TW201016677A - Novel derivatives - Google Patents
Novel derivatives Download PDFInfo
- Publication number
- TW201016677A TW201016677A TW098123842A TW98123842A TW201016677A TW 201016677 A TW201016677 A TW 201016677A TW 098123842 A TW098123842 A TW 098123842A TW 98123842 A TW98123842 A TW 98123842A TW 201016677 A TW201016677 A TW 201016677A
- Authority
- TW
- Taiwan
- Prior art keywords
- phenyl
- trifluoromethyl
- mmol
- carbonyl
- sulfonyl
- Prior art date
Links
- 238000000034 method Methods 0.000 claims abstract description 97
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 219
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 139
- -1 2-methyl-3-acridinyl Chemical group 0.000 claims description 100
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 91
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 88
- 150000003839 salts Chemical class 0.000 claims description 55
- 229910052739 hydrogen Inorganic materials 0.000 claims description 53
- 239000001257 hydrogen Substances 0.000 claims description 52
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 46
- 239000002253 acid Substances 0.000 claims description 43
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 40
- 125000000217 alkyl group Chemical group 0.000 claims description 37
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
- 208000002193 Pain Diseases 0.000 claims description 30
- 230000036407 pain Effects 0.000 claims description 27
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- 239000000463 material Substances 0.000 claims description 22
- 125000004076 pyridyl group Chemical group 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- 238000003971 tillage Methods 0.000 claims description 11
- 125000001188 haloalkyl group Chemical group 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 7
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Natural products C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims description 7
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 7
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 7
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 239000002689 soil Substances 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 4
- 230000000739 chaotic effect Effects 0.000 claims description 4
- 125000006612 decyloxy group Chemical group 0.000 claims description 4
- 229910052805 deuterium Inorganic materials 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 2
- XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical group [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 claims 1
- 125000005577 anthracene group Chemical group 0.000 claims 1
- 125000002393 azetidinyl group Chemical group 0.000 claims 1
- 229910052754 neon Inorganic materials 0.000 claims 1
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 claims 1
- 230000008569 process Effects 0.000 abstract description 36
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 12
- 101000935123 Homo sapiens Voltage-dependent N-type calcium channel subunit alpha-1B Proteins 0.000 abstract description 10
- 102100025342 Voltage-dependent N-type calcium channel subunit alpha-1B Human genes 0.000 abstract description 10
- 201000010099 disease Diseases 0.000 abstract description 8
- 230000000903 blocking effect Effects 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract 1
- 150000004885 piperazines Chemical class 0.000 abstract 1
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 362
- 235000019439 ethyl acetate Nutrition 0.000 description 179
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 135
- 239000000243 solution Substances 0.000 description 105
- 239000000203 mixture Substances 0.000 description 99
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 91
- 239000011541 reaction mixture Substances 0.000 description 76
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- 206010057190 Respiratory tract infections Diseases 0.000 description 66
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
- 238000006243 chemical reaction Methods 0.000 description 53
- 239000002585 base Substances 0.000 description 50
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 45
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- 239000012044 organic layer Substances 0.000 description 41
- XKRFYHLGVUSROY-UHFFFAOYSA-N argon Substances [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 40
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 32
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 31
- 238000003756 stirring Methods 0.000 description 31
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 30
- 239000007787 solid Substances 0.000 description 30
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- 239000000047 product Substances 0.000 description 29
- 239000010410 layer Substances 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 25
- UXRDAJMOOGEIAQ-CKOZHMEPSA-N [(8r,9s,10r,13s,14s,17r)-17-acetyl-10,13-dimethyl-16-methylidene-3-oxo-1,2,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1=CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC(=C)[C@](OC(=O)C)(C(C)=O)[C@@]1(C)CC2 UXRDAJMOOGEIAQ-CKOZHMEPSA-N 0.000 description 23
- 239000013058 crude material Substances 0.000 description 22
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
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- 239000007789 gas Substances 0.000 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- 230000002829 reductive effect Effects 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 15
- 239000003643 water by type Substances 0.000 description 15
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 14
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- 150000002148 esters Chemical class 0.000 description 12
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- 238000000746 purification Methods 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 11
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- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 11
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 11
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
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- 238000012360 testing method Methods 0.000 description 10
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- 239000000706 filtrate Substances 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
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- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 7
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- 230000008020 evaporation Effects 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
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- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
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- A—HUMAN NECESSITIES
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (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)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
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| GBGB0813142.7A GB0813142D0 (en) | 2008-07-17 | 2008-07-17 | Novel compounds |
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| ES (2) | ES2396962T3 (enExample) |
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| IL (1) | IL210446A (enExample) |
| MX (1) | MX2011000600A (enExample) |
| PL (1) | PL2300432T3 (enExample) |
| TW (1) | TW201016677A (enExample) |
| UY (1) | UY31990A (enExample) |
| WO (2) | WO2010007072A1 (enExample) |
| ZA (1) | ZA201100014B (enExample) |
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| GB0813142D0 (en) * | 2008-07-17 | 2008-08-27 | Glaxo Group Ltd | Novel compounds |
| GB201000685D0 (en) | 2010-01-15 | 2010-03-03 | Glaxo Group Ltd | Novel compounds |
| EP2665729B1 (en) * | 2011-01-19 | 2015-04-01 | Convergence Pharmaceuticals Limited | Piperazine derivatives as cav2.2 calcium channel blockers |
| CN103781759B (zh) | 2011-06-27 | 2016-01-13 | 纽朗制药有限公司 | 氟化的芳基烷基氨基甲酰胺衍生物 |
| EP3495360A1 (en) * | 2014-04-14 | 2019-06-12 | Grünenthal GmbH | Heteroaryl substituted heterocyclyl sulfones |
| US9896440B2 (en) | 2014-04-14 | 2018-02-20 | Grünenthal GmbH | Aryl substituted heterocyclyl sulfones |
| GB201516183D0 (en) * | 2015-09-14 | 2015-10-28 | Calchan Ltd | Novel pharmaceutical composition |
| TW201718557A (zh) | 2015-10-08 | 2017-06-01 | 歌林達有限公司 | 經吡唑基取代之四氫吡喃基碸 |
| TW201726128A (zh) | 2015-10-08 | 2017-08-01 | 歌林達有限公司 | 經吡唑基取代之四氫哌喃基碸 |
| MX2019012818A (es) * | 2017-04-26 | 2020-07-14 | Cavion Inc | Metodos para mejorar la memoria y la cognicion y para el tratamiento de trastornos de la memoria y cognitivos. |
| CN118085389B (zh) * | 2024-03-11 | 2024-11-05 | 伟建实业(苏州)有限公司 | 一种环保型抗菌海绵及其制备方法 |
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- 2009-07-15 JP JP2011517910A patent/JP5688850B2/ja not_active Expired - Fee Related
- 2009-07-15 PL PL09780587T patent/PL2300432T3/pl unknown
- 2009-07-15 EP EP09780587A patent/EP2300432B1/en not_active Not-in-force
- 2009-07-15 ES ES09780586T patent/ES2396960T3/es active Active
- 2009-07-15 EP EP09780586A patent/EP2346828B1/en not_active Not-in-force
- 2009-07-15 KR KR1020117001109A patent/KR101599087B1/ko not_active Expired - Fee Related
- 2009-07-15 JP JP2011517911A patent/JP5543966B2/ja not_active Expired - Fee Related
- 2009-07-15 AR ARP090102692A patent/AR072809A1/es unknown
- 2009-07-15 US US12/503,125 patent/US8288388B2/en not_active Expired - Fee Related
-
2011
- 2011-01-03 ZA ZA2011/00014A patent/ZA201100014B/en unknown
- 2011-01-03 IL IL210446A patent/IL210446A/en not_active IP Right Cessation
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2012
- 2012-08-07 US US13/568,211 patent/US8536183B2/en not_active Expired - Fee Related
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