DK2787998T3 - Krystallinske former af 2-(2-methylaminopyrimidin-4-yl)-1h-indol-5-carboxylsyre-[(s)-1-carbamoyl-2-(phenylpyrimidin-2-ylamino)-ethyl]-amid - Google Patents
Krystallinske former af 2-(2-methylaminopyrimidin-4-yl)-1h-indol-5-carboxylsyre-[(s)-1-carbamoyl-2-(phenylpyrimidin-2-ylamino)-ethyl]-amid Download PDFInfo
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- DK2787998T3 DK2787998T3 DK12794728.1T DK12794728T DK2787998T3 DK 2787998 T3 DK2787998 T3 DK 2787998T3 DK 12794728 T DK12794728 T DK 12794728T DK 2787998 T3 DK2787998 T3 DK 2787998T3
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- DK
- Denmark
- Prior art keywords
- pyrimidin
- amino
- polymorph
- carbamoyl
- indole
- Prior art date
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- XGXNTJHZPBRBHJ-UHFFFAOYSA-N n-phenylpyrimidin-2-amine Chemical compound N=1C=CC=NC=1NC1=CC=CC=C1 XGXNTJHZPBRBHJ-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
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- 238000002953 preparative HPLC Methods 0.000 description 1
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- 235000011803 sesame oil Nutrition 0.000 description 1
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- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000000373 single-crystal X-ray diffraction data Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- MREBZPOCUUKIEW-UHFFFAOYSA-M sodium;2-[2-(methylamino)pyrimidin-4-yl]-1h-indole-5-carboxylate Chemical compound [Na+].CNC1=NC=CC(C=2NC3=CC=C(C=C3C=2)C([O-])=O)=N1 MREBZPOCUUKIEW-UHFFFAOYSA-M 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000002336 sorption--desorption measurement Methods 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
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- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
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- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P35/00—Antineoplastic agents
-
- 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
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Claims (8)
1. Polymorf 1 af 2-(2-methylaminopyrimidin-4-yl)-lH-indol-5- carboxylsyre-[(S)-l-carbamoyl-2-(phenylpyrimidin-2-yl-amino)-ethyl]-amid, som har karakteristiske reflektioner i et røntgenpulverdiffraktogram ved anvendelse af CuK-alfal-stråling i reflektionsmodus ved 2 theta-vinkler (i grader) på 14,9 ± 0,2, 19,4 ± 0,2, 19,7 ± 0,2, 20,0 ± 0,2, 22,3 ± 0,2, 25,0 ± 0,2.
2. Farmaceutisk sammensætning, der omfatter polymorf 1 af 2-(2-methylaminopyrimidin-4-yl)-lH-indol-5-carboxylsyre-[(S)-1-carbamoyl-2-(phenylpyrimidin-2-yl-amino)-ethyl]-amid ifølge krav 1 og et eller flere farmaceutisk acceptable excipienser.
3. Polymorf 1 af 2-(2-methylaminopyrimidin-4-yl)-lH-indol-5-carboxylsyre-[(S)-l-carbamoyl-2-(phenylpyrimidin-2-yl-amino)-ethyl]-amid ifølge krav 1 til anvendelse som et lægmiddel.
4. Polymorf 1 af 2-(2-methylaminopyrimidin-4-yl)-lH-indol-5-carboxylsyre-[(S)-l-carbamoyl-2-(phenylpyrimidin-2-yl-amino)-ethyl]-amid ifølge krav 1 til anvendelse til behandling af en sygdom, hvis forløb inddrager forøget aktivitet af ΙκΒ-kinase.
5. Fremgangsmåde til fremstilling af polymorf 1 af 2 — (2 — methylaminopyrimidin-4-yl)-lH-indol-5-carboxylsyre-[(S)-1-carbamoyl-2-(phenylpyrimidin-2-yl-amino)-ethyl]-amid ifølge krav 1, der omfatter opvarmning af polymorf 2 af 2 —(2 — methylaminopyrimidin-4-yl)-lH-indol-5-carboxylsyre-[ (S)-1-carbamoyl-2-(phenylpyrimidin-2-yl-amino)-ethyl]-amid i en blanding af acetone og vand til en temperatur på 50 til 60 °C, nedkøling af blandingen til 20 til 25 °C og isolering af det fældede faststof.
6. Polymorf 1 af 2-(2-methylaminopyrimidin-4-yl)-lH-indol-5-carboxylsyre-[(S)-l-carbamoyl-2-(phenylpyrimidin-2-yl-amino)-ethyl]-amid ifølge krav 1 til anvendelse til behandling af inflammatorisk, immunologisk eller metabolisme-medieret akut og kronisk arthritis, artropatier, rheumatoid arthritis, degenerative ledsygdomme, spondyloser, diabetes type II, inflammatorisk tarmsygdom, tab af brusk efter ledtraume eller en relativ lang periode med ledimmobilisering efter menisk-eller patellaskader eller ligamentrupturer, sygdomme i bindevævet, myalgier og forstyrrelser i knoglemetabolisme.
7. Polymorf 1 af 2-(2-methylaminopyrimidin-4-yl)-lH-indol-5-carboxylsyre-[(S)-l-carbamoyl-2-(phenylpyrimidin-2-yl-amino)-ethyl]-amid ifølge krav 1 til anvendelse til behandling af smerter, herunder akutte smerter og kroniske smerter.
8. Polymorf 1 af 2-(2-methylaminopyrimidin-4-yl)-lH-indol-5-carboxylsyre-[(S)-l-carbamoyl-2-(phenylpyrimidin-2-yl-amino)-ethyl]-amid ifølge krav 1 til anvendelse til behandling af kroniske smerter ifølge krav 7, hvor de kroniske smerter er udvalgt blandt kroniske muskel- og knoglesygdomme, smerter i forbindelse med menstruationsblødning, smerter i forbindelse med osteoarthritis eller rheumatoid arthritis, smerter i forbindelse med intestinal inflammation, smerter i forbindelse med hjertemuskelinflammation, smerter i forbindelse med multipel sklerose, smerter i forbindelse med neuritis, smerter i forbindelse med karcinomer og sarkomer, smerter i forbindelse med AIDS, smerter i forbindelse med kemoterapi, amputationssmerter, trigeminusneuralgi, hovedpine og neuropatiske smerter.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11306618 | 2011-12-06 | ||
| PCT/EP2012/074339 WO2013083553A1 (en) | 2011-12-06 | 2012-12-04 | Crystalline forms of 2-(2-methylamino-pyrimidin-4-yl)-1h-indole-5-carboxylic acid [(s)-1-carbamoyl-2-(phenyl-pyrimidin-2-yl-amino)-ethyl]-amide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2787998T3 true DK2787998T3 (da) | 2017-02-06 |
Family
ID=47278314
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK12794728.1T DK2787998T3 (da) | 2011-12-06 | 2012-12-04 | Krystallinske former af 2-(2-methylaminopyrimidin-4-yl)-1h-indol-5-carboxylsyre-[(s)-1-carbamoyl-2-(phenylpyrimidin-2-ylamino)-ethyl]-amid |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US9067918B2 (da) |
| EP (1) | EP2787998B1 (da) |
| JP (1) | JP6078551B2 (da) |
| KR (1) | KR20140103968A (da) |
| CN (1) | CN104105483B (da) |
| AR (1) | AR089078A1 (da) |
| AU (1) | AU2012347393B2 (da) |
| BR (1) | BR112014013723A2 (da) |
| CA (1) | CA2856607C (da) |
| CY (1) | CY1118615T1 (da) |
| DK (1) | DK2787998T3 (da) |
| ES (1) | ES2612217T3 (da) |
| HR (1) | HRP20170092T1 (da) |
| HU (1) | HUE031525T2 (da) |
| IL (1) | IL232693B (da) |
| LT (1) | LT2787998T (da) |
| MX (1) | MX351994B (da) |
| PL (1) | PL2787998T3 (da) |
| PT (1) | PT2787998T (da) |
| RU (1) | RU2631320C2 (da) |
| SG (1) | SG11201402461RA (da) |
| SI (1) | SI2787998T1 (da) |
| UY (1) | UY34497A (da) |
| WO (1) | WO2013083553A1 (da) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2805705B1 (en) | 2013-05-23 | 2016-11-09 | IP Gesellschaft für Management mbH | Packaging with one or more administration units comprising a sodium salt of (R)-3-[6-amino-pyridin-3-yl]-2-(1-cyclohexyl-1 H-imidazol-4-yl)-propionic acid |
| EP3164131B1 (en) * | 2014-07-03 | 2018-08-22 | Sanofi | 2-(2-methylamino-pyrimidin-4-yl)-1h-indole-5-carboxylic acid [(s)-1-carbamoyl-2-(phenyl-pyrimidin-2-yl-amino)-ethyl]-amide for use in the treatment of pain associated to osteoarthritis |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10237723A1 (de) | 2002-08-17 | 2004-07-08 | Aventis Pharma Deutschland Gmbh | Verwendung von IKappaB-Kinase Inhibitoren in der Schmerztherapie |
| US7462638B2 (en) | 2002-08-17 | 2008-12-09 | Sanofi-Aventis Deutschland Gmbh | Use of IκB-kinase inhibitors in pain therapy |
| DE10237722A1 (de) * | 2002-08-17 | 2004-08-19 | Aventis Pharma Deutschland Gmbh | Indol- oder Benzimidazolderivate zur Modulation der IKappaB-Kinase |
| WO2006076318A1 (en) * | 2005-01-12 | 2006-07-20 | Aventis Pharmaceuticals Inc. | Monopotassium salt of an ikb kinase inhibitor |
| DE102005025225A1 (de) | 2005-06-01 | 2006-12-07 | Sanofi-Aventis Deutschland Gmbh | Verfahren zur Herstellung von 2-(2-Amino-pyrimidin-4-yl)-1H-indol-5-carbonsäure-derivaten |
| WO2010102968A1 (en) * | 2009-03-10 | 2010-09-16 | Glaxo Group Limited | Indole derivatives as ikk2 inhibitors |
| BR112013002985A2 (pt) | 2010-08-12 | 2017-11-07 | Sanofi Sa | processo para a preparação de formas enantiométrica de derivados de ácido 2,3-diaminopropiônico |
| MA34548B1 (fr) * | 2010-09-30 | 2013-09-02 | Boehringer Ingelheim Int | Formes solides d'un inhibiteur puissant du vhc |
-
2012
- 2012-12-04 CA CA2856607A patent/CA2856607C/en active Active
- 2012-12-04 KR KR1020147016860A patent/KR20140103968A/ko not_active Ceased
- 2012-12-04 DK DK12794728.1T patent/DK2787998T3/da active
- 2012-12-04 SI SI201230840A patent/SI2787998T1/sl unknown
- 2012-12-04 BR BR112014013723A patent/BR112014013723A2/pt not_active Application Discontinuation
- 2012-12-04 HR HRP20170092TT patent/HRP20170092T1/hr unknown
- 2012-12-04 AR ARP120104550A patent/AR089078A1/es unknown
- 2012-12-04 WO PCT/EP2012/074339 patent/WO2013083553A1/en not_active Ceased
- 2012-12-04 PT PT127947281T patent/PT2787998T/pt unknown
- 2012-12-04 MX MX2014006838A patent/MX351994B/es active IP Right Grant
- 2012-12-04 SG SG11201402461RA patent/SG11201402461RA/en unknown
- 2012-12-04 CN CN201280068949.4A patent/CN104105483B/zh active Active
- 2012-12-04 LT LTEP12794728.1T patent/LT2787998T/lt unknown
- 2012-12-04 US US14/363,146 patent/US9067918B2/en active Active
- 2012-12-04 ES ES12794728.1T patent/ES2612217T3/es active Active
- 2012-12-04 HU HUE12794728A patent/HUE031525T2/en unknown
- 2012-12-04 EP EP12794728.1A patent/EP2787998B1/en active Active
- 2012-12-04 AU AU2012347393A patent/AU2012347393B2/en active Active
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- 2012-12-04 RU RU2014127478A patent/RU2631320C2/ru active
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- 2014-05-19 IL IL232693A patent/IL232693B/en active IP Right Grant
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Also Published As
| Publication number | Publication date |
|---|---|
| KR20140103968A (ko) | 2014-08-27 |
| IL232693B (en) | 2018-07-31 |
| CY1118615T1 (el) | 2017-07-12 |
| CA2856607A1 (en) | 2013-06-13 |
| CN104105483B (zh) | 2017-03-22 |
| SG11201402461RA (en) | 2014-08-28 |
| AU2012347393A1 (en) | 2014-06-19 |
| JP2015500255A (ja) | 2015-01-05 |
| AR089078A1 (es) | 2014-07-30 |
| PL2787998T3 (pl) | 2017-04-28 |
| US20140336211A1 (en) | 2014-11-13 |
| SI2787998T1 (sl) | 2017-02-28 |
| MX351994B (es) | 2017-11-06 |
| RU2631320C2 (ru) | 2017-09-21 |
| LT2787998T (lt) | 2017-02-10 |
| AU2012347393B2 (en) | 2017-06-08 |
| EP2787998B1 (en) | 2016-11-09 |
| BR112014013723A8 (pt) | 2017-06-13 |
| MX2014006838A (es) | 2014-11-25 |
| CN104105483A (zh) | 2014-10-15 |
| UY34497A (es) | 2013-07-31 |
| BR112014013723A2 (pt) | 2017-06-13 |
| PT2787998T (pt) | 2017-01-03 |
| ES2612217T3 (es) | 2017-05-12 |
| CA2856607C (en) | 2020-03-10 |
| EP2787998A1 (en) | 2014-10-15 |
| RU2014127478A (ru) | 2016-02-10 |
| US9067918B2 (en) | 2015-06-30 |
| JP6078551B2 (ja) | 2017-02-08 |
| IL232693A0 (en) | 2014-07-31 |
| WO2013083553A1 (en) | 2013-06-13 |
| HRP20170092T1 (hr) | 2017-03-24 |
| HUE031525T2 (en) | 2017-07-28 |
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