NL8720049A - Oraal werkzame niet-verslavende pijnstillers. - Google Patents
Oraal werkzame niet-verslavende pijnstillers. Download PDFInfo
- Publication number
- NL8720049A NL8720049A NL8720049A NL8720049A NL8720049A NL 8720049 A NL8720049 A NL 8720049A NL 8720049 A NL8720049 A NL 8720049A NL 8720049 A NL8720049 A NL 8720049A NL 8720049 A NL8720049 A NL 8720049A
- Authority
- NL
- Netherlands
- Prior art keywords
- formula
- normorphine
- compound
- diesters
- derivatives
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims description 37
- 238000000034 method Methods 0.000 claims description 35
- 239000000203 mixture Substances 0.000 claims description 30
- 229950006134 normorphine Drugs 0.000 claims description 30
- ONBWJWYUHXVEJS-ZTYRTETDSA-N Normorphine Chemical class C([C@@H](NCC1)[C@@H]2C=C[C@@H]3O)C4=CC=C(O)C5=C4[C@@]21[C@H]3O5 ONBWJWYUHXVEJS-ZTYRTETDSA-N 0.000 claims description 28
- 150000005690 diesters Chemical class 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 18
- 238000002844 melting Methods 0.000 claims description 16
- 230000008018 melting Effects 0.000 claims description 15
- -1 methyl normorphine Chemical compound 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 13
- HKOIXWVRNLGFOR-KOFBORESSA-N norcodeine Chemical class O[C@H]([C@@H]1O2)C=C[C@H]3[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4 HKOIXWVRNLGFOR-KOFBORESSA-N 0.000 claims description 13
- 208000002193 Pain Diseases 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 10
- 238000000926 separation method Methods 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 229950004392 norcodeine Drugs 0.000 claims description 9
- HKOIXWVRNLGFOR-UHFFFAOYSA-N norcodeine Natural products O1C2C(O)C=CC3C4CC5=CC=C(OC)C1=C5C23CCN4 HKOIXWVRNLGFOR-UHFFFAOYSA-N 0.000 claims description 9
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 239000003638 chemical reducing agent Substances 0.000 claims description 5
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- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 2
- 101150065749 Churc1 gene Proteins 0.000 claims description 2
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- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical group [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 2
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- 239000008194 pharmaceutical composition Substances 0.000 claims 2
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- 230000000694 effects Effects 0.000 description 14
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- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 8
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- 229960000938 nalorphine Drugs 0.000 description 4
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- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
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- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
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- 239000011777 magnesium Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 150000002762 monocarboxylic acid derivatives Chemical class 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 description 1
- 229960004127 naloxone Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229940124641 pain reliever Drugs 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- FWMUJAIKEJWSSY-UHFFFAOYSA-N sulfur dichloride Chemical compound ClSCl FWMUJAIKEJWSSY-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- HADKRTWCOYPCPH-UHFFFAOYSA-M trimethylphenylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C1=CC=CC=C1 HADKRTWCOYPCPH-UHFFFAOYSA-M 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 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:
- C07D489/02—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 oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US84315086 | 1986-03-24 | ||
| US06/843,150 US4749706A (en) | 1986-03-24 | 1986-03-24 | Orally active nonaddicting analgesics |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL8720049A true NL8720049A (nl) | 1988-01-04 |
Family
ID=25289190
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL8720049A NL8720049A (nl) | 1986-03-24 | 1987-02-06 | Oraal werkzame niet-verslavende pijnstillers. |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US4749706A (no) |
| EP (1) | EP0261148B1 (no) |
| JP (1) | JPH085889B2 (no) |
| CA (1) | CA1313868C (no) |
| DE (2) | DE3790166C2 (no) |
| GB (1) | GB2198435B (no) |
| NL (1) | NL8720049A (no) |
| WO (1) | WO1987005903A2 (no) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5366979A (en) * | 1990-06-07 | 1994-11-22 | Pharmaco Development Partners | Orally active nonaddicting analgesics |
| KR950000705A (ko) * | 1993-06-19 | 1995-01-03 | 권기범 | 14-치환 몰피난 유도체 및 이를 함유하는 의약 |
| US5962477A (en) * | 1994-04-12 | 1999-10-05 | Adolor Corporation | Screening methods for cytokine inhibitors |
| US6190691B1 (en) | 1994-04-12 | 2001-02-20 | Adolor Corporation | Methods for treating inflammatory conditions |
| US6573282B1 (en) | 1995-09-12 | 2003-06-03 | Adolor Corporation | Peripherally active anti-hyperalgesic opiates |
| US5849761A (en) | 1995-09-12 | 1998-12-15 | Regents Of The University Of California | Peripherally active anti-hyperalgesic opiates |
| WO2005037212A2 (en) * | 2003-10-14 | 2005-04-28 | Phoenix Pharmalabs, Inc. | Treatment of chemical dependency with substantially nonaddicting normorphine and norcodeine derivatives |
| US8188067B2 (en) | 2004-04-01 | 2012-05-29 | Teva Pharmaceutical Industries Ltd. | Formulations of 6-mercaptopurine |
| US8691989B2 (en) * | 2008-06-20 | 2014-04-08 | Phoenix Pharmalabs, Inc. | Methods of synthesis of morphinans |
| WO2014031403A1 (en) * | 2012-08-22 | 2014-02-27 | Phoenix Pharmalabs, Inc. | Use of morphine analogs for animal health |
| WO2017066619A1 (en) | 2015-10-16 | 2017-04-20 | Teva Pharmaceutical Industries Ltd. | Treatment of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis with delayed-release 6-mercaptopurine |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4218454A (en) * | 1977-07-08 | 1980-08-19 | Sri International | N-αMethylcyclopropylmethyl derivatives of normorphine and noroodeine, and analgesic compositions and methods employing the normorphine derivatives |
| US4269843A (en) * | 1978-05-24 | 1981-05-26 | Sri International | N-Sec-alkyl analogs of norcodeine and normorphine and analgesic compositions and methods employing the normorphine derivatives |
-
1986
- 1986-03-24 US US06/843,150 patent/US4749706A/en not_active Expired - Lifetime
-
1987
- 1987-02-06 DE DE3790166A patent/DE3790166C2/de not_active Expired - Fee Related
- 1987-02-06 EP EP87901256A patent/EP0261148B1/en not_active Expired - Lifetime
- 1987-02-06 WO PCT/US1987/000253 patent/WO1987005903A2/en active IP Right Grant
- 1987-02-06 NL NL8720049A patent/NL8720049A/nl not_active Application Discontinuation
- 1987-02-06 DE DE19873790166 patent/DE3790166T1/de active Pending
- 1987-02-06 JP JP62501220A patent/JPH085889B2/ja not_active Expired - Lifetime
- 1987-02-06 GB GB8726032A patent/GB2198435B/en not_active Expired - Lifetime
- 1987-03-23 CA CA000532714A patent/CA1313868C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH085889B2 (ja) | 1996-01-24 |
| GB2198435A (en) | 1988-06-15 |
| JPS63502825A (ja) | 1988-10-20 |
| US4749706A (en) | 1988-06-07 |
| WO1987005903A3 (en) | 1987-11-05 |
| DE3790166C2 (de) | 1998-08-13 |
| GB8726032D0 (en) | 1987-12-09 |
| EP0261148A1 (en) | 1988-03-30 |
| EP0261148B1 (en) | 1992-01-02 |
| WO1987005903A2 (en) | 1987-10-08 |
| CA1313868C (en) | 1993-02-23 |
| DE3790166T1 (no) | 1988-06-23 |
| GB2198435B (en) | 1990-12-12 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| BV | The patent application has lapsed |