AP463A - "Indoline derivatives as 5HT2c antagonist". - Google Patents
"Indoline derivatives as 5HT2c antagonist". Download PDFInfo
- Publication number
- AP463A AP463A APAP/P/1994/000653A AP9400653A AP463A AP 463 A AP463 A AP 463A AP 9400653 A AP9400653 A AP 9400653A AP 463 A AP463 A AP 463A
- Authority
- AP
- ARIPO
- Prior art keywords
- indoline
- chloro
- pyridylcarbamoyl
- methyl
- nmr
- Prior art date
Links
- 125000003387 indolinyl group Chemical class N1(CCC2=CC=CC=C12)* 0.000 title description 5
- 239000002484 serotonin 2C antagonist Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 187
- 238000000034 method Methods 0.000 claims abstract description 98
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 40
- 239000001257 hydrogen Substances 0.000 claims abstract description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 32
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 16
- 150000002367 halogens Chemical class 0.000 claims abstract description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 14
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 12
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 230000008569 process Effects 0.000 claims abstract description 9
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims abstract description 7
- 125000005843 halogen group Chemical group 0.000 claims abstract description 7
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims abstract description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000005864 Sulphur Chemical group 0.000 claims abstract description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 5
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 5
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 5
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
- 239000001301 oxygen Chemical group 0.000 claims abstract description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 75
- 150000003839 salts Chemical class 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 238000005859 coupling reaction Methods 0.000 claims description 5
- JDEDDUYWHVGXBK-UHFFFAOYSA-N n-pyridin-3-yl-5-(trifluoromethyl)-2,3-dihydroindole-1-carboxamide Chemical compound C1CC2=CC(C(F)(F)F)=CC=C2N1C(=O)NC1=CC=CN=C1 JDEDDUYWHVGXBK-UHFFFAOYSA-N 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- IFMKJNSSPPAQOQ-UHFFFAOYSA-N 4-iodo-5-methyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC2=C(I)C(C)=CC=C2N1C(=O)NC1=CC=CN=C1 IFMKJNSSPPAQOQ-UHFFFAOYSA-N 0.000 claims description 4
- XNRDHEFXDKDCMQ-UHFFFAOYSA-N 5-chloro-6-methyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC=2C=C(Cl)C(C)=CC=2N1C(=O)NC1=CC=CN=C1 XNRDHEFXDKDCMQ-UHFFFAOYSA-N 0.000 claims description 4
- BYXYRVSXGVLRKM-UHFFFAOYSA-N 5-chloro-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC2=CC(Cl)=CC=C2N1C(=O)NC1=CC=CN=C1 BYXYRVSXGVLRKM-UHFFFAOYSA-N 0.000 claims description 4
- VUJXFEKATKVBBP-UHFFFAOYSA-N 6-bromo-5-ethylsulfanyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1=2C=C(Br)C(SCC)=CC=2CCN1C(=O)NC1=CC=CN=C1 VUJXFEKATKVBBP-UHFFFAOYSA-N 0.000 claims description 4
- FGTRCUOWUGYCLD-UHFFFAOYSA-N 6-chloro-5-propan-2-ylsulfanyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1=2C=C(Cl)C(SC(C)C)=CC=2CCN1C(=O)NC1=CC=CN=C1 FGTRCUOWUGYCLD-UHFFFAOYSA-N 0.000 claims description 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 229910006095 SO2F Inorganic materials 0.000 claims description 4
- 125000001589 carboacyl group Chemical group 0.000 claims description 4
- 230000008878 coupling Effects 0.000 claims description 4
- 238000010168 coupling process Methods 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 4
- YSGSQACIWFDMAJ-UHFFFAOYSA-N 5-phenyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC2=CC(C=3C=CC=CC=3)=CC=C2N1C(=O)NC1=CC=CN=C1 YSGSQACIWFDMAJ-UHFFFAOYSA-N 0.000 claims description 3
- LOLNBESEFOMRHG-UHFFFAOYSA-N 6-bromo-5-methyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1=2C=C(Br)C(C)=CC=2CCN1C(=O)NC1=CC=CN=C1 LOLNBESEFOMRHG-UHFFFAOYSA-N 0.000 claims description 3
- LOMPSBWQXLVHJX-UHFFFAOYSA-N 6-chloro-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C12=CC(Cl)=CC=C2CCN1C(=O)NC1=CC=CN=C1 LOMPSBWQXLVHJX-UHFFFAOYSA-N 0.000 claims description 3
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- NLNBNROVVZQUSP-UHFFFAOYSA-N 4-bromo-5-methyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC2=C(Br)C(C)=CC=C2N1C(=O)NC1=CC=CN=C1 NLNBNROVVZQUSP-UHFFFAOYSA-N 0.000 claims description 2
- FJUARYIMIPGIJS-UHFFFAOYSA-N 4-chloro-5-methyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC2=C(Cl)C(C)=CC=C2N1C(=O)NC1=CC=CN=C1 FJUARYIMIPGIJS-UHFFFAOYSA-N 0.000 claims description 2
- KBIGCTQWHDNTLK-UHFFFAOYSA-N 4-chloro-5-methylsulfanyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC2=C(Cl)C(SC)=CC=C2N1C(=O)NC1=CC=CN=C1 KBIGCTQWHDNTLK-UHFFFAOYSA-N 0.000 claims description 2
- DWZCCUPWPGYNMI-UHFFFAOYSA-N 5-iodo-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC2=CC(I)=CC=C2N1C(=O)NC1=CC=CN=C1 DWZCCUPWPGYNMI-UHFFFAOYSA-N 0.000 claims description 2
- IRRJKRJNCNEHIL-UHFFFAOYSA-N 5-methylsulfanyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC2=CC(SC)=CC=C2N1C(=O)NC1=CC=CN=C1 IRRJKRJNCNEHIL-UHFFFAOYSA-N 0.000 claims description 2
- VBIZDMWYWUAKCO-UHFFFAOYSA-N 5-nitro-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC2=CC([N+](=O)[O-])=CC=C2N1C(=O)NC1=CC=CN=C1 VBIZDMWYWUAKCO-UHFFFAOYSA-N 0.000 claims description 2
- KGFDFBKKNJTMJX-UHFFFAOYSA-N 5-tert-butyl-4-chloro-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC2=C(Cl)C(C(C)(C)C)=CC=C2N1C(=O)NC1=CC=CN=C1 KGFDFBKKNJTMJX-UHFFFAOYSA-N 0.000 claims description 2
- SUTFBUFCLSOFQF-UHFFFAOYSA-N 6,7-dichloro-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C12=C(Cl)C(Cl)=CC=C2CCN1C(=O)NC1=CC=CN=C1 SUTFBUFCLSOFQF-UHFFFAOYSA-N 0.000 claims description 2
- YDUBGXHYRPGOAZ-UHFFFAOYSA-N 6-bromo-5-propylsulfanyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1=2C=C(Br)C(SCCC)=CC=2CCN1C(=O)NC1=CC=CN=C1 YDUBGXHYRPGOAZ-UHFFFAOYSA-N 0.000 claims description 2
- ILEVMOFZKXQODL-UHFFFAOYSA-N 6-chloro-5-ethenyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC=2C=C(C=C)C(Cl)=CC=2N1C(=O)NC1=CC=CN=C1 ILEVMOFZKXQODL-UHFFFAOYSA-N 0.000 claims description 2
- WNWFIXVUQPDYNA-UHFFFAOYSA-N 6-chloro-5-ethylsulfanyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1=2C=C(Cl)C(SCC)=CC=2CCN1C(=O)NC1=CC=CN=C1 WNWFIXVUQPDYNA-UHFFFAOYSA-N 0.000 claims description 2
- JQICQYRHIKFUGD-UHFFFAOYSA-N 6-chloro-5-iodo-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC=2C=C(I)C(Cl)=CC=2N1C(=O)NC1=CC=CN=C1 JQICQYRHIKFUGD-UHFFFAOYSA-N 0.000 claims description 2
- YMQBRDYKNWNOQA-UHFFFAOYSA-N 6-chloro-5-methyl-n-(3-methyl-1,2-oxazol-5-yl)-2,3-dihydroindole-1-carboxamide Chemical compound O1N=C(C)C=C1NC(=O)N1C2=CC(Cl)=C(C)C=C2CC1 YMQBRDYKNWNOQA-UHFFFAOYSA-N 0.000 claims description 2
- MRLTTXUXAHTDRR-UHFFFAOYSA-N 6-chloro-5-methyl-n-pyridin-4-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1=2C=C(Cl)C(C)=CC=2CCN1C(=O)NC1=CC=NC=C1 MRLTTXUXAHTDRR-UHFFFAOYSA-N 0.000 claims description 2
- HOVMHIRTZYQSKM-UHFFFAOYSA-N 6-chloro-5-methyl-n-quinolin-5-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1=CC=C2C(NC(=O)N3CCC=4C=C(C(=CC=43)Cl)C)=CC=CC2=N1 HOVMHIRTZYQSKM-UHFFFAOYSA-N 0.000 claims description 2
- VQJYXENSGGKYBD-UHFFFAOYSA-N 6-chloro-5-methylsulfanyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1=2C=C(Cl)C(SC)=CC=2CCN1C(=O)NC1=CC=CN=C1 VQJYXENSGGKYBD-UHFFFAOYSA-N 0.000 claims description 2
- HDBXAVYYGFJNFM-UHFFFAOYSA-N 6-chloro-5-propan-2-yl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1=2C=C(Cl)C(C(C)C)=CC=2CCN1C(=O)NC1=CC=CN=C1 HDBXAVYYGFJNFM-UHFFFAOYSA-N 0.000 claims description 2
- GYVNZUJLZLMDFJ-UHFFFAOYSA-N 6-chloro-5-propyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1=2C=C(Cl)C(CCC)=CC=2CCN1C(=O)NC1=CC=CN=C1 GYVNZUJLZLMDFJ-UHFFFAOYSA-N 0.000 claims description 2
- JCRAEXACIZJAKA-UHFFFAOYSA-N 6-iodo-5-methyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1=2C=C(I)C(C)=CC=2CCN1C(=O)NC1=CC=CN=C1 JCRAEXACIZJAKA-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims description 2
- KIAWWMDXYYZGJQ-UHFFFAOYSA-N n-pyridin-3-yl-5-thiophen-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC2=CC(C3=CSC=C3)=CC=C2N1C(=O)NC1=CC=CN=C1 KIAWWMDXYYZGJQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- MCMJACABBYFBRJ-UHFFFAOYSA-N 4,6-dichloro-5-methyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC2=C(Cl)C(C)=C(Cl)C=C2N1C(=O)NC1=CC=CN=C1 MCMJACABBYFBRJ-UHFFFAOYSA-N 0.000 claims 1
- KBWLFKZKDRWOOP-UHFFFAOYSA-N 5-(dimethylamino)-n-(2-methylquinolin-4-yl)-2,3-dihydroindole-1-carboxamide Chemical compound C1=CC=C2C(NC(=O)N3C4=CC=C(C=C4CC3)N(C)C)=CC(C)=NC2=C1 KBWLFKZKDRWOOP-UHFFFAOYSA-N 0.000 claims 1
- NJCWASKCTHVLLT-UHFFFAOYSA-N 5-tert-butyl-6-chloro-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1=2C=C(Cl)C(C(C)(C)C)=CC=2CCN1C(=O)NC1=CC=CN=C1 NJCWASKCTHVLLT-UHFFFAOYSA-N 0.000 claims 1
- VFDSFIDQQPMNEX-UHFFFAOYSA-N 6-bromo-5-methylsulfanyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1=2C=C(Br)C(SC)=CC=2CCN1C(=O)NC1=CC=CN=C1 VFDSFIDQQPMNEX-UHFFFAOYSA-N 0.000 claims 1
- KXGXRAYAEKKRTR-UHFFFAOYSA-N 6-fluoro-5-methyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1=2C=C(F)C(C)=CC=2CCN1C(=O)NC1=CC=CN=C1 KXGXRAYAEKKRTR-UHFFFAOYSA-N 0.000 claims 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 claims 1
- ZYAVZXUEXDSCMB-UHFFFAOYSA-N methyl 6-chloro-1-(pyridin-3-ylcarbamoyl)-2,3-dihydroindole-5-carboxylate Chemical compound C1=2C=C(Cl)C(C(=O)OC)=CC=2CCN1C(=O)NC1=CC=CN=C1 ZYAVZXUEXDSCMB-UHFFFAOYSA-N 0.000 claims 1
- ZHENAFZDGOXHIQ-UHFFFAOYSA-N n-(5-bromopyridin-3-yl)-6-chloro-5-methyl-2,3-dihydroindole-1-carboxamide Chemical compound C1=2C=C(Cl)C(C)=CC=2CCN1C(=O)NC1=CN=CC(Br)=C1 ZHENAFZDGOXHIQ-UHFFFAOYSA-N 0.000 claims 1
- -1 c2-6 alkanonyl Chemical group 0.000 abstract description 9
- 239000003814 drug Substances 0.000 abstract description 4
- 125000003342 alkenyl group Chemical group 0.000 abstract description 2
- 125000000304 alkynyl group Chemical group 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 119
- 239000000203 mixture Substances 0.000 description 95
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 82
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 79
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 64
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 50
- 239000007787 solid Substances 0.000 description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 239000000243 solution Substances 0.000 description 35
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 34
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 32
- 229960004756 ethanol Drugs 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 25
- 239000003921 oil Substances 0.000 description 24
- SHVVSKCXWMEDRW-UHFFFAOYSA-N 3-isocyanatopyridine Chemical compound O=C=NC1=CC=CN=C1 SHVVSKCXWMEDRW-UHFFFAOYSA-N 0.000 description 23
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 235000019439 ethyl acetate Nutrition 0.000 description 17
- 229940093499 ethyl acetate Drugs 0.000 description 16
- 239000000284 extract Substances 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- ZAMJLADJGLXVOJ-UHFFFAOYSA-N 6-chloro-5-methyl-2,3-dihydro-1h-indole Chemical compound C1=C(Cl)C(C)=CC2=C1NCC2 ZAMJLADJGLXVOJ-UHFFFAOYSA-N 0.000 description 15
- 229960000583 acetic acid Drugs 0.000 description 15
- 229960004132 diethyl ether Drugs 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 239000007832 Na2SO4 Substances 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- 229910052938 sodium sulfate Inorganic materials 0.000 description 13
- 235000011152 sodium sulphate Nutrition 0.000 description 13
- 238000004587 chromatography analysis Methods 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 229960001866 silicon dioxide Drugs 0.000 description 12
- 239000012362 glacial acetic acid Substances 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 10
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- WUTIWOZYHHSBBU-UHFFFAOYSA-N 3-methoxy-4-nitrobenzaldehyde Chemical compound COC1=CC(C=O)=CC=C1[N+]([O-])=O WUTIWOZYHHSBBU-UHFFFAOYSA-N 0.000 description 8
- 239000000377 silicon dioxide Substances 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- RNTCWULFNYNFGI-UHFFFAOYSA-N 1-(2,3-dihydroindol-1-yl)ethanone Chemical compound C1=CC=C2N(C(=O)C)CCC2=C1 RNTCWULFNYNFGI-UHFFFAOYSA-N 0.000 description 7
- 239000012442 inert solvent Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- GQIYIYDVCZZZNV-UHFFFAOYSA-N 1-[5-(dimethylamino)-2,3-dihydroindol-1-yl]ethanone Chemical compound CN(C)C1=CC=C2N(C(C)=O)CCC2=C1 GQIYIYDVCZZZNV-UHFFFAOYSA-N 0.000 description 5
- PVHWNOJOJCOGOK-UHFFFAOYSA-N 4-chloro-5-methyl-1h-indole Chemical compound CC1=CC=C2NC=CC2=C1Cl PVHWNOJOJCOGOK-UHFFFAOYSA-N 0.000 description 5
- YRXORUFEMKBBNR-UHFFFAOYSA-N 4-chloro-5-methylsulfanyl-1h-indole Chemical compound CSC1=CC=C2NC=CC2=C1Cl YRXORUFEMKBBNR-UHFFFAOYSA-N 0.000 description 5
- LCFDJWUYKUPBJM-UHFFFAOYSA-N 5-(trifluoromethyl)-1h-indole Chemical compound FC(F)(F)C1=CC=C2NC=CC2=C1 LCFDJWUYKUPBJM-UHFFFAOYSA-N 0.000 description 5
- LJCGPVBAKRGTSE-UHFFFAOYSA-N 5-chloro-6-methyl-1h-indole Chemical compound C1=C(Cl)C(C)=CC2=C1C=CN2 LJCGPVBAKRGTSE-UHFFFAOYSA-N 0.000 description 5
- FZNUGPFFFCYBJJ-UHFFFAOYSA-N 6-chloro-5-propan-2-yl-2,3-dihydro-1h-indole Chemical compound C1=C(Cl)C(C(C)C)=CC2=C1NCC2 FZNUGPFFFCYBJJ-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 235000015320 potassium carbonate Nutrition 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- DHKHKXVYLBGOIT-UHFFFAOYSA-N 1,1-Diethoxyethane Chemical compound CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 4
- AOTWCYSQDSKAQT-UHFFFAOYSA-N 1,2-dichloro-4-methyl-5-nitrobenzene Chemical compound CC1=CC(Cl)=C(Cl)C=C1[N+]([O-])=O AOTWCYSQDSKAQT-UHFFFAOYSA-N 0.000 description 4
- NBUWBVVDVZANHK-UHFFFAOYSA-N 4-chloro-5-methylsulfanyl-2,3-dihydro-1h-indole Chemical compound CSC1=CC=C2NCCC2=C1Cl NBUWBVVDVZANHK-UHFFFAOYSA-N 0.000 description 4
- QUMDFCREMBCVGP-UHFFFAOYSA-N 5-(trifluoromethyl)-2,3-dihydro-1h-indole Chemical compound FC(F)(F)C1=CC=C2NCCC2=C1 QUMDFCREMBCVGP-UHFFFAOYSA-N 0.000 description 4
- QEDCHCLHHGGYBT-UHFFFAOYSA-N 5-bromo-2,3-dihydro-1h-indole Chemical compound BrC1=CC=C2NCCC2=C1 QEDCHCLHHGGYBT-UHFFFAOYSA-N 0.000 description 4
- WOISWFMWUILFBW-UHFFFAOYSA-N 5-chloro-6-methyl-2,3-dihydro-1h-indole Chemical compound C1=C(Cl)C(C)=CC2=C1CCN2 WOISWFMWUILFBW-UHFFFAOYSA-N 0.000 description 4
- LPYXADUZSWBHCT-UHFFFAOYSA-N 5-phenyl-1h-indole Chemical compound C=1C=C2NC=CC2=CC=1C1=CC=CC=C1 LPYXADUZSWBHCT-UHFFFAOYSA-N 0.000 description 4
- OTLWHHHZQLDXEK-UHFFFAOYSA-N 5-phenyl-2,3-dihydro-1h-indole Chemical compound C=1C=C2NCCC2=CC=1C1=CC=CC=C1 OTLWHHHZQLDXEK-UHFFFAOYSA-N 0.000 description 4
- LYKDVFKICMSAHM-UHFFFAOYSA-N 5-thiophen-3-yl-2,3-dihydro-1h-indole Chemical compound C=1C=C2NCCC2=CC=1C=1C=CSC=1 LYKDVFKICMSAHM-UHFFFAOYSA-N 0.000 description 4
- MAWGHOPSCKCTPA-UHFFFAOYSA-N 6-bromo-1h-indole Chemical compound BrC1=CC=C2C=CNC2=C1 MAWGHOPSCKCTPA-UHFFFAOYSA-N 0.000 description 4
- MTSYZAHZABCWMS-UHFFFAOYSA-N 6-bromo-2,3-dihydro-1h-indole Chemical compound BrC1=CC=C2CCNC2=C1 MTSYZAHZABCWMS-UHFFFAOYSA-N 0.000 description 4
- SBUSCJXUWKIDOQ-UHFFFAOYSA-N 6-bromo-5-ethylsulfanyl-2,3-dihydro-1h-indole Chemical compound C1=C(Br)C(SCC)=CC2=C1NCC2 SBUSCJXUWKIDOQ-UHFFFAOYSA-N 0.000 description 4
- DZPFAUCRIATHQM-UHFFFAOYSA-N 6-bromo-5-methyl-1h-indole Chemical compound C1=C(Br)C(C)=CC2=C1NC=C2 DZPFAUCRIATHQM-UHFFFAOYSA-N 0.000 description 4
- NDAOWFOZNKYSNN-UHFFFAOYSA-N 6-bromo-5-methylsulfanyl-2,3-dihydro-1h-indole Chemical compound C1=C(Br)C(SC)=CC2=C1NCC2 NDAOWFOZNKYSNN-UHFFFAOYSA-N 0.000 description 4
- MVRSRRJYTVAWHB-UHFFFAOYSA-N 6-bromo-5-propylsulfanyl-2,3-dihydro-1h-indole Chemical compound C1=C(Br)C(SCCC)=CC2=C1NCC2 MVRSRRJYTVAWHB-UHFFFAOYSA-N 0.000 description 4
- IBPLADFZYJEXFN-UHFFFAOYSA-N 6-chloro-5-ethyl-1h-indole Chemical compound C1=C(Cl)C(CC)=CC2=C1NC=C2 IBPLADFZYJEXFN-UHFFFAOYSA-N 0.000 description 4
- YBHLKOHSHTVHKL-UHFFFAOYSA-N 6-chloro-5-ethylsulfanyl-2,3-dihydro-1h-indole Chemical compound C1=C(Cl)C(SCC)=CC2=C1NCC2 YBHLKOHSHTVHKL-UHFFFAOYSA-N 0.000 description 4
- KHJBSNUBUOHZAG-UHFFFAOYSA-N 6-chloro-5-iodo-1h-indole Chemical compound C1=C(I)C(Cl)=CC2=C1C=CN2 KHJBSNUBUOHZAG-UHFFFAOYSA-N 0.000 description 4
- SZUUANOGBHUNNS-UHFFFAOYSA-N 6-chloro-5-methyl-1h-indole Chemical compound C1=C(Cl)C(C)=CC2=C1NC=C2 SZUUANOGBHUNNS-UHFFFAOYSA-N 0.000 description 4
- PDNGOOLQHBQWLW-UHFFFAOYSA-N 6-chloro-5-propan-2-ylsulfanyl-2,3-dihydro-1h-indole Chemical compound C1=C(Cl)C(SC(C)C)=CC2=C1NCC2 PDNGOOLQHBQWLW-UHFFFAOYSA-N 0.000 description 4
- RJKQAKJJPKUHLY-UHFFFAOYSA-N 6-chloro-5-propyl-1h-indole Chemical compound C1=C(Cl)C(CCC)=CC2=C1NC=C2 RJKQAKJJPKUHLY-UHFFFAOYSA-N 0.000 description 4
- IHGFGCFFVFSOBT-UHFFFAOYSA-N 6-chloro-5-propyl-2,3-dihydro-1h-indole Chemical compound C1=C(Cl)C(CCC)=CC2=C1NCC2 IHGFGCFFVFSOBT-UHFFFAOYSA-N 0.000 description 4
- ILHXQOBTUCVYPL-UHFFFAOYSA-N 6-fluoro-5-methyl-2,3-dihydro-1h-indole Chemical compound C1=C(F)C(C)=CC2=C1NCC2 ILHXQOBTUCVYPL-UHFFFAOYSA-N 0.000 description 4
- AIVZYBIUNRWFTO-UHFFFAOYSA-N 6-iodo-5-methyl-1h-indole Chemical compound C1=C(I)C(C)=CC2=C1NC=C2 AIVZYBIUNRWFTO-UHFFFAOYSA-N 0.000 description 4
- LQGHIDMCKRFDBD-UHFFFAOYSA-N 6-iodo-5-methyl-2,3-dihydro-1h-indole Chemical compound C1=C(I)C(C)=CC2=C1NCC2 LQGHIDMCKRFDBD-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 125000003396 thiol group Chemical class [H]S* 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
- ZHRZXZHYYPFCEF-UHFFFAOYSA-N 1-chloro-2-ethenyl-4-methyl-5-nitrobenzene Chemical compound CC1=CC(C=C)=C(Cl)C=C1[N+]([O-])=O ZHRZXZHYYPFCEF-UHFFFAOYSA-N 0.000 description 3
- UGAVPOYPEZYPDX-UHFFFAOYSA-N 4-chloro-5-methyl-2,3-dihydro-1h-indole Chemical compound CC1=CC=C2NCCC2=C1Cl UGAVPOYPEZYPDX-UHFFFAOYSA-N 0.000 description 3
- QUYCDINJTDAKPI-UHFFFAOYSA-N 5-ethylsulfanyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC2=CC(SCC)=CC=C2N1C(=O)NC1=CC=CN=C1 QUYCDINJTDAKPI-UHFFFAOYSA-N 0.000 description 3
- UWHWAXCLSNQVAG-UHFFFAOYSA-N 6,7-dichloro-1h-indole Chemical compound ClC1=CC=C2C=CNC2=C1Cl UWHWAXCLSNQVAG-UHFFFAOYSA-N 0.000 description 3
- KSNUCSMYTBROAK-UHFFFAOYSA-N 6-chloro-5-ethylsulfanyl-1h-indole Chemical compound C1=C(Cl)C(SCC)=CC2=C1NC=C2 KSNUCSMYTBROAK-UHFFFAOYSA-N 0.000 description 3
- OCAOGUGNWAVGNU-UHFFFAOYSA-N 6-chloro-5-iodo-2,3-dihydro-1h-indole Chemical compound C1=C(I)C(Cl)=CC2=C1CCN2 OCAOGUGNWAVGNU-UHFFFAOYSA-N 0.000 description 3
- NQQYNAPVGWDGAH-UHFFFAOYSA-N 6-chloro-5-methylsulfanyl-1h-indole Chemical compound C1=C(Cl)C(SC)=CC2=C1NC=C2 NQQYNAPVGWDGAH-UHFFFAOYSA-N 0.000 description 3
- UXWBQWDSPMQHGC-UHFFFAOYSA-N 6-chloro-5-propan-2-yl-1h-indole Chemical compound C1=C(Cl)C(C(C)C)=CC2=C1NC=C2 UXWBQWDSPMQHGC-UHFFFAOYSA-N 0.000 description 3
- BUJOSAQZKUJOCC-UHFFFAOYSA-N 6-chloro-5-propan-2-ylsulfanyl-1h-indole Chemical compound C1=C(Cl)C(SC(C)C)=CC2=C1NC=C2 BUJOSAQZKUJOCC-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- 208000015114 central nervous system disease Diseases 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- BQSKMPMXUNIDPY-UHFFFAOYSA-N methyl 6-chloro-2,3-dihydro-1h-indole-5-carboxylate Chemical compound C1=C(Cl)C(C(=O)OC)=CC2=C1NCC2 BQSKMPMXUNIDPY-UHFFFAOYSA-N 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 2
- ZNSIOEUWGZNHAQ-UHFFFAOYSA-N (3e)-n-diazoniopyridine-3-carboximidate Chemical compound [N-]=[N+]=NC(=O)C1=CC=CN=C1 ZNSIOEUWGZNHAQ-UHFFFAOYSA-N 0.000 description 2
- WYUIWKFIFOJVKW-UHFFFAOYSA-N 1,2-dichloro-4-methylbenzene Chemical compound CC1=CC=C(Cl)C(Cl)=C1 WYUIWKFIFOJVKW-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- NFQLUAMQZBFFHF-UHFFFAOYSA-N 1-(2,2-dimethoxyethyl)-2-(4-propan-2-ylphenyl)hydrazine Chemical compound COC(OC)CNNC1=CC=C(C(C)C)C=C1 NFQLUAMQZBFFHF-UHFFFAOYSA-N 0.000 description 2
- KBUOMEGCKGVATN-UHFFFAOYSA-N 1-(5-ethylsulfanyl-2,3-dihydroindol-1-yl)ethanone Chemical compound CCSC1=CC=C2N(C(C)=O)CCC2=C1 KBUOMEGCKGVATN-UHFFFAOYSA-N 0.000 description 2
- FIRXFHJQGIIJDB-UHFFFAOYSA-N 1-methyl-2,3-dihydroindole Chemical compound C1=CC=C2N(C)CCC2=C1 FIRXFHJQGIIJDB-UHFFFAOYSA-N 0.000 description 2
- SODLGZBTZDYZIK-UHFFFAOYSA-N 2,2,2-trifluoro-1-(5-propan-2-ylindol-1-yl)ethanone Chemical compound CC(C)C1=CC=C2N(C(=O)C(F)(F)F)C=CC2=C1 SODLGZBTZDYZIK-UHFFFAOYSA-N 0.000 description 2
- ZVCLROWCNYLPEH-UHFFFAOYSA-N 3-chloro-n-(2,2-diethoxyethyl)-4-methylaniline Chemical compound CCOC(OCC)CNC1=CC=C(C)C(Cl)=C1 ZVCLROWCNYLPEH-UHFFFAOYSA-N 0.000 description 2
- RQKFYFNZSHWXAW-UHFFFAOYSA-N 3-chloro-p-toluidine Chemical compound CC1=CC=C(N)C=C1Cl RQKFYFNZSHWXAW-UHFFFAOYSA-N 0.000 description 2
- DVCLJDAZHYRZHZ-UHFFFAOYSA-N 4-bromo-5-methyl-1h-indole Chemical compound CC1=CC=C2NC=CC2=C1Br DVCLJDAZHYRZHZ-UHFFFAOYSA-N 0.000 description 2
- WQJRMPMOWXMOTE-UHFFFAOYSA-N 4-chloro-5-ethylsulfanyl-1h-indole Chemical compound CCSC1=CC=C2NC=CC2=C1Cl WQJRMPMOWXMOTE-UHFFFAOYSA-N 0.000 description 2
- VOLDYBIIMQJLET-UHFFFAOYSA-N 4-chloro-5-propan-2-ylsulfanyl-1h-indole Chemical compound CC(C)SC1=CC=C2NC=CC2=C1Cl VOLDYBIIMQJLET-UHFFFAOYSA-N 0.000 description 2
- LMVSOQQEIVZNNC-UHFFFAOYSA-N 4-chloro-5-propyl-1h-indole Chemical compound CCCC1=CC=C2NC=CC2=C1Cl LMVSOQQEIVZNNC-UHFFFAOYSA-N 0.000 description 2
- LQKBSKFACIAEQZ-UHFFFAOYSA-N 4-iodo-5-methyl-2,3-dihydro-1h-indole Chemical compound CC1=CC=C2NCCC2=C1I LQKBSKFACIAEQZ-UHFFFAOYSA-N 0.000 description 2
- ZPTVNYMJQHSSEA-UHFFFAOYSA-N 4-nitrotoluene Chemical compound CC1=CC=C([N+]([O-])=O)C=C1 ZPTVNYMJQHSSEA-UHFFFAOYSA-N 0.000 description 2
- VXWVFZFZYXOBTA-UHFFFAOYSA-N 5-bromo-1h-indole Chemical compound BrC1=CC=C2NC=CC2=C1 VXWVFZFZYXOBTA-UHFFFAOYSA-N 0.000 description 2
- QWWIPMXYCFVJFJ-UHFFFAOYSA-N 5-bromo-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC2=CC(Br)=CC=C2N1C(=O)NC1=CC=CN=C1 QWWIPMXYCFVJFJ-UHFFFAOYSA-N 0.000 description 2
- YPKBCLZFIYBSHK-UHFFFAOYSA-N 5-methylindole Chemical compound CC1=CC=C2NC=CC2=C1 YPKBCLZFIYBSHK-UHFFFAOYSA-N 0.000 description 2
- HIZQSLNOCDPQQP-UHFFFAOYSA-N 5-methylsulfanyl-2,3-dihydro-1h-indole Chemical compound CSC1=CC=C2NCCC2=C1 HIZQSLNOCDPQQP-UHFFFAOYSA-N 0.000 description 2
- LBVLQBYXKBTHJA-UHFFFAOYSA-N 5-propan-2-yl-1h-indole Chemical compound CC(C)C1=CC=C2NC=CC2=C1 LBVLQBYXKBTHJA-UHFFFAOYSA-N 0.000 description 2
- LCIJJWUQMXUQQI-UHFFFAOYSA-N 5-propan-2-yl-2,3-dihydro-1h-indole Chemical compound CC(C)C1=CC=C2NCCC2=C1 LCIJJWUQMXUQQI-UHFFFAOYSA-N 0.000 description 2
- IIHUKJUKXSIOCN-UHFFFAOYSA-N 5-thiophen-3-yl-1h-indole Chemical compound C=1C=C2NC=CC2=CC=1C=1C=CSC=1 IIHUKJUKXSIOCN-UHFFFAOYSA-N 0.000 description 2
- OOGKBGZFWQVEGL-UHFFFAOYSA-N 6-bromo-5-methyl-2,3-dihydro-1h-indole Chemical compound C1=C(Br)C(C)=CC2=C1NCC2 OOGKBGZFWQVEGL-UHFFFAOYSA-N 0.000 description 2
- CFGKECNZKWERMQ-UHFFFAOYSA-N 6-chloro-5-ethenyl-2,3-dihydro-1h-indole Chemical compound C1=C(C=C)C(Cl)=CC2=C1CCN2 CFGKECNZKWERMQ-UHFFFAOYSA-N 0.000 description 2
- XQBLVFXJWMYPFV-UHFFFAOYSA-N 6-chloro-5-ethyl-2,3-dihydro-1h-indole Chemical compound C1=C(Cl)C(CC)=CC2=C1NCC2 XQBLVFXJWMYPFV-UHFFFAOYSA-N 0.000 description 2
- DBQMGUNMSRSHOS-UHFFFAOYSA-N 6-chloro-5-methylsulfanyl-2,3-dihydro-1h-indole Chemical compound C1=C(Cl)C(SC)=CC2=C1NCC2 DBQMGUNMSRSHOS-UHFFFAOYSA-N 0.000 description 2
- RCLYGQSMHKSQCL-UHFFFAOYSA-N 6-fluoro-5-methyl-1h-indole Chemical compound C1=C(F)C(C)=CC2=C1NC=C2 RCLYGQSMHKSQCL-UHFFFAOYSA-N 0.000 description 2
- ONYNOPPOVKYGRS-UHFFFAOYSA-N 6-methylindole Natural products CC1=CC=C2C=CNC2=C1 ONYNOPPOVKYGRS-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 208000032841 Bulimia Diseases 0.000 description 2
- 206010006550 Bulimia nervosa Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 206010013654 Drug abuse Diseases 0.000 description 2
- 208000019454 Feeding and Eating disease Diseases 0.000 description 2
- 206010019196 Head injury Diseases 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 208000019695 Migraine disease Diseases 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 2
- 206010033664 Panic attack Diseases 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 208000022531 anorexia Diseases 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 2
- 229940049706 benzodiazepine Drugs 0.000 description 2
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 150000007942 carboxylates Chemical class 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229960003920 cocaine Drugs 0.000 description 2
- 206010061428 decreased appetite Diseases 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 208000003906 hydrocephalus Diseases 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 150000002475 indoles Chemical class 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- LGAWJAFXFJNWOZ-UHFFFAOYSA-N n,n-dimethyl-2,3-dihydro-1h-indol-5-amine Chemical compound CN(C)C1=CC=C2NCCC2=C1 LGAWJAFXFJNWOZ-UHFFFAOYSA-N 0.000 description 2
- 229960002715 nicotine Drugs 0.000 description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 2
- 208000019906 panic disease Diseases 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 2
- 229940116357 potassium thiocyanate Drugs 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- KTOYYOQOGAZUHV-UHFFFAOYSA-N s-acetylsulfanyl ethanethioate Chemical compound CC(=O)SSC(C)=O KTOYYOQOGAZUHV-UHFFFAOYSA-N 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 208000019116 sleep disease Diseases 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 229960001922 sodium perborate Drugs 0.000 description 2
- YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 208000011117 substance-related disease Diseases 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- WYCMFCPHWDZHMR-UHFFFAOYSA-N 1-(4,7-dimethyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-9-yl)-n,n-dimethylmethanesulfonamide Chemical compound C1=CC(C2CC(CN(C)C2C2)CS(=O)(=O)N(C)C)=C3C2=CN(C)C3=C1 WYCMFCPHWDZHMR-UHFFFAOYSA-N 0.000 description 1
- OJKKTNFCWMBYMT-UHFFFAOYSA-N 1-(5-nitro-2,3-dihydroindol-1-yl)ethanone Chemical compound [O-][N+](=O)C1=CC=C2N(C(=O)C)CCC2=C1 OJKKTNFCWMBYMT-UHFFFAOYSA-N 0.000 description 1
- JMEXAQBBMDHIGQ-UHFFFAOYSA-N 1-chloro-2,5-dimethyl-4-nitrobenzene Chemical group CC1=CC([N+]([O-])=O)=C(C)C=C1Cl JMEXAQBBMDHIGQ-UHFFFAOYSA-N 0.000 description 1
- VSPZYLFNHKDKQI-UHFFFAOYSA-N 2,2,2-trifluoro-1-(1h-indol-2-yl)ethanone Chemical compound C1=CC=C2NC(C(=O)C(F)(F)F)=CC2=C1 VSPZYLFNHKDKQI-UHFFFAOYSA-N 0.000 description 1
- IKKUKDZKIIIKJK-UHFFFAOYSA-N 2,2-diethoxyethanol Chemical compound CCOC(CO)OCC IKKUKDZKIIIKJK-UHFFFAOYSA-N 0.000 description 1
- OGFKTAMJLKHRAZ-UHFFFAOYSA-N 2,2-dimethoxyacetaldehyde Chemical compound COC(OC)C=O OGFKTAMJLKHRAZ-UHFFFAOYSA-N 0.000 description 1
- SVPKNMBRVBMTLB-UHFFFAOYSA-N 2,3-dichloronaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(Cl)=C(Cl)C(=O)C2=C1 SVPKNMBRVBMTLB-UHFFFAOYSA-N 0.000 description 1
- LILXDMFJXYAKMK-UHFFFAOYSA-N 2-bromo-1,1-diethoxyethane Chemical compound CCOC(CBr)OCC LILXDMFJXYAKMK-UHFFFAOYSA-N 0.000 description 1
- XPOBLHHOXREWDD-UHFFFAOYSA-N 2-bromo-5-chloro-1h-imidazole Chemical compound ClC1=CNC(Br)=N1 XPOBLHHOXREWDD-UHFFFAOYSA-N 0.000 description 1
- QDLICMFWZGHBFX-UHFFFAOYSA-N 2-chloro-5-methyl-4-nitrobenzaldehyde Chemical compound CC1=CC(C=O)=C(Cl)C=C1[N+]([O-])=O QDLICMFWZGHBFX-UHFFFAOYSA-N 0.000 description 1
- OPXHWEVLBGQQRA-UHFFFAOYSA-N 2-chloro-5-methyl-4-nitrobenzoic acid Chemical compound CC1=CC(C(O)=O)=C(Cl)C=C1[N+]([O-])=O OPXHWEVLBGQQRA-UHFFFAOYSA-N 0.000 description 1
- BWNBLGQCCSCCHF-UHFFFAOYSA-N 2-ethyl-1h-indole Chemical compound C1=CC=C2NC(CC)=CC2=C1 BWNBLGQCCSCCHF-UHFFFAOYSA-N 0.000 description 1
- COCFIBRMFPWUDW-UHFFFAOYSA-N 2-methylquinolin-4-amine Chemical compound C1=CC=CC2=NC(C)=CC(N)=C21 COCFIBRMFPWUDW-UHFFFAOYSA-N 0.000 description 1
- GRXMMIBZRMKADT-UHFFFAOYSA-N 3-bromo-4-methylaniline Chemical compound CC1=CC=C(N)C=C1Br GRXMMIBZRMKADT-UHFFFAOYSA-N 0.000 description 1
- LBGGMEGRRIBANG-UHFFFAOYSA-N 3-chloro-4-ethylaniline Chemical compound CCC1=CC=C(N)C=C1Cl LBGGMEGRRIBANG-UHFFFAOYSA-N 0.000 description 1
- LNXLUAQFYHQATK-UHFFFAOYSA-N 3-chloro-4-ethylsulfanylaniline Chemical compound CCSC1=CC=C(N)C=C1Cl LNXLUAQFYHQATK-UHFFFAOYSA-N 0.000 description 1
- ONZHMGRKWJMTDE-UHFFFAOYSA-N 3-chloro-4-iodoaniline Chemical compound NC1=CC=C(I)C(Cl)=C1 ONZHMGRKWJMTDE-UHFFFAOYSA-N 0.000 description 1
- AIUFATMGALKMOI-UHFFFAOYSA-N 3-chloro-4-methylsulfanylaniline Chemical compound CSC1=CC=C(N)C=C1Cl AIUFATMGALKMOI-UHFFFAOYSA-N 0.000 description 1
- RROSMHZQLKYMGM-UHFFFAOYSA-N 3-chloro-4-propan-2-ylaniline Chemical compound CC(C)C1=CC=C(N)C=C1Cl RROSMHZQLKYMGM-UHFFFAOYSA-N 0.000 description 1
- YRAVCIDRZGHVSI-UHFFFAOYSA-N 3-chloro-4-propan-2-ylsulfanylaniline Chemical compound CC(C)SC1=CC=C(N)C=C1Cl YRAVCIDRZGHVSI-UHFFFAOYSA-N 0.000 description 1
- UMVPRJXTJZVUOX-UHFFFAOYSA-N 3-chloro-4-propylaniline Chemical compound CCCC1=CC=C(N)C=C1Cl UMVPRJXTJZVUOX-UHFFFAOYSA-N 0.000 description 1
- MGRHBBRSAFPBIN-UHFFFAOYSA-N 3-fluoro-4-methylaniline Chemical compound CC1=CC=C(N)C=C1F MGRHBBRSAFPBIN-UHFFFAOYSA-N 0.000 description 1
- RRUDMHNAMZFNEK-UHFFFAOYSA-N 3-iodo-4-methylaniline Chemical compound CC1=CC=C(N)C=C1I RRUDMHNAMZFNEK-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- KOKCBQMIPIZDIU-UHFFFAOYSA-N 4,5-dichloro-2,3-dihydro-1h-indole Chemical compound ClC1=CC=C2NCCC2=C1Cl KOKCBQMIPIZDIU-UHFFFAOYSA-N 0.000 description 1
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
- SRGBYCTWSLKNFH-UHFFFAOYSA-N 4-bromo-5-methyl-2,3-dihydro-1h-indole Chemical compound CC1=CC=C2NCCC2=C1Br SRGBYCTWSLKNFH-UHFFFAOYSA-N 0.000 description 1
- FRUFDYVMCSMXGT-UHFFFAOYSA-N 4-chloro-5-ethyl-1h-indole Chemical compound CCC1=CC=C2NC=CC2=C1Cl FRUFDYVMCSMXGT-UHFFFAOYSA-N 0.000 description 1
- ZCGPVBZXOKPQLW-UHFFFAOYSA-N 4-chloro-5-iodo-1h-indole Chemical compound ClC1=C(I)C=CC2=C1C=CN2 ZCGPVBZXOKPQLW-UHFFFAOYSA-N 0.000 description 1
- NYYLZOTVYXXTFY-UHFFFAOYSA-N 4-chloro-5-propan-2-yl-1h-indole Chemical compound CC(C)C1=CC=C2NC=CC2=C1Cl NYYLZOTVYXXTFY-UHFFFAOYSA-N 0.000 description 1
- YNSFOCGDLSHPDE-UHFFFAOYSA-N 4-iodo-5-methyl-1h-indole Chemical compound CC1=CC=C2NC=CC2=C1I YNSFOCGDLSHPDE-UHFFFAOYSA-N 0.000 description 1
- ODGIMMLDVSWADK-UHFFFAOYSA-N 4-trifluoromethylaniline Chemical compound NC1=CC=C(C(F)(F)F)C=C1 ODGIMMLDVSWADK-UHFFFAOYSA-N 0.000 description 1
- ICJRWHOYRYFHIL-UHFFFAOYSA-N 5,6-dichloro-2,3-dihydro-1h-indole Chemical compound C1=C(Cl)C(Cl)=CC2=C1NCC2 ICJRWHOYRYFHIL-UHFFFAOYSA-N 0.000 description 1
- CBDUBPRIZSXHOV-UHFFFAOYSA-N 5-(dimethylamino)-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC2=CC(N(C)C)=CC=C2N1C(=O)NC1=CC=CN=C1 CBDUBPRIZSXHOV-UHFFFAOYSA-N 0.000 description 1
- LBVLLEAKKBHEDJ-UHFFFAOYSA-N 5-bromopyridine-3-carbonyl azide Chemical compound BrC1=CN=CC(C(=O)N=[N+]=[N-])=C1 LBVLLEAKKBHEDJ-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
- YMCIVAPEOZDEGH-UHFFFAOYSA-N 5-chloro-2,3-dihydro-1h-indole Chemical compound ClC1=CC=C2NCCC2=C1 YMCIVAPEOZDEGH-UHFFFAOYSA-N 0.000 description 1
- AADZERKEXPUPGY-UHFFFAOYSA-N 5-iodo-2,3-dihydro-1h-indole Chemical compound IC1=CC=C2NCCC2=C1 AADZERKEXPUPGY-UHFFFAOYSA-N 0.000 description 1
- FKPXGNGUVSHWQQ-UHFFFAOYSA-N 5-methyl-1,2-oxazol-3-amine Chemical compound CC1=CC(N)=NO1 FKPXGNGUVSHWQQ-UHFFFAOYSA-N 0.000 description 1
- WJQWYAJTPPYORB-UHFFFAOYSA-N 5-nitro-2,3-dihydro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2NCCC2=C1 WJQWYAJTPPYORB-UHFFFAOYSA-N 0.000 description 1
- MZVQWJKKBXCASB-UHFFFAOYSA-N 5-nitro-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide;hydrochloride Chemical compound Cl.C1CC2=CC([N+](=O)[O-])=CC=C2N1C(=O)NC1=CC=CN=C1 MZVQWJKKBXCASB-UHFFFAOYSA-N 0.000 description 1
- VQGNSIKUHZPKMT-UHFFFAOYSA-N 5-tert-butyl-4-chloro-1h-indole Chemical compound CC(C)(C)C1=CC=C2NC=CC2=C1Cl VQGNSIKUHZPKMT-UHFFFAOYSA-N 0.000 description 1
- XTXIILHWOQZVAQ-UHFFFAOYSA-N 6,7-dichloro-1h-indole-2,3-dione Chemical compound ClC1=CC=C2C(=O)C(=O)NC2=C1Cl XTXIILHWOQZVAQ-UHFFFAOYSA-N 0.000 description 1
- GKLMFHNVJBILTB-UHFFFAOYSA-N 6,7-dichloro-2,3-dihydro-1h-indole Chemical compound ClC1=CC=C2CCNC2=C1Cl GKLMFHNVJBILTB-UHFFFAOYSA-N 0.000 description 1
- YTYIMDRWPTUAHP-UHFFFAOYSA-N 6-Chloroindole Chemical compound ClC1=CC=C2C=CNC2=C1 YTYIMDRWPTUAHP-UHFFFAOYSA-N 0.000 description 1
- HSLNYVREDLDESE-UHFFFAOYSA-N 6-chloro-2,3-dihydro-1h-indole Chemical compound ClC1=CC=C2CCNC2=C1 HSLNYVREDLDESE-UHFFFAOYSA-N 0.000 description 1
- UFWVDYDZMXVCCJ-UHFFFAOYSA-N 6-chloro-5-methyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1=2C=C(Cl)C(C)=CC=2CCN1C(=O)NC1=CC=CN=C1 UFWVDYDZMXVCCJ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 101000742062 Bos taurus Protein phosphatase 1G Proteins 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 101000761348 Homo sapiens 5-hydroxytryptamine receptor 2C Proteins 0.000 description 1
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 101000761350 Rattus norvegicus 5-hydroxytryptamine receptor 2C Proteins 0.000 description 1
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 238000007080 aromatic substitution reaction Methods 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229960004979 fampridine Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 150000002476 indolines Chemical class 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- IGOUVTSYCXABHI-UHFFFAOYSA-N methyl 6-chloro-1h-indole-5-carboxylate Chemical compound C1=C(Cl)C(C(=O)OC)=CC2=C1NC=C2 IGOUVTSYCXABHI-UHFFFAOYSA-N 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Substances [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- WURFKUQACINBSI-UHFFFAOYSA-M ozonide Chemical compound [O]O[O-] WURFKUQACINBSI-UHFFFAOYSA-M 0.000 description 1
- 238000005949 ozonolysis reaction Methods 0.000 description 1
- LRTFPLFDLJYEKT-UHFFFAOYSA-N para-isopropylaniline Chemical compound CC(C)C1=CC=C(N)C=C1 LRTFPLFDLJYEKT-UHFFFAOYSA-N 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- XMIAFAKRAAMSGX-UHFFFAOYSA-N quinolin-5-amine Chemical compound C1=CC=C2C(N)=CC=CC2=N1 XMIAFAKRAAMSGX-UHFFFAOYSA-N 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000002278 tabletting lubricant Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000006365 thiocyanation reaction Methods 0.000 description 1
- 125000004014 thioethyl group Chemical group [H]SC([H])([H])C([H])([H])* 0.000 description 1
- QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 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
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 238000006886 vinylation reaction Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- 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
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Eyeglasses (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB939313913A GB9313913D0 (en) | 1993-07-06 | 1993-07-06 | Novel compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AP9400653A0 AP9400653A0 (en) | 1994-07-31 |
| AP463A true AP463A (en) | 1996-02-19 |
Family
ID=10738344
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| APAP/P/1994/000653A AP463A (en) | 1993-07-06 | 1994-07-04 | "Indoline derivatives as 5HT2c antagonist". |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US5834494A (2) |
| EP (1) | EP0707581B1 (2) |
| JP (1) | JPH08512299A (2) |
| CN (1) | CN1129937A (2) |
| AP (1) | AP463A (2) |
| AT (1) | ATE149163T1 (2) |
| AU (1) | AU7228394A (2) |
| CA (1) | CA2166624A1 (2) |
| DE (1) | DE69401823T2 (2) |
| GB (1) | GB9313913D0 (2) |
| IL (1) | IL110204A0 (2) |
| MA (1) | MA23254A1 (2) |
| TW (1) | TW297023B (2) |
| WO (1) | WO1995001976A1 (2) |
| ZA (1) | ZA944807B (2) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5618824A (en) * | 1994-03-09 | 1997-04-08 | Merrell Pharmaceuticals Inc. | Treatment of obsessive-compulsive disorders with 5-HT2 antagonists |
| GB9414139D0 (en) * | 1994-07-13 | 1994-08-31 | Smithkline Beecham Plc | Novel compounds |
| GB9420521D0 (en) * | 1994-10-12 | 1994-11-30 | Smithkline Beecham Plc | Novel compounds |
| EP0807104A2 (en) * | 1995-02-02 | 1997-11-19 | Smithkline Beecham Plc | Heterocyclic compounds possessing 5ht 2c? receptor antagonist activity |
| DK0808312T3 (da) * | 1995-02-02 | 2001-02-12 | Smithkline Beecham Plc | Indolderivater som 5-HT-receptorantagonist |
| GB9517559D0 (en) * | 1995-08-26 | 1995-10-25 | Smithkline Beecham Plc | Novel compounds |
| AU2759597A (en) * | 1996-05-16 | 1997-12-05 | Allelix Biopharmaceuticals Inc. | Thiophene- and furan-tryptamine derivatives |
| GB9612883D0 (en) | 1996-06-20 | 1996-08-21 | Smithkline Beecham Plc | Novel compounds |
| GB9612885D0 (en) | 1996-06-20 | 1996-08-21 | Smithkline Beecham Plc | Novel compounds |
| US6362009B1 (en) | 1997-11-21 | 2002-03-26 | Merck & Co., Inc. | Solid phase synthesis of heterocycles |
| FR2778662B1 (fr) * | 1998-05-12 | 2000-06-16 | Adir | Nouveaux composes cycliques substitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| CA2347095A1 (en) * | 1998-10-16 | 2000-04-27 | Takeda Chemical Industries, Ltd. | Nitrogen-containing condensed heterocyclic derivatives, their production and agent |
| US6453357B1 (en) | 1999-01-07 | 2002-09-17 | Cisco Technology, Inc. | Method and system for processing fragments and their out-of-order delivery during address translation |
| WO2000076984A2 (en) * | 1999-05-21 | 2000-12-21 | Biovitrum Ab | Novel compounds, their use and preparation |
| US6465467B1 (en) | 1999-05-21 | 2002-10-15 | Biovitrum Ab | Certain aryl-aliphatic and heteroaryl-aliphatic piperazinyl pyrazines and their use in the treatment of serotonin-related diseases |
| UA77650C2 (en) | 1999-12-06 | 2007-01-15 | Lundbeck & Co As H | Use of serotonin reuptake inhibitor in combination with deramcyclane |
| FR2810979B1 (fr) * | 2000-06-29 | 2002-08-23 | Adir | Nouveaux derives de diphenyluree, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| GB0019950D0 (en) * | 2000-08-12 | 2000-09-27 | Smithkline Beecham Plc | Compounds |
| SE0004245D0 (sv) | 2000-11-20 | 2000-11-20 | Pharmacia Ab | Novel compounds and their use |
| DE60100294T2 (de) * | 2001-07-09 | 2003-12-11 | Alcatel Sel Ag | Verbinder für optische Fasern |
| US6861440B2 (en) | 2001-10-26 | 2005-03-01 | Hoffmann-La Roche Inc. | DPP IV inhibitors |
| FR2837823B1 (fr) * | 2002-03-27 | 2005-04-08 | Servier Lab | Nouveaux derives d'indoline, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| JP4460450B2 (ja) | 2002-06-19 | 2010-05-12 | ビオヴィトルム・アクチボラゲット（プブリクト） | 新規化合物、その使用および製造法 |
| ATE437876T1 (de) | 2003-06-20 | 2009-08-15 | Hoffmann La Roche | Hexahydropyridoisochinoline als dpp-iv- inhibitoren |
| WO2005000848A1 (en) | 2003-06-20 | 2005-01-06 | F. Hoffmann-La Roche Ag | Pyrido` 2, 1-a - isoquinoline derivatives as dpp-iv inhibitors |
| BRPI0616000B1 (pt) * | 2005-09-13 | 2016-04-19 | Bayer Cropscience Ag | composto derivado de fenil-amidina, processo de preparação de composto, composto derivado de nitrofeniléter, composto derivado de aminofeniléter, método de controle de fungos fitopatogênicos de safras e método de controle de insetos daninhos. |
| US9052304B2 (en) | 2009-03-13 | 2015-06-09 | Terrasep, Llc | Methods and apparatus for centrifugal liquid chromatography |
| CN106278987A (zh) * | 2016-08-16 | 2017-01-04 | 都创(上海)医药科技有限公司 | 吲哚啉类化合物的制备方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4428881A (en) * | 1977-12-23 | 1984-01-31 | Gulf Oil Corporation | Control of unwanted vegetation with N-carbamylindolines |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE913204A1 (en) * | 1990-09-13 | 1992-02-25 | Beecham Group Plc | Novel compounds |
| EP0656003A1 (en) * | 1992-08-20 | 1995-06-07 | Smithkline Beecham Plc | Condensed indole derivatives as 5ht2c and 5ht2b antagonists |
-
1993
- 1993-07-06 GB GB939313913A patent/GB9313913D0/en active Pending
-
1994
- 1994-06-30 AU AU72283/94A patent/AU7228394A/en not_active Abandoned
- 1994-06-30 CN CN94193185A patent/CN1129937A/zh active Pending
- 1994-06-30 WO PCT/EP1994/002148 patent/WO1995001976A1/en not_active Ceased
- 1994-06-30 CA CA002166624A patent/CA2166624A1/en not_active Abandoned
- 1994-06-30 JP JP7503812A patent/JPH08512299A/ja active Pending
- 1994-06-30 AT AT94921638T patent/ATE149163T1/de not_active IP Right Cessation
- 1994-06-30 DE DE69401823T patent/DE69401823T2/de not_active Expired - Fee Related
- 1994-06-30 EP EP94921638A patent/EP0707581B1/en not_active Expired - Lifetime
- 1994-07-04 ZA ZA944807A patent/ZA944807B/xx unknown
- 1994-07-04 MA MA23564A patent/MA23254A1/fr unknown
- 1994-07-04 IL IL11020494A patent/IL110204A0/xx unknown
- 1994-07-04 AP APAP/P/1994/000653A patent/AP463A/en active
- 1994-07-05 TW TW083106150A patent/TW297023B/zh active
-
1996
- 1996-09-23 US US08/717,957 patent/US5834494A/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4428881A (en) * | 1977-12-23 | 1984-01-31 | Gulf Oil Corporation | Control of unwanted vegetation with N-carbamylindolines |
Also Published As
| Publication number | Publication date |
|---|---|
| US5834494A (en) | 1998-11-10 |
| DE69401823D1 (de) | 1997-04-03 |
| CN1129937A (zh) | 1996-08-28 |
| AU7228394A (en) | 1995-02-06 |
| ATE149163T1 (de) | 1997-03-15 |
| IL110204A0 (en) | 1995-01-24 |
| EP0707581A1 (en) | 1996-04-24 |
| TW297023B (2) | 1997-02-01 |
| MA23254A1 (fr) | 1995-04-01 |
| EP0707581B1 (en) | 1997-02-26 |
| CA2166624A1 (en) | 1995-01-19 |
| DE69401823T2 (de) | 1997-08-28 |
| JPH08512299A (ja) | 1996-12-24 |
| WO1995001976A1 (en) | 1995-01-19 |
| ZA944807B (en) | 1996-01-04 |
| GB9313913D0 (en) | 1993-08-18 |
| AP9400653A0 (en) | 1994-07-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AP463A (en) | "Indoline derivatives as 5HT2c antagonist". | |
| KR950010163B1 (ko) | 신규 인돌 유도체 | |
| DE69610822T2 (de) | Indolderivate als 5-ht rezeptorantagoniste | |
| EP0690843B1 (en) | Formyl- or cyano- substituted indole derivatives having dopaminergic activity | |
| JPH11513391A (ja) | Ｃｃ−１０６５ 及びズオカーマイシンのｃｂｉ 類縁体 | |
| FR2804114A1 (fr) | Nouveaux derives de 1,3-dihydro-2h-indol-2-one, un procede pour leur preparation et les compositions pharmaceutiques en contenant | |
| EP1414442A1 (en) | 3-arylsulfonyl-7-piperazinyl- indoles, -benzofurans and -benzothiophenes with 5-ht6 receptor affinity for treating cns disorders | |
| CN101351446A (zh) | 新的稠合吡咯衍生物 | |
| EP1296976B1 (fr) | Derives de 1,3-dihydro-2h-indol-2-one et leur utilisation en tant que ligands des recepteurs v1b et v1a de l'arginine-vasopressine | |
| EP1216239A1 (en) | Piperazine derivatives as 5-ht1b antagonists | |
| KR20070114123A (ko) | 염증 치료에 유용한 인돌 | |
| EA011320B1 (ru) | N-арилсульфонил-3-замещенные индолы, обладающие афинностью к серотониновому рецептору, способ их получения и содержащая их фармацевтическая композиция | |
| FR2827604A1 (fr) | Nouveaux derives de 1-phenylsulfonyl-1,3-dihydro-2h-indol-2- one, un procede pour leur preparation et les compositions pharmaceutiques en contenant | |
| EP2887803A1 (en) | Pro-neurogenic compounds | |
| JP2001526643A (ja) | ５ｈｔ１ａ、５ｈｔ１ｂおよび５ｈｔ１ｄ受容体アンタゴニスト活性を合わせ持つ化合物を含む二環式アリールまたは二環式複素環 | |
| KR20020027622A (ko) | 중추신경계 질병 치료용 아미노알콕시 카르바졸 | |
| AU2006237920A1 (en) | Nitrogen-containing heterocyclic compound | |
| FR2805536A1 (fr) | Nouveaux derives de 1,3-dihydro-2h-indol-2-one, un procede pour leur preparation et les compositions pharmaceutiques en contenant | |
| JP2005516951A (ja) | 尿素誘導体およびバニロイド受容体アンタゴニストとしてのその使用 | |
| EP1487801A1 (en) | 7-arylsulfonamido-2,3,4,5-tetrahydro-1h-benzo[d]azepine derivatives with 5-ht6 receptor affinity for the treatment of cns disorders | |
| JP2021506965A (ja) | 置換ピロリジンアミドｉｉ | |
| CN1437597A (zh) | 取代的苯基－哌嗪衍生物及其制备和用途 | |
| WO2009115685A1 (fr) | Nouveaux derives de 3-aminoalkyl-1,3-dihydro-2h-indol-2-one, leur preparation et leur application en therapeutique. | |
| CZ289799B6 (cs) | Indolinový derivát jako antagonista 5-HT-2C receptoru | |
| KR100363484B1 (ko) | 3-치환1-아릴인돌화합물 |