CA2603249C - Tricyclic indeno-pyrrole derivatives as serotonin receptor modulators - Google Patents
Tricyclic indeno-pyrrole derivatives as serotonin receptor modulators Download PDFInfo
- Publication number
- CA2603249C CA2603249C CA2603249A CA2603249A CA2603249C CA 2603249 C CA2603249 C CA 2603249C CA 2603249 A CA2603249 A CA 2603249A CA 2603249 A CA2603249 A CA 2603249A CA 2603249 C CA2603249 C CA 2603249C
- Authority
- CA
- Canada
- Prior art keywords
- hexahydroindeno
- pyrrole
- methyl
- mmol
- observed
- 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
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 title abstract description 8
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 title abstract description 8
- CNAFOLPGHNAMBW-UHFFFAOYSA-N indeno[2,1-b]pyrrole Chemical class C1=CC=CC2=CC3=NC=CC3=C21 CNAFOLPGHNAMBW-UHFFFAOYSA-N 0.000 title abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 364
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 17
- 208000035475 disorder Diseases 0.000 claims abstract description 14
- 201000010099 disease Diseases 0.000 claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- LJFGIJGOJASCOG-UHFFFAOYSA-N 6-chloro-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C1C2=CC(Cl)=CC=C2C2C1CNC2 LJFGIJGOJASCOG-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- VPRCZXUCLMGRFJ-UHFFFAOYSA-N 4,6-dimethyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C12=CC=C(C)C=C2C(C)C2C1CNC2 VPRCZXUCLMGRFJ-UHFFFAOYSA-N 0.000 claims description 4
- OAZZLOFRPKQVFH-UHFFFAOYSA-N 5,6-dichloro-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C12=CC=C(Cl)C(Cl)=C2C(C)C2C1CNC2 OAZZLOFRPKQVFH-UHFFFAOYSA-N 0.000 claims description 4
- JJOCQOJERGQSTR-UHFFFAOYSA-N 6-chloro-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C12=CC=C(Cl)C=C2C(C)C2C1CNC2 JJOCQOJERGQSTR-UHFFFAOYSA-N 0.000 claims description 4
- VWXSBTYFAQPLEE-UHFFFAOYSA-N 7,8-dimethoxy-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C12=C(OC)C(OC)=CC=C2C(C)C2C1CNC2 VWXSBTYFAQPLEE-UHFFFAOYSA-N 0.000 claims description 4
- CUWZDAXKKWBGLQ-UHFFFAOYSA-N 7-methoxy-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C12=CC(OC)=CC=C2C(C)C2C1CNC2 CUWZDAXKKWBGLQ-UHFFFAOYSA-N 0.000 claims description 4
- QXWBUZGTHPJGMR-UHFFFAOYSA-N 4,5-dimethyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C12=CC=CC(C)=C2C(C)C2C1CNC2 QXWBUZGTHPJGMR-UHFFFAOYSA-N 0.000 claims description 3
- FXFVLTAAVCUFQB-UHFFFAOYSA-N 4,7-dimethyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C12=CC(C)=CC=C2C(C)C2C1CNC2 FXFVLTAAVCUFQB-UHFFFAOYSA-N 0.000 claims description 3
- JPBRVIBTWROCQF-UHFFFAOYSA-N 4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrol-7-ol Chemical compound C12=CC(O)=CC=C2C(C)C2C1CNC2 JPBRVIBTWROCQF-UHFFFAOYSA-N 0.000 claims description 3
- VRECLQQMMYLGAN-UHFFFAOYSA-N 6,7-dichloro-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C12=CC(Cl)=C(Cl)C=C2C(C)C2C1CNC2 VRECLQQMMYLGAN-UHFFFAOYSA-N 0.000 claims description 3
- LUGIUJARXVQSJO-UHFFFAOYSA-N 6,7-dimethoxy-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C1=C(OC)C(OC)=CC2=C1C1CNCC1C2C LUGIUJARXVQSJO-UHFFFAOYSA-N 0.000 claims description 3
- QZEXFZJNWUVTRO-UHFFFAOYSA-N 6,8-dichloro-7-methoxy-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C12=C(Cl)C(OC)=C(Cl)C=C2C(C)C2C1CNC2 QZEXFZJNWUVTRO-UHFFFAOYSA-N 0.000 claims description 3
- BQZWDRLVRWOAQX-UHFFFAOYSA-N 6-chloro-7-methoxy-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C1=C(Cl)C(OC)=CC2=C1CC1CNCC12 BQZWDRLVRWOAQX-UHFFFAOYSA-N 0.000 claims description 3
- LANLSVUKINPKJD-UHFFFAOYSA-N 6-chloro-7-methoxy-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C1=C(Cl)C(OC)=CC2=C1C(C)C1CNCC12 LANLSVUKINPKJD-UHFFFAOYSA-N 0.000 claims description 3
- WNMYWPKNFVTVMC-UHFFFAOYSA-N 6-fluoro-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C12=CC=C(F)C=C2C(C)C2C1CNC2 WNMYWPKNFVTVMC-UHFFFAOYSA-N 0.000 claims description 3
- LZLVURUTDDLJQS-UHFFFAOYSA-N 7-chloro-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C12=CC(Cl)=CC=C2C(C)C2C1CNC2 LZLVURUTDDLJQS-UHFFFAOYSA-N 0.000 claims description 3
- MAUNMIUGHCWSTC-UHFFFAOYSA-N 8-fluoro-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C1=CC=C(F)C2=C1C(C)C1CNCC12 MAUNMIUGHCWSTC-UHFFFAOYSA-N 0.000 claims description 3
- ZNWTVKSPGXOFTC-UHFFFAOYSA-N 4,8-dimethyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C1=CC=C(C)C2=C1C(C)C1CNCC12 ZNWTVKSPGXOFTC-UHFFFAOYSA-N 0.000 claims description 2
- KWNBOZNREJQWLD-UHFFFAOYSA-N 6,8-dichloro-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C1=C(Cl)C=C(Cl)C2=C1C(C)C1CNCC12 KWNBOZNREJQWLD-UHFFFAOYSA-N 0.000 claims description 2
- QMAORUZVLVMNEI-UHFFFAOYSA-N 6-bromo-4,7-dimethyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C12=CC(C)=C(Br)C=C2C(C)C2C1CNC2 QMAORUZVLVMNEI-UHFFFAOYSA-N 0.000 claims description 2
- MSRJIHNBCXQCFM-UHFFFAOYSA-N 6-bromo-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrol-7-ol Chemical compound C12=CC(O)=C(Br)C=C2C(C)C2C1CNC2 MSRJIHNBCXQCFM-UHFFFAOYSA-N 0.000 claims description 2
- FSZFLFCDNDLXGV-UHFFFAOYSA-N 6-bromo-7-methoxy-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C1=C(Br)C(OC)=CC2=C1C(C)C1CNCC12 FSZFLFCDNDLXGV-UHFFFAOYSA-N 0.000 claims description 2
- LARRGEXQHAFKNV-UHFFFAOYSA-N 6-chloro-4,7-dimethyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C12=CC(C)=C(Cl)C=C2C(C)C2C1CNC2 LARRGEXQHAFKNV-UHFFFAOYSA-N 0.000 claims description 2
- OLQSLIJTAIJKGM-UHFFFAOYSA-N 6-chloro-4-methyl-7-phenylmethoxy-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound ClC=1C=C2C(C)C3CNCC3C2=CC=1OCC1=CC=CC=C1 OLQSLIJTAIJKGM-UHFFFAOYSA-N 0.000 claims description 2
- KSEVSUJMFNVQAB-UHFFFAOYSA-N 6-chloro-7,8-dimethoxy-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound CC1C2=CC(Cl)=C(OC)C(OC)=C2C2C1CNC2 KSEVSUJMFNVQAB-UHFFFAOYSA-N 0.000 claims description 2
- QGIJLBFEWYSEMA-UHFFFAOYSA-N 7-bromo-4,6-dimethyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C12=CC(Br)=C(C)C=C2C(C)C2C1CNC2 QGIJLBFEWYSEMA-UHFFFAOYSA-N 0.000 claims description 2
- LKSWCKLOGNAERN-UHFFFAOYSA-N 7-chloro-4,6-dimethyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C12=CC(Cl)=C(C)C=C2C(C)C2C1CNC2 LKSWCKLOGNAERN-UHFFFAOYSA-N 0.000 claims description 2
- GQXLGZHFSNXXBN-UHFFFAOYSA-N 7-fluoro-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C12=CC(F)=CC=C2C(C)C2C1CNC2 GQXLGZHFSNXXBN-UHFFFAOYSA-N 0.000 claims description 2
- CVCBVBLSTQQHRH-UHFFFAOYSA-N 7-methoxy-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole-6-carbonitrile Chemical compound C1=C(C#N)C(OC)=CC2=C1C(C)C1CNCC12 CVCBVBLSTQQHRH-UHFFFAOYSA-N 0.000 claims description 2
- JDMLENYLCFYLBJ-UHFFFAOYSA-N 8-chloro-7-methoxy-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C12=C(Cl)C(OC)=CC=C2C(C)C2C1CNC2 JDMLENYLCFYLBJ-UHFFFAOYSA-N 0.000 claims description 2
- DRUYNACZJGPYJG-UHFFFAOYSA-N 6-chloro-7-[(2-fluorophenyl)methoxy]-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound ClC=1C=C2C(C)C3CNCC3C2=CC=1OCC1=CC=CC=C1F DRUYNACZJGPYJG-UHFFFAOYSA-N 0.000 claims 1
- CYYSUFQMPAPDRX-UHFFFAOYSA-N 6-chloro-7-[(3-fluorophenyl)methoxy]-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound ClC=1C=C2C(C)C3CNCC3C2=CC=1OCC1=CC=CC(F)=C1 CYYSUFQMPAPDRX-UHFFFAOYSA-N 0.000 claims 1
- TUQATKYXOFSONT-UHFFFAOYSA-N 6-chloro-7-[(4-fluorophenyl)methoxy]-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound ClC=1C=C2C(C)C3CNCC3C2=CC=1OCC1=CC=C(F)C=C1 TUQATKYXOFSONT-UHFFFAOYSA-N 0.000 claims 1
- HLNCOTOWVOPTNR-UHFFFAOYSA-N 6-chloro-7-ethoxy-4-methyl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C1=C(Cl)C(OCC)=CC2=C1C(C)C1CNCC12 HLNCOTOWVOPTNR-UHFFFAOYSA-N 0.000 claims 1
- GCJLVFSFYSCIQH-UHFFFAOYSA-N 7-methoxy-4-methyl-6-thiophen-2-yl-1,2,3,3a,4,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound COC1=CC=2C3CNCC3C(C)C=2C=C1C1=CC=CS1 GCJLVFSFYSCIQH-UHFFFAOYSA-N 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 32
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 abstract description 17
- 230000000694 effects Effects 0.000 abstract description 11
- 208000019901 Anxiety disease Diseases 0.000 abstract description 6
- 230000036506 anxiety Effects 0.000 abstract description 6
- 208000008589 Obesity Diseases 0.000 abstract description 5
- 235000020824 obesity Nutrition 0.000 abstract description 5
- 239000003446 ligand Substances 0.000 abstract description 4
- 229940124597 therapeutic agent Drugs 0.000 abstract description 2
- 239000012043 crude product Substances 0.000 description 189
- 238000000034 method Methods 0.000 description 163
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 95
- 239000000243 solution Substances 0.000 description 95
- 238000000746 purification Methods 0.000 description 84
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 68
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 56
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 51
- 238000004440 column chromatography Methods 0.000 description 49
- -1 E- and Z-pentenyl Chemical group 0.000 description 43
- 238000005160 1H NMR spectroscopy Methods 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 35
- 239000011541 reaction mixture Substances 0.000 description 30
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 28
- 235000019341 magnesium sulphate Nutrition 0.000 description 28
- 239000000706 filtrate Substances 0.000 description 26
- 239000000284 extract Substances 0.000 description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- 239000000377 silicon dioxide Substances 0.000 description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 16
- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 15
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 14
- PPOWAGATRAVSPP-UHFFFAOYSA-N 1,2,3,8,8a,8b-hexahydroindeno[1,2-c]pyrrole Chemical compound C1=CCC2C3CNCC3=CC2=C1 PPOWAGATRAVSPP-UHFFFAOYSA-N 0.000 description 13
- 229940079593 drug Drugs 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 12
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
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- 238000002390 rotary evaporation Methods 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
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- UFENPRNTNZTTRS-UHFFFAOYSA-N 8bh-cyclopenta[a]inden-4-one Chemical compound C1=CC=C2C(=O)C3=CC=CC3C2=C1 UFENPRNTNZTTRS-UHFFFAOYSA-N 0.000 description 7
- 229910015845 BBr3 Inorganic materials 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
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- 229910052739 hydrogen Inorganic materials 0.000 description 7
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- 229920001223 polyethylene glycol Polymers 0.000 description 5
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- 239000000843 powder Substances 0.000 description 5
- 239000000651 prodrug Chemical group 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- ZWUSBSHBFFPRNE-UHFFFAOYSA-N 3,4-dichlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1Cl ZWUSBSHBFFPRNE-UHFFFAOYSA-N 0.000 description 4
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
-
- 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
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/90—Benzo [c, d] indoles; Hydrogenated benzo [c, d] indoles
-
- 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
- A61K31/403—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 condensed with carbocyclic rings, e.g. carbazole
-
- 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
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- 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
- A61P25/06—Antimigraine agents
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- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/22—Anxiolytics
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- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
-
- 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
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/70—[b]- or [c]-condensed containing carbocyclic rings other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Child & Adolescent Psychology (AREA)
- Addiction (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US59204704P | 2004-07-29 | 2004-07-29 | |
| US60/592,047 | 2004-07-29 | ||
| PCT/US2005/026415 WO2007081299A2 (en) | 2004-07-29 | 2005-07-26 | Tricyclic indeno-pyrrole derivatives as serotonin receptor modulators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2603249A1 CA2603249A1 (en) | 2007-07-19 |
| CA2603249C true CA2603249C (en) | 2014-01-21 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2603249A Expired - Fee Related CA2603249C (en) | 2004-07-29 | 2005-07-26 | Tricyclic indeno-pyrrole derivatives as serotonin receptor modulators |
Country Status (16)
| Country | Link |
|---|---|
| US (5) | US20060025601A1 (enExample) |
| EP (1) | EP1841738A4 (enExample) |
| JP (1) | JP4990164B2 (enExample) |
| KR (2) | KR20130047765A (enExample) |
| CN (1) | CN101516372A (enExample) |
| AR (1) | AR050274A1 (enExample) |
| AU (1) | AU2005333518B2 (enExample) |
| BR (1) | BRPI0512869A (enExample) |
| CA (1) | CA2603249C (enExample) |
| IL (1) | IL180977A (enExample) |
| NO (1) | NO20071102L (enExample) |
| NZ (1) | NZ552806A (enExample) |
| RU (1) | RU2007107494A (enExample) |
| TW (1) | TWI377195B (enExample) |
| WO (1) | WO2007081299A2 (enExample) |
| ZA (1) | ZA200700684B (enExample) |
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| US20060025601A1 (en) | 2004-07-29 | 2006-02-02 | Athersys, Inc. | Tricyclic indeno-pyrrole derivatives as serotonin receptor modulators |
| JP5528699B2 (ja) | 2006-05-16 | 2014-06-25 | 武田薬品工業株式会社 | 縮合複素環化合物およびその用途 |
| JP4866901B2 (ja) | 2007-02-07 | 2012-02-01 | 協和発酵キリン株式会社 | ３環系化合物 |
| JP5520051B2 (ja) | 2007-11-15 | 2014-06-11 | 武田薬品工業株式会社 | 縮合ピリジン誘導体およびその用途 |
| WO2009097995A1 (de) * | 2008-02-07 | 2009-08-13 | Sanofi-Aventis | Neue phenyl-substituierte imidazolidine, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP3081213B1 (en) | 2008-08-06 | 2020-04-01 | Kyowa Kirin Co., Ltd. | Tricyclic compound |
| TW201041851A (en) | 2009-03-10 | 2010-12-01 | Organon Nv | Tricyclic heterocyclic derivatives |
| WO2012120055A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2766349B1 (de) | 2011-03-08 | 2016-06-01 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2012120054A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120056A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2683704B1 (de) | 2011-03-08 | 2014-12-17 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| CN106380440B (zh) * | 2016-08-30 | 2019-02-01 | 华东师范大学 | 一种茚酮并吡咯类衍生物及其合成方法和应用 |
| CN106631989B (zh) * | 2016-11-26 | 2019-07-16 | 威海迪素制药有限公司 | 一种盐酸多奈哌齐有关物质e的制备方法 |
| WO2019131902A1 (ja) | 2017-12-27 | 2019-07-04 | 武田薬品工業株式会社 | 腹圧性尿失禁および便失禁の治療薬 |
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| DE3576334D1 (de) * | 1984-07-25 | 1990-04-12 | Abbott Lab | 1,2,3,3a,8,8a-hexahydro-indeno-(1,2-c)pyrrde. |
| US4622405A (en) * | 1984-07-25 | 1986-11-11 | Abbott Laboratories | 1,2,3,3a,8,8a-hexahydro-indeno[1,2-c]pyrroles useful in the treatment of hypertension |
| EP0422134B1 (en) * | 1988-12-15 | 1996-06-12 | Abbott Laboratories | 5-ht selective agents |
| US5049564A (en) * | 1989-11-17 | 1991-09-17 | Abbott Laboratories | 5-HT selective agents |
| US5244888A (en) * | 1989-11-17 | 1993-09-14 | Abbott Laboratories | 5-HT selective agents |
| TW334423B (en) * | 1993-10-22 | 1998-06-21 | Hoffmann La Roche | Tricyclic 1-aminoethylpyrrole-derivatives |
| US7351711B2 (en) * | 2003-07-31 | 2008-04-01 | Janssen Pharmaceutical, N.V. | Tricyclic indanyls as integrin inhibitors |
| TWI350168B (en) * | 2004-05-07 | 2011-10-11 | Incyte Corp | Amido compounds and their use as pharmaceuticals |
| US20060025601A1 (en) * | 2004-07-29 | 2006-02-02 | Athersys, Inc. | Tricyclic indeno-pyrrole derivatives as serotonin receptor modulators |
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2005
- 2005-07-26 US US11/189,952 patent/US20060025601A1/en not_active Abandoned
- 2005-07-26 JP JP2007554065A patent/JP4990164B2/ja not_active Expired - Fee Related
- 2005-07-26 KR KR1020137007788A patent/KR20130047765A/ko not_active Withdrawn
- 2005-07-26 CA CA2603249A patent/CA2603249C/en not_active Expired - Fee Related
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- 2005-07-26 NZ NZ552806A patent/NZ552806A/en not_active IP Right Cessation
- 2005-07-26 KR KR1020077002230A patent/KR101257233B1/ko not_active Expired - Fee Related
- 2005-07-26 AU AU2005333518A patent/AU2005333518B2/en not_active Ceased
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- 2005-07-26 WO PCT/US2005/026415 patent/WO2007081299A2/en not_active Ceased
- 2005-07-26 EP EP05858534A patent/EP1841738A4/en not_active Withdrawn
- 2005-07-26 BR BRPI0512869-2A patent/BRPI0512869A/pt not_active Application Discontinuation
- 2005-07-28 AR ARP050103146A patent/AR050274A1/es not_active Application Discontinuation
- 2005-07-29 TW TW094125988A patent/TWI377195B/zh not_active IP Right Cessation
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2007
- 2007-01-24 ZA ZA200700684A patent/ZA200700684B/xx unknown
- 2007-01-25 IL IL180977A patent/IL180977A/en not_active IP Right Cessation
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2009
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2011
- 2011-03-25 US US13/071,732 patent/US8232311B2/en not_active Expired - Fee Related
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2012
- 2012-06-18 US US13/526,249 patent/US8716324B2/en not_active Expired - Fee Related
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2014
- 2014-03-21 US US14/221,809 patent/US9096520B2/en not_active Expired - Fee Related
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