NO170579B - Analogifremgangsmaate for fremstilling av den terapeutisk aktive d-enantiomeren av medetomidin - Google Patents
Analogifremgangsmaate for fremstilling av den terapeutisk aktive d-enantiomeren av medetomidin Download PDFInfo
- Publication number
- NO170579B NO170579B NO883155A NO883155A NO170579B NO 170579 B NO170579 B NO 170579B NO 883155 A NO883155 A NO 883155A NO 883155 A NO883155 A NO 883155A NO 170579 B NO170579 B NO 170579B
- Authority
- NO
- Norway
- Prior art keywords
- pyrone
- dihydro
- methoxy
- medetomidine
- enantiomer
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 6
- HRLIOXLXPOHXTA-UHFFFAOYSA-N medetomidine Chemical compound C=1C=CC(C)=C(C)C=1C(C)C1=CN=C[N]1 HRLIOXLXPOHXTA-UHFFFAOYSA-N 0.000 title abstract 2
- 229960002140 medetomidine Drugs 0.000 title abstract 2
- RSIWXFIBHXYNFM-NSHDSACASA-N Dihydromethysticin Chemical compound C1C(OC)=CC(=O)O[C@H]1CCC1=CC=C(OCO2)C2=C1 RSIWXFIBHXYNFM-NSHDSACASA-N 0.000 claims description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
- ZPSJGADGUYYRKE-UHFFFAOYSA-N 2H-pyran-2-one Chemical compound O=C1C=CC=CO1 ZPSJGADGUYYRKE-UHFFFAOYSA-N 0.000 claims description 6
- VOOYTQRREPYRIW-LBPRGKRZSA-N Dihydrokavain Chemical compound C1C(OC)=CC(=O)O[C@H]1CCC1=CC=CC=C1 VOOYTQRREPYRIW-LBPRGKRZSA-N 0.000 claims description 5
- VOOYTQRREPYRIW-UHFFFAOYSA-N dihydrokawain Natural products C1C(OC)=CC(=O)OC1CCC1=CC=CC=C1 VOOYTQRREPYRIW-UHFFFAOYSA-N 0.000 claims description 5
- 238000005984 hydrogenation reaction Methods 0.000 claims description 5
- 229910052763 palladium Inorganic materials 0.000 claims description 4
- 230000036571 hydration Effects 0.000 claims description 3
- 238000006703 hydration reaction Methods 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 230000000977 initiatory effect Effects 0.000 claims 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 abstract 1
- 230000003389 potentiating effect Effects 0.000 abstract 1
- 239000000018 receptor agonist Substances 0.000 abstract 1
- 229940044601 receptor agonist Drugs 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- XEAQIWGXBXCYFX-GUOLPTJISA-N Kawain Chemical compound C1C(OC)=CC(=O)O[C@H]1\C=C\C1=CC=CC=C1 XEAQIWGXBXCYFX-GUOLPTJISA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- GTEXBOVBADJOQH-FWEMWIAWSA-N Methysticin Chemical compound C1C(OC)=CC(=O)O[C@H]1\C=C\C1=CC=C(OCO2)C2=C1 GTEXBOVBADJOQH-FWEMWIAWSA-N 0.000 description 2
- CGGHGWCWEAXPLK-CYBMUJFWSA-N Methysticin Natural products CC(=O)C1=CC(=O)O[C@@H](C1)C=Cc2ccc3OCOc3c2 CGGHGWCWEAXPLK-CYBMUJFWSA-N 0.000 description 2
- XEAQIWGXBXCYFX-UHFFFAOYSA-N dl-kavain Natural products C1C(OC)=CC(=O)OC1C=CC1=CC=CC=C1 XEAQIWGXBXCYFX-UHFFFAOYSA-N 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000001741 anti-phlogistic effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/58—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P9/06—Antiarrhythmics
-
- 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
- A61P9/12—Antihypertensives
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Optical Fibers, Optical Fiber Cores, And Optical Fiber Bundles (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Optical Record Carriers And Manufacture Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Saccharide Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Photoreceptors In Electrophotography (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Fremgangsmåte til fremstilling av dihydrometysticin eller dihydrokawain.
Oppfinnelsen vedrører en fremgangsmåte til fremstilling
av 4-metoksy-6-(3',4'-metylendioksyfenyletyl)-5,6-dihydro-a-pyron (dihydrometysticin) og i>-metoksy-6- (f enyletyl) - 5 ,6-dihydro-a-pyron (dihydrokawain).
Den partielle katalytiske hydrering av forbindelsene av typen metysticin, altså av dihydro-a-pyron-forbindelser, som inneholder en unettet alifatisk bro, støter ofte for så vidt på vanske-ligheter som ved hydreringen angripes ikke bare den alifatiske dobbeltbinding, men også 3,4-dobbeltbindingen i pyronringen.
Det er riktignok allerede kjent (Berichte der Deutschen Chemischen Gesellschaft, bind 62, 1929, side 360 til 367) katalytisk å hydrere den alifatiske dobbeltbinding av et a-pyronderivat av Kfr. kl. 12q-25 ovennevnte type ved værelsetemperatur. De ved denne fremgangsmåte oppnådde utbytter er imidlertid dårlige.
Videre omtales i US-patent nr. 2.870.164 hydreringen av metysticin til dihydrometysticin ved værelsetemperatur og under trykk. Også de her oppnådde utbytter er dårlige.
Det ble nå overraskende funnet at man får 4-metoksy-6-(3', 4'-metylendioksyfenyletyl)-5,6-dihydro-a-pyron (dihydrometysticin) eller 4-metoksy-6-(fenyletyl)-5,6-dihydro-a-pyron (dihydrokawain) ved hydrering av 4-metoksy-6-(3',4'-metylendioksy-styryl)-5,6-dihydro-a-pyron eller 4-metoksy-6-styryl-5,6-dihydro-a-pyron i nærvær av metanol og kolloidalt palladium som katalysator i bedre utbytter ved at man anvender en metanolisk oppløsning som inneholder en del av a-pyronet som skal hydreres. som bunnlegeme, og innleder eller gjennomfører hydreringen til bunnlegemet har for-svunnet, ved en temperatur fra -10 til -5°C og ikke lar temperaturen stige over 15°C.
Ved fremgangsmåten ifølge oppfinnelsen forløper den partielle hydrering praktisk talt kvantitativt. Utbyttene utgjør eksempelvis 95 til 9&% av det teoretiske, a-pyronringens 3,4-dobbeltbinding angripes således ikke ved hydreringen, og det finner heller ikke sted noen spaltning av pyronringen. Et slikt reaksjons-forløp ved fremgangsmåten ifølge oppfinnelsen kunne ikke uten videre forutsees.
Dihydrokawainet virker som antiflogistikum og endoanestetikum, dihydrometysticin som soveinduserende middel og likeledes som endoanestetikum.
Oppfinnelsen skal forklares nærmere ved hjelp av følgende eksempler.
Eksempel 1.
300 g 4-metoksy-6-(3)4-metylendioksystyryl)-5,6-dihydro-a-pyron (metysticin) tilsettes 10 1 metanol, og anbringes i kjøleskap ved -10 til -5°C. Til den avkjølte oppløsning, som inneholder 4-metoksy-6-(3,4-metylen-dioksystyryl) -5,6-dihydro-a-pyron (metysticin) som fast stoff på bunnen, innføres 50 cm-' palladium-oppløsning ifølge Paal, og man hydrerer så lenge med hydrogen i rysteapparat at det faste stoffet på bunnen akkurat oppløser seg.
Herved må slutt-temperaturen ikke overstige 15°C.
Utbyttet av 4-metoksy-6-(3,4-metylendioksy-fenyletyl)-5,6-dihydro-a-pyron (dihydrometysticin) blir 290 til 295 g.
Smeltepunkt = 116 til 117°C.
Svovelsyrereaksjon = vinrød.
Eksempel 2.
100 g 4-metoksy-6-styryl-5,6-dihydro-a-pyron (kawain) tilsettes 500 cm^ metanol og anbringes i kjøleskap ved -10 til
-5°C. Til den avkjølte oppløsning som inneholder ii-metoksy-6-styryl-5,6-dihydro-a-pyron (kawain) som i hovedsaken uoppløst stoff på bunnen, innføres 20 cm^ palladiumoppløsning ifølge Paal. Man hydrerer inntil det faste bunnstoffet nettopp er oppløst. Det er en fordel likeledes å avkjøle det innførte hydrogen til -10 til -5°C, siden metningen i begynnelsen skjer hurtig. Utbyttet av 4-metoksy-6-fenyletyl-5,6-dihydro-a-pyron (dihydrokawain) = 98,5 g.
Smeltepunkt etter omkrystallisering fra eter (+ petrol-eter) = 58 til 60°C.
Svovelsyrereaksjon = fargeløs.
Claims (1)
- Fremgangsmåte til fremstilling av 4-metoksy-6-(3', H'-metylendioksyfenyletyl)-5,6-dihydro-a-pyron (dihydrometysticin) eller 4-metoksy-6-(fenyletyl)-5,6-dihydro-a-pyron (dihydrokawain) ved hydrering av 4-metoksy-6-(3',4'-metylendioksystyryl)-5>6-dihydro-a-pyron eller 4-metoksy-6-styryl-5,6-dihydro-a-pyron i nærvær av metanol og kolloidalt palladium som katalysator, karakterisert ved at man anvender en metanolisk opp-løsning som inneholder en del av a-pyronet som skal hydreres, som uoppløst bunnstoff, innleder eller gjennomfører hydreringen til forsvinning av bunnlegemet ved en temperatur fra -10 til -5°Cog ikke lar temperaturen stige over 15°C.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8716803A GB2206880B (en) | 1987-07-16 | 1987-07-16 | Optical isomers of an imidazole derivative |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| NO883155D0 NO883155D0 (no) | 1988-07-15 |
| NO883155L NO883155L (no) | 1989-01-17 |
| NO170579B true NO170579B (no) | 1992-07-27 |
| NO170579C NO170579C (no) | 1992-11-04 |
Family
ID=10620775
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO883155A NO170579C (no) | 1987-07-16 | 1988-07-15 | Analogifremgangsmaate for fremstilling av den terapeutisk aktive d-enantiomeren av medetomidin |
| NO2003004C NO2003004I2 (no) | 1987-07-16 | 2003-07-01 | Dexmedetomidin |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO2003004C NO2003004I2 (no) | 1987-07-16 | 2003-07-01 | Dexmedetomidin |
Country Status (29)
| Country | Link |
|---|---|
| US (1) | US4910214A (no) |
| EP (1) | EP0300652B1 (no) |
| JP (1) | JPH0625138B2 (no) |
| KR (1) | KR940007311B1 (no) |
| CN (1) | CN1022323C (no) |
| AT (1) | ATE71941T1 (no) |
| AU (1) | AU600839B2 (no) |
| BG (1) | BG60473B2 (no) |
| CA (1) | CA1337659C (no) |
| CY (2) | CY1787A (no) |
| DD (1) | DD281807A5 (no) |
| DE (2) | DE10399005I2 (no) |
| DK (1) | DK165788C (no) |
| ES (1) | ES2038757T3 (no) |
| FI (1) | FI95375C (no) |
| GB (1) | GB2206880B (no) |
| GR (1) | GR3003878T3 (no) |
| HK (1) | HK56094A (no) |
| HU (1) | HU198693B (no) |
| IE (1) | IE60456B1 (no) |
| IL (1) | IL87076A0 (no) |
| LU (1) | LU91010I2 (no) |
| NL (1) | NL300117I2 (no) |
| NO (2) | NO170579C (no) |
| NZ (1) | NZ225362A (no) |
| PT (1) | PT88013B (no) |
| SU (1) | SU1648248A3 (no) |
| UA (1) | UA5560A1 (no) |
| ZA (1) | ZA885134B (no) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2215206B (en) * | 1988-02-29 | 1991-07-03 | Farmos Oy | 4-substituted imidazole derivatives useful in perioperative care |
| US5124157A (en) | 1989-08-18 | 1992-06-23 | Cygnus Therapeutic Systems | Method and device for administering dexmedetomidine transdermally |
| US5120713A (en) * | 1990-09-10 | 1992-06-09 | Applied Research Systems Ars Holding N.V. | Treatment of obesity with an alpha-2-adrenergic agonist and a growth hormone releasing peptide |
| GB9111732D0 (en) * | 1991-05-31 | 1991-07-24 | Orion Yhtymae Oy | The use of certain salts of medetomidine and its optically active enantiomers to regulate the rate of transdermal administration of the drugs |
| GB2281206A (en) * | 1993-08-25 | 1995-03-01 | Orion Yhtymae Oy | Use of dexmedetomidine |
| GB9425211D0 (en) * | 1994-12-14 | 1995-02-15 | Ucb Sa | Substituted 1H-imidazoles |
| IN187238B (no) * | 1995-06-30 | 2002-03-09 | Astra Ab | |
| GB9521680D0 (en) * | 1995-10-23 | 1996-01-03 | Orion Yhtymo Oy | New use of imidazole derivatives |
| US5866579A (en) * | 1997-04-11 | 1999-02-02 | Synaptic Pharmaceutical Corporation | Imidazole and imidazoline derivatives and uses thereof |
| US6716867B1 (en) | 1998-04-01 | 2004-04-06 | Orion Corporation | Use of dexmedetomidine for ICU sedation |
| AR015744A1 (es) * | 1998-04-01 | 2001-05-16 | Orion Corp | Uso de dexmedetomidina para sedacion en terapia intensiva |
| EP1223931B1 (en) | 1999-10-29 | 2005-12-14 | Orion Corporation | Use of a imidazole derivative for the treatment or prevention of hypotension and shock |
| US6388090B2 (en) * | 2000-01-14 | 2002-05-14 | Orion Corporation | Imidazole derivatives |
| US7141597B2 (en) * | 2003-09-12 | 2006-11-28 | Allergan, Inc. | Nonsedating α-2 agonists |
| EP2218442A1 (en) | 2005-11-09 | 2010-08-18 | CombinatoRx, Inc. | Methods, compositions, and kits for the treatment of ophthalmic disorders |
| BRPI0709606B8 (pt) | 2006-03-16 | 2021-05-25 | Tris Pharma Inc | suspensão líquida administrável oralmente com características de liberação modificada |
| US7795263B2 (en) * | 2008-07-08 | 2010-09-14 | Wildlife Laboratories, Inc. | Pharmaceutical combination for and method of anesthetizing and immobilizing non-domesticated mammals |
| US20100196286A1 (en) * | 2008-12-01 | 2010-08-05 | Armer Thomas A | Inhalation delivery methods and devices |
| WO2010074753A1 (en) * | 2008-12-23 | 2010-07-01 | Map Pharmaceuticals, Inc. | Inhalation devices and related methods for administration of sedative hypnotic compounds |
| AU2010248776B2 (en) * | 2009-05-15 | 2013-06-06 | Baudax Bio, Inc. | Sublingual dexmedetomidine compositions and methods of use thereof |
| CN101671305A (zh) * | 2009-09-29 | 2010-03-17 | 北京华禧联合科技发展有限公司 | 一种拆分美托咪定的左旋及右旋对映体的方法 |
| CN102464619A (zh) * | 2010-11-17 | 2012-05-23 | 桑迪亚医药技术（上海）有限责任公司 | 一种左旋4-[1-(2,3-二甲基苯基)乙基]-1r-咪唑消旋化方法 |
| US20130096170A1 (en) | 2011-10-14 | 2013-04-18 | Hospira, Inc. | Methods of treating pediatric patients using dexmedetomidine |
| WO2013069025A1 (en) | 2011-11-11 | 2013-05-16 | Neon Laboratories Ltd. | "process for the preparation of dexmedetomidine" |
| SG11201403094TA (en) | 2011-12-11 | 2014-10-30 | Recro Pharma Inc | Intranasal dexmedetomidine compositions and methods of use thereof |
| US8242158B1 (en) | 2012-01-04 | 2012-08-14 | Hospira, Inc. | Dexmedetomidine premix formulation |
| ITMI20120311A1 (it) * | 2012-02-29 | 2013-08-30 | Edmond Pharma Srl | Procedimento per la risoluzione di medetomidina e recupero dell'enantiomero indesiderato |
| EP2884961B1 (en) | 2012-08-15 | 2019-03-06 | Tris Pharma Inc. | Methylphenidate extended release chewable tablet |
| DK2906213T3 (en) * | 2012-10-15 | 2018-02-19 | Orion Corp | VETERINARY PROCEDURE FOR RELIEFING NOISE SENSITIVITY |
| TWI629066B (zh) | 2013-10-07 | 2018-07-11 | 帝國製藥美國股份有限公司 | 使用右美托咪啶經皮組成物用於治療注意力不足過動症、焦慮及失眠的方法及組成物 |
| KR101948779B1 (ko) | 2013-10-07 | 2019-05-21 | 테이코쿠 팔마 유에스에이, 인코포레이티드 | 덱스메데토미딘 경피 전달 장치 및 이의 사용 방법 |
| US10987342B2 (en) | 2013-10-07 | 2021-04-27 | Teikoku Pharma Usa, Inc. | Methods and compositions for transdermal delivery of a non-sedative amount of dexmedetomidine |
| CN105175339B (zh) * | 2015-10-09 | 2018-01-16 | 辰欣药业股份有限公司 | 一种制备盐酸右美托咪定的方法 |
| US9717796B1 (en) | 2016-04-20 | 2017-08-01 | Slypharma, Llc | Heat sterilizeable, premixed, ready to use dexmedetomidine solution packaged in a flexible plastic container |
| FR3054218B1 (fr) * | 2016-07-22 | 2020-03-06 | Universite De Rouen | Procede de dedoublement de sels de baclofene |
| US11160791B2 (en) | 2018-11-01 | 2021-11-02 | Medefil, Inc. | Dexmedetomidine injection premix formulation in ready to use (RTU) bags |
| CN114671811A (zh) * | 2022-04-14 | 2022-06-28 | 南京正科医药股份有限公司 | 一种右美托咪定拆分副产物的外消旋化回收方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU518569B2 (en) * | 1979-08-07 | 1981-10-08 | Farmos-Yhtyma Oy | 4-benzyl- and 4-benzoyl imidazole derivatives |
| GB2092569B (en) * | 1981-02-05 | 1984-09-19 | Farmos Oy | Substituted imidazole derivatives and their preparation and use |
| GB2101114B (en) * | 1981-07-10 | 1985-05-22 | Farmos Group Ltd | Substituted imidazole derivatives and their preparation and use |
| FI844786A0 (fi) | 1984-12-04 | 1984-12-04 | Farmos Oy | Terapeutiskt utnyttjbar foerening. |
| DE3531682A1 (de) * | 1985-09-05 | 1987-03-12 | Thomae Gmbh Dr K | (+)-6-chlor-5,10-dihydro-5-((1-methyl-4- piperidinyl)acetyl)-11h-dibenzo(b,e)(1,4) diazepin-11-on, seine isolierung und verwendung als arzneimittel |
-
1987
- 1987-07-16 GB GB8716803A patent/GB2206880B/en not_active Expired - Lifetime
-
1988
- 1988-06-14 FI FI882819A patent/FI95375C/fi active Protection Beyond IP Right Term
- 1988-06-28 SU SU884356076A patent/SU1648248A3/ru active
- 1988-06-28 UA UA4356076A patent/UA5560A1/uk unknown
- 1988-07-08 EP EP88306250A patent/EP0300652B1/en not_active Expired - Lifetime
- 1988-07-08 ES ES198888306250T patent/ES2038757T3/es not_active Expired - Lifetime
- 1988-07-08 DE DE2003199005 patent/DE10399005I2/de active Active
- 1988-07-08 DE DE8888306250T patent/DE3867945D1/de not_active Expired - Lifetime
- 1988-07-08 AT AT88306250T patent/ATE71941T1/de active
- 1988-07-11 DK DK386288A patent/DK165788C/da not_active IP Right Cessation
- 1988-07-11 AU AU18941/88A patent/AU600839B2/en not_active Expired
- 1988-07-11 NZ NZ225362A patent/NZ225362A/xx unknown
- 1988-07-12 IL IL87076A patent/IL87076A0/xx not_active IP Right Cessation
- 1988-07-14 DD DD88317936A patent/DD281807A5/de not_active IP Right Cessation
- 1988-07-14 CA CA000572086A patent/CA1337659C/en not_active Expired - Lifetime
- 1988-07-15 KR KR1019880008937A patent/KR940007311B1/ko not_active IP Right Cessation
- 1988-07-15 NO NO883155A patent/NO170579C/no not_active IP Right Cessation
- 1988-07-15 IE IE217488A patent/IE60456B1/en not_active IP Right Cessation
- 1988-07-15 PT PT88013A patent/PT88013B/pt not_active IP Right Cessation
- 1988-07-15 ZA ZA885134A patent/ZA885134B/xx unknown
- 1988-07-15 HU HU883708A patent/HU198693B/hu unknown
- 1988-07-15 US US07/219,637 patent/US4910214A/en not_active Expired - Lifetime
- 1988-07-16 JP JP63177959A patent/JPH0625138B2/ja not_active Expired - Lifetime
- 1988-07-16 CN CN88104440A patent/CN1022323C/zh not_active Expired - Lifetime
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1992
- 1992-02-21 GR GR920400299T patent/GR3003878T3/el unknown
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1994
- 1994-01-18 BG BG98380A patent/BG60473B2/bg unknown
- 1994-05-24 HK HK56094A patent/HK56094A/xx not_active IP Right Cessation
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1995
- 1995-10-20 CY CY178795A patent/CY1787A/xx unknown
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2003
- 2003-02-14 LU LU91010C patent/LU91010I2/fr unknown
- 2003-03-03 NL NL300117C patent/NL300117I2/nl unknown
- 2003-07-01 NO NO2003004C patent/NO2003004I2/no unknown
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2004
- 2004-10-27 CY CY200400006C patent/CY2004006I2/el unknown
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| SPCF | Filing of supplementary protection certificate |
Free format text: PRODUCT NAME: DEXMEDETOMIDIN; NAT. REG. NO/DATE: NO , MTN EU/2/0 20030116; FIRST REG. NO/DATE: FI , EU/2/033/0 20030830 Spc suppl protection certif: 2003004 Filing date: 20030701 Extension date: 20130715 |
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Spc suppl protection certif: 2003004 Effective date: 20130715 |