RU2403255C2 - 6,7-ненасыщенное 7-карбамоилзамещенное производное морфинана - Google Patents
6,7-ненасыщенное 7-карбамоилзамещенное производное морфинана Download PDFInfo
- Publication number
- RU2403255C2 RU2403255C2 RU2007148412/04A RU2007148412A RU2403255C2 RU 2403255 C2 RU2403255 C2 RU 2403255C2 RU 2007148412/04 A RU2007148412/04 A RU 2007148412/04A RU 2007148412 A RU2007148412 A RU 2007148412A RU 2403255 C2 RU2403255 C2 RU 2403255C2
- Authority
- RU
- Russia
- Prior art keywords
- optionally substituted
- compound
- lower alkyl
- solvate
- pharmaceutically acceptable
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims abstract description 196
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 116
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 68
- 239000001257 hydrogen Substances 0.000 claims abstract description 68
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 45
- 230000000694 effects Effects 0.000 claims abstract description 42
- 150000003839 salts Chemical class 0.000 claims abstract description 40
- 239000012453 solvate Substances 0.000 claims abstract description 37
- 206010047700 Vomiting Diseases 0.000 claims abstract description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 35
- 230000008673 vomiting Effects 0.000 claims abstract description 34
- 206010010774 Constipation Diseases 0.000 claims abstract description 32
- 206010028813 Nausea Diseases 0.000 claims abstract description 28
- 230000008693 nausea Effects 0.000 claims abstract description 28
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 27
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 230000002265 prevention Effects 0.000 claims abstract description 11
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 8
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims abstract description 8
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 47
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- 150000002431 hydrogen Chemical class 0.000 claims description 33
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 28
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- 102000003840 Opioid Receptors Human genes 0.000 claims description 24
- 108090000137 Opioid Receptors Proteins 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 125000002252 acyl group Chemical group 0.000 claims description 17
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 16
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- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
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- 230000002829 reductive effect Effects 0.000 description 9
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- 239000008187 granular material Substances 0.000 description 7
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- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 6
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
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- GNWBLLYJQXKPIP-ZOGIJGBBSA-N (1s,3as,3bs,5ar,9ar,9bs,11as)-n,n-diethyl-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1h-indeno[5,4-f]quinoline-1-carboxamide Chemical compound CN([C@@H]1CC2)C(=O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)N(CC)CC)[C@@]2(C)CC1 GNWBLLYJQXKPIP-ZOGIJGBBSA-N 0.000 description 4
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- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 208000030401 vitamin deficiency disease Diseases 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/06—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with a hetero atom directly attached in position 14
- C07D489/08—Oxygen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2005151864 | 2005-05-25 | ||
| JP2005-151864 | 2005-05-25 | ||
| JP2006/065762 | 2006-03-10 | ||
| JP2006065762 | 2006-03-10 | ||
| JPPCT/JP2006/310231 | 2006-05-23 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2007148412A RU2007148412A (ru) | 2009-06-27 |
| RU2403255C2 true RU2403255C2 (ru) | 2010-11-10 |
Family
ID=37451954
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2007148412/04A RU2403255C2 (ru) | 2005-05-25 | 2006-05-25 | 6,7-ненасыщенное 7-карбамоилзамещенное производное морфинана |
Country Status (20)
| Country | Link |
|---|---|
| US (4) | USRE46365E1 (enExample) |
| EP (1) | EP1889848B8 (enExample) |
| JP (1) | JP4323547B2 (enExample) |
| KR (1) | KR100912782B1 (enExample) |
| CN (1) | CN101228172B (enExample) |
| AU (1) | AU2006250390B2 (enExample) |
| BE (1) | BE2019C533I2 (enExample) |
| BR (1) | BRPI0610343B8 (enExample) |
| CA (1) | CA2609733C (enExample) |
| DK (1) | DK1889848T3 (enExample) |
| ES (1) | ES2525215T3 (enExample) |
| FR (1) | FR19C1042I2 (enExample) |
| HU (1) | HUS1900034I1 (enExample) |
| MX (1) | MX2007014588A (enExample) |
| NL (1) | NL300996I2 (enExample) |
| PL (1) | PL1889848T3 (enExample) |
| PT (1) | PT1889848E (enExample) |
| RU (1) | RU2403255C2 (enExample) |
| TW (1) | TWI311056B (enExample) |
| WO (2) | WO2006126529A1 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006126529A1 (ja) | 2005-05-25 | 2006-11-30 | Shionogi & Co., Ltd. | ６，７－不飽和－７－カルバモイル置換モルヒナン誘導体 |
| US10512644B2 (en) | 2007-03-12 | 2019-12-24 | Inheris Pharmaceuticals, Inc. | Oligomer-opioid agonist conjugates |
| US8173666B2 (en) | 2007-03-12 | 2012-05-08 | Nektar Therapeutics | Oligomer-opioid agonist conjugates |
| CA3066426A1 (en) * | 2008-01-09 | 2009-07-16 | Charleston Laboratories, Inc. | Pharmaceutical compositions comprising an antiemetic and an opioid analgesic |
| JP5252391B2 (ja) * | 2008-02-21 | 2013-07-31 | 学校法人北里研究所 | オキサビシクロ［２．２．２］オクタンを有するモルヒナン誘導体およびその医薬用途 |
| CA2734333A1 (en) * | 2008-09-16 | 2010-03-25 | Nektar Therapeutics | Pegylated opioids with low potential for abuse |
| WO2011035142A1 (en) * | 2009-09-18 | 2011-03-24 | Adolor Corporation | Use of opioid receptor antagonist for gastrointestinal tract disorders |
| WO2011142620A2 (en) * | 2010-05-13 | 2011-11-17 | Green Cross Corporation | (+)-3-hydroxymorphinan-based polycycle derivatives as neuroprotectants |
| AU2011327113B9 (en) | 2010-11-12 | 2015-07-30 | Shionogi & Co., Ltd. | Crystalline 6,7-unsaturated-7-carbamoyl morphinane derivative, and method for producing same |
| US10952968B2 (en) | 2012-05-14 | 2021-03-23 | Shionogi & Co., Ltd. | Preparation containing 6,7-unsaturated-7-carbamoyl morphinan derivatives |
| EP3560487A4 (en) | 2016-12-26 | 2020-07-29 | Shionogi & Co., Ltd. | PRODUCTION METHOD FOR FORMULATION WITH IMPROVED UNIFORMITY OF CONTENT |
| WO2019200202A1 (en) | 2018-04-12 | 2019-10-17 | Morphic Therapeutic, Inc. | Antagonists of human integrin (alpha4)(beta7) |
| KR102201609B1 (ko) | 2019-04-19 | 2021-01-12 | 연성정밀화학(주) | 날데메딘의 제조방법 |
| MX2022004406A (es) | 2019-10-16 | 2022-08-25 | Morphic Therapeutic Inc | INHIBICIÓN DE INTEGRINA A4ß7 HUMANA. |
| JP7582961B2 (ja) | 2019-11-20 | 2024-11-13 | 塩野義製薬株式会社 | ６，７－不飽和－７－カルバモイルモルヒナン誘導体含有固形製剤 |
| CN111905111B (zh) * | 2020-09-16 | 2023-03-31 | 地奥集团成都药业股份有限公司 | 一种评价复方谷氨酰胺组方对腹泻型肠易激综合征疗效的方法 |
| IT202300009864A1 (it) | 2023-05-16 | 2024-11-16 | Procos Spa | Processo per la preparazione di naldemedina |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU1508960A3 (ru) * | 1984-07-05 | 1989-09-15 | Е.И.Дюпон Де Немур Энд Компани (Фирма) | Способ получени производных бензоатных эфиров 3-оксиморфинанов |
| US20010047005A1 (en) * | 1999-09-29 | 2001-11-29 | Farrar John J. | Novel methods and compositions involving opioids and antagonists thereof |
| WO2004007503A1 (ja) * | 2002-07-11 | 2004-01-22 | Toray Industries, Inc. | 悪心・嘔吐の治療または予防剤 |
| RU2004108210A (ru) * | 2001-08-23 | 2005-04-10 | Акцо Нобель Н.В. (NL) | C-14 окисление производных морфина |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4272541A (en) | 1978-06-02 | 1981-06-09 | Miles Laboratories, Inc. | 7,8 and 7-8 Substituted 4,5α-epoxymorphinan-6-one compounds, and methods of treating pain and drug dependence with them |
| US4275205A (en) * | 1980-05-05 | 1981-06-23 | Miles Laboratories, Inc. | 7,7-Ditosyloxymethyl-4,5α-epoxy-morphinan-6-ols |
| US4347361A (en) * | 1980-12-10 | 1982-08-31 | Sisa, Incorporated | 4,5α-Epoxy-3-hydroxy or methoxy-7-(1-hydroxy-alkyl or 1-oxoalkyl)morphinan-6-one compounds |
| US4370333A (en) | 1981-06-29 | 1983-01-25 | Sisa, Incorporated | 17-Cyclopropylmethyl-3-hydroxy-14-methoxy 7α-methyl-morphinan-6-one and therapeutic method of treating pain with it |
| US4443605A (en) * | 1982-07-30 | 1984-04-17 | Miles Laboratories, Inc. | 7β-Arylalkyl-6α, 7 α-oxymethylene-3-methoxy or 3-hydroxy-4, 5α-epoxy-17 methyl or 17-cycloalkyl-methyl morphinans |
| US4440932A (en) * | 1982-09-09 | 1984-04-03 | Miles Laboratories, Inc. | 7β-Arylalkyl-7α-methyl-6-oxo or 6α-hydroxy-3-methoxy or 3-hydroxy-4,5α-epoxy-17-methyl or 17-cycloalkyl-methylmorphinans |
| EP0663401B1 (en) * | 1993-07-23 | 2000-06-07 | Toray Industries, Inc. | Morphinan derivative and medicinal use |
| US5464841A (en) | 1993-11-08 | 1995-11-07 | Univ Minnesota | Use of delta opioid receptor antagonists to treat immunoregulatory disorders |
| KR19990077125A (ko) | 1996-01-10 | 1999-10-25 | 파올로 비지, 엔리꼬 카쭐라니 | 헤테로고리-축합 모르핀 유도체 (ⅱ) |
| AU5891600A (en) | 1999-07-01 | 2001-01-22 | Chemrx Advanced Technologies, Inc. | Process for synthesizing oxadiazoles |
| WO2001037785A2 (en) * | 1999-11-29 | 2001-05-31 | Adolor Corporation | Novel methods and compositions involving opioids and antagonists thereof |
| US20040024004A1 (en) | 2001-05-04 | 2004-02-05 | Sherman Barry M. | Novel compositions and methods for enhancing potency or reducing adverse side effects of opioid agonists |
| CA2408106A1 (en) | 2000-05-05 | 2001-11-15 | Pain Therapeutics, Inc. | Opioid antagonist compositions and dosage forms |
| AU2001259560B2 (en) | 2000-05-05 | 2007-02-15 | Albert Einstein College Of Medicine Of Yeshiva University | Opioid antagonist containing composition for enhancing the potency or reducing adverse side effects of opioid agonists |
| ES2304477T3 (es) * | 2000-10-31 | 2008-10-16 | Rensselaer Polytechnic Institute | Procedimiento de preparacion de compuestos con afinidad a receptores opioides. |
| CA2427931A1 (en) * | 2000-11-22 | 2002-05-30 | Toray Industries, Inc. | Indole derivatives and medical applications thereof |
| DE10161963A1 (de) | 2001-12-17 | 2003-07-03 | Johannes Schuetz | 6-Aminomorphinanderivate, Herstellungsverfahren dafür und deren Verwendung |
| DE10229842A1 (de) * | 2002-07-03 | 2004-02-05 | Helmut Prof. Dr. Schmidhammer | Morphinanderivate und deren quartäre Ammoniumsalze substituiert in Position 14, Herstellungsverfahren und Verwendung |
| AU2003299045A1 (en) | 2002-09-18 | 2004-04-08 | The Curators Of The University Of Missouri | OPIATE ANALOGS SELECTIVE FOR THE delta-OPIOID RECEPTOR |
| US20040157784A1 (en) * | 2003-02-10 | 2004-08-12 | Jame Fine Chemicals, Inc. | Opiod tannate compositions |
| WO2005105093A2 (en) | 2003-08-26 | 2005-11-10 | Duke University | METHOD OF ARRESTING THE SIDE EFFECTS OF µ-OPIOID RECEPTOR AGONISTS DURING THEIR ADMINISTRATION |
| EP1758452B1 (en) | 2004-05-28 | 2017-01-25 | Human Biomolecular Research Institute | Metabolically stable analgesics and pain medications |
| US20060063792A1 (en) | 2004-09-17 | 2006-03-23 | Adolor Corporation | Substituted morphinans and methods of their use |
| US7142420B2 (en) | 2004-09-20 | 2006-11-28 | Qualcomm, Incorporated | Devices and methods for controlling relative movement between layers of an electronic device |
| WO2006126529A1 (ja) | 2005-05-25 | 2006-11-30 | Shionogi & Co., Ltd. | ６，７－不飽和－７－カルバモイル置換モルヒナン誘導体 |
| AU2011327113B9 (en) | 2010-11-12 | 2015-07-30 | Shionogi & Co., Ltd. | Crystalline 6,7-unsaturated-7-carbamoyl morphinane derivative, and method for producing same |
-
2006
- 2006-05-23 WO PCT/JP2006/310231 patent/WO2006126529A1/ja not_active Ceased
- 2006-05-24 TW TW095118443A patent/TWI311056B/zh active
- 2006-05-25 DK DK06746833.0T patent/DK1889848T3/en active
- 2006-05-25 RU RU2007148412/04A patent/RU2403255C2/ru active
- 2006-05-25 EP EP06746833.0A patent/EP1889848B8/en active Active
- 2006-05-25 CA CA2609733A patent/CA2609733C/en active Active
- 2006-05-25 MX MX2007014588A patent/MX2007014588A/es active IP Right Grant
- 2006-05-25 US US15/064,511 patent/USRE46365E1/en active Active
- 2006-05-25 PT PT67468330T patent/PT1889848E/pt unknown
- 2006-05-25 ES ES06746833.0T patent/ES2525215T3/es active Active
- 2006-05-25 BR BRPI0610343A patent/BRPI0610343B8/pt not_active IP Right Cessation
- 2006-05-25 AU AU2006250390A patent/AU2006250390B2/en not_active Ceased
- 2006-05-25 CN CN2006800271187A patent/CN101228172B/zh active Active
- 2006-05-25 JP JP2007517895A patent/JP4323547B2/ja active Active
- 2006-05-25 US US11/920,851 patent/US8084460B2/en not_active Ceased
- 2006-05-25 PL PL06746833T patent/PL1889848T3/pl unknown
- 2006-05-25 WO PCT/JP2006/310454 patent/WO2006126637A1/ja not_active Ceased
-
2007
- 2007-11-23 KR KR1020077027287A patent/KR100912782B1/ko active Active
-
2011
- 2011-11-30 US US13/308,483 patent/US8536192B2/en not_active Ceased
-
2016
- 2016-03-08 US US15/064,538 patent/USRE46375E1/en active Active
-
2019
- 2019-06-20 FR FR19C1042C patent/FR19C1042I2/fr active Active
- 2019-06-24 BE BE2019C533C patent/BE2019C533I2/nl unknown
- 2019-06-26 NL NL300996C patent/NL300996I2/nl unknown
- 2019-07-03 HU HUS1900034C patent/HUS1900034I1/hu unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU1508960A3 (ru) * | 1984-07-05 | 1989-09-15 | Е.И.Дюпон Де Немур Энд Компани (Фирма) | Способ получени производных бензоатных эфиров 3-оксиморфинанов |
| US20010047005A1 (en) * | 1999-09-29 | 2001-11-29 | Farrar John J. | Novel methods and compositions involving opioids and antagonists thereof |
| RU2004108210A (ru) * | 2001-08-23 | 2005-04-10 | Акцо Нобель Н.В. (NL) | C-14 окисление производных морфина |
| WO2004007503A1 (ja) * | 2002-07-11 | 2004-01-22 | Toray Industries, Inc. | 悪心・嘔吐の治療または予防剤 |
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