HU210179B - Process for preparing alfa-oxopyrrolo[2,3b]indole acetic acid, ester and amid derivatives and pharmaceutical compositions containing them as active ingredients - Google Patents
Process for preparing alfa-oxopyrrolo[2,3b]indole acetic acid, ester and amid derivatives and pharmaceutical compositions containing them as active ingredients Download PDFInfo
- Publication number
- HU210179B HU210179B HU911658A HU165891A HU210179B HU 210179 B HU210179 B HU 210179B HU 911658 A HU911658 A HU 911658A HU 165891 A HU165891 A HU 165891A HU 210179 B HU210179 B HU 210179B
- Authority
- HU
- Hungary
- Prior art keywords
- alkyl
- formula
- acetic acid
- hexahydro
- phenyl
- Prior art date
Links
- SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 title claims description 34
- 239000003617 indole-3-acetic acid Substances 0.000 title claims description 26
- 150000002148 esters Chemical class 0.000 title claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 title description 53
- 239000004480 active ingredient Substances 0.000 title description 7
- 235000019439 ethyl acetate Nutrition 0.000 title 1
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 44
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 23
- -1 oxalate ester Chemical class 0.000 claims description 22
- JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium ethoxide Chemical compound [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- DZOVKFKIEXWGBE-UHFFFAOYSA-N 2-(3,4,8b-trimethyl-2,3a-dihydro-1h-pyrrolo[2,3-b]indol-7-yl)-2-oxoacetic acid Chemical compound C1=C(C(=O)C(O)=O)C=C2C3(C)CCN(C)C3N(C)C2=C1 DZOVKFKIEXWGBE-UHFFFAOYSA-N 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 229910052744 lithium Inorganic materials 0.000 claims 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
- 239000000243 solution Substances 0.000 description 57
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 239000003921 oil Substances 0.000 description 21
- 239000002904 solvent Substances 0.000 description 20
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
- 229920006395 saturated elastomer Polymers 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 235000011152 sodium sulphate Nutrition 0.000 description 12
- 102100033639 Acetylcholinesterase Human genes 0.000 description 10
- 108010022752 Acetylcholinesterase Proteins 0.000 description 10
- 235000019270 ammonium chloride Nutrition 0.000 description 10
- 239000003480 eluent Substances 0.000 description 10
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229940022698 acetylcholinesterase Drugs 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- 239000012267 brine Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000008363 phosphate buffer Substances 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 238000002953 preparative HPLC Methods 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 4
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 4
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 4
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- NSBNSZAXNUGWDJ-UHFFFAOYSA-O monopyridin-1-ium tribromide Chemical compound Br[Br-]Br.C1=CC=[NH+]C=C1 NSBNSZAXNUGWDJ-UHFFFAOYSA-O 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 4
- 229960002646 scopolamine Drugs 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- DNQLRFDHCMZQNI-UHFFFAOYSA-N CCCCOC(=O)CC1=CC2=CC=CC=C2N1 Chemical compound CCCCOC(=O)CC1=CC2=CC=CC=C2N1 DNQLRFDHCMZQNI-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 230000001713 cholinergic effect Effects 0.000 description 3
- 150000001860 citric acid derivatives Chemical class 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000030214 innervation Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 2
- BBMCTIGTTCKYKF-UHFFFAOYSA-N 1-heptanol Chemical compound CCCCCCCO BBMCTIGTTCKYKF-UHFFFAOYSA-N 0.000 description 2
- ONKPJHUBFSGBBI-UHFFFAOYSA-N 2-(3,4,8b-trimethyl-2,3a-dihydro-1h-pyrrolo[2,3-b]indol-7-yl)-n,n-diethyl-2-oxoacetamide Chemical compound C12=CC(C(=O)C(=O)N(CC)CC)=CC=C2N(C)C2C1(C)CCN2C ONKPJHUBFSGBBI-UHFFFAOYSA-N 0.000 description 2
- PJFSATAJQZIYRT-UHFFFAOYSA-N 7-bromo-3,4,8b-trimethyl-2,3a-dihydro-1h-pyrrolo[2,3-b]indole Chemical compound C1=C(Br)C=C2C3(C)CCN(C)C3N(C)C2=C1 PJFSATAJQZIYRT-UHFFFAOYSA-N 0.000 description 2
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- 102000003914 Cholinesterases Human genes 0.000 description 2
- 108090000322 Cholinesterases Proteins 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
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- 241001460678 Napo <wasp> Species 0.000 description 2
- JKRZOJADNVOXPM-UHFFFAOYSA-N Oxalic acid dibutyl ester Chemical compound CCCCOC(=O)C(=O)OCCCC JKRZOJADNVOXPM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
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- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
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- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
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- 239000012298 atmosphere Substances 0.000 description 2
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 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
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 210000001577 neostriatum Anatomy 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
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- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
- VOWHONRMOCHCGC-UHFFFAOYSA-N 1,2,3,3a,4,8b-hexahydropyrrolo[2,3-b]indole Chemical group C1=CC=C2C3CCNC3NC2=C1 VOWHONRMOCHCGC-UHFFFAOYSA-N 0.000 description 1
- SWLGXZVYIRBJSL-UHFFFAOYSA-N 2-(3,4,8b-trimethyl-2,3a-dihydro-1h-pyrrolo[2,3-b]indol-7-yl)-2-oxo-n,n-di(propan-2-yl)acetamide Chemical compound C12=CC(C(=O)C(=O)N(C(C)C)C(C)C)=CC=C2N(C)C2C1(C)CCN2C SWLGXZVYIRBJSL-UHFFFAOYSA-N 0.000 description 1
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- 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
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- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US52462790A | 1990-05-17 | 1990-05-17 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| HU911658D0 HU911658D0 (en) | 1991-11-28 |
| HUT61310A HUT61310A (en) | 1992-12-28 |
| HU210179B true HU210179B (en) | 1995-02-28 |
Family
ID=24090019
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU911658A HU210179B (en) | 1990-05-17 | 1991-05-17 | Process for preparing alfa-oxopyrrolo[2,3b]indole acetic acid, ester and amid derivatives and pharmaceutical compositions containing them as active ingredients |
Country Status (22)
| Country | Link |
|---|---|
| EP (1) | EP0457318B1 (en, 2012) |
| JP (1) | JPH0826024B2 (en, 2012) |
| KR (2) | KR100215615B1 (en, 2012) |
| AR (1) | AR247888A1 (en, 2012) |
| AT (1) | ATE141273T1 (en, 2012) |
| AU (1) | AU634380B2 (en, 2012) |
| CA (1) | CA2042737A1 (en, 2012) |
| CZ (1) | CZ280922B6 (en, 2012) |
| DE (1) | DE69121299T2 (en, 2012) |
| DK (1) | DK0457318T3 (en, 2012) |
| ES (1) | ES2094768T3 (en, 2012) |
| FI (1) | FI96689C (en, 2012) |
| GR (1) | GR3021043T3 (en, 2012) |
| HU (1) | HU210179B (en, 2012) |
| IE (1) | IE76318B1 (en, 2012) |
| IL (1) | IL98162A (en, 2012) |
| MX (2) | MX25777A (en, 2012) |
| NO (1) | NO177710C (en, 2012) |
| NZ (2) | NZ260210A (en, 2012) |
| PL (1) | PL290273A1 (en, 2012) |
| PT (1) | PT97688B (en, 2012) |
| ZA (1) | ZA913711B (en, 2012) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4983616A (en) * | 1990-02-01 | 1991-01-08 | Hoechst-Roussel Pharmaceuticals Inc. | Hexahydropyrrolo(2,3-B)indole carbamates, ureas, amides and related compounds |
| AU634654B2 (en) * | 1990-05-11 | 1993-02-25 | Hoechst-Roussel Pharmaceuticals Incorporated | Pyrrolo(2,3-b)indole-ketones and analogs, a process for their preparation and their use as medicaments |
| EP0538248B1 (en) * | 1990-06-27 | 1998-02-11 | Hoechst Marion Roussel, Inc. | Tetrahydroisoquinolinylcarbamates of 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo [2,3-b]indole |
| EP1283199A4 (en) * | 2000-05-16 | 2003-12-17 | Takeda Chemical Industries Ltd | MELANINE CONCENTRATING HORMONE ANTAGONISTS |
| CN102203097B (zh) * | 2008-09-03 | 2015-08-26 | 新加坡南洋理工大学 | 三环手性化合物及其在不对称催化中的用途 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1199076B (it) * | 1984-03-01 | 1988-12-30 | Consiglio Nazionale Ricerche | Derivati della fisostigmina con proprieta'di inibizione della aceticolinesterasi e relativo procedimento di produzione |
| US4791107A (en) * | 1986-07-16 | 1988-12-13 | Hoechst-Roussel Pharmaceuticals, Inc. | Memory enhancing and analgesic 1,2,3,3A,8,8A-hexahydro-3A,8 (and) 1,3A,8)-di(and tri)methylpyrrolo(2,3-B)indoles, compositions and use |
| US4971992A (en) * | 1989-03-27 | 1990-11-20 | Hoechst-Roussel Pharmaceuticals Inc. | Carbonate derivatives of eseroline |
-
1991
- 1991-04-29 AU AU76182/91A patent/AU634380B2/en not_active Ceased
- 1991-05-14 MX MX2577791A patent/MX25777A/es unknown
- 1991-05-14 AR AR91319694A patent/AR247888A1/es active
- 1991-05-15 CZ CS911429A patent/CZ280922B6/cs not_active IP Right Cessation
- 1991-05-15 NZ NZ260210A patent/NZ260210A/en unknown
- 1991-05-15 FI FI912363A patent/FI96689C/fi active
- 1991-05-15 NO NO911892A patent/NO177710C/no not_active IP Right Cessation
- 1991-05-15 NZ NZ238151A patent/NZ238151A/en unknown
- 1991-05-16 KR KR1019910007922A patent/KR100215615B1/ko not_active Expired - Fee Related
- 1991-05-16 IE IE167891A patent/IE76318B1/en not_active IP Right Cessation
- 1991-05-16 CA CA002042737A patent/CA2042737A1/en not_active Abandoned
- 1991-05-16 PL PL29027391A patent/PL290273A1/xx unknown
- 1991-05-16 PT PT97688A patent/PT97688B/pt not_active IP Right Cessation
- 1991-05-16 ES ES91107942T patent/ES2094768T3/es not_active Expired - Lifetime
- 1991-05-16 IL IL9816291A patent/IL98162A/en unknown
- 1991-05-16 MX MX2581691A patent/MX25816A/es unknown
- 1991-05-16 ZA ZA913711A patent/ZA913711B/xx unknown
- 1991-05-16 JP JP3139418A patent/JPH0826024B2/ja not_active Expired - Lifetime
- 1991-05-16 DK DK91107942.4T patent/DK0457318T3/da active
- 1991-05-16 AT AT91107942T patent/ATE141273T1/de not_active IP Right Cessation
- 1991-05-16 EP EP91107942A patent/EP0457318B1/en not_active Expired - Lifetime
- 1991-05-16 DE DE69121299T patent/DE69121299T2/de not_active Expired - Fee Related
- 1991-05-17 HU HU911658A patent/HU210179B/hu not_active IP Right Cessation
-
1996
- 1996-09-13 GR GR960402402T patent/GR3021043T3/el unknown
-
1999
- 1999-02-03 KR KR1019990003497A patent/KR100227715B1/ko not_active Expired - Fee Related
Also Published As
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HPC4 | Succession in title of patentee |
Owner name: HOECHST MARION ROUSSEL, INCORPORATED, US |
|
| HMM4 | Cancellation of final prot. due to non-payment of fee |