CN1073085C - O－去甲基曲马多对映体的制备方法 - Google Patents
O－去甲基曲马多对映体的制备方法 Download PDFInfo
- Publication number
- CN1073085C CN1073085C CN97102072A CN97102072A CN1073085C CN 1073085 C CN1073085 C CN 1073085C CN 97102072 A CN97102072 A CN 97102072A CN 97102072 A CN97102072 A CN 97102072A CN 1073085 C CN1073085 C CN 1073085C
- Authority
- CN
- China
- Prior art keywords
- tramadol
- base
- enantiomer
- salt
- alkali
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims abstract description 20
- 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 title 1
- UWJUQVWARXYRCG-UHFFFAOYSA-N o-desmethyltramadol Chemical compound CN(C)CC1CCCCC1(O)C1=CC=CC(O)=C1 UWJUQVWARXYRCG-UHFFFAOYSA-N 0.000 title 1
- 239000000730 antalgic agent Substances 0.000 claims abstract description 6
- UWJUQVWARXYRCG-HIFRSBDPSA-N O-Desmethyltramadol Chemical class CN(C)C[C@H]1CCCC[C@]1(O)C1=CC=CC(O)=C1 UWJUQVWARXYRCG-HIFRSBDPSA-N 0.000 claims abstract 6
- 229940035676 analgesics Drugs 0.000 claims abstract 3
- 239000003513 alkali Substances 0.000 claims description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 28
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 25
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- TVYLLZQTGLZFBW-ZBFHGGJFSA-N (R,R)-tramadol Chemical class COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-ZBFHGGJFSA-N 0.000 claims description 14
- 230000000202 analgesic effect Effects 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 10
- 229960004380 tramadol Drugs 0.000 claims description 10
- 239000002585 base Substances 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 8
- TVYLLZQTGLZFBW-GOEBONIOSA-N tramadol Natural products COC1=CC=CC([C@@]2(O)[C@@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-GOEBONIOSA-N 0.000 claims description 8
- 238000002425 crystallisation Methods 0.000 claims description 7
- 230000008025 crystallization Effects 0.000 claims description 7
- 229940095064 tartrate Drugs 0.000 claims description 7
- 239000012452 mother liquor Substances 0.000 claims description 6
- 238000001556 precipitation Methods 0.000 claims description 3
- 125000001931 aliphatic group Chemical group 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims 3
- 235000011002 L(+)-tartaric acid Nutrition 0.000 claims 2
- 239000001358 L(+)-tartaric acid Substances 0.000 claims 2
- FEWJPZIEWOKRBE-LWMBPPNESA-N L-(+)-Tartaric acid Natural products OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 claims 2
- 239000004480 active ingredient Substances 0.000 claims 2
- 238000003916 acid precipitation Methods 0.000 claims 1
- 235000002906 tartaric acid Nutrition 0.000 claims 1
- 239000011975 tartaric acid Substances 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- PPKXEPBICJTCRU-XMZRARIVSA-N (R,R)-tramadol hydrochloride Chemical compound Cl.COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 PPKXEPBICJTCRU-XMZRARIVSA-N 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 239000000243 solution Substances 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- 230000036407 pain Effects 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000000967 suction filtration Methods 0.000 description 6
- 238000010253 intravenous injection Methods 0.000 description 5
- 235000011121 sodium hydroxide Nutrition 0.000 description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 150000004054 benzoquinones Chemical class 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 239000005046 Chlorosilane Substances 0.000 description 3
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical compound Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 description 3
- 238000005336 cracking Methods 0.000 description 3
- -1 demethyl U-26225A Chemical compound 0.000 description 3
- 238000007599 discharging Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000010813 municipal solid waste Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 230000036592 analgesia Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229940127240 opiate Drugs 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical class O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 1
- IRGWVAWLHXDKIX-PBCQUBLHSA-N 3-[(1r,2r)-2-[(dimethylamino)methyl]-1-hydroxycyclohexyl]phenol;hydrochloride Chemical compound Cl.CN(C)C[C@H]1CCCC[C@]1(O)C1=CC=CC(O)=C1 IRGWVAWLHXDKIX-PBCQUBLHSA-N 0.000 description 1
- IRGWVAWLHXDKIX-NQQJLSKUSA-N 3-[(1s,2s)-2-[(dimethylamino)methyl]-1-hydroxycyclohexyl]phenol;hydrochloride Chemical compound Cl.CN(C)C[C@@H]1CCCC[C@@]1(O)C1=CC=CC(O)=C1 IRGWVAWLHXDKIX-NQQJLSKUSA-N 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 206010052804 Drug tolerance Diseases 0.000 description 1
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 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 1
- 229960004126 codeine Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000026781 habituation Effects 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 description 1
- 229960000240 hydrocodone Drugs 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 description 1
- 229960002085 oxycodone Drugs 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- LLPOLZWFYMWNKH-UHFFFAOYSA-N trans-dihydrocodeinone Natural products C1C(N(CCC234)C)C2CCC(=O)C3OC2=C4C1=CC=C2OC LLPOLZWFYMWNKH-UHFFFAOYSA-N 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/10—Separation; Purification; Stabilisation; Use of additives
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19601744.0 | 1996-01-19 | ||
| DE19601744A DE19601744C2 (de) | 1996-01-19 | 1996-01-19 | Verfahren zur Herstellung der Enantiomeren von O-Demethyltramadol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1167107A CN1167107A (zh) | 1997-12-10 |
| CN1073085C true CN1073085C (zh) | 2001-10-17 |
Family
ID=7783111
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN97102072A Expired - Fee Related CN1073085C (zh) | 1996-01-19 | 1997-01-17 | O－去甲基曲马多对映体的制备方法 |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US5728885A (enExample) |
| EP (1) | EP0786450B1 (enExample) |
| JP (1) | JPH09216857A (enExample) |
| KR (1) | KR100507396B1 (enExample) |
| CN (1) | CN1073085C (enExample) |
| AR (1) | AR005390A1 (enExample) |
| AT (1) | ATE191454T1 (enExample) |
| AU (1) | AU705195B2 (enExample) |
| BR (1) | BR9700079A (enExample) |
| CA (1) | CA2195372C (enExample) |
| CO (1) | CO4520186A1 (enExample) |
| CZ (1) | CZ292427B6 (enExample) |
| DE (2) | DE19601744C2 (enExample) |
| DK (1) | DK0786450T3 (enExample) |
| ES (1) | ES2147341T3 (enExample) |
| GR (1) | GR3033390T3 (enExample) |
| HU (1) | HU223661B1 (enExample) |
| IL (1) | IL120029A (enExample) |
| IN (1) | IN181540B (enExample) |
| MY (1) | MY116593A (enExample) |
| NO (1) | NO306943B1 (enExample) |
| NZ (1) | NZ299998A (enExample) |
| PE (1) | PE29998A1 (enExample) |
| PL (1) | PL187373B1 (enExample) |
| PT (1) | PT786450E (enExample) |
| RU (1) | RU2185371C2 (enExample) |
| SI (1) | SI0786450T1 (enExample) |
| SK (1) | SK282629B6 (enExample) |
| UA (1) | UA45342C2 (enExample) |
| UY (1) | UY24438A1 (enExample) |
| ZA (1) | ZA97367B (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19712398A1 (de) * | 1997-03-25 | 1998-10-01 | Gruenenthal Gmbh | Orale Anwendung von (+)-0-Demethyltramadol als Schmerzmittel |
| PE20010623A1 (es) | 1999-10-05 | 2001-07-07 | Gruenenthal Chemie | Uso de (+)-tramadol y/o o-demetiltramadol para tratamiento de urgencia urinaria incrementada y/o incontinencia urinaria |
| US6297286B1 (en) * | 1999-11-09 | 2001-10-02 | Darwin Discovery, Ltd. | Therapeutic use and formulation |
| DE10049483A1 (de) | 2000-09-29 | 2002-05-02 | Gruenenthal Gmbh | Substituierte 1-Aminobutan-3-ol-Derivate |
| DE10108122A1 (de) | 2001-02-21 | 2002-10-02 | Gruenenthal Gmbh | Arzneimittel auf Basis von Tramadol |
| DE10108123A1 (de) * | 2001-02-21 | 2002-10-02 | Gruenenthal Gmbh | Wirkstoffkombination |
| DE10109763A1 (de) * | 2001-02-28 | 2002-09-05 | Gruenenthal Gmbh | Pharmazeutische Salze |
| US20050176790A1 (en) | 2001-02-28 | 2005-08-11 | Johannes Bartholomaus | Pharmaceutical salts |
| DE60211689T2 (de) | 2001-03-16 | 2007-01-11 | DMI Biosciences, Inc., Englewood | Verwendung von Tramadol zur Verzögerung der Ejakulation |
| US6649783B2 (en) | 2001-10-03 | 2003-11-18 | Euro-Celtique, S.A. | Synthesis of (+/-)-2-((dimethylamino)methyl)-1-(aryl)cyclohexanols |
| AU2002364517A1 (en) | 2001-11-30 | 2003-06-17 | Sepracor Inc. | Tramadol analogs and uses thereof |
| US20040248979A1 (en) * | 2003-06-03 | 2004-12-09 | Dynogen Pharmaceuticals, Inc. | Method of treating lower urinary tract disorders |
| DE102005033732B4 (de) | 2005-05-27 | 2014-02-13 | Grünenthal GmbH | Trennung stereoisomerer N,N-Dialkylamino-2-alkyl-3-hydroxy-3-phenyl-alkane |
| EP1785412A1 (en) * | 2005-11-14 | 2007-05-16 | IPCA Laboratories Limited | Tramadol recovery process |
| MX2009008511A (es) | 2007-02-12 | 2010-01-20 | Dmi Biosciences Inc | Reduccion de efectos secundarios de tramadol. |
| EP2120570B1 (en) | 2007-02-12 | 2012-05-16 | DMI Biosciences, Inc. | Treatment of comorbid premature ejaculation and erectile dysfunction |
| EP2545027A1 (de) * | 2010-03-10 | 2013-01-16 | Grünenthal GmbH | Kristalline salze und/oder cokristalle von o-desmethyltramadol |
| EP2383255A1 (en) | 2010-04-28 | 2011-11-02 | Lacer, S.A. | New compounds, synthesis and use thereof in the treatment of pain |
| EP2530072A1 (en) | 2011-06-03 | 2012-12-05 | Lacer, S.A. | New compounds, synthesis and use thereof in the treatment of pain |
| US10702485B2 (en) | 2011-07-09 | 2020-07-07 | Syntrix Biosystems Inc. | Compositions and methods for overcoming resistance to tramadol |
| US10781163B2 (en) | 2017-09-18 | 2020-09-22 | R L Finechem Private Limited | Process for preparation of O-Desmethyltramadol and salts thereof |
| US11000488B2 (en) | 2019-03-22 | 2021-05-11 | Syntrix Biosystems Inc. | Treating pain using desmetramadol |
| CN118108610B (zh) * | 2024-04-30 | 2025-01-10 | 山东新华制药股份有限公司 | 盐酸去甲曲马多的制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0534628A1 (en) * | 1991-09-06 | 1993-03-31 | Mcneilab, Inc. | Compositions comprising a tramadol material and any of codeine, oxycodone or hydrocodone, and their use |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1518663A1 (de) * | 1965-08-02 | 1969-12-18 | Gruenenthal Chemie | Basisch substituierte Cycloalken-derivate und Verfahren zu ihrer Herstellung |
| US3652589A (en) * | 1967-07-27 | 1972-03-28 | Gruenenthal Chemie | 1-(m-substituted phenyl)-2-aminomethyl cyclohexanols |
| US3652289A (en) * | 1970-07-20 | 1972-03-28 | Eastman Kodak Co | Silver halide emulsions and elements comprising trimethine hemioxonal dyes |
| WO1993004675A1 (en) | 1991-09-06 | 1993-03-18 | Mcneilab, Inc. | Composition comprising a tramadol material and acetaminophen and its use |
| JPH06122686A (ja) * | 1992-10-12 | 1994-05-06 | Fujisawa Pharmaceut Co Ltd | ラセミ体の光学分割法 |
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| EP0534628A1 (en) * | 1991-09-06 | 1993-03-31 | Mcneilab, Inc. | Compositions comprising a tramadol material and any of codeine, oxycodone or hydrocodone, and their use |
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| ENANTIOMERS,RACEOATES AND RESOLUTIONS 1991.1.1 U.UACQUES ET AL. KRIEGER PUBLISHING COMPANY. MALABAR,FLORIDA * |
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