6-oxo-2-piperidinyl]amino]-3-methoxy-n-(1-methyl-4-piperidinyl)-benzamide, son procede de production et son utilisation comme medicament
EP0222191B1 (fr) Dérivés de benzyl-4 (2H)-phtalazinone-1
DE60202958T2 (de) Stabiles polymorph von flibanserin, industrielles verfahren zu dessen herstellung und dessen verwendung zur herstellung von medikamenten
DE2540633A1 (de) Neue quartaere n-beta-substituierte benzilsaeure-n-alkyl-nortropinester und verfahren zu deren herstellung
DE29724281U1 (de) 4-Phenylpiperidin-Verbindungen
AT7109U2 (de) Verfahren zur herstellung von amlodipinmaleat
DE3336024A1 (de) 4-amino-l-benzyl-pyrrolidinone und ihre saeureadditionssalze, verfahren zu ihrer herstellung und arzneimittel
EP0101574B1 (fr) 1-aminoalkyl-1,2,3,4-tétrahydro-beta-carbolines, leur préparation et leur utilisation comme médicaments
DE68910211T2 (de) Estramustin-ester.
DE3586411T2 (de) Dopamin-antagoniste.
CH637653A5 (de) In 11-stellung substituierte 5,11-dihydro-6h-pyrido(2,3-b)(1,4)benzodiazepin-6-one, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel.
DE19945594A1 (de) Substituierte Piperazinderivate, ihre Herstellung und ihre Verwendung als Arzneimittel
WO1979000426A1 (fr) Diamine cyclique n, n'-disubstituee et procede pour sa preparation
DE3634942A1 (de) Neue 4-benzyl-1-(2h)-phthalazinon-derivate
EP0233483A2 (fr) Pyrrolo[1,2-a][4,1]benzoxazépines, procédé pour leur préparation, compositions pharmaceutiques contenant ces composés et application therapeutique
DE2724478A1 (de) Neue, in 11-stellung substituierte 5,11-dihydro-6h-pyrido eckige klammer auf 2,3-b eckige klammer zu eckige klammer auf 1,4 eckige klammer zu benzodiazepin-6-one, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
EP0117531B1 (fr) N-(trifluorométhyl-3-phényl)-N'-propargyl-pipérazine, son procédé de préparation et son utilisation
DE2644121A1 (de) Neue pyridobenzodiazepinone, verfahren zu ihrer herstellung und diese enthaltende arzneimittel
DE3423003A1 (de) Benzo(c)(1,8)naphthyridine, verfahren zu ihrer herstellung und ihre verwendung sowie diese verbindungen enthaltende zubereitungen
DE2012667C3 (de) 3- (4-substituierte-1-Piperazinyl)-carbonylmethyl-2-benzothiazolinone und ihre Säureadditionssalze, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende pharamazeutische Präparate
DE69500156T2 (de) Imidazopyridin-Derivate und Verfahren zu ihrer Herstellung
DE2402989C3 (de) Neue Benzylamine, sie enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
EP0000727A1 (fr) 3-(4-(1,3-Diazacycloalcen-2-yl)-phenyl)-1,2-benzisothiazole, procédé pour leur préparation et médicaments les contenant.
AT414305B (de) Neue (3aalpha,8balpha)-1,2,3,3a,4,8b-hexahydro- pyrrolo(2',3':3,4) cyclopenta(1,2-b)- pyridin-derivate, verfahren zu ihrer herstellung und ihre verwendung
AT387964B (de) Verfahren zur herstellung von neuen piperazinderivaten und von enantiomeren oder diastereomeren davon

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20070314

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: BA HR YU

RAX Requested extension states of the european patent have changed

Extension state: YU

Payment date: 20070314

Extension state: HR

Payment date: 20070314

Extension state: BA

Payment date: 20070314

17Q First examination report despatched

Effective date: 20080813

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: BOEHRINGER INGELHEIM PHARMA GMBH & CO. KG

Owner name: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

INTG Intention to grant announced

Effective date: 20130430

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20130911