CA2876306C - Deuterated derivatives of ruxolitinib - Google Patents
Deuterated derivatives of ruxolitinib Download PDFInfo
- Publication number
- CA2876306C CA2876306C CA2876306A CA2876306A CA2876306C CA 2876306 C CA2876306 C CA 2876306C CA 2876306 A CA2876306 A CA 2876306A CA 2876306 A CA2876306 A CA 2876306A CA 2876306 C CA2876306 C CA 2876306C
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- CA
- Canada
- Prior art keywords
- compound
- salt
- deuterium
- hydrogen
- myelofibrosis
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims abstract description 186
- 150000003839 salts Chemical class 0.000 claims abstract description 62
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- 229910052805 deuterium Inorganic materials 0.000 claims description 111
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 109
- 239000003814 drug Substances 0.000 claims description 87
- 229910052739 hydrogen Inorganic materials 0.000 claims description 82
- 239000001257 hydrogen Substances 0.000 claims description 82
- 239000000203 mixture Substances 0.000 claims description 55
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 53
- 229940124597 therapeutic agent Drugs 0.000 claims description 38
- 206010028537 myelofibrosis Diseases 0.000 claims description 36
- 238000002360 preparation method Methods 0.000 claims description 22
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- 230000000694 effects Effects 0.000 claims description 19
- 238000010348 incorporation Methods 0.000 claims description 17
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- 208000032027 Essential Thrombocythemia Diseases 0.000 claims description 15
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- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 7
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- HFNKQEVNSGCOJV-OAHLLOKOSA-N ruxolitinib Chemical class C1([C@@H](CC#N)N2N=CC(=C2)C=2C=3C=CNC=3N=CN=2)CCCC1 HFNKQEVNSGCOJV-OAHLLOKOSA-N 0.000 description 9
- 238000000926 separation method Methods 0.000 description 9
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
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- 239000012317 TBTU Substances 0.000 description 6
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 6
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- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
- A61K31/5685—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone having an oxo group in position 17, e.g. androsterone
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- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
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| PCT/US2013/045919 WO2013188783A1 (en) | 2012-06-15 | 2013-06-14 | Deuterated derivatives of ruxolitinib |
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| JP5858484B2 (ja) | 2010-03-10 | 2016-02-10 | インサイト・ホールディングス・コーポレイションＩｎｃｙｔｅ Ｈｏｌｄｉｎｇｓ Ｃｏｒｐｏｒａｔｉｏｎ | Ｊａｋ１阻害剤としてのピペリジン−４−イルアゼチジン誘導体 |
| US8691807B2 (en) | 2011-06-20 | 2014-04-08 | Incyte Corporation | Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors |
| EP2861600A1 (en) | 2012-06-15 | 2015-04-22 | Concert Pharmaceuticals Inc. | Deuterated derivatives of ruxolitinib |
| CR20190073A (es) | 2012-11-15 | 2019-04-25 | Incyte Holdings Corp | FORMAS DE DOSIFICACIÓN DE RUXOLITINIB DE LIBERACIÓN SOTENIDA (Divisional 2015-265) |
| US9655854B2 (en) | 2013-08-07 | 2017-05-23 | Incyte Corporation | Sustained release dosage forms for a JAK1 inhibitor |
| WO2015184087A2 (en) * | 2014-05-28 | 2015-12-03 | Institute For Myeloma & Bone Cancer Research | Anti-cancer effects of jak2 inhibitors in combination with thalidomide derivatives and glucocorticoids |
| WO2016196961A1 (en) | 2015-06-03 | 2016-12-08 | Uwm Research Foundation, Inc. | Ligands selective to alpha 6 subunit-containing gabaa receptors ans their methods of use |
| US11364226B2 (en) | 2017-06-30 | 2022-06-21 | Cinrx Pharma, Llc | Deuterated domperidone compositions, methods, and preparation |
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| KR20250070139A (ko) | 2016-05-04 | 2025-05-20 | 썬 파마슈티칼 인더스트리즈 인코포레이티드 | 중수소화된 jak 저해제를 이용한 탈모 장애의 치료 |
| JP2020502126A (ja) * | 2016-12-14 | 2020-01-23 | プロジェニティ， インコーポレイテッド | 消化管疾病のｊａｋ阻害薬による治療 |
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| US11624751B2 (en) | 2019-03-19 | 2023-04-11 | Incyte Corporation | Biomarkers for vitiligo |
| WO2020210125A1 (en) | 2019-04-10 | 2020-10-15 | University Of Notre Dame Du Lac | Deuterated antimicrobial compounds |
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2013
- 2013-06-14 EP EP13732046.1A patent/EP2861600A1/en not_active Withdrawn
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- 2013-06-14 EA EA201492287A patent/EA201492287A1/ru unknown
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- 2013-06-14 WO PCT/US2013/045919 patent/WO2013188783A1/en active Application Filing
- 2013-06-14 PT PT211563986T patent/PT3882249T/pt unknown
- 2013-06-14 EP EP18188152.5A patent/EP3450434B1/en active Active
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2014
- 2014-12-15 US US14/570,954 patent/US20150197525A1/en not_active Abandoned
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2015
- 2015-05-08 US US14/707,912 patent/US9249149B2/en active Active
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2016
- 2016-10-05 AU AU2016238877A patent/AU2016238877B2/en active Active
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2017
- 2017-03-09 US US15/454,844 patent/US20170239254A1/en not_active Abandoned
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2018
- 2018-11-26 AU AU2018271227A patent/AU2018271227B2/en active Active
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2019
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2020
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2022
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