DE69401823T2 - Indolin derivate als 5ht2c antagonisten - Google Patents
Indolin derivate als 5ht2c antagonistenInfo
- Publication number
- DE69401823T2 DE69401823T2 DE69401823T DE69401823T DE69401823T2 DE 69401823 T2 DE69401823 T2 DE 69401823T2 DE 69401823 T DE69401823 T DE 69401823T DE 69401823 T DE69401823 T DE 69401823T DE 69401823 T2 DE69401823 T2 DE 69401823T2
- Authority
- DE
- Germany
- Prior art keywords
- indoline
- pyridylcarbamoyl
- chloro
- methyl
- nmr
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 150000002476 indolines Chemical class 0.000 title description 2
- 239000005557 antagonist Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 181
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 26
- -1 C1−6-alkyl radicals Chemical class 0.000 claims description 23
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 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 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 6
- 230000008878 coupling Effects 0.000 claims description 6
- 238000010168 coupling process Methods 0.000 claims description 6
- 238000005859 coupling reaction Methods 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 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 5
- 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 5
- 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 5
- 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 5
- 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 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
- 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 5
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 4
- 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 description 4
- 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 4
- 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 4
- 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 4
- 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
- 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 description 4
- 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 claims description 4
- 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 claims description 4
- 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 claims description 4
- 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 4
- 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 4
- 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 4
- 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 description 4
- 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 4
- 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 4
- 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 4
- OUQBLYJEKPCIMP-UHFFFAOYSA-N 6-chloro-5-ethyl-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1=2C=C(Cl)C(CC)=CC=2CCN1C(=O)NC1=CC=CN=C1 OUQBLYJEKPCIMP-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- 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 4
- 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 4
- 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 4
- 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 4
- 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 4
- 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 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
- 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 4
- 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 4
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 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 description 4
- 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 description 4
- ZDDXCYKFUQNTQB-UHFFFAOYSA-N 4,5-dichloro-n-pyridin-3-yl-2,3-dihydroindole-1-carboxamide Chemical compound C1CC2=C(Cl)C(Cl)=CC=C2N1C(=O)NC1=CC=CN=C1 ZDDXCYKFUQNTQB-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 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 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 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
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- 229910006095 SO2F Inorganic materials 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 174
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 119
- 239000000203 mixture Substances 0.000 description 96
- 238000000034 method Methods 0.000 description 91
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 80
- 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
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 49
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 239000007787 solid Substances 0.000 description 46
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 44
- 239000000243 solution Substances 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
- 229960004756 ethanol Drugs 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 26
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 25
- SHVVSKCXWMEDRW-UHFFFAOYSA-N 3-isocyanatopyridine Chemical compound O=C=NC1=CC=CN=C1 SHVVSKCXWMEDRW-UHFFFAOYSA-N 0.000 description 23
- 239000003921 oil Substances 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- 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 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- 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 17
- 239000000284 extract Substances 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- 229960000583 acetic acid Drugs 0.000 description 15
- 235000019439 ethyl acetate Nutrition 0.000 description 15
- 150000003254 radicals Chemical class 0.000 description 15
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 238000010992 reflux Methods 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 239000012362 glacial acetic acid Substances 0.000 description 11
- 239000003208 petroleum Substances 0.000 description 11
- 239000012043 crude product Substances 0.000 description 10
- 239000000377 silicon dioxide Substances 0.000 description 10
- 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 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 9
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 9
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 239000001257 hydrogen Substances 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- WUTIWOZYHHSBBU-UHFFFAOYSA-N 3-methoxy-4-nitrobenzaldehyde Chemical compound COC1=CC(C=O)=CC=C1[N+]([O-])=O WUTIWOZYHHSBBU-UHFFFAOYSA-N 0.000 description 7
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 239000012442 inert solvent Substances 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
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- 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
- 239000004480 active ingredient Substances 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
- 125000004414 alkyl thio 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
- 125000003277 amino group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000004458 analytical method Methods 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
- 125000001246 bromo group Chemical group Br* 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
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 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
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 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
- 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
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 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
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000012452 mother liquor Substances 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
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002687 nonaqueous vehicle 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
- 229910052763 palladium Inorganic materials 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
- 238000001556 precipitation Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 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
- 230000004044 response Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000002891 serotonin 2B antagonist Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 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
- 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
- 239000011975 tartaric acid Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 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
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 238000007832 transition metal-catalyzed coupling reaction Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 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
- 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)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (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)
- Eyeglasses (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB939313913A GB9313913D0 (en) | 1993-07-06 | 1993-07-06 | Novel compounds |
| PCT/EP1994/002148 WO1995001976A1 (en) | 1993-07-06 | 1994-06-30 | Indoline derivatives as 5ht2c antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69401823D1 DE69401823D1 (de) | 1997-04-03 |
| DE69401823T2 true DE69401823T2 (de) | 1997-08-28 |
Family
ID=10738344
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69401823T Expired - Fee Related DE69401823T2 (de) | 1993-07-06 | 1994-06-30 | Indolin derivate als 5ht2c antagonisten |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US5834494A (enExample) |
| EP (1) | EP0707581B1 (enExample) |
| JP (1) | JPH08512299A (enExample) |
| CN (1) | CN1129937A (enExample) |
| AP (1) | AP463A (enExample) |
| AT (1) | ATE149163T1 (enExample) |
| AU (1) | AU7228394A (enExample) |
| CA (1) | CA2166624A1 (enExample) |
| DE (1) | DE69401823T2 (enExample) |
| GB (1) | GB9313913D0 (enExample) |
| IL (1) | IL110204A0 (enExample) |
| MA (1) | MA23254A1 (enExample) |
| TW (1) | TW297023B (enExample) |
| WO (1) | WO1995001976A1 (enExample) |
| ZA (1) | ZA944807B (enExample) |
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 |
| WO1996023769A2 (en) * | 1995-02-02 | 1996-08-08 | Smithkline Beecham Plc | Heterocyclic compounds possessing 5ht2c receptor antagonist activity |
| NZ301265A (en) * | 1995-02-02 | 1998-12-23 | Smithkline Beecham Plc | Indole derivatives as 5ht receptor antagonists, preparation and pharmaceutical compositions thereof |
| GB9517559D0 (en) * | 1995-08-26 | 1995-10-25 | Smithkline Beecham Plc | Novel compounds |
| WO1997043281A1 (en) * | 1996-05-16 | 1997-11-20 | Allelix Biopharmaceuticals Inc. | Thiophene- and furan-tryptamine derivatives |
| GB9612885D0 (en) * | 1996-06-20 | 1996-08-21 | Smithkline Beecham Plc | Novel compounds |
| GB9612883D0 (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 |
| 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 |
| CA2374898C (en) * | 1999-05-21 | 2009-12-08 | Biovitrum Ab | Pyrazinyl-piperazine compounds, their use and preparation |
| 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 |
| ATE241155T1 (de) * | 2001-07-09 | 2003-06-15 | Cit Alcatel | 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 |
| BR0311970A (pt) | 2002-06-19 | 2005-03-29 | Biovitrum Ab | Novos compostos, seu uso e preparação |
| ATE437876T1 (de) | 2003-06-20 | 2009-08-15 | Hoffmann La Roche | Hexahydropyridoisochinoline als dpp-iv- inhibitoren |
| MXPA05013904A (es) | 2003-06-20 | 2006-02-24 | Hoffmann La Roche | Derivados de pirido[2,1-a] isoquinolinas como inhibidores de dipeptidil-peptidasa iv(dpp-iv). |
| EP1931622B1 (en) * | 2005-09-13 | 2011-08-24 | Bayer CropScience AG | Phenyloxy substituted phenylamidine derivatives as pesticides |
| 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 |
Family Cites Families (3)
| 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 |
| JPH06500551A (ja) * | 1990-09-13 | 1994-01-20 | ビーチャム・グループ・パブリック・リミテッド・カンパニー | ５ｈｔ受容体アンタゴニストとしてのインドールウレア |
| CA2142721A1 (en) * | 1992-08-20 | 1994-03-03 | Ian T. Forbes | Condensed indole derivatives as 5ht and 5ht antagonists |
-
1993
- 1993-07-06 GB GB939313913A patent/GB9313913D0/en active Pending
-
1994
- 1994-06-30 EP EP94921638A patent/EP0707581B1/en not_active Expired - Lifetime
- 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 DE DE69401823T patent/DE69401823T2/de not_active Expired - Fee Related
- 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 WO PCT/EP1994/002148 patent/WO1995001976A1/en not_active Ceased
- 1994-06-30 CA CA002166624A patent/CA2166624A1/en not_active Abandoned
- 1994-07-04 AP APAP/P/1994/000653A patent/AP463A/en active
- 1994-07-04 MA MA23564A patent/MA23254A1/fr unknown
- 1994-07-04 IL IL11020494A patent/IL110204A0/xx unknown
- 1994-07-04 ZA ZA944807A patent/ZA944807B/xx unknown
- 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
Also Published As
| Publication number | Publication date |
|---|---|
| WO1995001976A1 (en) | 1995-01-19 |
| EP0707581A1 (en) | 1996-04-24 |
| DE69401823D1 (de) | 1997-04-03 |
| MA23254A1 (fr) | 1995-04-01 |
| IL110204A0 (en) | 1995-01-24 |
| AP463A (en) | 1996-02-19 |
| ATE149163T1 (de) | 1997-03-15 |
| CN1129937A (zh) | 1996-08-28 |
| EP0707581B1 (en) | 1997-02-26 |
| ZA944807B (en) | 1996-01-04 |
| US5834494A (en) | 1998-11-10 |
| TW297023B (enExample) | 1997-02-01 |
| CA2166624A1 (en) | 1995-01-19 |
| GB9313913D0 (en) | 1993-08-18 |
| AP9400653A0 (en) | 1994-07-31 |
| JPH08512299A (ja) | 1996-12-24 |
| AU7228394A (en) | 1995-02-06 |
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