DE60313640T2 - 1-(indol-3-yl)carbonyl piperazinderivate - Google Patents
1-(indol-3-yl)carbonyl piperazinderivate Download PDFInfo
- Publication number
- DE60313640T2 DE60313640T2 DE60313640T DE60313640T DE60313640T2 DE 60313640 T2 DE60313640 T2 DE 60313640T2 DE 60313640 T DE60313640 T DE 60313640T DE 60313640 T DE60313640 T DE 60313640T DE 60313640 T2 DE60313640 T2 DE 60313640T2
- Authority
- DE
- Germany
- Prior art keywords
- indol
- carbonyl
- 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 - Lifetime
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 28
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 208000002193 Pain Diseases 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 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 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 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
- 125000005843 halogen 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
- 125000001041 indolyl group Chemical group 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
- 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 102
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 88
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 78
- 150000001875 compounds Chemical class 0.000 description 73
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- 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 59
- 239000000243 solution Substances 0.000 description 51
- 239000000203 mixture Substances 0.000 description 47
- 238000000034 method Methods 0.000 description 35
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- 239000012458 free base Substances 0.000 description 22
- 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
- 239000007787 solid Substances 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- -1 2- (4-morpholinyl) ethyl side chain Chemical group 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-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
- 239000000047 product Substances 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 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 9
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 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
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- 229930003827 cannabinoid Natural products 0.000 description 9
- 239000003557 cannabinoid Substances 0.000 description 9
- 239000012230 colorless oil Substances 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 8
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 239000000556 agonist Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 102000009132 CB1 Cannabinoid Receptor Human genes 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 7
- 230000027455 binding Effects 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 6
- 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 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- FSOPPXYMWZOKRM-UHFFFAOYSA-N 7-methoxy-1h-indole Chemical compound COC1=CC=CC2=C1NC=C2 FSOPPXYMWZOKRM-UHFFFAOYSA-N 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 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
- 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 4
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 4
- 101710187010 Cannabinoid receptor 1 Proteins 0.000 description 4
- 102100033868 Cannabinoid receptor 1 Human genes 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
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 4
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 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
- 229940005483 opioid analgesics Drugs 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000008569 process Effects 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
- 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 3
- 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 3
- JTLAIKFGRHDNQM-UHFFFAOYSA-N 1-bromo-2-fluoroethane Chemical compound FCCBr JTLAIKFGRHDNQM-UHFFFAOYSA-N 0.000 description 3
- QJRWYBIKLXNYLF-UHFFFAOYSA-N 6-methoxy-1h-indole Chemical compound COC1=CC=C2C=CNC2=C1 QJRWYBIKLXNYLF-UHFFFAOYSA-N 0.000 description 3
- 102000009135 CB2 Cannabinoid Receptor Human genes 0.000 description 3
- 108010073376 CB2 Cannabinoid Receptor Proteins 0.000 description 3
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 3
- 108050007331 Cannabinoid receptor Proteins 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
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 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
- XEEBZISSHFFRHG-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(3,3-dimethylpiperazin-1-yl)methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2CC(C)(C)NCC2)=CN1CC1CCCCC1 XEEBZISSHFFRHG-UHFFFAOYSA-N 0.000 description 3
- WMPOPJACZVLYEN-INIZCTEOSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-[(3s)-3-methylpiperazin-1-yl]methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2C[C@H](C)NCC2)=CN1CC1CCCCC1 WMPOPJACZVLYEN-INIZCTEOSA-N 0.000 description 3
- ITYFWPJHVBTJAO-HNNXBMFYSA-N [1-(cyclopentylmethyl)-7-methoxyindol-3-yl]-[(3s)-3-methylpiperazin-1-yl]methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2C[C@H](C)NCC2)=CN1CC1CCCC1 ITYFWPJHVBTJAO-HNNXBMFYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 description 3
- 239000002260 anti-inflammatory agent Substances 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 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
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 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
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 239000011976 maleic acid 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
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 208000018198 spasticity Diseases 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
- JQAOHGMPAAWWQO-QMMMGPOBSA-N (2s)-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCCC[C@H]1C(O)=O JQAOHGMPAAWWQO-QMMMGPOBSA-N 0.000 description 2
- ZQEBQGAAWMOMAI-ZETCQYMHSA-N (2s)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C(O)=O ZQEBQGAAWMOMAI-ZETCQYMHSA-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
- 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
- ICJUEVKACUMGHT-UHFFFAOYSA-N 1-(cyclopentylmethyl)-7-methoxyindole Chemical compound C1=2C(OC)=CC=CC=2C=CN1CC1CCCC1 ICJUEVKACUMGHT-UHFFFAOYSA-N 0.000 description 2
- FAPFUJFYNVAFHI-UHFFFAOYSA-N 1-(cyclopentylmethyl)-7-methoxyindole-3-carboxylic acid Chemical compound C1=2C(OC)=CC=CC=2C(C(O)=O)=CN1CC1CCCC1 FAPFUJFYNVAFHI-UHFFFAOYSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- ZQEBQGAAWMOMAI-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCCC1C(O)=O ZQEBQGAAWMOMAI-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
- SZSZDBFJCQKTRG-UHFFFAOYSA-N 1h-indole-6-carbonitrile Chemical compound N#CC1=CC=C2C=CNC2=C1 SZSZDBFJCQKTRG-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
- IFNWESYYDINUHV-UHFFFAOYSA-N 2,6-dimethylpiperazine Chemical compound CC1CNCC(C)N1 IFNWESYYDINUHV-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
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- ODFFPRGJZRXNHZ-UHFFFAOYSA-N 5-fluoroindole Chemical compound FC1=CC=C2NC=CC2=C1 ODFFPRGJZRXNHZ-UHFFFAOYSA-N 0.000 description 2
- YTYIMDRWPTUAHP-UHFFFAOYSA-N 6-Chloroindole Chemical compound ClC1=CC=C2C=CNC2=C1 YTYIMDRWPTUAHP-UHFFFAOYSA-N 0.000 description 2
- MAWGHOPSCKCTPA-UHFFFAOYSA-N 6-bromo-1h-indole Chemical compound BrC1=CC=C2C=CNC2=C1 MAWGHOPSCKCTPA-UHFFFAOYSA-N 0.000 description 2
- YYFFEPUCAKVRJX-UHFFFAOYSA-N 6-fluoro-1h-indole Chemical compound FC1=CC=C2C=CNC2=C1 YYFFEPUCAKVRJX-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
- 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
- 206010058019 Cancer Pain Diseases 0.000 description 2
- 101710187022 Cannabinoid receptor 2 Proteins 0.000 description 2
- 102100036214 Cannabinoid receptor 2 Human genes 0.000 description 2
- 208000000094 Chronic Pain Diseases 0.000 description 2
- 241000400611 Eucalyptus deanei Species 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
- 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 group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-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
- 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 description 2
- SYMHOCNPYMEMSS-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(3,5-dimethylpiperazin-1-yl)methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2CC(C)NC(C)C2)=CN1CC1CCCCC1 SYMHOCNPYMEMSS-UHFFFAOYSA-N 0.000 description 2
- WMPOPJACZVLYEN-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(3-methylpiperazin-1-yl)methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2CC(C)NCC2)=CN1CC1CCCCC1 WMPOPJACZVLYEN-UHFFFAOYSA-N 0.000 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 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 description 2
- DKMGBFZWEGLBMY-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-nitroindol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(=C11)[N+]([O-])=O)=CN1CC1CCCCC1 DKMGBFZWEGLBMY-UHFFFAOYSA-N 0.000 description 2
- AXVLUTOFYLGGNV-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-phenylmethoxyindol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(OCC=2C=CC=CC=2)=C11)=CN1CC1CCCCC1 AXVLUTOFYLGGNV-UHFFFAOYSA-N 0.000 description 2
- ITYFWPJHVBTJAO-OAHLLOKOSA-N [1-(cyclopentylmethyl)-7-methoxyindol-3-yl]-[(3r)-3-methylpiperazin-1-yl]methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2C[C@@H](C)NCC2)=CN1CC1CCCC1 ITYFWPJHVBTJAO-OAHLLOKOSA-N 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000001270 agonistic 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
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000003520 cannabinoid receptor affecting agent Substances 0.000 description 2
- 239000003537 cannabinoid receptor agonist Substances 0.000 description 2
- 229940121376 cannabinoid receptor agonist Drugs 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- ISQVBYGGNVVVHB-UHFFFAOYSA-N cyclopentylmethanol Chemical compound OCC1CCCC1 ISQVBYGGNVVVHB-UHFFFAOYSA-N 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
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 208000035475 disorder 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
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000005764 inhibitory process Effects 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
- 150000002689 maleic acids Chemical class 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 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
- 235000015097 nutrients Nutrition 0.000 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 description 2
- 239000005022 packaging material Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 208000023504 respiratory system disease Diseases 0.000 description 2
- 238000000926 separation method Methods 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
- 230000000638 stimulation Effects 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
- 229940124597 therapeutic agent Drugs 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
- ZQEBQGAAWMOMAI-SSDOTTSWSA-N (2r)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC[C@@H]1C(O)=O ZQEBQGAAWMOMAI-SSDOTTSWSA-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
- 125000000229 (C1-C4)alkoxy group Chemical group 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
- RXYPXQSKLGGKOL-UHFFFAOYSA-N 1,4-dimethylpiperazine Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-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
- BMEMBBFDTYHTLH-UHFFFAOYSA-N 1-(2-methoxyethyl)piperazine Chemical compound COCCN1CCNCC1 BMEMBBFDTYHTLH-UHFFFAOYSA-N 0.000 description 1
- YBMQOZLRHVNVAB-UHFFFAOYSA-N 1-(cyclohexylmethyl)-3-(4-ethylpiperazine-1-carbonyl)indole-6-carbonitrile Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=C(C=C11)C#N)=CN1CC1CCCCC1 YBMQOZLRHVNVAB-UHFFFAOYSA-N 0.000 description 1
- RYAKKMVPKFMZBD-UHFFFAOYSA-N 1-(cyclohexylmethyl)-3-(4-methylpiperazine-1-carbonyl)indole-6-carbonitrile Chemical compound C1CN(C)CCN1C(=O)C(C1=CC=C(C=C11)C#N)=CN1CC1CCCCC1 RYAKKMVPKFMZBD-UHFFFAOYSA-N 0.000 description 1
- NRUJFIWNKXQLBY-UHFFFAOYSA-N 1-(cyclohexylmethyl)-5-fluoroindole Chemical compound C1=CC2=CC(F)=CC=C2N1CC1CCCCC1 NRUJFIWNKXQLBY-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
- PIPWSBOFSUJCCO-UHFFFAOYSA-N 2,2-dimethylpiperazine Chemical compound CC1(C)CNCCN1 PIPWSBOFSUJCCO-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
- 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
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-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
- PSWCIARYGITEOY-UHFFFAOYSA-N 6-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2C=CNC2=C1 PSWCIARYGITEOY-UHFFFAOYSA-N 0.000 description 1
- RDSVSEFWZUWZHW-UHFFFAOYSA-N 7-bromo-1h-indole Chemical compound BrC1=CC=CC2=C1NC=C2 RDSVSEFWZUWZHW-UHFFFAOYSA-N 0.000 description 1
- PIIZLMYXLGYWTN-UHFFFAOYSA-N 7-ethyl-1h-indole Chemical compound CCC1=CC=CC2=C1NC=C2 PIIZLMYXLGYWTN-UHFFFAOYSA-N 0.000 description 1
- KGWPHCDTOLQQEP-UHFFFAOYSA-N 7-methylindole Chemical compound CC1=CC=CC2=C1NC=C2 KGWPHCDTOLQQEP-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
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase 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
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- KRHNFOWHGJVECQ-UHFFFAOYSA-N C(=O)=C1NCCN(C1)CC Chemical compound C(=O)=C1NCCN(C1)CC KRHNFOWHGJVECQ-UHFFFAOYSA-N 0.000 description 1
- FEOOUWCWZQVKTF-UHFFFAOYSA-N CC1=CC=C(C=C1)S(=O)(=O)OC.C1CCCCCCC1 Chemical compound CC1=CC=C(C=C1)S(=O)(=O)OC.C1CCCCCCC1 FEOOUWCWZQVKTF-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- SXVMENMIZXPCNC-UHFFFAOYSA-N Cl.CCN1CCN(CC1)C(=O)c2cn(CC3CCCCC3)c4ccc(F)cc24 Chemical compound Cl.CCN1CCN(CC1)C(=O)c2cn(CC3CCCCC3)c4ccc(F)cc24 SXVMENMIZXPCNC-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
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-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
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 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
- 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
- 208000019695 Migraine disease Diseases 0.000 description 1
- 206010052904 Musculoskeletal stiffness Diseases 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
- 108091027981 Response element Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229920002472 Starch Chemical class 0.000 description 1
- 208000006011 Stroke Diseases 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
- 206010047700 Vomiting 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
- 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
- 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
- FYDLPADTOIOHRX-UHFFFAOYSA-N [1-(1-cyclohexylethyl)-6-methoxyindol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=C(OC)C=C11)=CN1C(C)C1CCCCC1 FYDLPADTOIOHRX-UHFFFAOYSA-N 0.000 description 1
- SBKHWWOIAPWZQQ-UHFFFAOYSA-N [1-(1-cyclohexylethyl)-7-methoxyindol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(OC)=C11)=CN1C(C)C1CCCCC1 SBKHWWOIAPWZQQ-UHFFFAOYSA-N 0.000 description 1
- XXWDHXISAUVGPS-UHFFFAOYSA-N [1-(1-cyclohexylethyl)indol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC=C11)=CN1C(C)C1CCCCC1 XXWDHXISAUVGPS-UHFFFAOYSA-N 0.000 description 1
- FWIQSRCDYNAYBV-UHFFFAOYSA-N [1-(1-cyclohexylpropyl)indol-3-yl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1=C(C(=O)N2CCN(C)CC2)C2=CC=CC=C2N1C(CC)C1CCCCC1 FWIQSRCDYNAYBV-UHFFFAOYSA-N 0.000 description 1
- LXRFHCDHTIPUIB-UHFFFAOYSA-N [1-(cycloheptylmethyl)-7-methoxyindol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(OC)=C11)=CN1CC1CCCCCC1 LXRFHCDHTIPUIB-UHFFFAOYSA-N 0.000 description 1
- DZNPEONMNUJEEV-UHFFFAOYSA-N [1-(cyclohex-3-en-1-ylmethyl)-7-methoxyindol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(OC)=C11)=CN1CC1CC=CCC1 DZNPEONMNUJEEV-UHFFFAOYSA-N 0.000 description 1
- SXYHMAXZTOPLAS-UHFFFAOYSA-N [1-(cyclohexylmethyl)-5-fluoroindol-3-yl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C(C1=CC(F)=CC=C11)=CN1CC1CCCCC1 SXYHMAXZTOPLAS-UHFFFAOYSA-N 0.000 description 1
- WUVPFZWPIXFYSD-UHFFFAOYSA-N [1-(cyclohexylmethyl)-6-fluoroindol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=C(F)C=C11)=CN1CC1CCCCC1 WUVPFZWPIXFYSD-UHFFFAOYSA-N 0.000 description 1
- KBRTWCSEXXKYAV-UHFFFAOYSA-N [1-(cyclohexylmethyl)-6-fluoroindol-3-yl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C(C1=CC=C(F)C=C11)=CN1CC1CCCCC1 KBRTWCSEXXKYAV-UHFFFAOYSA-N 0.000 description 1
- SJKXWRLGCZSMSX-UHFFFAOYSA-N [1-(cyclohexylmethyl)-6-methoxyindol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=C(OC)C=C11)=CN1CC1CCCCC1 SJKXWRLGCZSMSX-UHFFFAOYSA-N 0.000 description 1
- ONSLDLFWOYIALK-UHFFFAOYSA-N [1-(cyclohexylmethyl)-6-nitroindol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=C(C=C11)[N+]([O-])=O)=CN1CC1CCCCC1 ONSLDLFWOYIALK-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
- GMQPYBAADZQNIA-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-ethylindol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(CC)=C11)=CN1CC1CCCCC1 GMQPYBAADZQNIA-UHFFFAOYSA-N 0.000 description 1
- KKTUSLHXJTVCKO-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-fluoroindol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(F)=C11)=CN1CC1CCCCC1 KKTUSLHXJTVCKO-UHFFFAOYSA-N 0.000 description 1
- VBOZRMUYZAAHPC-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-fluoroindol-3-yl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C(C1=CC=CC(F)=C11)=CN1CC1CCCCC1 VBOZRMUYZAAHPC-UHFFFAOYSA-N 0.000 description 1
- ZPGPWCJKICQQEB-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-hydroxyindol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(O)=C11)=CN1CC1CCCCC1 ZPGPWCJKICQQEB-UHFFFAOYSA-N 0.000 description 1
- ZHWFVDDWFITQLT-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(2,3,5,6-tetramethylpiperazin-1-yl)methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2C(C(C)NC(C)C2C)C)=CN1CC1CCCCC1 ZHWFVDDWFITQLT-UHFFFAOYSA-N 0.000 description 1
- ZCKGRKAFAPBGTM-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(2,6-dimethylpiperazin-1-yl)methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2C(CNCC2C)C)=CN1CC1CCCCC1 ZCKGRKAFAPBGTM-UHFFFAOYSA-N 0.000 description 1
- PRIXWUKWUTUQOM-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(3,3,4-trimethylpiperazin-1-yl)methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2CC(C)(C)N(C)CC2)=CN1CC1CCCCC1 PRIXWUKWUTUQOM-UHFFFAOYSA-N 0.000 description 1
- DSARICDMKZKRJI-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(4-ethyl-2,3,5,6-tetramethylpiperazin-1-yl)methanone Chemical compound CC1C(C)N(CC)C(C)C(C)N1C(=O)C(C1=CC=CC(OC)=C11)=CN1CC1CCCCC1 DSARICDMKZKRJI-UHFFFAOYSA-N 0.000 description 1
- DRFPUFOKWKJCFL-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(4-ethyl-2,6-dimethylpiperazin-1-yl)methanone Chemical compound CC1CN(CC)CC(C)N1C(=O)C(C1=CC=CC(OC)=C11)=CN1CC1CCCCC1 DRFPUFOKWKJCFL-UHFFFAOYSA-N 0.000 description 1
- UHNMZKXKDDISSX-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(4-ethyl-3,3-dimethylpiperazin-1-yl)methanone Chemical compound C1C(C)(C)N(CC)CCN1C(=O)C(C1=CC=CC(OC)=C11)=CN1CC1CCCCC1 UHNMZKXKDDISSX-UHFFFAOYSA-N 0.000 description 1
- FCJAQMHQTHNQML-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(4-ethyl-3-methylpiperazin-1-yl)methanone Chemical compound C1C(C)N(CC)CCN1C(=O)C(C1=CC=CC(OC)=C11)=CN1CC1CCCCC1 FCJAQMHQTHNQML-UHFFFAOYSA-N 0.000 description 1
- KRDQZFKUVXRPEQ-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(OC)=C11)=CN1CC1CCCCC1 KRDQZFKUVXRPEQ-UHFFFAOYSA-N 0.000 description 1
- JRELJYKELGNHQH-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-(4-propan-2-ylpiperazin-1-yl)methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2CCN(CC2)C(C)C)=CN1CC1CCCCC1 JRELJYKELGNHQH-UHFFFAOYSA-N 0.000 description 1
- WXYWCTBVLBCFNV-MOPGFXCFSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-[(2s,5r)-4-ethyl-2,5-dimethylpiperazin-1-yl]methanone Chemical compound C1[C@@H](C)N(CC)C[C@H](C)N1C(=O)C(C1=CC=CC(OC)=C11)=CN1CC1CCCCC1 WXYWCTBVLBCFNV-MOPGFXCFSA-N 0.000 description 1
- WMPOPJACZVLYEN-MRXNPFEDSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-[(3r)-3-methylpiperazin-1-yl]methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2C[C@@H](C)NCC2)=CN1CC1CCCCC1 WMPOPJACZVLYEN-MRXNPFEDSA-N 0.000 description 1
- CGWQUQMQXXPNTC-SFHVURJKSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-[(3s)-4-(2-fluoroethyl)-3-methylpiperazin-1-yl]methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2C[C@H](C)N(CCF)CC2)=CN1CC1CCCCC1 CGWQUQMQXXPNTC-SFHVURJKSA-N 0.000 description 1
- DHFLOPNNDHZSEU-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-[3-(fluoromethyl)piperazin-1-yl]methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2CC(CF)NCC2)=CN1CC1CCCCC1 DHFLOPNNDHZSEU-UHFFFAOYSA-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
- HKLBQUAIUUUPOO-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-[4-(2-hydroxyethyl)piperazin-1-yl]methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2CCN(CCO)CC2)=CN1CC1CCCCC1 HKLBQUAIUUUPOO-UHFFFAOYSA-N 0.000 description 1
- NFXMTSGPLUZOOS-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-[4-(2-methoxyethyl)piperazin-1-yl]methanone Chemical compound C1CN(CCOC)CCN1C(=O)C(C1=CC=CC(OC)=C11)=CN1CC1CCCCC1 NFXMTSGPLUZOOS-UHFFFAOYSA-N 0.000 description 1
- AUIPMCSBQQHEAF-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methoxyindol-3-yl]-[4-cyclopropyl-3-(fluoromethyl)piperazin-1-yl]methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2CC(CF)N(C3CC3)CC2)=CN1CC1CCCCC1 AUIPMCSBQQHEAF-UHFFFAOYSA-N 0.000 description 1
- RPRYTMAQVWICAO-UHFFFAOYSA-N [1-(cyclohexylmethyl)-7-methylindol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(C)=C11)=CN1CC1CCCCC1 RPRYTMAQVWICAO-UHFFFAOYSA-N 0.000 description 1
- NKBVCQCNLNIHFS-UHFFFAOYSA-N [1-(cyclooctylmethyl)-7-methoxyindol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(OC)=C11)=CN1CC1CCCCCCC1 NKBVCQCNLNIHFS-UHFFFAOYSA-N 0.000 description 1
- LCEJLFBFJHGSLY-UHFFFAOYSA-N [1-(cyclopentylmethyl)-7-methoxyindol-3-yl]-(3,4,5-trimethylpiperazin-1-yl)methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2CC(C)N(C)C(C)C2)=CN1CC1CCCC1 LCEJLFBFJHGSLY-UHFFFAOYSA-N 0.000 description 1
- FUGDTPOIKMQLKE-UHFFFAOYSA-N [1-(cyclopentylmethyl)-7-methoxyindol-3-yl]-(3,5-dimethylpiperazin-1-yl)methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2CC(C)NC(C)C2)=CN1CC1CCCC1 FUGDTPOIKMQLKE-UHFFFAOYSA-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
- ZGQIYPCNUBCYNQ-MRXNPFEDSA-N [1-(cyclopentylmethyl)-7-methoxyindol-3-yl]-[(3r)-3,4-dimethylpiperazin-1-yl]methanone Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2C[C@@H](C)N(C)CC2)=CN1CC1CCCC1 ZGQIYPCNUBCYNQ-MRXNPFEDSA-N 0.000 description 1
- ZGQIYPCNUBCYNQ-INIZCTEOSA-N [1-(cyclopentylmethyl)-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)=CN1CC1CCCC1 ZGQIYPCNUBCYNQ-INIZCTEOSA-N 0.000 description 1
- BXNFEBNMXGKHEA-KRWDZBQOSA-N [1-(cyclopentylmethyl)-7-methoxyindol-3-yl]-[(3s)-4-ethyl-3-methylpiperazin-1-yl]methanone Chemical compound C1[C@H](C)N(CC)CCN1C(=O)C(C1=CC=CC(OC)=C11)=CN1CC1CCCC1 BXNFEBNMXGKHEA-KRWDZBQOSA-N 0.000 description 1
- ZXCOEKVTJOTMTN-UHFFFAOYSA-N [5-chloro-1-(cyclohexylmethyl)indol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC(Cl)=CC=C11)=CN1CC1CCCCC1 ZXCOEKVTJOTMTN-UHFFFAOYSA-N 0.000 description 1
- BNVZIYOVSFRKTH-UHFFFAOYSA-N [6-bromo-1-(cyclohexylmethyl)indol-3-yl]-(4-methylpiperazin-1-yl)methanone hydrochloride Chemical compound Cl.BrC1=CC=C2C(=CN(C2=C1)CC1CCCCC1)C(=O)N1CCN(CC1)C BNVZIYOVSFRKTH-UHFFFAOYSA-N 0.000 description 1
- BUFXSUQUZPTETQ-UHFFFAOYSA-N [6-chloro-1-(cyclohexylmethyl)indol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=C(Cl)C=C11)=CN1CC1CCCCC1 BUFXSUQUZPTETQ-UHFFFAOYSA-N 0.000 description 1
- GLMXFFOAUWLHPV-UHFFFAOYSA-N [6-chloro-1-(cyclohexylmethyl)indol-3-yl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C(C1=CC=C(Cl)C=C11)=CN1CC1CCCCC1 GLMXFFOAUWLHPV-UHFFFAOYSA-N 0.000 description 1
- VGLWNXOHYCKIOV-UHFFFAOYSA-N [7-amino-1-(cyclohexylmethyl)indol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(N)=C11)=CN1CC1CCCCC1 VGLWNXOHYCKIOV-UHFFFAOYSA-N 0.000 description 1
- WAVJJPWCGPIOGQ-UHFFFAOYSA-N [7-bromo-1-(cyclohexylmethyl)indol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(Br)=C11)=CN1CC1CCCCC1 WAVJJPWCGPIOGQ-UHFFFAOYSA-N 0.000 description 1
- FJCNONNSYILBKJ-UHFFFAOYSA-N [7-chloro-1-(cyclohexylmethyl)indol-3-yl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(Cl)=C11)=CN1CC1CCCCC1 FJCNONNSYILBKJ-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
- 208000005298 acute pain Diseases 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 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
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003502 anti-nociceptive effect Effects 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
- 238000011914 asymmetric synthesis Methods 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
- 230000004071 biological effect Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 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
- 239000003554 cannabinoid 1 receptor agonist Substances 0.000 description 1
- 229940065144 cannabinoids Drugs 0.000 description 1
- 229910052799 carbon Inorganic materials 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
- 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
- 230000008859 change Effects 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001805 chlorine compounds Chemical group 0.000 description 1
- 239000012501 chromatography medium Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229940111134 coxibs Drugs 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
- 230000001419 dependent effect Effects 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- OENICUBCLXKLJQ-UHFFFAOYSA-N ethyl 2,3-dibromopropanoate Chemical compound CCOC(=O)C(Br)CBr OENICUBCLXKLJQ-UHFFFAOYSA-N 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
- 239000011737 fluorine Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000001530 fumaric acid Substances 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
- 125000004435 hydrogen atom Chemical group [H]* 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
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 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
- 229910052500 inorganic mineral Inorganic materials 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
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 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
- 239000010410 layer Substances 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- OZSJLLVVZFTDEY-RFKZQXLXSA-N methyl (2r,3s)-2-amino-3-hydroxybutanoate;hydrochloride Chemical compound Cl.COC(=O)[C@H](N)[C@H](C)O OZSJLLVVZFTDEY-RFKZQXLXSA-N 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
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 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
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- ONXJNAIZJKLJGA-UHFFFAOYSA-N org 28611 Chemical compound C1=2C(OC)=CC=CC=2C(C(=O)N2CC(C)N(C)CC2)=CN1CC1CCCCC1 ONXJNAIZJKLJGA-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 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
- 239000012071 phase Substances 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- BXRNXXXXHLBUKK-UHFFFAOYSA-N piperazine-2,5-dione Chemical compound O=C1CNC(=O)CN1 BXRNXXXXHLBUKK-UHFFFAOYSA-N 0.000 description 1
- 229920005596 polymer binder Polymers 0.000 description 1
- 239000002491 polymer binding agent Substances 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
- 238000002360 preparation method Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 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
- 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
- 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
- 230000000241 respiratory effect 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
- 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
- 230000003637 steroidlike Effects 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
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- NUZXPHIQZUYMOR-UHFFFAOYSA-N tert-butyl 3,5-dimethylpiperazine-1-carboxylate Chemical compound CC1CN(C(=O)OC(C)(C)C)CC(C)N1 NUZXPHIQZUYMOR-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-M toluene-4-sulfonate Chemical group CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Rheumatology (AREA)
- Ophthalmology & Optometry (AREA)
- Pulmonology (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Anesthesiology (AREA)
- Immunology (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 (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP02077505 | 2002-06-21 | ||
| EP02077505 | 2002-06-21 | ||
| PCT/EP2003/050226 WO2004000832A1 (en) | 2002-06-21 | 2003-06-13 | 1-[(indol-3-yl)carbonyl] piperazine derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60313640D1 DE60313640D1 (de) | 2007-06-14 |
| DE60313640T2 true DE60313640T2 (de) | 2007-12-27 |
Family
ID=29797228
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60313640T Expired - Lifetime DE60313640T2 (de) | 2002-06-21 | 2003-06-13 | 1-(indol-3-yl)carbonyl piperazinderivate |
Country Status (32)
Families Citing this family (19)
| 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 |
| ATE375349T1 (de) | 2002-08-02 | 2007-10-15 | Merck & Co Inc | Substituierte furo(2,3-b)pyridin derivate |
| DE10253426B4 (de) | 2002-11-15 | 2005-09-22 | Elbion Ag | Neue Hydroxyindole, deren Verwendung als Inhibitoren der Phosphodiesterase 4 und Verfahren zu deren Herstellung |
| DE602004005893T2 (de) | 2003-12-17 | 2007-09-06 | N.V. Organon | Trizyklische 1-((3-indol-3-yl)-carbonyl)-piperazin-derivate als cannabinoid-cb1-rezeptoragonisten |
| TWI330635B (en) * | 2004-03-05 | 2010-09-21 | Organon Nv | (indol-3-yl)-heterocycle derivatives |
| US20090029984A1 (en) * | 2005-07-11 | 2009-01-29 | N.V. Organon | Synergistic combination for the treatment of pain (cannabinoid receptor agonist and opioid receptor agonist) |
| CN102295636A (zh) * | 2005-07-29 | 2011-12-28 | 弗·哈夫曼-拉罗切有限公司 | 吲哚-3-基-羰基-哌啶和哌嗪衍生物 |
| 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 |
| CA2623525A1 (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 |
| CN115368356B (zh) | 2013-12-20 | 2025-05-09 | 阿斯特克斯治疗有限公司 | 双环杂环化合物及其治疗用途 |
| EP3737680A1 (en) | 2018-01-08 | 2020-11-18 | F. Hoffmann-La Roche AG | Octahydropyrido[1,2-alpha]pyrazines as magl inhibitors |
| 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 |
| CN114072405A (zh) | 2019-07-03 | 2022-02-18 | 豪夫迈·罗氏有限公司 | 杂环单酰基甘油脂肪酶(magl)抑制剂 |
| KR20220034104A (ko) | 2019-07-09 | 2022-03-17 | 에프. 호프만-라 로슈 아게 | 신규 헤테로고리 화합물 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX9203454A (es) * | 1989-12-28 | 1992-08-01 | Upjohn Co | Compuestos anti sida diaromaticos substituidos. |
| 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 |
| JP2004502642A (ja) * | 2000-02-11 | 2004-01-29 | ブリストル−マイヤーズ スクイブ カンパニー | カンナビノイドレセプターモジュレーター、それらの製造方法、および呼吸系および非呼吸系疾患の処置のためのカンナビノイドレセプターモジュレーターの使用 |
-
2003
- 2003-06-11 TW TW092115888A patent/TW200402417A/zh unknown
- 2003-06-13 RS YUP-1111/04A patent/RS111104A/sr unknown
- 2003-06-13 DK DK03760704T patent/DK1549637T3/da active
- 2003-06-13 AT AT03760704T patent/ATE361290T1/de active
- 2003-06-13 DE DE60313640T patent/DE60313640T2/de not_active Expired - Lifetime
- 2003-06-13 PT PT03760704T patent/PT1549637E/pt unknown
- 2003-06-13 RU RU2005101349/04A patent/RU2318821C2/ru not_active IP Right Cessation
- 2003-06-13 HR HR20041186A patent/HRP20041186A2/xx not_active Application Discontinuation
- 2003-06-13 US US10/518,279 patent/US7304064B2/en not_active Expired - Fee Related
- 2003-06-13 AU AU2003250245A patent/AU2003250245B2/en not_active Ceased
- 2003-06-13 WO PCT/EP2003/050226 patent/WO2004000832A1/en not_active Ceased
- 2003-06-13 BR BR0311960-2A patent/BR0311960A/pt not_active IP Right Cessation
- 2003-06-13 NZ NZ537143A patent/NZ537143A/en unknown
- 2003-06-13 CN CNB038170906A patent/CN1298716C/zh not_active Expired - Fee Related
- 2003-06-13 JP JP2004514874A patent/JP4408804B2/ja not_active Expired - Fee Related
- 2003-06-13 KR KR10-2004-7020734A patent/KR20050009755A/ko not_active Ceased
- 2003-06-13 UA UA20041210112A patent/UA78317C2/uk unknown
- 2003-06-13 EP EP03760704A patent/EP1549637B1/en not_active Expired - Lifetime
- 2003-06-13 SI SI200330855T patent/SI1549637T1/sl unknown
- 2003-06-13 CA CA2490141A patent/CA2490141C/en not_active Expired - Fee Related
- 2003-06-13 PL PL03375152A patent/PL375152A1/xx not_active Application Discontinuation
- 2003-06-13 MX MXPA04012856A patent/MXPA04012856A/es active IP Right Grant
- 2003-06-13 ES ES03760704T patent/ES2285183T3/es not_active Expired - Lifetime
- 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 |
|---|---|---|
| EP0397060B1 (de) | Maleinimid-Derivate und deren Verwendung als Arzneimittel | |
| EP0546388B1 (de) | Azaheterocyclylmethyl-chromane als Wirkstoffe zur Behandlung von Erkrankungen des Zentralnervensystems | |
| AT403917B (de) | Indolderivate | |
| DE68908040T2 (de) | 3-(4-Piperidin)-5-(2-sulphonylaminoethyl)-indol-Derivate. | |
| DE69716062T2 (de) | Benzofuran-derivate und deren verwendung | |
| JP4408804B2 (ja) | １−［（インドル−３−イル）カルボニル］ピペラジン誘導体 | |
| EP0683166B1 (de) | 3-Indolylpiperidine | |
| DE3784401T2 (de) | Karbostyril-derivate und ihre salze, verfahren zu ihrer herstellung und diese enthaltende kardiotonische zusammensetzung. | |
| DE4333254A1 (de) | Piperidine und Piperazine | |
| DE69531476T2 (de) | Serotonergische Modulatoren | |
| DE60316672T2 (de) | Polycyclische verbindungen als potente alpha2-adrenoceptor antagonisten | |
| DE3522604A1 (de) | Neue feste formen von 2-(gamma)thoxy-4-(n-(1-(2-piperidino-phenyl)-3-methyl-1-butyl)-aminocarbonylmethyl)-benzoesaeure, diese formen enthaltende arzneimittel und verfahren zu ihrer herstellung | |
| DD216716A5 (de) | Verfahren zur herstellung von octahydrobenzo (f)chinolinen | |
| DE68904342T2 (de) | Cyclische amide. | |
| DE3409237A1 (de) | Kondensierte diazepinone, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel | |
| DE4443891A1 (de) | Heterocyclisch substituierte Oxy-phenyl-(phenyl)glycinolamide | |
| DE60112725T2 (de) | Phenoxyalkylaminderivate als agonisten des opioid-delta rezeptors | |
| DE602004005893T2 (de) | Trizyklische 1-((3-indol-3-yl)-carbonyl)-piperazin-derivate als cannabinoid-cb1-rezeptoragonisten | |
| EP0254955A2 (de) | Substituierte Pyrido-[2,3-b][1,4]benzodiazepin-6-one, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| DE19725664A1 (de) | 3-Benzylpiperidine | |
| DE60007625T2 (de) | Substituierte benzolactamverbindungen | |
| DE2840770A1 (de) | Dibenzo eckige klammer auf a.d eckige klammer zu cycloocten-5,12(und 6,12)-imine | |
| DE3523002A1 (de) | Neue in 11-stellung substituierte 5,11-dihydro-6h-pyrido(2,3-b) (1,4)benzodiazepin-6-one, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel | |
| AT375079B (de) | Verfahren zur herstellung von neuen trans-2,3,4,4a ,5,9b-hexahydro-1h-pyrido(4,3-b)indolen und ihren pharmazeutisch annehmbaren salzen | |
| HK1076630B (en) | 1-(indol-3-yl) carbonyl piperazine derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| R082 | Change of representative |
Ref document number: 1549637 Country of ref document: EP Representative=s name: WUESTHOFF & WUESTHOFF PATENT- UND RECHTSANWAEL, DE |