NZ537143A - 1-[(indol-3-yl)carbonyl]piperazine derivatives - Google Patents
1-[(indol-3-yl)carbonyl]piperazine derivativesInfo
- Publication number
- NZ537143A NZ537143A NZ537143A NZ53714303A NZ537143A NZ 537143 A NZ537143 A NZ 537143A NZ 537143 A NZ537143 A NZ 537143A NZ 53714303 A NZ53714303 A NZ 53714303A NZ 537143 A NZ537143 A NZ 537143A
- Authority
- NZ
- New Zealand
- Prior art keywords
- indol
- carbonyl
- methoxy
- alkyl
- halogen
- Prior art date
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 abstract description 30
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 22
- 208000002193 Pain Diseases 0.000 claims abstract description 20
- 150000002367 halogens Chemical class 0.000 claims abstract description 18
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 239000001257 hydrogen Substances 0.000 claims abstract description 12
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 5
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 5
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
- 125000001424 substituent group Chemical group 0.000 claims abstract description 4
- 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 claims abstract description 3
- 125000005843 halogen group Chemical group 0.000 claims abstract 4
- 150000001875 compounds Chemical class 0.000 claims description 82
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 27
- 238000012360 testing method Methods 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 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 3
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 241000699670 Mus sp. Species 0.000 claims 2
- VUMDEFASFOCYQN-UHFFFAOYSA-N (1-benzyl-7-methoxyindol-3-yl)-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(OC)=C11)=CN1CC1=CC=CC=C1 VUMDEFASFOCYQN-UHFFFAOYSA-N 0.000 claims 1
- FDKRQCRZEBKBGP-UHFFFAOYSA-N (4-ethylpiperazin-1-yl)-[7-methoxy-1-(2-morpholin-4-ylethyl)indazol-3-yl]methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(OC)=C11)=NN1CCN1CCOCC1 FDKRQCRZEBKBGP-UHFFFAOYSA-N 0.000 claims 1
- ZGARQGHOXSTBAX-UHFFFAOYSA-N (4-ethylpiperazin-1-yl)-[7-methoxy-1-(2-morpholin-4-ylethyl)indol-3-yl]methanone Chemical compound C1CN(CC)CCN1C(=O)C(C1=CC=CC(OC)=C11)=CN1CCN1CCOCC1 ZGARQGHOXSTBAX-UHFFFAOYSA-N 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 230000000451 tissue damage Effects 0.000 claims 1
- 231100000827 tissue damage Toxicity 0.000 claims 1
- 208000008238 Muscle Spasticity Diseases 0.000 abstract description 4
- 201000006417 multiple sclerosis Diseases 0.000 abstract description 4
- 208000004296 neuralgia Diseases 0.000 abstract description 4
- 208000021722 neuropathic pain Diseases 0.000 abstract description 4
- 208000018198 spasticity Diseases 0.000 abstract description 4
- 206010058019 Cancer Pain Diseases 0.000 abstract description 3
- 208000000094 Chronic Pain Diseases 0.000 abstract description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 4
- 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
- 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 71
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 68
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- 239000000243 solution Substances 0.000 description 49
- 239000000203 mixture Substances 0.000 description 44
- 238000005160 1H NMR spectroscopy Methods 0.000 description 40
- 238000000034 method Methods 0.000 description 35
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 239000007787 solid Substances 0.000 description 19
- -1 2-(4-morpholinyl)ethyl side chain Chemical group 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 17
- 239000003921 oil Substances 0.000 description 17
- 235000019198 oils Nutrition 0.000 description 17
- 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
- 238000003818 flash chromatography Methods 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- 239000003557 cannabinoid Substances 0.000 description 11
- 229930003827 cannabinoid Natural products 0.000 description 11
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- 239000000556 agonist Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-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
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 230000014509 gene expression Effects 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 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 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
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
- 229910052757 nitrogen Inorganic materials 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 102000009132 CB1 Cannabinoid Receptor Human genes 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
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 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
- 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 5
- 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 description 5
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000000047 product Substances 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
- 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
- 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 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
- 239000008346 aqueous phase Substances 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- UUWSLBWDFJMSFP-UHFFFAOYSA-N bromomethylcyclohexane Chemical compound BrCC1CCCCC1 UUWSLBWDFJMSFP-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-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
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 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
- 239000000725 suspension Substances 0.000 description 4
- 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
- QJRWYBIKLXNYLF-UHFFFAOYSA-N 6-methoxy-1h-indole Chemical compound COC1=CC=C2C=CNC2=C1 QJRWYBIKLXNYLF-UHFFFAOYSA-N 0.000 description 3
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 3
- 108050007331 Cannabinoid receptor Proteins 0.000 description 3
- 101710187010 Cannabinoid receptor 1 Proteins 0.000 description 3
- 102100033868 Cannabinoid receptor 1 Human genes 0.000 description 3
- 101710187022 Cannabinoid receptor 2 Proteins 0.000 description 3
- 102100036214 Cannabinoid receptor 2 Human genes 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 235000019502 Orange oil Nutrition 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
- 239000002253 acid Substances 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 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
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 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
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000010502 orange oil Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 208000023504 respiratory system disease 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
- JOMNTHCQHJPVAZ-YFKPBYRVSA-N (2s)-2-methylpiperazine Chemical compound C[C@H]1CNCCN1 JOMNTHCQHJPVAZ-YFKPBYRVSA-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
- 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
- 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
- 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
- YNZFFALZMRAPHQ-SYYKKAFVSA-N 2-[(1r,2r,5r)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol Chemical compound OC1=CC(C(C)(C)CCCCCC)=CC=C1[C@H]1[C@H](CCCO)CC[C@@H](O)C1 YNZFFALZMRAPHQ-SYYKKAFVSA-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
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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 (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 (1)
| Publication Number | Publication Date |
|---|---|
| NZ537143A true NZ537143A (en) | 2005-05-27 |
Family
ID=29797228
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ537143A NZ537143A (en) | 2002-06-21 | 2003-06-13 | 1-[(indol-3-yl)carbonyl]piperazine derivatives |
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
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