CA2922340A1 - Ketamine derivatives - Google Patents
Ketamine derivatives Download PDFInfo
- Publication number
- CA2922340A1 CA2922340A1 CA2922340A CA2922340A CA2922340A1 CA 2922340 A1 CA2922340 A1 CA 2922340A1 CA 2922340 A CA2922340 A CA 2922340A CA 2922340 A CA2922340 A CA 2922340A CA 2922340 A1 CA2922340 A1 CA 2922340A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- optionally substituted
- oxocyclohexyl
- amino
- halo
- 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.)
- Abandoned
Links
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical class C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 title abstract description 35
- 238000000034 method Methods 0.000 claims abstract description 76
- 208000002193 Pain Diseases 0.000 claims abstract description 18
- 230000036407 pain Effects 0.000 claims abstract description 18
- 230000001624 sedative effect Effects 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 137
- 239000001257 hydrogen Substances 0.000 claims description 69
- 229910052739 hydrogen Inorganic materials 0.000 claims description 69
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 64
- 125000005843 halogen group Chemical group 0.000 claims description 55
- 125000000217 alkyl group Chemical group 0.000 claims description 51
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 48
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
- 150000002431 hydrogen Chemical group 0.000 claims description 31
- -1 NR11-12 Chemical group 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 27
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 25
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 25
- 101100240517 Caenorhabditis elegans nhr-11 gene Proteins 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 claims description 20
- 206010039897 Sedation Diseases 0.000 claims description 20
- 230000036280 sedation Effects 0.000 claims description 19
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 18
- 206010002091 Anaesthesia Diseases 0.000 claims description 15
- 230000037005 anaesthesia Effects 0.000 claims description 14
- 125000000623 heterocyclic group Chemical group 0.000 claims description 14
- 230000001939 inductive effect Effects 0.000 claims description 14
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 13
- 238000001949 anaesthesia Methods 0.000 claims description 13
- 239000012453 solvate Substances 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 10
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 125000001931 aliphatic group Chemical group 0.000 claims description 6
- 230000036592 analgesia Effects 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 238000001356 surgical procedure Methods 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- BEMFAESGNZMDAI-UHFFFAOYSA-N 3-[[1-(2-chlorophenyl)-2-oxocyclohexyl]amino]propyl acetate Chemical compound C=1C=CC=C(Cl)C=1C1(NCCCOC(=O)C)CCCCC1=O BEMFAESGNZMDAI-UHFFFAOYSA-N 0.000 claims 1
- GNIZNSSNZICSGW-UHFFFAOYSA-N ethyl 3-[[1-(2-chlorophenyl)-2-oxocyclohexyl]-methylamino]propanoate Chemical compound C=1C=CC=C(Cl)C=1C1(N(C)CCC(=O)OCC)CCCCC1=O GNIZNSSNZICSGW-UHFFFAOYSA-N 0.000 claims 1
- OSYLIDUZSLQOIW-UHFFFAOYSA-N ethyl 3-[[1-(2-chlorophenyl)-2-oxocyclohexyl]amino]propanoate Chemical compound C=1C=CC=C(Cl)C=1C1(NCCC(=O)OCC)CCCCC1=O OSYLIDUZSLQOIW-UHFFFAOYSA-N 0.000 claims 1
- FZIHUEMGZWQMJF-UHFFFAOYSA-N ethyl 4-[[1-(2-chlorophenyl)-2-oxocyclohexyl]amino]butanoate Chemical compound C=1C=CC=C(Cl)C=1C1(NCCCC(=O)OCC)CCCCC1=O FZIHUEMGZWQMJF-UHFFFAOYSA-N 0.000 claims 1
- KFZMXHQTFSGYLL-UHFFFAOYSA-N ethyl 5-[[1-(2-chlorophenyl)-2-oxocyclohexyl]amino]pentanoate Chemical compound C=1C=CC=C(Cl)C=1C1(NCCCCC(=O)OCC)CCCCC1=O KFZMXHQTFSGYLL-UHFFFAOYSA-N 0.000 claims 1
- DXFKXPYVXFWPHN-UHFFFAOYSA-N methyl 4-[[1-(2-chlorophenyl)-2-oxocyclohexyl]amino]pentanoate Chemical compound C=1C=CC=C(Cl)C=1C1(NC(C)CCC(=O)OC)CCCCC1=O DXFKXPYVXFWPHN-UHFFFAOYSA-N 0.000 claims 1
- FRANGXMVILSKAR-UHFFFAOYSA-N methyl 5-[[1-(2-chlorophenyl)-2-oxocyclohexyl]-methylamino]pentanoate Chemical compound C=1C=CC=C(Cl)C=1C1(N(C)CCCCC(=O)OC)CCCCC1=O FRANGXMVILSKAR-UHFFFAOYSA-N 0.000 claims 1
- OYHDMPDRGZQTIM-UHFFFAOYSA-N propan-2-yl 3-[[1-(2-chlorophenyl)-2-oxocyclohexyl]amino]propanoate Chemical compound C=1C=CC=C(Cl)C=1C1(NCCC(=O)OC(C)C)CCCCC1=O OYHDMPDRGZQTIM-UHFFFAOYSA-N 0.000 claims 1
- UMTAVENMCNHZKS-UHFFFAOYSA-N propan-2-yl 4-[[1-(2-chlorophenyl)-2-oxocyclohexyl]amino]butanoate Chemical compound C=1C=CC=C(Cl)C=1C1(NCCCC(=O)OC(C)C)CCCCC1=O UMTAVENMCNHZKS-UHFFFAOYSA-N 0.000 claims 1
- VELFQRXGQQEDQS-UHFFFAOYSA-N propan-2-yl 5-[[1-(2-chlorophenyl)-2-oxocyclohexyl]amino]pentanoate Chemical compound C=1C=CC=C(Cl)C=1C1(NCCCCC(=O)OC(C)C)CCCCC1=O VELFQRXGQQEDQS-UHFFFAOYSA-N 0.000 claims 1
- GSLQTNIISBAJKM-UHFFFAOYSA-N propyl 3-[[1-(2-chlorophenyl)-2-oxocyclohexyl]amino]propanoate Chemical compound C=1C=CC=C(Cl)C=1C1(NCCC(=O)OCCC)CCCCC1=O GSLQTNIISBAJKM-UHFFFAOYSA-N 0.000 claims 1
- MDFUNBBVYZXYJZ-UHFFFAOYSA-N propyl 5-[[1-(2-chlorophenyl)-2-oxocyclohexyl]amino]pentanoate Chemical compound C=1C=CC=C(Cl)C=1C1(NCCCCC(=O)OCCC)CCCCC1=O MDFUNBBVYZXYJZ-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 22
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 101150041968 CDC13 gene Proteins 0.000 description 44
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 44
- 229960003299 ketamine Drugs 0.000 description 43
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 28
- 239000000203 mixture Substances 0.000 description 24
- 238000005160 1H NMR spectroscopy Methods 0.000 description 22
- 239000000243 solution Substances 0.000 description 22
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 20
- 239000002904 solvent Substances 0.000 description 19
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 241001465754 Metazoa Species 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 238000001802 infusion Methods 0.000 description 15
- 230000003444 anaesthetic effect Effects 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- BEQZHFIKTBVCAU-UHFFFAOYSA-N 2-amino-2-(2-chlorophenyl)-1-cyclohexanone Chemical compound C=1C=CC=C(Cl)C=1C1(N)CCCCC1=O BEQZHFIKTBVCAU-UHFFFAOYSA-N 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000011084 recovery Methods 0.000 description 12
- 230000028527 righting reflex Effects 0.000 description 12
- 238000001990 intravenous administration Methods 0.000 description 11
- 230000003389 potentiating effect Effects 0.000 description 11
- 125000003118 aryl group Chemical group 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 125000004122 cyclic group Chemical group 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 125000003342 alkenyl group Chemical group 0.000 description 8
- 239000007789 gas Substances 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- BEQZHFIKTBVCAU-LBPRGKRZSA-N (2s)-2-amino-2-(2-chlorophenyl)cyclohexan-1-one Chemical compound C=1C=CC=C(Cl)C=1[C@@]1(N)CCCCC1=O BEQZHFIKTBVCAU-LBPRGKRZSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
- 230000000202 analgesic effect Effects 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical group [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 208000012802 recumbency Diseases 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 235000015320 potassium carbonate Nutrition 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 230000011514 reflex Effects 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- QIJMMRNZBJHXRI-UHFFFAOYSA-N (2-chlorophenyl)-cyclopentylmethanone Chemical compound ClC1=CC=CC=C1C(=O)C1CCCC1 QIJMMRNZBJHXRI-UHFFFAOYSA-N 0.000 description 4
- YQEZLKZALYSWHR-ZDUSSCGKSA-N (S)-ketamine Chemical compound C=1C=CC=C(Cl)C=1[C@@]1(NC)CCCCC1=O YQEZLKZALYSWHR-ZDUSSCGKSA-N 0.000 description 4
- FGTRLPFQPZJCQO-UHFFFAOYSA-N 2-iminocyclopentan-1-ol Chemical compound OC1CCCC1=N FGTRLPFQPZJCQO-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 101001132698 Homo sapiens Retinoic acid receptor beta Proteins 0.000 description 4
- 102100033909 Retinoic acid receptor beta Human genes 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 150000001350 alkyl halides Chemical class 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 230000000147 hypnotic effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 229940090181 propyl acetate Drugs 0.000 description 4
- 238000006485 reductive methylation reaction Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- 239000000932 sedative agent Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- DDVNLGGCSRULIL-UHFFFAOYSA-N (1-bromocyclopentyl)-(2-chlorophenyl)methanone Chemical compound ClC1=CC=CC=C1C(=O)C1(Br)CCCC1 DDVNLGGCSRULIL-UHFFFAOYSA-N 0.000 description 3
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical group N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- WNXNUPJZWYOKMW-UHFFFAOYSA-M 5-bromopentanoate Chemical compound [O-]C(=O)CCCCBr WNXNUPJZWYOKMW-UHFFFAOYSA-M 0.000 description 3
- 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 description 3
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229940124326 anaesthetic agent Drugs 0.000 description 3
- 229940035676 analgesics Drugs 0.000 description 3
- 239000000730 antalgic agent Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- FQTIYMRSUOADDK-UHFFFAOYSA-N ethyl 3-bromopropanoate Chemical compound CCOC(=O)CCBr FQTIYMRSUOADDK-UHFFFAOYSA-N 0.000 description 3
- AFRWBGJRWRHQOV-UHFFFAOYSA-N ethyl 5-bromopentanoate Chemical compound CCOC(=O)CCCCBr AFRWBGJRWRHQOV-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- KQNJUTDIDREYGN-UHFFFAOYSA-N propan-2-yl 3-bromopropanoate Chemical compound CC(C)OC(=O)CCBr KQNJUTDIDREYGN-UHFFFAOYSA-N 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 229940125723 sedative agent Drugs 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical class NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
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- 241000282326 Felis catus Species 0.000 description 2
- 241000270322 Lepidosauria Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 238000000065 atmospheric pressure chemical ionisation Methods 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
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- 229910052731 fluorine Inorganic materials 0.000 description 2
- 210000004744 fore-foot Anatomy 0.000 description 2
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- 239000012458 free base Substances 0.000 description 2
- 125000004438 haloalkoxy group Chemical group 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 229940005483 opioid analgesics Drugs 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
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- 238000000746 purification Methods 0.000 description 2
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- 238000011160 research Methods 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
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- DXFHVUUGWSXHQY-UHFFFAOYSA-N propyl 3-bromopropanoate Chemical compound CCCOC(=O)CCBr DXFHVUUGWSXHQY-UHFFFAOYSA-N 0.000 description 1
- FZPPRDIJOYTGRS-UHFFFAOYSA-N propyl 4-bromobutanoate Chemical compound CCCOC(=O)CCCBr FZPPRDIJOYTGRS-UHFFFAOYSA-N 0.000 description 1
- GKTWIJVDNVTXCV-UHFFFAOYSA-N propyl 5-bromopentanoate Chemical compound CCCOC(=O)CCCCBr GKTWIJVDNVTXCV-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000036387 respiratory rate Effects 0.000 description 1
- 235000019515 salmon Nutrition 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
- 230000001953 sensory effect Effects 0.000 description 1
- 230000020341 sensory perception of pain Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 238000013223 sprague-dawley female rat Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003419 tautomerization reaction Methods 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
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000005304 thiadiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000005455 trithianyl group Chemical group 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 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
- 230000001755 vocal effect Effects 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
- C07C229/10—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
- C07C229/14—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of carbon skeletons containing rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
- C07C225/20—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/46—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino or carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
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)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Anesthesiology (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NZ60288512 | 2012-10-08 | ||
| NZ602885 | 2012-10-08 | ||
| NZ61120213 | 2013-05-28 | ||
| NZ611202 | 2013-05-28 | ||
| PCT/IB2013/059191 WO2014057414A1 (en) | 2012-10-08 | 2013-10-08 | Ketamine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2922340A1 true CA2922340A1 (en) | 2014-04-17 |
Family
ID=50476991
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2922340A Abandoned CA2922340A1 (en) | 2012-10-08 | 2013-10-08 | Ketamine derivatives |
Country Status (13)
| Country | Link |
|---|---|
| US (3) | US20150259277A1 (show.php) |
| EP (1) | EP2903963A4 (show.php) |
| JP (2) | JP6309957B2 (show.php) |
| KR (1) | KR20150065873A (show.php) |
| CN (1) | CN104837810B (show.php) |
| AU (1) | AU2013328280B2 (show.php) |
| BR (1) | BR112015007647A2 (show.php) |
| CA (1) | CA2922340A1 (show.php) |
| EA (1) | EA201590697A1 (show.php) |
| HK (1) | HK1212673A1 (show.php) |
| IN (1) | IN2015DN03854A (show.php) |
| MX (1) | MX2015004362A (show.php) |
| WO (1) | WO2014057414A1 (show.php) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112015007647A2 (pt) * | 2012-10-08 | 2017-07-04 | Auckland Uniservices Ltd | derivados de quetamina |
| US20160332962A1 (en) * | 2015-05-13 | 2016-11-17 | Janssen Pharmaceutica Nv | (s)-csa salt of s-ketamine, (r)-csa salt of s-ketamine and processes for the preparation of s-ketamine |
| JP6845162B2 (ja) | 2015-06-27 | 2021-03-17 | シェノックス・ファーマシューティカルズ・エルエルシー | ケタミン経皮送達システム |
| US11827606B2 (en) | 2015-11-18 | 2023-11-28 | Spirify Pharma Inc. | Phenyl cyclohexanone derivatives and methods of making and using them |
| WO2017087388A1 (en) * | 2015-11-18 | 2017-05-26 | Mitchell Woods Pharmaceuticals, Inc. | Phenyl cyclohexanone derivatives and methods of making and using them |
| US10919842B2 (en) * | 2016-03-25 | 2021-02-16 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Crystal forms and methods of synthesis of (2R, 6R)-hydroxynorketamine and (2S, 6S)-hydroxynorketamine |
| JP7167168B2 (ja) * | 2018-01-10 | 2022-11-08 | エックスダブリューファルマ リミテッド | ケタミンのプロドラッグ、組成物及びそれらの使用 |
| EP3761970A4 (en) * | 2018-03-26 | 2022-06-08 | Cellix Bio Private Limited | COMPOSITIONS AND METHODS FOR THE TREATMENT OF NEUROLOGICAL DISEASES |
| US11186539B2 (en) | 2018-06-04 | 2021-11-30 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Process for synthesis and purification of (2R,6R)-hydroxynorketamine |
| CN112125816A (zh) * | 2020-03-17 | 2020-12-25 | 国药集团工业有限公司 | 一种氯胺酮、其衍生物或其盐的消旋化方法 |
| DE102021105268A1 (de) * | 2021-03-04 | 2022-09-08 | Lts Lohmann Therapie-Systeme Ag. | Oraler Dünnfilm |
| JP7737544B2 (ja) | 2021-08-13 | 2025-09-10 | エックスダブリューファーマ リミテッド | ケタミン誘導体の医薬組成物及び経口剤形 |
| CN115677444A (zh) * | 2022-10-26 | 2023-02-03 | 公安部第三研究所 | 同位素毒品代谢物标记化合物及其制备方法、用途 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3254124A (en) * | 1962-06-29 | 1966-05-31 | Parke Davis & Co | Aminoketones and methods for their production |
| GB1134146A (en) * | 1967-09-15 | 1968-11-20 | Parke Davis & Co | New organic amines and methods for their production |
| US5019583A (en) | 1989-02-15 | 1991-05-28 | Glaxo Inc. | N-phenyl-N-(4-piperidinyl)amides useful as analgesics |
| US5466700A (en) | 1993-08-30 | 1995-11-14 | Glaxo Wellcome Inc. | Anesthetic use of N-phenyl-N-(4-piperidinyl)amides |
| US5866591A (en) | 1996-09-11 | 1999-02-02 | Glaxo Wellcome Inc. | Stable formulations of remifentanil |
| CN1441790A (zh) * | 2000-01-28 | 2003-09-10 | 罗姆和哈斯公司 | 增强性质的药物 |
| US20040248963A1 (en) | 2001-11-23 | 2004-12-09 | Bueno Melendo Ana Belen | Prodrugs of excitatory amino acids |
| DE60335428D1 (de) | 2002-01-31 | 2011-02-03 | Randox Lab Ltd | Immunogene, Antikörper und Konjugate für Ketamin und dessen Metaboliten |
| AU2003291037A1 (en) * | 2002-11-18 | 2004-06-15 | Yaupon Therapeutics, Inc. | Analgesic uses of norketamine and ketamine/norketamine prodrugs |
| CN101309667A (zh) * | 2005-09-28 | 2008-11-19 | 奥里斯医学股份有限公司 | 治疗内耳疾病的药用合成物 |
| CN101765582A (zh) * | 2007-04-26 | 2010-06-30 | 奥斯拜客斯制药有限公司 | 氘标记的氯胺酮 |
| EP3904332B1 (en) | 2011-10-14 | 2024-12-04 | The United States of America, as represented by The Secretary, Department of Health and Human Services | The use of (2r, 6r)-hydroxynorketamine, (s)-dehydronorketamine and other stereoisomeric dehydro and hydroxylated metabolites of (r,s)- ketamine in the treatment of depression and neuropathic pain |
| BR112015007647A2 (pt) * | 2012-10-08 | 2017-07-04 | Auckland Uniservices Ltd | derivados de quetamina |
-
2013
- 2013-10-08 BR BR112015007647A patent/BR112015007647A2/pt not_active Application Discontinuation
- 2013-10-08 AU AU2013328280A patent/AU2013328280B2/en not_active Ceased
- 2013-10-08 WO PCT/IB2013/059191 patent/WO2014057414A1/en not_active Ceased
- 2013-10-08 KR KR1020157012009A patent/KR20150065873A/ko not_active Ceased
- 2013-10-08 CA CA2922340A patent/CA2922340A1/en not_active Abandoned
- 2013-10-08 MX MX2015004362A patent/MX2015004362A/es unknown
- 2013-10-08 US US14/433,957 patent/US20150259277A1/en not_active Abandoned
- 2013-10-08 CN CN201380061537.2A patent/CN104837810B/zh not_active Expired - Fee Related
- 2013-10-08 HK HK16100661.0A patent/HK1212673A1/zh unknown
- 2013-10-08 EA EA201590697A patent/EA201590697A1/ru unknown
- 2013-10-08 IN IN3854DEN2015 patent/IN2015DN03854A/en unknown
- 2013-10-08 EP EP13846133.0A patent/EP2903963A4/en not_active Withdrawn
- 2013-10-08 JP JP2015535162A patent/JP6309957B2/ja not_active Expired - Fee Related
-
2017
- 2017-03-20 US US15/463,532 patent/US10239825B2/en not_active Expired - Fee Related
-
2018
- 2018-03-14 JP JP2018046540A patent/JP2018127466A/ja active Pending
-
2019
- 2019-02-06 US US16/269,015 patent/US20190169113A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20150259277A1 (en) | 2015-09-17 |
| MX2015004362A (es) | 2015-12-08 |
| AU2013328280B2 (en) | 2017-12-21 |
| US20170190653A1 (en) | 2017-07-06 |
| EA201590697A1 (ru) | 2015-09-30 |
| EP2903963A4 (en) | 2016-05-25 |
| JP2018127466A (ja) | 2018-08-16 |
| JP6309957B2 (ja) | 2018-04-11 |
| US10239825B2 (en) | 2019-03-26 |
| AU2013328280A1 (en) | 2015-05-14 |
| KR20150065873A (ko) | 2015-06-15 |
| HK1212673A1 (zh) | 2016-06-17 |
| JP2015535847A (ja) | 2015-12-17 |
| CN104837810B (zh) | 2019-08-06 |
| WO2014057414A9 (en) | 2014-12-18 |
| WO2014057414A1 (en) | 2014-04-17 |
| BR112015007647A2 (pt) | 2017-07-04 |
| CN104837810A (zh) | 2015-08-12 |
| EP2903963A1 (en) | 2015-08-12 |
| IN2015DN03854A (show.php) | 2015-10-02 |
| US20190169113A1 (en) | 2019-06-06 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20180725 |
|
| FZDE | Discontinued |
Effective date: 20210831 |