JP4408804B2 - １−［（インドル−３−イル）カルボニル］ピペラジン誘導体 - Google Patents
１−［（インドル−３−イル）カルボニル］ピペラジン誘導体 Download PDFInfo
- Publication number
- JP4408804B2 JP4408804B2 JP2004514874A JP2004514874A JP4408804B2 JP 4408804 B2 JP4408804 B2 JP 4408804B2 JP 2004514874 A JP2004514874 A JP 2004514874A JP 2004514874 A JP2004514874 A JP 2004514874A JP 4408804 B2 JP4408804 B2 JP 4408804B2
- Authority
- JP
- Japan
- Prior art keywords
- carbonyl
- indol
- methoxy
- cyclohexylmethyl
- mmol
- 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
- FBXWDVALKBNEJV-UHFFFAOYSA-N 1h-indol-3-yl(piperazin-1-yl)methanone Chemical class C=1NC2=CC=CC=C2C=1C(=O)N1CCNCC1 FBXWDVALKBNEJV-UHFFFAOYSA-N 0.000 title claims description 25
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 31
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 24
- -1 R 2 is H Chemical group 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 208000002193 Pain Diseases 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 150000002367 halogens Chemical group 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 10
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 2
- NTIFEVGVXWYYHK-FQEVSTJZSA-N [(9as)-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-2-yl]-[1-(cyclohexylmethyl)-7-methoxyindol-3-yl]methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2C[C@@H]3CCCCN3CC2)=CN1CC1CCCCC1 NTIFEVGVXWYYHK-FQEVSTJZSA-N 0.000 claims description 2
- FSNJWYVUDGWBOO-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(4-ethyl-3,5-dimethylpiperazin-1-yl)methanone Chemical compound C1C(C)N(CC)C(C)CN1C(=O)C(C1=CC=CC(OC)=C11)=CN1CC1CCCCC1 FSNJWYVUDGWBOO-UHFFFAOYSA-N 0.000 claims description 2
- ONXJNAIZJKLJGA-KRWDZBQOSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-[(3s)-3,4-dimethylpiperazin-1-yl]methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2C[C@H](C)N(C)CC2)=CN1CC1CCCCC1 ONXJNAIZJKLJGA-KRWDZBQOSA-N 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- DMYGECJTVMCGEP-UHFFFAOYSA-N org 28312 Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2CC(C)N(C)C(C)C2)=CN1CC1CCCCC1 DMYGECJTVMCGEP-UHFFFAOYSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 2
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 96
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 88
- 150000001875 compounds Chemical class 0.000 description 85
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 78
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 48
- 239000000203 mixture Substances 0.000 description 43
- 238000005160 1H NMR spectroscopy Methods 0.000 description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 238000000034 method Methods 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 239000012458 free base Substances 0.000 description 21
- 239000007787 solid Substances 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 18
- 238000003818 flash chromatography Methods 0.000 description 13
- 239000002244 precipitate Substances 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 10
- 229930003827 cannabinoid Natural products 0.000 description 10
- 239000003557 cannabinoid Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 9
- 102000009132 CB1 Cannabinoid Receptor Human genes 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 239000000556 agonist Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 7
- 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 description 7
- 230000027455 binding Effects 0.000 description 7
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 229940005483 opioid analgesics Drugs 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- 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 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- 108700008625 Reporter Genes Proteins 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 150000001350 alkyl halides Chemical class 0.000 description 4
- UUWSLBWDFJMSFP-UHFFFAOYSA-N bromomethylcyclohexane Chemical compound BrCC1CCCCC1 UUWSLBWDFJMSFP-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- IBCZLOMXNJRQBF-UHFFFAOYSA-N 1-(1-cyclohexylethylsulfonyl)-4-methylbenzene Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)C(C)C1CCCCC1 IBCZLOMXNJRQBF-UHFFFAOYSA-N 0.000 description 3
- LEXVLCRGSBTKBD-UHFFFAOYSA-N 1-(cyclohexylmethyl)-7-methoxyindole-3-carboxylic acid Chemical compound C1=2C(OC)=CC=CC=2C(C(O)=O)=CN1CC1CCCCC1 LEXVLCRGSBTKBD-UHFFFAOYSA-N 0.000 description 3
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
- JTLAIKFGRHDNQM-UHFFFAOYSA-N 1-bromo-2-fluoroethane Chemical compound FCCBr JTLAIKFGRHDNQM-UHFFFAOYSA-N 0.000 description 3
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 3
- IFNWESYYDINUHV-UHFFFAOYSA-N 2,6-dimethylpiperazine Chemical compound CC1CNCC(C)N1 IFNWESYYDINUHV-UHFFFAOYSA-N 0.000 description 3
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 3
- 108050007331 Cannabinoid receptor Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 101000710899 Homo sapiens Cannabinoid receptor 1 Proteins 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 208000008238 Muscle Spasticity Diseases 0.000 description 3
- 235000019502 Orange oil Nutrition 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000002260 anti-inflammatory agent Substances 0.000 description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000003554 cannabinoid 1 receptor agonist Substances 0.000 description 3
- 239000003537 cannabinoid receptor agonist Substances 0.000 description 3
- 229940121376 cannabinoid receptor agonist Drugs 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 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
- 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 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 208000004296 neuralgia Diseases 0.000 description 3
- 208000021722 neuropathic pain Diseases 0.000 description 3
- 239000010502 orange oil Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 208000023504 respiratory system disease Diseases 0.000 description 3
- 208000018198 spasticity Diseases 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- SOUPGWGAPDMYFM-UHFFFAOYSA-N (1,4-dibenzylpiperazin-2-yl)methanol Chemical compound C1CN(CC=2C=CC=CC=2)C(CO)CN1CC1=CC=CC=C1 SOUPGWGAPDMYFM-UHFFFAOYSA-N 0.000 description 2
- JOMNTHCQHJPVAZ-YFKPBYRVSA-N (2s)-2-methylpiperazine Chemical compound C[C@H]1CNCCN1 JOMNTHCQHJPVAZ-YFKPBYRVSA-N 0.000 description 2
- ONHPOXROAPYCGT-MRVPVSSYSA-N (9ar)-2,3,4,6,7,8,9,9a-octahydro-1h-pyrido[1,2-a]pyrazine Chemical compound C1CNC[C@H]2CCCCN21 ONHPOXROAPYCGT-MRVPVSSYSA-N 0.000 description 2
- YXBLPNSWHUPKPH-ZCFIWIBFSA-N (9ar)-3,6,7,8,9,9a-hexahydro-2h-pyrido[1,2-a]pyrazine-1,4-dione Chemical compound C1CCC[C@@H]2C(=O)NCC(=O)N21 YXBLPNSWHUPKPH-ZCFIWIBFSA-N 0.000 description 2
- SDEMZAXQOIWPPI-UHFFFAOYSA-N 1,4-dibenzyl-2-(fluoromethyl)piperazine Chemical compound C1CN(CC=2C=CC=CC=2)C(CF)CN1CC1=CC=CC=C1 SDEMZAXQOIWPPI-UHFFFAOYSA-N 0.000 description 2
- NRUJFIWNKXQLBY-UHFFFAOYSA-N 1-(cyclohexylmethyl)-5-fluoroindole Chemical compound C1=CC2=CC(F)=CC=C2N1CC1CCCCC1 NRUJFIWNKXQLBY-UHFFFAOYSA-N 0.000 description 2
- SKOMDRUYRDPBLW-UHFFFAOYSA-N 1-(cyclohexylmethyl)-7-methoxyindole Chemical compound C1=2C(OC)=CC=CC=2C=CN1CC1CCCCC1 SKOMDRUYRDPBLW-UHFFFAOYSA-N 0.000 description 2
- AEHOLYXYGLDBHZ-UHFFFAOYSA-N 1-(cyclohexylmethyl)-7-methoxyindole-3-carbonyl chloride Chemical compound C1=2C(OC)=CC=CC=2C(C(Cl)=O)=CN1CC1CCCCC1 AEHOLYXYGLDBHZ-UHFFFAOYSA-N 0.000 description 2
- ICJUEVKACUMGHT-UHFFFAOYSA-N 1-(cyclopentylmethyl)-7-methoxyindole Chemical compound C1=2C(OC)=CC=CC=2C=CN1CC1CCCC1 ICJUEVKACUMGHT-UHFFFAOYSA-N 0.000 description 2
- TXIOGJHPPVXTOY-UHFFFAOYSA-N 1-ethyl-4-methylpiperazine Chemical compound CCN1CCN(C)CC1 TXIOGJHPPVXTOY-UHFFFAOYSA-N 0.000 description 2
- ICGDKKACLISIAM-UHFFFAOYSA-N 2,3,5,6-tetramethylpiperazine Chemical compound CC1NC(C)C(C)NC1C ICGDKKACLISIAM-UHFFFAOYSA-N 0.000 description 2
- ONUCCUGDWPXAJG-UHFFFAOYSA-N 2-(fluoromethyl)piperazine Chemical compound FCC1CNCCN1 ONUCCUGDWPXAJG-UHFFFAOYSA-N 0.000 description 2
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- 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 compound 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 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- WMYQAKANKREQLM-UHFFFAOYSA-N 7-chloro-1h-indole Chemical compound ClC1=CC=CC2=C1NC=C2 WMYQAKANKREQLM-UHFFFAOYSA-N 0.000 description 2
- XONKJZDHGCMRRF-UHFFFAOYSA-N 7-fluoro-1h-indole Chemical compound FC1=CC=CC2=C1NC=C2 XONKJZDHGCMRRF-UHFFFAOYSA-N 0.000 description 2
- FSOPPXYMWZOKRM-UHFFFAOYSA-N 7-methoxy-1h-indole Chemical compound COC1=CC=CC2=C1NC=C2 FSOPPXYMWZOKRM-UHFFFAOYSA-N 0.000 description 2
- MSALXMDIYCKASR-UHFFFAOYSA-N 7-methoxy-1h-indole-3-carboxylic acid Chemical compound COC1=CC=CC2=C1NC=C2C(O)=O MSALXMDIYCKASR-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- PBQULTIIYZCOQV-FJXQXJEOSA-N C(C)(C)(C)OC(=O)N1[C@@H](CCC1)C(=O)O.N1=CC=NC=C1 Chemical compound C(C)(C)(C)OC(=O)N1[C@@H](CCC1)C(=O)O.N1=CC=NC=C1 PBQULTIIYZCOQV-FJXQXJEOSA-N 0.000 description 2
- 102000009135 CB2 Cannabinoid Receptor Human genes 0.000 description 2
- 108010073376 CB2 Cannabinoid Receptor Proteins 0.000 description 2
- 206010058019 Cancer Pain Diseases 0.000 description 2
- 101710187010 Cannabinoid receptor 1 Proteins 0.000 description 2
- 102100033868 Cannabinoid receptor 1 Human genes 0.000 description 2
- 102100036214 Cannabinoid receptor 2 Human genes 0.000 description 2
- 101710187022 Cannabinoid receptor 2 Proteins 0.000 description 2
- 208000000094 Chronic Pain Diseases 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 2
- 239000003520 cannabinoid receptor affecting agent Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- VROBVTOKXNHTBI-UHFFFAOYSA-N cyclopentylmethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1CCCC1 VROBVTOKXNHTBI-UHFFFAOYSA-N 0.000 description 2
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
- 239000012971 dimethylpiperazine Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- KKXWTUYDLQVOOO-UHFFFAOYSA-N ethyl 1,4-dibenzylpiperazine-2-carboxylate Chemical compound C1CN(CC=2C=CC=CC=2)C(C(=O)OCC)CN1CC1=CC=CC=C1 KKXWTUYDLQVOOO-UHFFFAOYSA-N 0.000 description 2
- 150000004820 halides Chemical group 0.000 description 2
- KMAKOBLIOCQGJP-UHFFFAOYSA-N indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CNC2=C1 KMAKOBLIOCQGJP-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000005022 packaging material Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- BXRNXXXXHLBUKK-UHFFFAOYSA-N piperazine-2,5-dione Chemical compound O=C1CNC(=O)CN1 BXRNXXXXHLBUKK-UHFFFAOYSA-N 0.000 description 2
- 150000004885 piperazines Chemical class 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 1
- UGOXNBMKNGXLMK-UHFFFAOYSA-N (1-benzylindol-3-yl)-piperazin-1-ylmethanone Chemical class C=1N(CC=2C=CC=CC=2)C2=CC=CC=C2C=1C(=O)N1CCNCC1 UGOXNBMKNGXLMK-UHFFFAOYSA-N 0.000 description 1
- BZMMRNKDONDVIB-UHFFFAOYSA-N (1-ethoxycyclopropyl)oxy-trimethylsilane Chemical compound CCOC1(O[Si](C)(C)C)CC1 BZMMRNKDONDVIB-UHFFFAOYSA-N 0.000 description 1
- JOMNTHCQHJPVAZ-RXMQYKEDSA-N (2r)-2-methylpiperazine Chemical compound C[C@@H]1CNCCN1 JOMNTHCQHJPVAZ-RXMQYKEDSA-N 0.000 description 1
- NSMWYRLQHIXVAP-OLQVQODUSA-N (2r,5s)-2,5-dimethylpiperazine Chemical compound C[C@H]1CN[C@H](C)CN1 NSMWYRLQHIXVAP-OLQVQODUSA-N 0.000 description 1
- LRWMOBOBKJNRQR-BTJKTKAUSA-N (z)-but-2-enedioic acid;[1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound OC(=O)\C=C/C(O)=O.C1CN(CC)CCN1C(=O)C(C1=CC=CC(OC)=C11)=CN1CC1CCCCC1 LRWMOBOBKJNRQR-BTJKTKAUSA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical group C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 1
- GWXWMMZFCVXCLU-UHFFFAOYSA-N 1-(1-cyclohexylpropylsulfonyl)-4-methylbenzene Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)C(CC)C1CCCCC1 GWXWMMZFCVXCLU-UHFFFAOYSA-N 0.000 description 1
- LIUAALCHBQSCCX-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octane-2-carboxylate Chemical compound C1CN2C(C(=O)O)CC1CC2 LIUAALCHBQSCCX-UHFFFAOYSA-N 0.000 description 1
- XBZQMVYXYKDYPA-UHFFFAOYSA-N 1-ethylsulfonyl-4-methylbenzene Chemical compound CCS(=O)(=O)C1=CC=C(C)C=C1 XBZQMVYXYKDYPA-UHFFFAOYSA-N 0.000 description 1
- WHKWMTXTYKVFLK-UHFFFAOYSA-N 1-propan-2-ylpiperazine Chemical compound CC(C)N1CCNCC1 WHKWMTXTYKVFLK-UHFFFAOYSA-N 0.000 description 1
- VVSCWULFMZPYPU-UHFFFAOYSA-N 2,2,2-trifluoro-1-(7-methoxy-1h-indol-3-yl)ethanone Chemical compound COC1=CC=CC2=C1NC=C2C(=O)C(F)(F)F VVSCWULFMZPYPU-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- HEXPZRMQHIMYOK-UHFFFAOYSA-N 2-methoxy-1h-indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(O)=O)=C(OC)NC2=C1 HEXPZRMQHIMYOK-UHFFFAOYSA-N 0.000 description 1
- JOMNTHCQHJPVAZ-UHFFFAOYSA-N 2-methylpiperazine Chemical compound CC1CNCCN1 JOMNTHCQHJPVAZ-UHFFFAOYSA-N 0.000 description 1
- WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 1
- HTDQAXMOYVXCDD-UHFFFAOYSA-N 3,5-dimethylpiperazine-1-carboxylic acid Chemical compound CC1CN(C(O)=O)CC(C)N1 HTDQAXMOYVXCDD-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- MYTGFBZJLDLWQG-UHFFFAOYSA-N 5-chloro-1h-indole Chemical compound ClC1=CC=C2NC=CC2=C1 MYTGFBZJLDLWQG-UHFFFAOYSA-N 0.000 description 1
- ODFFPRGJZRXNHZ-UHFFFAOYSA-N 5-fluoroindole Chemical compound FC1=CC=C2NC=CC2=C1 ODFFPRGJZRXNHZ-UHFFFAOYSA-N 0.000 description 1
- YTYIMDRWPTUAHP-UHFFFAOYSA-N 6-Chloroindole Chemical compound ClC1=CC=C2C=CNC2=C1 YTYIMDRWPTUAHP-UHFFFAOYSA-N 0.000 description 1
- LZJGQIVWUKFTRD-UHFFFAOYSA-N 7-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=CC2=C1NC=C2 LZJGQIVWUKFTRD-UHFFFAOYSA-N 0.000 description 1
- DIGZMTAFOACVBW-UHFFFAOYSA-N 7-phenylmethoxy-1h-indole Chemical compound C=1C=CC=2C=CNC=2C=1OCC1=CC=CC=C1 DIGZMTAFOACVBW-UHFFFAOYSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108010087765 Antipain Proteins 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- RBHSFIBRBWXFQR-UHFFFAOYSA-N BrC1=CC=C2C=CNC2=C1.Cl.BrC1=CC=C2C(=CN(C2=C1)CC1CCCCC1)C(=O)N1CCN(CC1)C Chemical compound BrC1=CC=C2C=CNC2=C1.Cl.BrC1=CC=C2C(=CN(C2=C1)CC1CCCCC1)C(=O)N1CCN(CC1)C RBHSFIBRBWXFQR-UHFFFAOYSA-N 0.000 description 1
- CIUWDTGMPVXELX-UHFFFAOYSA-N BrC1=CC=C2C=CNC2=C1.Cl.BrC1=CC=C2C(=CN(C2=C1)CC1CCCCC1)C(=O)N1CCN(CC1)CC Chemical compound BrC1=CC=C2C=CNC2=C1.Cl.BrC1=CC=C2C(=CN(C2=C1)CC1CCCCC1)C(=O)N1CCN(CC1)CC CIUWDTGMPVXELX-UHFFFAOYSA-N 0.000 description 1
- ZCWUFSOAJUBZJL-UHFFFAOYSA-N BrC1=CC=C2C=CNC2=C1.Cl.BrC=1C=CC=C2C(=CN(C12)CC1CCCCC1)C(=O)N1CCN(CC1)CC Chemical compound BrC1=CC=C2C=CNC2=C1.Cl.BrC=1C=CC=C2C(=CN(C12)CC1CCCCC1)C(=O)N1CCN(CC1)CC ZCWUFSOAJUBZJL-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- XBKQMCAJVSRTFA-UHFFFAOYSA-N C(#N)C1=CC=C2C=CNC2=C1.Cl.C(#N)C1=CC=C2C(=CN(C2=C1)CC1CCCCC1)C(=O)N1CCN(CC1)C Chemical compound C(#N)C1=CC=C2C=CNC2=C1.Cl.C(#N)C1=CC=C2C(=CN(C2=C1)CC1CCCCC1)C(=O)N1CCN(CC1)C XBKQMCAJVSRTFA-UHFFFAOYSA-N 0.000 description 1
- OLEBCSJDHDZGIH-UHFFFAOYSA-N C(#N)C1=CC=C2C=CNC2=C1.Cl.C(#N)C1=CC=C2C(=CN(C2=C1)CC1CCCCC1)C(=O)N1CCN(CC1)CC Chemical compound C(#N)C1=CC=C2C=CNC2=C1.Cl.C(#N)C1=CC=C2C(=CN(C2=C1)CC1CCCCC1)C(=O)N1CCN(CC1)CC OLEBCSJDHDZGIH-UHFFFAOYSA-N 0.000 description 1
- WEESNQGIBYUWGE-FARDYXINSA-N C(C)(C)(C)OC(=O)N1[C@H](CCC1)C(=O)O.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C[C@@H]2N(CC1)CCCC2 Chemical compound C(C)(C)(C)OC(=O)N1[C@H](CCC1)C(=O)O.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C[C@@H]2N(CC1)CCCC2 WEESNQGIBYUWGE-FARDYXINSA-N 0.000 description 1
- NWXZVKNLMMSIJP-UHFFFAOYSA-N C(C)(C)N(CC)C(C)C.Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C(C(NC(C1C)C)C)C Chemical compound C(C)(C)N(CC)C(C)C.Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C(C(NC(C1C)C)C)C NWXZVKNLMMSIJP-UHFFFAOYSA-N 0.000 description 1
- GTEARUCAFCFFII-UHFFFAOYSA-N C(C)C=1C=CC=C2C=CNC12.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)CC)C(=O)N1CCN(CC1)CC Chemical compound C(C)C=1C=CC=C2C=CNC12.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)CC)C(=O)N1CCN(CC1)CC GTEARUCAFCFFII-UHFFFAOYSA-N 0.000 description 1
- NBLSECFFBORSEB-UHFFFAOYSA-N C(C)N1CCNCC1.FC(C(=O)O)(F)F.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CCN(CC1)CCO Chemical compound C(C)N1CCNCC1.FC(C(=O)O)(F)F.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CCN(CC1)CCO NBLSECFFBORSEB-UHFFFAOYSA-N 0.000 description 1
- HLMSSHBZZSBYRJ-CKUXDGONSA-N C1(CCCC1)CN1C=CC2=CC=CC(=C12)OC.Cl.C1(CCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C[C@@H](NCC1)C Chemical compound C1(CCCC1)CN1C=CC2=CC=CC(=C12)OC.Cl.C1(CCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C[C@@H](NCC1)C HLMSSHBZZSBYRJ-CKUXDGONSA-N 0.000 description 1
- YWLNUQVERQZHCS-UHFFFAOYSA-N C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C(CN(CC1C)C(=O)O)C.Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C(CNCC1C)C Chemical compound C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C(CN(CC1C)C(=O)O)C.Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C(CNCC1C)C YWLNUQVERQZHCS-UHFFFAOYSA-N 0.000 description 1
- RFLOHTKSSHIOMF-UHFFFAOYSA-N C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)[N+](=O)[O-])C(=O)N1CCN(CC1)CC.NC=1C=CC=C2C(=CN(C12)CC1CCCCC1)C(=O)N1CCN(CC1)CC Chemical compound C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)[N+](=O)[O-])C(=O)N1CCN(CC1)CC.NC=1C=CC=C2C(=CN(C12)CC1CCCCC1)C(=O)N1CCN(CC1)CC RFLOHTKSSHIOMF-UHFFFAOYSA-N 0.000 description 1
- DMJWSDSPOXZPSM-SQKCAUCHSA-N C1(CCCCC1)CN1C=CC2=CC=CC(=C12)OC.Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C[C@@H](NCC1)C Chemical compound C1(CCCCC1)CN1C=CC2=CC=CC(=C12)OC.Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C[C@@H](NCC1)C DMJWSDSPOXZPSM-SQKCAUCHSA-N 0.000 description 1
- DMJWSDSPOXZPSM-GGMCWBHBSA-N C1(CCCCC1)CN1C=CC2=CC=CC(=C12)OC.Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C[C@H](NCC1)C Chemical compound C1(CCCCC1)CN1C=CC2=CC=CC(=C12)OC.Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C[C@H](NCC1)C DMJWSDSPOXZPSM-GGMCWBHBSA-N 0.000 description 1
- USHPCSDKASNLGG-UHFFFAOYSA-N CC1=CC=C(C=C1)S(=O)(=O)OCC1CCCC1.Cl.C1(CCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CCN(CC1)CC Chemical compound CC1=CC=C(C=C1)S(=O)(=O)OCC1CCCC1.Cl.C1(CCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CCN(CC1)CC USHPCSDKASNLGG-UHFFFAOYSA-N 0.000 description 1
- IZHDMQQKEICPND-UHFFFAOYSA-N CC1=CC=C(C=C1)S(=O)(=O)OCC1CCCCCC1.Cl.C1(CCCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CCN(CC1)CC Chemical compound CC1=CC=C(C=C1)S(=O)(=O)OCC1CCCCCC1.Cl.C1(CCCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CCN(CC1)CC IZHDMQQKEICPND-UHFFFAOYSA-N 0.000 description 1
- LLIPLBVGYKKBSZ-UHFFFAOYSA-N CC1=CC=C(C=C1)S(=O)(=O)OCC1CCCCCCC1.Cl.C1(CCCCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CCN(CC1)CC Chemical compound CC1=CC=C(C=C1)S(=O)(=O)OCC1CCCCCCC1.Cl.C1(CCCCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CCN(CC1)CC LLIPLBVGYKKBSZ-UHFFFAOYSA-N 0.000 description 1
- NJTMYUZBZYTZHU-UHFFFAOYSA-N CC=1C=CC=C2C=CNC12.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)C)C(=O)N1CCN(CC1)CC Chemical compound CC=1C=CC=C2C=CNC12.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)C)C(=O)N1CCN(CC1)CC NJTMYUZBZYTZHU-UHFFFAOYSA-N 0.000 description 1
- ORVGUWXGBPZEDV-UHFFFAOYSA-N COC(C(N)C(=O)O)=O.N1CCCCC1 Chemical compound COC(C(N)C(=O)O)=O.N1CCCCC1 ORVGUWXGBPZEDV-UHFFFAOYSA-N 0.000 description 1
- ABGXBKFMCUCSGL-KSBRXOFISA-N COC1=CC=C2C=CNC2=C1.C(\C=C/C(=O)O)(=O)O.C1(CCCCC1)CN1C=C(C2=CC=C(C=C12)OC)C(=O)N1CCN(CC1)CC Chemical compound COC1=CC=C2C=CNC2=C1.C(\C=C/C(=O)O)(=O)O.C1(CCCCC1)CN1C=C(C2=CC=C(C=C12)OC)C(=O)N1CCN(CC1)CC ABGXBKFMCUCSGL-KSBRXOFISA-N 0.000 description 1
- HJQPLAZAQURDKB-UHFFFAOYSA-N COC1=CC=C2C=CNC2=C1.Cl.C1(CCCCC1)CCN1C=C(C2=CC=C(C=C12)OC)C(=O)N1CCN(CC1)C Chemical compound COC1=CC=C2C=CNC2=C1.Cl.C1(CCCCC1)CCN1C=C(C2=CC=C(C=C12)OC)C(=O)N1CCN(CC1)C HJQPLAZAQURDKB-UHFFFAOYSA-N 0.000 description 1
- QAWRJMVJOXJAST-UHFFFAOYSA-N COC1=CC=C2C=CNC2=C1.Cl.C1(CCCCC1)CCN1C=C(C2=CC=C(C=C12)OC)C(=O)N1CCN(CC1)CC Chemical compound COC1=CC=C2C=CNC2=C1.Cl.C1(CCCCC1)CCN1C=C(C2=CC=C(C=C12)OC)C(=O)N1CCN(CC1)CC QAWRJMVJOXJAST-UHFFFAOYSA-N 0.000 description 1
- YIOMAMAFGPWKIH-UHFFFAOYSA-N COC=1C=CC=C2C=CNC12.C1(CC=CCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CCN(CC1)CC Chemical compound COC=1C=CC=C2C=CNC12.C1(CC=CCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CCN(CC1)CC YIOMAMAFGPWKIH-UHFFFAOYSA-N 0.000 description 1
- NCGHPQVVJDSCFZ-UHFFFAOYSA-N COC=1C=CC=C2C=CNC12.Cl.C1(CCCCC1)CCN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CCN(CC1)CC Chemical compound COC=1C=CC=C2C=CNC12.Cl.C1(CCCCC1)CCN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CCN(CC1)CC NCGHPQVVJDSCFZ-UHFFFAOYSA-N 0.000 description 1
- PXKHRUSQUXPWMI-UHFFFAOYSA-N COCCN1CCNCC1.FC(C(=O)O)(F)F.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CCN(CC1)CCOC Chemical compound COCCN1CCNCC1.FC(C(=O)O)(F)F.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CCN(CC1)CCOC PXKHRUSQUXPWMI-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- DZOWFBSBMJBVCC-VOMIJIAVSA-N Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1[C@H](CN([C@@H](C1)C)CC)C Chemical compound Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1[C@H](CN([C@@H](C1)C)CC)C DZOWFBSBMJBVCC-VOMIJIAVSA-N 0.000 description 1
- JVWVHWQMYBOCRO-UHFFFAOYSA-N Cl.CCN1CCN(CC1(C)C)C(=O)c2cn(CC3CCCCC3)c4c(OC)cccc24 Chemical compound Cl.CCN1CCN(CC1(C)C)C(=O)c2cn(CC3CCCCC3)c4c(OC)cccc24 JVWVHWQMYBOCRO-UHFFFAOYSA-N 0.000 description 1
- AHGWAIIBUTYNFT-UHFFFAOYSA-N Cl.CCN1CCN(CC1)C(=O)c2cn(CC3CCCCC3)c4c(Cl)cccc24 Chemical compound Cl.CCN1CCN(CC1)C(=O)c2cn(CC3CCCCC3)c4c(Cl)cccc24 AHGWAIIBUTYNFT-UHFFFAOYSA-N 0.000 description 1
- QMRUDPFQGULEKY-UHFFFAOYSA-N Cl.CCN1CCN(CC1)C(=O)c2cn(CC3CCCCC3)c4c(F)cccc24 Chemical compound Cl.CCN1CCN(CC1)C(=O)c2cn(CC3CCCCC3)c4c(F)cccc24 QMRUDPFQGULEKY-UHFFFAOYSA-N 0.000 description 1
- GPVZAERKQDFRNW-UHFFFAOYSA-N Cl.CCN1CCN(CC1)C(=O)c2cn(CC3CCCCC3)c4ccc(Cl)cc24 Chemical compound Cl.CCN1CCN(CC1)C(=O)c2cn(CC3CCCCC3)c4ccc(Cl)cc24 GPVZAERKQDFRNW-UHFFFAOYSA-N 0.000 description 1
- GHXUGASYEODOOW-UHFFFAOYSA-N ClC1=CC=C2C=CNC2=C1.Cl.ClC1=CC=C2C(=CN(C2=C1)CC1CCCCC1)C(=O)N1CCN(CC1)CC Chemical compound ClC1=CC=C2C=CNC2=C1.Cl.ClC1=CC=C2C(=CN(C2=C1)CC1CCCCC1)C(=O)N1CCN(CC1)CC GHXUGASYEODOOW-UHFFFAOYSA-N 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 241000400611 Eucalyptus deanei Species 0.000 description 1
- CKICPKGMORHRAT-UHFFFAOYSA-N FC1=CC=C2C=CNC2=C1.Cl.C1(CCCCC1)CN1C=C(C2=CC=C(C=C12)F)C(=O)N1CCN(CC1)C Chemical compound FC1=CC=C2C=CNC2=C1.Cl.C1(CCCCC1)CN1C=C(C2=CC=C(C=C12)F)C(=O)N1CCN(CC1)C CKICPKGMORHRAT-UHFFFAOYSA-N 0.000 description 1
- JDMLQRGEGCTUHF-UHFFFAOYSA-N FC1=CC=C2C=CNC2=C1.Cl.C1(CCCCC1)CN1C=C(C2=CC=C(C=C12)F)C(=O)N1CCN(CC1)CC Chemical compound FC1=CC=C2C=CNC2=C1.Cl.C1(CCCCC1)CN1C=C(C2=CC=C(C=C12)F)C(=O)N1CCN(CC1)CC JDMLQRGEGCTUHF-UHFFFAOYSA-N 0.000 description 1
- SNGFWKHJCINCRZ-UHFFFAOYSA-N FC=1C=C2C=CNC2=CC1.Cl.C1(CCCCC1)CN1C=C(C2=CC(=CC=C12)F)C(=O)N1CCN(CC1)CC Chemical compound FC=1C=C2C=CNC2=CC1.Cl.C1(CCCCC1)CN1C=C(C2=CC(=CC=C12)F)C(=O)N1CCN(CC1)CC SNGFWKHJCINCRZ-UHFFFAOYSA-N 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 102000003834 Histamine H1 Receptors Human genes 0.000 description 1
- 108090000110 Histamine H1 Receptors Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010065390 Inflammatory pain Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 1
- HUPVBLIFOJHMOM-UHFFFAOYSA-N N1C=CC2=CC=CC=C12.Cl.C1(CCCCC1)CCCN1C=C(C2=CC=CC=C12)C(=O)N1CCN(CC1)C Chemical compound N1C=CC2=CC=CC=C12.Cl.C1(CCCCC1)CCCN1C=C(C2=CC=CC=C12)C(=O)N1CCN(CC1)C HUPVBLIFOJHMOM-UHFFFAOYSA-N 0.000 description 1
- RXXKUFGJMZJMCJ-UHFFFAOYSA-N N1C=CC2=CC=CC=C12.Cl.C1(CCCCC1)CCN1C=C(C2=CC=CC=C12)C(=O)N1CCN(CC1)CC Chemical compound N1C=CC2=CC=CC=C12.Cl.C1(CCCCC1)CCN1C=C(C2=CC=CC=C12)C(=O)N1CCN(CC1)CC RXXKUFGJMZJMCJ-UHFFFAOYSA-N 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- VYCIJZAJITXPAW-FYZOBXCZSA-N O=C1[C@@H]2N(C(CN1)=O)CCCC2.N2=CC=NC=C2 Chemical compound O=C1[C@@H]2N(C(CN1)=O)CCCC2.N2=CC=NC=C2 VYCIJZAJITXPAW-FYZOBXCZSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 206010038678 Respiratory depression Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229920002472 Starch Chemical class 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 206010046555 Urinary retention Diseases 0.000 description 1
- HQVHOQAKMCMIIM-HXUWFJFHSA-N WIN 55212-2 Chemical compound C([C@@H]1COC=2C=CC=C3C(C(=O)C=4C5=CC=CC=C5C=CC=4)=C(N1C3=2)C)N1CCOCC1 HQVHOQAKMCMIIM-HXUWFJFHSA-N 0.000 description 1
- LLNKMAJJARQZMO-FYZYNONXSA-N [(9aS)-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-2-yl]-[1-(cyclopentylmethyl)-7-methoxyindol-3-yl]methanone hydrochloride Chemical compound Cl.C1(CCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C[C@H]2N(CC1)CCCC2 LLNKMAJJARQZMO-FYZYNONXSA-N 0.000 description 1
- NTIFEVGVXWYYHK-HXUWFJFHSA-N [(9ar)-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-2-yl]-[1-(cyclohexylmethyl)-7-methoxyindol-3-yl]methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2C[C@H]3CCCCN3CC2)=CN1CC1CCCCC1 NTIFEVGVXWYYHK-HXUWFJFHSA-N 0.000 description 1
- HKTAIRAIGRBEIO-BDQAORGHSA-N [(9as)-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-2-yl]-[1-(cyclohexylmethyl)-7-methoxyindol-3-yl]methanone;hydrochloride Chemical compound Cl.C1=2C(OC)=CC=CC=2C(C(=O)N2C[C@@H]3CCCCN3CC2)=CN1CC1CCCCC1 HKTAIRAIGRBEIO-BDQAORGHSA-N 0.000 description 1
- ASTFZTFIDVUJON-IBGZPJMESA-N [(9as)-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-2-yl]-[1-(cyclopentylmethyl)-7-methoxyindol-3-yl]methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2C[C@@H]3CCCCN3CC2)=CN1CC1CCCC1 ASTFZTFIDVUJON-IBGZPJMESA-N 0.000 description 1
- HHLRIHHKRXBBLL-UHFFFAOYSA-N [1-(cyclohexylmethyl)-5-fluoroindol-3-yl]-(4-methylpiperazin-1-yl)methanone hydrochloride Chemical compound Cl.C1(CCCCC1)CN1C=C(C2=CC(=CC=C12)F)C(=O)N1CCN(CC1)C HHLRIHHKRXBBLL-UHFFFAOYSA-N 0.000 description 1
- DMSOAHNBJYAPPT-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-(2-fluoroethoxy)indol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(OCCF)=C11)=CN1CC1CCCCC1 DMSOAHNBJYAPPT-UHFFFAOYSA-N 0.000 description 1
- NPAASZPXKFNZND-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-ethoxyindol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1=2C(OCC)=CC=CC=2C(C(=O)N2CCN(CC)CC2)=CN1CC1CCCCC1 NPAASZPXKFNZND-UHFFFAOYSA-N 0.000 description 1
- BPLLRXQISZRLIC-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-fluoroindol-3-yl]-(4-methylpiperazin-1-yl)methanone hydrochloride Chemical compound Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)F)C(=O)N1CCN(CC1)C BPLLRXQISZRLIC-UHFFFAOYSA-N 0.000 description 1
- LNOYEXPAVDHLFX-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-hydroxyindol-3-yl]-(4-ethylpiperazin-1-yl)methanone hydrochloride Chemical compound Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)O)C(=O)N1CCN(CC1)CC LNOYEXPAVDHLFX-UHFFFAOYSA-N 0.000 description 1
- ZLWTYKHPXKVREA-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(2,3,5,6-tetramethylpiperazin-1-yl)methanone hydrochloride Chemical compound Cl.COc1cccc2c(cn(CC3CCCCC3)c12)C(=O)N1C(C)C(C)NC(C)C1C ZLWTYKHPXKVREA-UHFFFAOYSA-N 0.000 description 1
- FGPOVBVIHIVWFP-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(3,3-dimethylpiperazin-1-yl)methanone hydrochloride Chemical compound Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CC(NCC1)(C)C FGPOVBVIHIVWFP-UHFFFAOYSA-N 0.000 description 1
- HKDNZWSVLVVYEP-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(3,4-dimethylpiperazin-1-yl)methanone hydrochloride Chemical compound Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CC(N(CC1)C)C HKDNZWSVLVVYEP-UHFFFAOYSA-N 0.000 description 1
- UFZDKJXVGTXHGO-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(3,5-dimethylpiperazin-1-yl)methanone hydrochloride Chemical compound Cl.COc1cccc2c(cn(CC3CCCCC3)c12)C(=O)N1CC(C)NC(C)C1 UFZDKJXVGTXHGO-UHFFFAOYSA-N 0.000 description 1
- WGZJADXKXMJPBT-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(4-ethyl-2,6-dimethylpiperazin-1-yl)methanone hydrochloride Chemical compound Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C(CN(CC1C)CC)C WGZJADXKXMJPBT-UHFFFAOYSA-N 0.000 description 1
- PGGOWTCRZAQDJI-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(4-ethyl-3,5-dimethylpiperazin-1-yl)methanone hydrochloride Chemical compound Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CC(N(C(C1)C)CC)C PGGOWTCRZAQDJI-UHFFFAOYSA-N 0.000 description 1
- YVNLJRQPWFDVJR-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(4-ethyl-3-methylpiperazin-1-yl)methanone hydrochloride Chemical compound Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CC(N(CC1)CC)C YVNLJRQPWFDVJR-UHFFFAOYSA-N 0.000 description 1
- UQRRPDFBONRPTG-FERBBOLQSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-[(3S)-4-(2-fluoroethyl)-3-methylpiperazin-1-yl]methanone hydrochloride Chemical compound Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C[C@@H](N(CC1)CCF)C UQRRPDFBONRPTG-FERBBOLQSA-N 0.000 description 1
- HKDNZWSVLVVYEP-LMOVPXPDSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-[(3s)-3,4-dimethylpiperazin-1-yl]methanone;hydrochloride Chemical compound Cl.C1=2C(OC)=CC=CC=2C(C(=O)N2C[C@H](C)N(C)CC2)=CN1CC1CCCCC1 HKDNZWSVLVVYEP-LMOVPXPDSA-N 0.000 description 1
- QLBZFPKIPCALJQ-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-[3-(fluoromethyl)piperazin-1-yl]methanone hydrochloride Chemical compound Cl.COc1cccc2c(cn(CC3CCCCC3)c12)C(=O)N1CCNC(CF)C1 QLBZFPKIPCALJQ-UHFFFAOYSA-N 0.000 description 1
- PMQYDOBAWFCYDG-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-[4-cyclopropyl-3-(fluoromethyl)piperazin-1-yl]methanone hydrochloride Chemical compound Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CC(N(CC1)C1CC1)CF PMQYDOBAWFCYDG-UHFFFAOYSA-N 0.000 description 1
- ILTXQGDSBGMOEA-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-nitroindol-3-yl]-(4-ethylpiperazin-1-yl)methanone hydrochloride Chemical compound Cl.C1(CCCCC1)CN1C=C(C2=CC=CC(=C12)[N+](=O)[O-])C(=O)N1CCN(CC1)CC ILTXQGDSBGMOEA-UHFFFAOYSA-N 0.000 description 1
- RLHCQMSPQCRRNT-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-phenylmethoxyindol-3-yl]-(4-ethylpiperazin-1-yl)methanone hydrochloride Chemical compound Cl.C(C1=CC=CC=C1)OC=1C=CC=C2C(=CN(C12)CC1CCCCC1)C(=O)N1CCN(CC1)CC RLHCQMSPQCRRNT-UHFFFAOYSA-N 0.000 description 1
- XKVHPRBYMGYWPA-UHFFFAOYSA-N [1-(cyclopentylmethyl)-7-methoxyindol-3-yl]-(3,5-dimethylpiperazin-1-yl)methanone hydrochloride Chemical compound Cl.C1(CCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CC(NC(C1)C)C XKVHPRBYMGYWPA-UHFFFAOYSA-N 0.000 description 1
- FDEPUNHSOKSQJP-UHFFFAOYSA-N [1-(cyclopentylmethyl)-7-methoxyindol-3-yl]-(4-ethyl-3,5-dimethylpiperazin-1-yl)methanone hydrochloride Chemical compound Cl.C1(CCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1CC(N(C(C1)C)CC)C FDEPUNHSOKSQJP-UHFFFAOYSA-N 0.000 description 1
- SESAJGYOTBUNRA-PKLMIRHRSA-N [1-(cyclopentylmethyl)-7-methoxyindol-3-yl]-[(3R)-3,4-dimethylpiperazin-1-yl]methanone hydrochloride Chemical compound Cl.C1(CCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C[C@H](N(CC1)C)C SESAJGYOTBUNRA-PKLMIRHRSA-N 0.000 description 1
- DJKFQXDOXNLCCN-UNTBIKODSA-N [1-(cyclopentylmethyl)-7-methoxyindol-3-yl]-[(3R)-4-ethyl-3-methylpiperazin-1-yl]methanone hydrochloride Chemical compound Cl.CCN1CCN(C[C@H]1C)C(=O)c1cn(CC2CCCC2)c2c(OC)cccc12 DJKFQXDOXNLCCN-UNTBIKODSA-N 0.000 description 1
- SESAJGYOTBUNRA-NTISSMGPSA-N [1-(cyclopentylmethyl)-7-methoxyindol-3-yl]-[(3S)-3,4-dimethylpiperazin-1-yl]methanone hydrochloride Chemical compound Cl.C1(CCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C[C@@H](N(CC1)C)C SESAJGYOTBUNRA-NTISSMGPSA-N 0.000 description 1
- DJKFQXDOXNLCCN-LMOVPXPDSA-N [1-(cyclopentylmethyl)-7-methoxyindol-3-yl]-[(3S)-4-ethyl-3-methylpiperazin-1-yl]methanone hydrochloride Chemical compound Cl.C1(CCCC1)CN1C=C(C2=CC=CC(=C12)OC)C(=O)N1C[C@@H](N(CC1)CC)C DJKFQXDOXNLCCN-LMOVPXPDSA-N 0.000 description 1
- IPUZWMVQJSWJFY-UHFFFAOYSA-N [6-chloro-1-(cyclohexylmethyl)indol-3-yl]-(4-methylpiperazin-1-yl)methanone hydrochloride Chemical compound Cl.ClC1=CC=C2C(=CN(C2=C1)CC1CCCCC1)C(=O)N1CCN(CC1)C IPUZWMVQJSWJFY-UHFFFAOYSA-N 0.000 description 1
- NHTXWVIESCGYIM-UHFFFAOYSA-N [7-chloro-1-(cyclohexylmethyl)indol-3-yl]-(4-methylpiperazin-1-yl)methanone hydrochloride Chemical compound Cl.ClC=1C=CC=C2C(=CN(C12)CC1CCCCC1)C(=O)N1CCN(CC1)C NHTXWVIESCGYIM-UHFFFAOYSA-N 0.000 description 1
- MLPIZJHKEWTTDX-UHFFFAOYSA-N [N+](=O)([O-])C1=CC=C2C=CNC2=C1.Cl.C1(CCCCC1)CN1C=C(C2=CC=C(C=C12)[N+](=O)[O-])C(=O)N1CCN(CC1)CC Chemical compound [N+](=O)([O-])C1=CC=C2C=CNC2=C1.Cl.C1(CCCCC1)CN1C=C(C2=CC=C(C=C12)[N+](=O)[O-])C(=O)N1CCN(CC1)CC MLPIZJHKEWTTDX-UHFFFAOYSA-N 0.000 description 1
- DXGTUUQHTDOFFQ-UHFFFAOYSA-N [N].C1=CC=C2NC=CC2=C1 Chemical group [N].C1=CC=C2NC=CC2=C1 DXGTUUQHTDOFFQ-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- SDNYTAYICBFYFH-TUFLPTIASA-N antipain Chemical compound NC(N)=NCCC[C@@H](C=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SDNYTAYICBFYFH-TUFLPTIASA-N 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- DCBDOYDVQJVXOH-UHFFFAOYSA-N azane;1h-indole Chemical class N.C1=CC=C2NC=CC2=C1 DCBDOYDVQJVXOH-UHFFFAOYSA-N 0.000 description 1
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical group N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940065144 cannabinoids Drugs 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000001913 cellulose Chemical class 0.000 description 1
- 229920002678 cellulose Chemical class 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001805 chlorine compounds Chemical group 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 229940111134 coxibs Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- SNXBTWWUFFCPEG-UHFFFAOYSA-N cyclohex-3-en-1-ylmethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1CC=CCC1 SNXBTWWUFFCPEG-UHFFFAOYSA-N 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- ISQVBYGGNVVVHB-UHFFFAOYSA-N cyclopentylmethanol Chemical compound OCC1CCCC1 ISQVBYGGNVVVHB-UHFFFAOYSA-N 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000009982 effect on human Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000005090 green fluorescent protein Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- IYUKFAFDFHZKPI-DFWYDOINSA-N methyl (2s)-2-aminopropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@H](C)N IYUKFAFDFHZKPI-DFWYDOINSA-N 0.000 description 1
- OZSJLLVVZFTDEY-HJXLNUONSA-N methyl (2s,3r)-2-amino-3-hydroxybutanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)[C@@H](C)O OZSJLLVVZFTDEY-HJXLNUONSA-N 0.000 description 1
- NVWZNEDLYYLQJC-UHFFFAOYSA-N methyl 2-amino-2-methylpropanoate;hydrochloride Chemical compound Cl.COC(=O)C(C)(C)N NVWZNEDLYYLQJC-UHFFFAOYSA-N 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 230000031990 negative regulation of inflammatory response Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000002856 peripheral neuron Anatomy 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920005596 polymer binder Polymers 0.000 description 1
- 239000002491 polymer binding agent Substances 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 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
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Chemical class 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- STJOLJMOERSAJV-UHFFFAOYSA-N tert-butyl 4-[1-(cyclohexylmethyl)-7-methoxyindole-3-carbonyl]-3,5-dimethylpiperazine-1-carboxylate Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2C(CN(CC2C)C(=O)OC(C)(C)C)C)=CN1CC1CCCCC1 STJOLJMOERSAJV-UHFFFAOYSA-N 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
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- 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]
-
- 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]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Ophthalmology & Optometry (AREA)
- Hospice & Palliative Care (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Anesthesiology (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Nutrition Science (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP02077505 | 2002-06-21 | ||
| PCT/EP2003/050226 WO2004000832A1 (en) | 2002-06-21 | 2003-06-13 | 1-[(indol-3-yl)carbonyl] piperazine derivatives |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2005533801A JP2005533801A (ja) | 2005-11-10 |
| JP2005533801A5 JP2005533801A5 (enExample) | 2006-07-13 |
| JP4408804B2 true JP4408804B2 (ja) | 2010-02-03 |
Family
ID=29797228
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004514874A Expired - Fee Related JP4408804B2 (ja) | 2002-06-21 | 2003-06-13 | １−［（インドル−３−イル）カルボニル］ピペラジン誘導体 |
Country Status (32)
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI242015B (en) | 1999-11-29 | 2005-10-21 | Akzo Nobel Nv | 6-mercapto-cyclodextrin derivatives: reversal agents for drug-induced neuromuscular block |
| ES2294330T3 (es) | 2002-08-02 | 2008-04-01 | MERCK & CO., INC. | Derivados de furo(2,3-b)piridina sustituidos. |
| DE10253426B4 (de) * | 2002-11-15 | 2005-09-22 | Elbion Ag | Neue Hydroxyindole, deren Verwendung als Inhibitoren der Phosphodiesterase 4 und Verfahren zu deren Herstellung |
| ES2284076T3 (es) | 2003-12-17 | 2007-11-01 | N.V. Organon | Derivados triciclicos de 1-(indol-3-il)carbonil)piperazina como agonistas del receptor de cannabinoides cb1. |
| TWI330635B (en) | 2004-03-05 | 2010-09-21 | Organon Nv | (indol-3-yl)-heterocycle derivatives |
| JP2009500439A (ja) * | 2005-07-11 | 2009-01-08 | ナームローゼ・フエンノートチヤツプ・オルガノン | 疼痛の治療のための相乗的組み合わせ（カンナビノイド受容体アゴニスト及びオピオイド受容体アゴニスト） |
| KR101020351B1 (ko) * | 2005-07-29 | 2011-03-08 | 에프. 호프만-라 로슈 아게 | 인돌-3-일-카본일-피페리딘 및 피페라진 유도체 |
| TW200745096A (en) * | 2005-08-23 | 2007-12-16 | Organon Nv | Indole derivatives |
| US7763732B2 (en) | 2005-08-24 | 2010-07-27 | N.V. Organon | Indole derivatives |
| AU2006295130A1 (en) * | 2005-09-23 | 2007-04-05 | Janssen Pharmaceutica, N.V. | Tetrahydro-indazolyl cannabinoid modulators |
| TW200848417A (en) | 2007-02-22 | 2008-12-16 | Organon Nv | Indole derivatives |
| RU2387642C2 (ru) | 2007-10-31 | 2010-04-27 | Общество С Ограниченной Ответственностью "Бинатех" | Производные 5-замещенных индол-3-карбоновой кислоты, обладающие противовирусной активностью, способ их получения и применение |
| GB201106817D0 (en) | 2011-04-21 | 2011-06-01 | Astex Therapeutics Ltd | New compound |
| CN105829310B (zh) | 2013-12-20 | 2019-04-12 | 阿斯特克斯治疗有限公司 | 双环杂环化合物及其治疗用途 |
| CN111566105A (zh) | 2018-01-08 | 2020-08-21 | 豪夫迈·罗氏有限公司 | 作为MAGL抑制剂的八氢吡啶并[1,2-α]吡嗪类化合物 |
| CN108752342A (zh) * | 2018-08-17 | 2018-11-06 | 西安瑞联新材料股份有限公司 | 1-H-吡啶并[1,2-a]-6-氢吡嗪-1,4-二酮的制备方法 |
| CN111100063B (zh) * | 2018-10-25 | 2022-05-17 | 南京药石科技股份有限公司 | 一种合成2-氟甲基取代的吡咯烷、哌啶以及哌嗪衍生物的制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE142621T1 (de) * | 1989-12-28 | 1996-09-15 | Upjohn Co | Diaromatische substituierte verbindungen gegen den aids-virus |
| WO1998006715A1 (en) | 1996-08-09 | 1998-02-19 | Smithkline Beecham Corporation | Novel piperazine containing compounds |
| AU1887401A (en) * | 1999-12-14 | 2001-06-25 | Nippon Shinyaku Co. Ltd. | Medicinal composition |
| EP1254115A2 (en) * | 2000-02-11 | 2002-11-06 | Bristol-Myers Squibb Company | Cannabinoid receptor modulators, their processes of preparation, and use of cannabinoid receptor modulators for treating respiratory and non-respiratory diseases |
-
2003
- 2003-06-11 TW TW092115888A patent/TW200402417A/zh unknown
- 2003-06-13 NZ NZ537143A patent/NZ537143A/en unknown
- 2003-06-13 HR HR20041186A patent/HRP20041186A2/xx not_active Application Discontinuation
- 2003-06-13 ES ES03760704T patent/ES2285183T3/es not_active Expired - Lifetime
- 2003-06-13 AT AT03760704T patent/ATE361290T1/de active
- 2003-06-13 US US10/518,279 patent/US7304064B2/en not_active Expired - Fee Related
- 2003-06-13 DK DK03760704T patent/DK1549637T3/da active
- 2003-06-13 RS YUP-1111/04A patent/RS111104A/sr unknown
- 2003-06-13 KR KR10-2004-7020734A patent/KR20050009755A/ko not_active Ceased
- 2003-06-13 SI SI200330855T patent/SI1549637T1/sl unknown
- 2003-06-13 JP JP2004514874A patent/JP4408804B2/ja not_active Expired - Fee Related
- 2003-06-13 CN CNB038170906A patent/CN1298716C/zh not_active Expired - Fee Related
- 2003-06-13 CA CA2490141A patent/CA2490141C/en not_active Expired - Fee Related
- 2003-06-13 RU RU2005101349/04A patent/RU2318821C2/ru not_active IP Right Cessation
- 2003-06-13 BR BR0311960-2A patent/BR0311960A/pt not_active IP Right Cessation
- 2003-06-13 EP EP03760704A patent/EP1549637B1/en not_active Expired - Lifetime
- 2003-06-13 PT PT03760704T patent/PT1549637E/pt unknown
- 2003-06-13 AU AU2003250245A patent/AU2003250245B2/en not_active Ceased
- 2003-06-13 DE DE60313640T patent/DE60313640T2/de not_active Expired - Lifetime
- 2003-06-13 UA UA20041210112A patent/UA78317C2/uk unknown
- 2003-06-13 WO PCT/EP2003/050226 patent/WO2004000832A1/en not_active Ceased
- 2003-06-13 PL PL03375152A patent/PL375152A1/xx not_active Application Discontinuation
- 2003-06-13 MX MXPA04012856A patent/MXPA04012856A/es active IP Right Grant
- 2003-06-18 PE PE2003000614A patent/PE20040578A1/es not_active Application Discontinuation
- 2003-06-19 AR ARP030102174A patent/AR040274A1/es unknown
-
2004
- 2004-12-06 IL IL16557204A patent/IL165572A0/xx unknown
- 2004-12-07 NO NO20045351A patent/NO20045351L/no not_active Application Discontinuation
- 2004-12-09 IS IS7590A patent/IS2443B/is unknown
- 2004-12-13 ZA ZA200410057A patent/ZA200410057B/en unknown
- 2004-12-21 EC EC2004005503A patent/ECSP045503A/es unknown
-
2005
- 2005-01-20 CO CO05004561A patent/CO5680419A2/es not_active Application Discontinuation
-
2007
- 2007-06-18 CY CY20071100804T patent/CY1107677T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4408804B2 (ja) | １−［（インドル−３−イル）カルボニル］ピペラジン誘導体 | |
| JP6665169B2 (ja) | 新規化合物αｖβ６インテグリンアンタゴニスト | |
| EP0345808B1 (en) | 1-Indolylalkyl-4-(substituted-pyridinyl)piperazines | |
| US5834493A (en) | Indole derivatives as 5-HT1A and/or 5-HT2 ligands | |
| JP2004531506A (ja) | 選択的なセロトニン再取り込みインヒビターとしてのシクロプロピルインドール誘導体 | |
| JPH07149762A (ja) | ピペリジン類およびピペラジン類 | |
| HRP20010854A2 (en) | INDOLE-TYPE DERIVATIVES AS INHIBITORS OF p38 KINASE | |
| US5693655A (en) | 3-indolylpiperidines | |
| JPH0649027A (ja) | インドール誘導体 | |
| US20040132710A1 (en) | Lactams as tachkinin antagonists | |
| JP2012518612A (ja) | ガンの治療のための新規なオルトアミノアミド類 | |
| WO2022170947A1 (zh) | 一类作为kras突变体g12c抑制剂的四氢萘啶类衍生物、其制备方法及其应用 | |
| JPH09208582A (ja) | ３−アザ及び３−オキサピペリドンタキキニン拮抗薬 | |
| JP2013534928A (ja) | 新規テトラヒドロキノリン誘導体 | |
| JP2006523626A (ja) | ピラゾール化合物 | |
| CA2727669C (fr) | Nouveaux derives de (piperazinyl ponte)-1-alcanone et leur utilisation comme inhibiteurs de p75 | |
| JP2002544223A (ja) | 精神病性障害の治療方法 | |
| US6562809B1 (en) | 3-bicycloindole compounds | |
| JP2021514372A (ja) | デュアルの５−ｈｔ２ａおよび５−ｈｔ６受容体アンタゴニストとしての新しいインドールおよびベンゾイミダゾール誘導体 | |
| HK1076630B (en) | 1-(indol-3-yl) carbonyl piperazine derivatives | |
| CN101679385A (zh) | 作为nk3受体拮抗剂的脯氨酰胺-四唑衍生物 | |
| WO2022022364A1 (zh) | 一种吡咯烷类整合素调节剂及其用途 | |
| FR2678270A1 (fr) | Derives de 2-(piperidin-1-yl)ethanol, leur preparation et leur application en therapeutique. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060526 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060526 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20070416 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20091020 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20091110 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121120 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121120 Year of fee payment: 3 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313111 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121120 Year of fee payment: 3 |
|
| R371 | Transfer withdrawn |
Free format text: JAPANESE INTERMEDIATE CODE: R371 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313111 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121120 Year of fee payment: 3 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20131120 Year of fee payment: 4 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313111 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| LAPS | Cancellation because of no payment of annual fees |