CA1079739A - Basically substituted indole derivatives and process for their manufacture - Google Patents
Basically substituted indole derivatives and process for their manufactureInfo
- Publication number
- CA1079739A CA1079739A CA268,139A CA268139A CA1079739A CA 1079739 A CA1079739 A CA 1079739A CA 268139 A CA268139 A CA 268139A CA 1079739 A CA1079739 A CA 1079739A
- Authority
- CA
- Canada
- Prior art keywords
- phenyl
- indole
- chloro
- resultant
- carbon atoms
- 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
Links
- 238000000034 method Methods 0.000 title claims abstract description 35
- 238000004519 manufacturing process Methods 0.000 title abstract description 4
- 229940054051 antipsychotic indole derivative Drugs 0.000 title abstract 2
- 150000002475 indoles Chemical class 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 42
- 125000004432 carbon atom Chemical group C* 0.000 claims description 54
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 28
- 239000002253 acid Substances 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- -1 methylene-dioxy Chemical group 0.000 claims description 20
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- OWPNVXATCSXTBK-UHFFFAOYSA-N 1-phenyl-3h-indol-2-one Chemical compound O=C1CC2=CC=CC=C2N1C1=CC=CC=C1 OWPNVXATCSXTBK-UHFFFAOYSA-N 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000003277 amino group Chemical group 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- RLELAQIJEUVHMV-UHFFFAOYSA-N (2-chloro-1-phenylindol-3-yl)-piperazin-1-ylmethanone Chemical compound C12=CC=CC=C2N(C=2C=CC=CC=2)C(Cl)=C1C(=O)N1CCNCC1 RLELAQIJEUVHMV-UHFFFAOYSA-N 0.000 claims description 5
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 4
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000006193 alkinyl group Chemical group 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 229940100198 alkylating agent Drugs 0.000 claims description 3
- 239000002168 alkylating agent Substances 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- NIBFJPXGNVPNHK-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-4-carbaldehyde Chemical group C1=CC(C=O)=C2OC(F)(F)OC2=C1 NIBFJPXGNVPNHK-UHFFFAOYSA-N 0.000 claims description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000002431 aminoalkoxy group Chemical group 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 2
- 239000000057 synthetic resin Substances 0.000 claims description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 33
- 238000002360 preparation method Methods 0.000 claims 13
- FWZUBSMPPRSUSD-UHFFFAOYSA-N 2-chloro-1-phenylindole-3-carboxylic acid Chemical compound C12=CC=CC=C2C(C(=O)O)=C(Cl)N1C1=CC=CC=C1 FWZUBSMPPRSUSD-UHFFFAOYSA-N 0.000 claims 12
- IOEMMFHEICHTSW-UHFFFAOYSA-N 2-chloro-1-phenylindole-3-carbaldehyde Chemical compound ClC1=C(C=O)C2=CC=CC=C2N1C1=CC=CC=C1 IOEMMFHEICHTSW-UHFFFAOYSA-N 0.000 claims 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 9
- 239000012286 potassium permanganate Substances 0.000 claims 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 6
- MSSDTZLYNMFTKN-UHFFFAOYSA-N 1-Piperazinecarboxaldehyde Chemical compound O=CN1CCNCC1 MSSDTZLYNMFTKN-UHFFFAOYSA-N 0.000 claims 3
- FULQKYGOYMPNFP-UHFFFAOYSA-N (2-chloro-1-phenylindol-3-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C(C1=CC=CC=C11)=C(Cl)N1C1=CC=CC=C1 FULQKYGOYMPNFP-UHFFFAOYSA-N 0.000 claims 2
- FHCHKTHJIBKRFM-UHFFFAOYSA-N 4-(2-chloro-1-phenylindole-3-carbonyl)piperazine-1-carbaldehyde Chemical compound C(=O)N1CCN(CC1)C(=O)C1=C(N(C2=CC=CC=C12)C1=CC=CC=C1)Cl FHCHKTHJIBKRFM-UHFFFAOYSA-N 0.000 claims 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims 2
- 150000001299 aldehydes Chemical class 0.000 claims 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims 1
- GBKZPLIJKMRYTE-UHFFFAOYSA-N 2-(2-chloroethyl)-1,3-dioxolane Chemical compound ClCCC1OCCO1 GBKZPLIJKMRYTE-UHFFFAOYSA-N 0.000 claims 1
- MGUMZJAQENFQKN-UHFFFAOYSA-N 2-(cyclohexylamino)ethanol Chemical compound OCCNC1CCCCC1 MGUMZJAQENFQKN-UHFFFAOYSA-N 0.000 claims 1
- INUOMGXEYFMQEX-UHFFFAOYSA-N 2-(cyclohexylamino)ethyl 2-chloro-1-phenylindole-3-carboxylate;hydrochloride Chemical compound Cl.C12=CC=CC=C2N(C=2C=CC=CC=2)C(Cl)=C1C(=O)OCCNC1CCCCC1 INUOMGXEYFMQEX-UHFFFAOYSA-N 0.000 claims 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 claims 1
- MNJTUDKRNUPDKP-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-1-phenylindol-2-one Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC=CC=C1 MNJTUDKRNUPDKP-UHFFFAOYSA-N 0.000 claims 1
- DWSUJONSJJTODA-UHFFFAOYSA-N 5-(chloromethyl)-1,3-benzodioxole Chemical compound ClCC1=CC=C2OCOC2=C1 DWSUJONSJJTODA-UHFFFAOYSA-N 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 125000004103 aminoalkyl group Chemical group 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
- 125000004663 dialkyl amino group Chemical group 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 claims 1
- 229920003002 synthetic resin Polymers 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- 239000002904 solvent Substances 0.000 description 8
- 229960001701 chloroform Drugs 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 5
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 5
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- GHPYJLCQYMAXGG-WCCKRBBISA-N (2R)-2-amino-3-(2-boronoethylsulfanyl)propanoic acid hydrochloride Chemical compound Cl.N[C@@H](CSCCB(O)O)C(O)=O GHPYJLCQYMAXGG-WCCKRBBISA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 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 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- CBDVVMQAOSFOAM-UHFFFAOYSA-N 2-chloro-1-phenylindole Chemical compound ClC1=CC2=CC=CC=C2N1C1=CC=CC=C1 CBDVVMQAOSFOAM-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 241000907681 Morpho Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 2
- RCJVRSBWZCNNQT-UHFFFAOYSA-N dichloridooxygen Chemical compound ClOCl RCJVRSBWZCNNQT-UHFFFAOYSA-N 0.000 description 2
- MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 2
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 2
- KMAKOBLIOCQGJP-UHFFFAOYSA-N indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CNC2=C1 KMAKOBLIOCQGJP-UHFFFAOYSA-N 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 description 1
- XXBNLUKLCXTTPH-LECHCGJUSA-N (2S,3R,4S,5R)-2,3,4,5,6-pentahydroxyhexanoyl chloride Chemical compound ClC(=O)[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)CO XXBNLUKLCXTTPH-LECHCGJUSA-N 0.000 description 1
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 1
- BROVFBHLXAOTKQ-UHFFFAOYSA-N 2-(3-methoxyphenyl)-1h-indole Chemical compound COC1=CC=CC(C=2NC3=CC=CC=C3C=2)=C1 BROVFBHLXAOTKQ-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 101150092509 Actn gene Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 102100021394 CST complex subunit CTC1 Human genes 0.000 description 1
- 241000905957 Channa melasoma Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 241000861718 Chloris <Aves> Species 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- 241000518994 Conta Species 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 240000002989 Euphorbia neriifolia Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 101000894433 Homo sapiens CST complex subunit CTC1 Proteins 0.000 description 1
- 101001050607 Homo sapiens KH domain-containing, RNA-binding, signal transduction-associated protein 3 Proteins 0.000 description 1
- 206010021113 Hypothermia Diseases 0.000 description 1
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 1
- 102100023428 KH domain-containing, RNA-binding, signal transduction-associated protein 3 Human genes 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241001435619 Lile Species 0.000 description 1
- 241000234435 Lilium Species 0.000 description 1
- 241001024304 Mino Species 0.000 description 1
- JBZRLVKMCLOFLG-UHFFFAOYSA-N O=S=Cl Chemical compound O=S=Cl JBZRLVKMCLOFLG-UHFFFAOYSA-N 0.000 description 1
- 229910019201 POBr3 Inorganic materials 0.000 description 1
- 241001387976 Pera Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241001666190 Quiva Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 235000004443 Ricinus communis Nutrition 0.000 description 1
- KHPCPRHQVVSZAH-HUOMCSJISA-N Rosin Natural products O(C/C=C/c1ccccc1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KHPCPRHQVVSZAH-HUOMCSJISA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 241000009298 Trigla lyra Species 0.000 description 1
- 244000172533 Viola sororia Species 0.000 description 1
- 235000012544 Viola sororia Nutrition 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 239000011717 all-trans-retinol Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 206010061592 cardiac fibrillation Diseases 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229940106681 chloroacetic acid Drugs 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 230000002600 fibrillogenic effect Effects 0.000 description 1
- 239000000727 fraction Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical compound C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 description 1
- OLNJUISKUQQNIM-UHFFFAOYSA-N indole-3-carboxaldehyde Natural products C1=CC=C2C(C=O)=CNC2=C1 OLNJUISKUQQNIM-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- 235000014786 phosphorus Nutrition 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 1
- 229940114926 stearate Drugs 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 1
- 229940086542 triethylamine Drugs 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19752557342 DE2557342A1 (de) | 1975-12-19 | 1975-12-19 | Basisch substituierte indolderivate und verfahren zu ihrer herstellung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1079739A true CA1079739A (en) | 1980-06-17 |
Family
ID=5964905
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA268,139A Expired CA1079739A (en) | 1975-12-19 | 1976-12-17 | Basically substituted indole derivatives and process for their manufacture |
Country Status (11)
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5936675A (ja) * | 1982-07-13 | 1984-02-28 | サンド・アクチエンゲゼルシヤフト | 二環性複素環式カルボン酸アザビシクロアルキルエステルまたはアミド |
| US4861880A (en) * | 1982-09-20 | 1989-08-29 | Pfizer Inc. | 1-phenyl-2(1H,3H)-indolone psycho-therapeutic agents |
| US4476307A (en) * | 1982-09-20 | 1984-10-09 | Pfizer Inc. | Heteroylidene indolone compounds |
| US4879391A (en) * | 1982-09-20 | 1989-11-07 | Pfizer Inc. | 1-Phenyl-2(1H,3H)-indolone psychotherapeutic agents |
| US4977178A (en) * | 1982-09-20 | 1990-12-11 | Pfizer Inc. | Method of treating anxiety and depression with 1-phenyl-2(1H,3H)-indolone psycho-therapeutic agents |
| JPS6084281A (ja) * | 1983-09-14 | 1985-05-13 | Yoshitomi Pharmaceut Ind Ltd | ３−インド−ルカルボキサミド類 |
| DE3445377A1 (de) * | 1983-12-23 | 1985-07-04 | Sandoz-Patent-GmbH, 7850 Lörrach | Carbocylische und heterocyclische carbonsaeureester und -amide von ueberbrueckten und nicht ueberbrueckten cyclischen stickstoffhaltigen aminen oder alkoholen |
| US5852014A (en) * | 1992-03-12 | 1998-12-22 | Smithkline Beecham P.L.C. | Condensed indole derivatives as 5HT4 -receptor antagonists |
| EP0630376B1 (en) * | 1992-03-12 | 1999-06-02 | Smithkline Beecham Plc | Condensed indole derivatives as 5-ht4-receptor antagonists |
| EP0802183B1 (en) * | 1996-04-19 | 2001-10-10 | American Home Products Corporation | Estrogenic agents |
| US6069153A (en) * | 1998-05-12 | 2000-05-30 | American Home Products Corporation | Indenoindoles and benzocarbazoles as estrogenic agents |
| US6479535B1 (en) | 1998-05-15 | 2002-11-12 | Wyeth | 2-phenyl-1-[4-(2-aminoethoxy)-benzyl]-indole and estrogen formulations |
| US6159959A (en) * | 1999-05-06 | 2000-12-12 | American Home Products Corporation | Combined estrogen and antiestrogen therapy |
| ES2600460T3 (es) | 2005-05-10 | 2017-02-09 | Intermune, Inc. | Derivados de piridona-2-ona como moduladores del sistema de proteína cinasa activada por estrés |
| JP2009502859A (ja) * | 2005-07-29 | 2009-01-29 | エフ．ホフマン−ラ ロシュ アーゲー | インドール−３−イル−カルボニル−ピペリジン及びピペラジン誘導体 |
| JP2009508872A (ja) * | 2005-09-16 | 2009-03-05 | セレネックス， インコーポレイテッド | カルバゾール誘導体 |
| SG183699A1 (en) * | 2007-08-10 | 2012-09-27 | Lundbeck & Co As H | Heteroaryl amide analogues |
| ES2567283T3 (es) | 2008-06-03 | 2016-04-21 | Intermune, Inc. | Compuestos y métodos para tratar trastornos inflamatorios y fibróticos |
| AR092742A1 (es) | 2012-10-02 | 2015-04-29 | Intermune Inc | Piridinonas antifibroticas |
| CA2943363A1 (en) | 2014-04-02 | 2015-10-08 | Intermune, Inc. | Anti-fibrotic pyridinones |
-
1975
- 1975-12-19 DE DE19752557342 patent/DE2557342A1/de not_active Withdrawn
-
1976
- 1976-12-17 NL NL7614050A patent/NL7614050A/xx not_active Application Discontinuation
- 1976-12-17 DK DK571376A patent/DK571376A/da not_active Application Discontinuation
- 1976-12-17 LU LU76427A patent/LU76427A1/xx unknown
- 1976-12-17 CA CA268,139A patent/CA1079739A/en not_active Expired
- 1976-12-17 AT AT936276A patent/ATA936276A/de not_active Application Discontinuation
- 1976-12-17 IT IT30582/76A patent/IT1065683B/it active
- 1976-12-18 JP JP51151501A patent/JPS5277060A/ja active Pending
- 1976-12-20 GB GB53124/76A patent/GB1566307A/en not_active Expired
- 1976-12-20 FR FR7638400A patent/FR2335216A1/fr not_active Withdrawn
- 1976-12-20 BE BE173447A patent/BE849626A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GB1566307A (en) | 1980-04-30 |
| BE849626A (fr) | 1977-06-20 |
| DE2557342A1 (de) | 1977-06-30 |
| LU76427A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1977-07-05 |
| FR2335216A1 (fr) | 1977-07-15 |
| NL7614050A (nl) | 1977-06-21 |
| JPS5277060A (en) | 1977-06-29 |
| ATA936276A (de) | 1980-02-15 |
| IT1065683B (it) | 1985-03-04 |
| DK571376A (da) | 1977-06-20 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |