CA1107729A - Preparation of derivatives of fluorenes and fluoranthenes - Google Patents
Preparation of derivatives of fluorenes and fluoranthenesInfo
- Publication number
- CA1107729A CA1107729A CA332,589A CA332589A CA1107729A CA 1107729 A CA1107729 A CA 1107729A CA 332589 A CA332589 A CA 332589A CA 1107729 A CA1107729 A CA 1107729A
- Authority
- CA
- Canada
- Prior art keywords
- radical
- alkyl
- hydrogen atom
- formula
- benzyl
- 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
- 150000002219 fluoranthenes Chemical class 0.000 title claims abstract description 6
- 150000002220 fluorenes Chemical class 0.000 title claims abstract 4
- 238000002360 preparation method Methods 0.000 title claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 39
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 14
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 14
- 125000002252 acyl group Chemical group 0.000 claims abstract description 13
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 13
- 239000002253 acid Substances 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 125000004175 fluorobenzyl group Chemical group 0.000 claims abstract description 9
- 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 claims abstract description 8
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 7
- 229910052731 fluorine Chemical group 0.000 claims abstract description 7
- 239000001257 hydrogen Substances 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 6
- LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical compound O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 claims abstract description 6
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical group ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000006307 alkoxy benzyl group Chemical group 0.000 claims abstract description 4
- 125000006177 alkyl benzyl group Chemical group 0.000 claims abstract description 4
- 239000000460 chlorine Chemical group 0.000 claims abstract description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 12
- 150000001875 compounds Chemical class 0.000 claims description 101
- -1 C1-C4 alkoxy radical Chemical group 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 21
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 20
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 9
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical group [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 239000012458 free base Substances 0.000 claims description 4
- 239000012948 isocyanate Substances 0.000 claims description 4
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- PCDHSSHKDZYLLI-UHFFFAOYSA-N butan-1-one Chemical compound CCC[C]=O PCDHSSHKDZYLLI-UHFFFAOYSA-N 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical group [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims description 3
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 3
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- 230000002152 alkylating effect Effects 0.000 claims description 2
- 230000008707 rearrangement Effects 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims 5
- TUCNEACPLKLKNU-UHFFFAOYSA-N acetyl Chemical group C[C]=O TUCNEACPLKLKNU-UHFFFAOYSA-N 0.000 claims 2
- 206010002660 Anoxia Diseases 0.000 abstract description 5
- 206010021143 Hypoxia Diseases 0.000 abstract description 5
- 239000004089 psychotropic agent Substances 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 69
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
- 239000000203 mixture Substances 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 22
- 239000000243 solution Substances 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000155 melt Substances 0.000 description 15
- 238000001953 recrystallisation Methods 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- 238000002844 melting Methods 0.000 description 13
- 230000008018 melting Effects 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 11
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 239000007832 Na2SO4 Substances 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 238000009835 boiling Methods 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 238000007792 addition Methods 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000012280 lithium aluminium hydride Substances 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical class C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 229910010084 LiAlH4 Inorganic materials 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 229940073584 methylene chloride Drugs 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000976983 Anoxia Species 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000007953 anoxia Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- RERZNCLIYCABFS-UHFFFAOYSA-N harmaline Chemical compound C1CN=C(C)C2=C1C1=CC=C(OC)C=C1N2 RERZNCLIYCABFS-UHFFFAOYSA-N 0.000 description 3
- 150000004678 hydrides Chemical class 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- XYGBKMMCQDZQOZ-UHFFFAOYSA-M sodium;4-hydroxybutanoate Chemical compound [Na+].OCCCC([O-])=O XYGBKMMCQDZQOZ-UHFFFAOYSA-M 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- XIUUPSVCFNTVQZ-UHFFFAOYSA-N 1-(12-fluoro-3,5-dimethyl-1,3,6-triazatetracyclo[7.6.1.05,16.010,15]hexadeca-9(16),10(15),11,13-tetraen-6-yl)ethanone Chemical compound C12=CC(F)=CC=C2N2CN(C)CC3(C)N(C(C)=O)CCC1=C32 XIUUPSVCFNTVQZ-UHFFFAOYSA-N 0.000 description 2
- GXZDYPJXYURBDP-UHFFFAOYSA-N 3-methyl-2,4,6,7,12,12b-hexahydro-1h-pyrimido[6,1-a]$b-carboline Chemical compound N1C2=CC=CC=C2C2=C1C1CCN(C)CN1CC2 GXZDYPJXYURBDP-UHFFFAOYSA-N 0.000 description 2
- JTEJPPKMYBDEMY-UHFFFAOYSA-N 5-methoxytryptamine Chemical compound COC1=CC=C2NC=C(CCN)C2=C1 JTEJPPKMYBDEMY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 239000002026 chloroform extract Substances 0.000 description 2
- 238000006264 debenzylation reaction Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- YXFXKGBICGUOJR-UHFFFAOYSA-N ethyl 2-(2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indol-1-yl)acetate Chemical compound N1C2=CC=CC=C2C2=C1C(CC(=O)OCC)NCC2 YXFXKGBICGUOJR-UHFFFAOYSA-N 0.000 description 2
- 239000008098 formaldehyde solution Substances 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 235000011118 potassium hydroxide Nutrition 0.000 description 2
- 229940093932 potassium hydroxide Drugs 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 description 2
- JPTKZRPOIUYFTM-UHFFFAOYSA-N sodium;diethyl 2-oxobutanedioate Chemical compound [Na+].CCOC(=O)[CH-]C(=O)C(=O)OCC JPTKZRPOIUYFTM-UHFFFAOYSA-N 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- COOXFRRYJJKLSQ-UHFFFAOYSA-N 1-(8-benzyl-4,8,10-triazatetracyclo[8.6.1.05,17.011,16]heptadeca-1(17),11,13,15-tetraen-4-yl)ethanone Chemical compound CC(=O)N1CCC(C2=CC=CC=C2N2C3)=C2C1CCN3CC1=CC=CC=C1 COOXFRRYJJKLSQ-UHFFFAOYSA-N 0.000 description 1
- YZAWADGJXKCLTI-UHFFFAOYSA-N 2-(5-fluoro-1h-indol-3-yl)ethanamine;hydrochloride Chemical compound Cl.C1=C(F)C=C2C(CCN)=CNC2=C1 YZAWADGJXKCLTI-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
- WTTWWYCKYPPWGK-UHFFFAOYSA-N 3-benzyl-1,4,6,7,12,12b-hexahydropyrimido[6,1-a]$b-carbolin-2-one Chemical compound O=C1CC(C2=C(C3=CC=CC=C3N2)CC2)N2CN1CC1=CC=CC=C1 WTTWWYCKYPPWGK-UHFFFAOYSA-N 0.000 description 1
- XLVWCTGHQNVTCK-UHFFFAOYSA-N 3-methyl-6,7,12,12b-tetrahydro-1h-pyrimido[6,1-a]$b-carboline-2,4-quinone Chemical compound N1C2=CC=CC=C2C2=C1C1CC(=O)N(C)C(=O)N1CC2 XLVWCTGHQNVTCK-UHFFFAOYSA-N 0.000 description 1
- GFAWJACTIWSKCP-UHFFFAOYSA-N 4-benzyl-4,8,10-triazatetracyclo[8.6.1.05,17.011,16]heptadeca-1(17),11,13,15-tetraene Chemical compound C1CC(C2=CC=CC=C2N2CNCC3)=C2C3N1CC1=CC=CC=C1 GFAWJACTIWSKCP-UHFFFAOYSA-N 0.000 description 1
- 229940097276 5-methoxytryptamine Drugs 0.000 description 1
- BKRLQPBDKFPWNO-UHFFFAOYSA-N 8-fluoro-2,11b-dimethyl-3,5,6,11-tetrahydroimidazo[5,1-a]$b-carbolin-1-one Chemical compound C1=C(F)C=C2C(CCN3CN(C(C33C)=O)C)=C3NC2=C1 BKRLQPBDKFPWNO-UHFFFAOYSA-N 0.000 description 1
- VUMLPDFWUNKMTK-UHFFFAOYSA-N 9-fluoro-n,1-dimethyl-3,4-dihydro-2h-pyrido[3,4-b]indole-1-carboxamide Chemical compound FN1C2=CC=CC=C2C2=C1C(C(=O)NC)(C)NCC2 VUMLPDFWUNKMTK-UHFFFAOYSA-N 0.000 description 1
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
- 102100025597 Caspase-4 Human genes 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 241000283014 Dama Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 101100273284 Homo sapiens CASP4 gene Proteins 0.000 description 1
- 101001001462 Homo sapiens Importin subunit alpha-5 Proteins 0.000 description 1
- 102100036186 Importin subunit alpha-5 Human genes 0.000 description 1
- 229910017974 NH40H Inorganic materials 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 208000012886 Vertigo Diseases 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910000091 aluminium hydride Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- JNSGIVNNHKGGRU-JYRVWZFOSA-N diethoxyphosphinothioyl (2z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetate Chemical compound CCOP(=S)(OCC)OC(=O)C(=N/OC)\C1=CSC(N)=N1 JNSGIVNNHKGGRU-JYRVWZFOSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000001037 epileptic effect Effects 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- WDRTXIRUOLFXHQ-UHFFFAOYSA-N ethyl 2-(2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indol-1-yl)acetate;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C2=C1C(CC(=O)OCC)NCC2 WDRTXIRUOLFXHQ-UHFFFAOYSA-N 0.000 description 1
- ZEKBMQCANJAOGD-UHFFFAOYSA-N ethyl 2-(2-carbamoyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl)acetate Chemical compound N1C2=CC=CC=C2C2=C1C(CC(=O)OCC)N(C(N)=O)CC2 ZEKBMQCANJAOGD-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- KDFBGNBTTMPNIG-UHFFFAOYSA-N hydron;2-(1h-indol-3-yl)ethanamine;chloride Chemical compound Cl.C1=CC=C2C(CCN)=CNC2=C1 KDFBGNBTTMPNIG-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002513 isocyanates Chemical class 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
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- CWKLZLBVOJRSOM-UHFFFAOYSA-N methyl pyruvate Chemical compound COC(=O)C(C)=O CWKLZLBVOJRSOM-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000006213 oxygenation reaction Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 230000000506 psychotropic effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000000287 tissue oxygenation Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 208000009999 tuberous sclerosis Diseases 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 231100000889 vertigo Toxicity 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Steroid Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7822353A FR2432026A1 (fr) | 1978-07-28 | 1978-07-28 | Derives de fluorenes et de fluoranthenes et leur application en therapeutique |
| FR7822352 | 1978-07-28 | ||
| FR7822352A FR2432025A1 (fr) | 1978-07-28 | 1978-07-28 | Derives d'imidazo et de pyrimido-pyrido-indoles, leur preparation et leur application en therapeutique |
| FR7822353 | 1978-07-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1107729A true CA1107729A (en) | 1981-08-25 |
Family
ID=26220699
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA332,589A Expired CA1107729A (en) | 1978-07-28 | 1979-07-26 | Preparation of derivatives of fluorenes and fluoranthenes |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US4277476A (enExample) |
| EP (1) | EP0008249B1 (enExample) |
| AT (1) | ATE165T1 (enExample) |
| AU (1) | AU524307B2 (enExample) |
| CA (1) | CA1107729A (enExample) |
| DE (1) | DE2960689D1 (enExample) |
| DK (1) | DK316279A (enExample) |
| ES (1) | ES482889A1 (enExample) |
| FI (1) | FI65250C (enExample) |
| GR (1) | GR75070B (enExample) |
| NO (1) | NO792476L (enExample) |
| NZ (1) | NZ191141A (enExample) |
| PT (1) | PT69988A (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2455044A1 (fr) * | 1979-04-26 | 1980-11-21 | Synthelabo | Pyrido-indoles et leur application en therapeutique |
| US4367230A (en) * | 1980-01-04 | 1983-01-04 | Tanabe Seiyaku Co., Ltd. | Novel triazafluoranthene compound and processes for preparing the same |
| US4428880A (en) | 1981-05-04 | 1984-01-31 | S.A. Omnichem | Azepino[4,5-d]indole derivatives and preparation thereof |
| FR2594070B1 (fr) * | 1985-12-19 | 1991-06-14 | Braas & Co Gmbh | Materiau composite deformable pour le recouvrement dans l'industrie du batiment |
| EP1554572B1 (en) | 2001-07-25 | 2009-10-14 | Raptor Pharmaceutical Inc. | Compositions and methods for modulating blood-brain barrier transport |
| PL1737461T3 (pl) | 2004-03-15 | 2013-05-31 | Ptc Therapeutics Inc | Pochodne karbolinowe użyteczne w hamowaniu angiogenezy |
| US8076353B2 (en) | 2004-03-15 | 2011-12-13 | Ptc Therapeutics, Inc. | Inhibition of VEGF translation |
| US7767689B2 (en) | 2004-03-15 | 2010-08-03 | Ptc Therapeutics, Inc. | Carboline derivatives useful in the treatment of cancer |
| US8076352B2 (en) | 2004-03-15 | 2011-12-13 | Ptc Therapeutics, Inc. | Administration of carboline derivatives useful in the treatment of cancer and other diseases |
| DK1889198T3 (da) | 2005-04-28 | 2015-02-09 | Proteus Digital Health Inc | Farma-informatiksystem |
| KR20090071598A (ko) | 2006-09-18 | 2009-07-01 | 랩터 파마슈티컬 인코포레이티드 | 수용체 결합 단백질(ｒａｐ)-접합체 투여에 의한 간 질환의 치료 |
| WO2010095940A2 (en) | 2009-02-20 | 2010-08-26 | To-Bbb Holding B.V. | Glutathione-based drug delivery system |
| TWI556839B (zh) | 2009-05-06 | 2016-11-11 | 研究室護膚股份有限公司 | 包含活性劑－磷酸鈣粒子複合物之皮膚遞送組成物及其使用方法 |
| US20120077778A1 (en) | 2010-09-29 | 2012-03-29 | Andrea Bourdelais | Ladder-Frame Polyether Conjugates |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2556574A (en) * | 1949-06-24 | 1951-06-12 | Allen & Hanburys Ltd | Indolopteridines and process for preparing same |
| US3108108A (en) * | 1959-09-25 | 1963-10-22 | Bayer Ag | Aza analogues of polynuclear o-quinones |
| US3122544A (en) * | 1962-11-13 | 1964-02-25 | American Home Prod | 4-amino-2-aryl-6h-indeno(2, 3-g)-pteridin-6-ones |
| US3470181A (en) * | 1967-10-23 | 1969-09-30 | American Home Prod | Fused 2-pyrimidinepropionic acid compounds,related compounds,and the process for their preparation |
| US3631046A (en) * | 1969-05-28 | 1971-12-28 | Sandoz Ag | Tetracyclic quinazolin-ones |
| BE759337A (fr) * | 1969-11-24 | 1971-05-24 | Lilly Co Eli | Benzimidazol (2,1-b)-quinazolin (6h) ones qui sont des immuno-depresseurs, et nouvelles benzimidazo (2,1-b) quinazolin-12-(6h) ones |
| US3963720A (en) * | 1972-10-27 | 1976-06-15 | Sandoz, Inc. | Tetracyclic imidazo [2,1-b] quinazolinone derivatives |
| CH601299A5 (en) * | 1973-11-07 | 1978-07-14 | Vni Khim Farmatsevtichesky I I | Pyrazino(1,2,3-ab)beta carbolines and homologues |
-
1979
- 1979-07-05 AT AT79400459T patent/ATE165T1/de not_active IP Right Cessation
- 1979-07-05 DE DE7979400459T patent/DE2960689D1/de not_active Expired
- 1979-07-05 EP EP79400459A patent/EP0008249B1/fr not_active Expired
- 1979-07-26 AU AU49278/79A patent/AU524307B2/en not_active Ceased
- 1979-07-26 CA CA332,589A patent/CA1107729A/en not_active Expired
- 1979-07-26 DK DK316279A patent/DK316279A/da not_active Application Discontinuation
- 1979-07-26 PT PT69988A patent/PT69988A/pt unknown
- 1979-07-26 US US06/060,857 patent/US4277476A/en not_active Expired - Lifetime
- 1979-07-26 NO NO792476A patent/NO792476L/no unknown
- 1979-07-27 NZ NZ191141A patent/NZ191141A/xx unknown
- 1979-07-27 ES ES482889A patent/ES482889A1/es not_active Expired
- 1979-07-27 FI FI792366A patent/FI65250C/fi not_active IP Right Cessation
-
1981
- 1981-01-05 GR GR59709A patent/GR75070B/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP0008249B1 (fr) | 1981-08-26 |
| FI792366A7 (fi) | 1980-01-29 |
| US4277476A (en) | 1981-07-07 |
| AU4927879A (en) | 1980-01-31 |
| ATE165T1 (de) | 1981-09-15 |
| DE2960689D1 (en) | 1981-11-19 |
| PT69988A (fr) | 1979-08-01 |
| EP0008249A2 (fr) | 1980-02-20 |
| FI65250C (fi) | 1984-04-10 |
| GR75070B (enExample) | 1984-07-13 |
| FI65250B (fi) | 1983-12-30 |
| ES482889A1 (es) | 1980-04-16 |
| NZ191141A (en) | 1983-02-15 |
| EP0008249A3 (en) | 1980-05-14 |
| NO792476L (no) | 1980-01-29 |
| DK316279A (da) | 1980-01-29 |
| AU524307B2 (en) | 1982-09-09 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |