AU680583B2 - N-substituted azabicycloalkane derivatives as neuroleptika ASF - Google Patents
N-substituted azabicycloalkane derivatives as neuroleptika ASFInfo
- Publication number
- AU680583B2 AU680583B2 AU12403/95A AU1240395A AU680583B2 AU 680583 B2 AU680583 B2 AU 680583B2 AU 12403/95 A AU12403/95 A AU 12403/95A AU 1240395 A AU1240395 A AU 1240395A AU 680583 B2 AU680583 B2 AU 680583B2
- Authority
- AU
- Australia
- Prior art keywords
- cis
- document
- fluorophenyl
- azabicyclo
- mmol
- 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.)
- Ceased
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 21
- -1 C 1 -C 4 -alkoxy Chemical group 0.000 claims description 35
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 11
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 7
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 3
- 229960003638 dopamine Drugs 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 239000000935 antidepressant agent Substances 0.000 claims description 2
- 229940005513 antidepressants Drugs 0.000 claims description 2
- 239000003693 atypical antipsychotic agent Substances 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical group 0.000 claims description 2
- 230000000147 hypnotic effect Effects 0.000 claims description 2
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 239000003158 myorelaxant agent Substances 0.000 claims description 2
- 239000003176 neuroleptic agent Substances 0.000 claims description 2
- 230000000701 neuroleptic effect Effects 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 239000000932 sedative agent Substances 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- YMHUKZXNJIYMES-UHFFFAOYSA-N 4-azatricyclo[5.2.1.02,6]deca-1,3,6,8-tetraene Chemical class C1C2=C3CN=CC3=C1C=C2 YMHUKZXNJIYMES-UHFFFAOYSA-N 0.000 claims 1
- 241001420734 Fisera Species 0.000 claims 1
- 230000001430 anti-depressive effect Effects 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical group [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims 1
- 230000001624 sedative effect Effects 0.000 claims 1
- 230000000707 stereoselective effect Effects 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 4
- 201000010099 disease Diseases 0.000 abstract description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
- 239000000203 mixture Substances 0.000 description 46
- 238000003756 stirring Methods 0.000 description 40
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 29
- 238000001816 cooling Methods 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
- 238000004440 column chromatography Methods 0.000 description 22
- 238000001035 drying Methods 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000012074 organic phase Substances 0.000 description 21
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 239000003480 eluent Substances 0.000 description 18
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- 239000012043 crude product Substances 0.000 description 16
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- 239000012280 lithium aluminium hydride Substances 0.000 description 11
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 150000004679 hydroxides Chemical class 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 239000005457 ice water Substances 0.000 description 7
- RMHJJUOPOWPRBP-UHFFFAOYSA-N naphthalene-1-carboxamide Chemical compound C1=CC=C2C(C(=O)N)=CC=CC2=C1 RMHJJUOPOWPRBP-UHFFFAOYSA-N 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- CIGBERQUNYDMHH-UHFFFAOYSA-N 1H-indene-3-carboxamide Chemical compound C1=CC=C2C(C(=O)N)=CCC2=C1 CIGBERQUNYDMHH-UHFFFAOYSA-N 0.000 description 6
- LDCYZAJDBXYCGN-VIFPVBQESA-N 5-hydroxy-L-tryptophan Chemical compound C1=C(O)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-VIFPVBQESA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 235000011114 ammonium hydroxide Nutrition 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 6
- 229960001252 methamphetamine Drugs 0.000 description 6
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- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
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- 239000003054 catalyst Substances 0.000 description 5
- GJYXGIIWJFZCLN-UHFFFAOYSA-N octane-2,4-dione Chemical compound CCCCC(=O)CC(C)=O GJYXGIIWJFZCLN-UHFFFAOYSA-N 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
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- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
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- PMYYBYUVSOGKKD-UHFFFAOYSA-N 5-phenyl-3,4,4a,5,6,7-hexahydro-2h-cyclopenta[c]pyridine Chemical compound C1CC2=CNCCC2C1C1=CC=CC=C1 PMYYBYUVSOGKKD-UHFFFAOYSA-N 0.000 description 1
- 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
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 241000196224 Codium Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- 102000020897 Formins Human genes 0.000 description 1
- 108091022623 Formins Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- KIMWOULVHFLJIU-UHFFFAOYSA-N N-Methylanthranilamide Chemical compound CNC(=O)C1=CC=CC=C1N KIMWOULVHFLJIU-UHFFFAOYSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 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
- 206010044565 Tremor Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 229940054053 antipsychotics butyrophenone derivative Drugs 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 150000003936 benzamides Chemical class 0.000 description 1
- RJTJVVYSTUQWNI-UHFFFAOYSA-N beta-ethyl naphthalene Natural products C1=CC=CC2=CC(CC)=CC=C21 RJTJVVYSTUQWNI-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- FFSAXUULYPJSKH-UHFFFAOYSA-N butyrophenone Chemical class CCCC(=O)C1=CC=CC=C1 FFSAXUULYPJSKH-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000001966 cerebroprotective effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000002493 climbing effect Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000021824 exploration behavior Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 210000004744 fore-foot Anatomy 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 229940035363 muscle relaxants Drugs 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- FYQJUYCGPLFWQR-UHFFFAOYSA-N n-(2-chloroethyl)benzamide Chemical compound ClCCNC(=O)C1=CC=CC=C1 FYQJUYCGPLFWQR-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000013223 sprague-dawley female rat Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000010414 supernatant solution Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/24—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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D497/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms
- C07D497/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D497/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
- Ink Jet (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4341403 | 1993-12-04 | ||
| DE4341403A DE4341403A1 (de) | 1993-12-04 | 1993-12-04 | N-substituierte 3-Azabicycloalkan-Derivate, ihre Herstellung und Verwendung |
| PCT/EP1994/003913 WO1995015327A1 (en) | 1993-12-04 | 1994-11-26 | N-substituted azabicycloalkane derivatives as neuroleptika asf |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU1240395A AU1240395A (en) | 1995-06-19 |
| AU680583B2 true AU680583B2 (en) | 1997-07-31 |
Family
ID=6504205
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU12403/95A Ceased AU680583B2 (en) | 1993-12-04 | 1994-11-26 | N-substituted azabicycloalkane derivatives as neuroleptika ASF |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US5703091A (enExample) |
| EP (1) | EP0731802B1 (enExample) |
| JP (1) | JP3935201B2 (enExample) |
| AT (1) | ATE194620T1 (enExample) |
| AU (1) | AU680583B2 (enExample) |
| BR (1) | BR9408246A (enExample) |
| DE (2) | DE4341403A1 (enExample) |
| ES (1) | ES2148476T3 (enExample) |
| FI (1) | FI113644B (enExample) |
| IL (1) | IL111861A (enExample) |
| NO (1) | NO306346B1 (enExample) |
| TW (1) | TW285667B (enExample) |
| WO (1) | WO1995015327A1 (enExample) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19848521A1 (de) * | 1998-10-21 | 2000-04-27 | Basf Ag | Verfahren zur Herstellung von (+)-exo-6-Phenyl-3-azabicyclo-[3.2.0]heptanen |
| DE19854147A1 (de) * | 1998-11-24 | 2000-05-25 | Basf Ag | Verwendung von N-substituierten Azabicycloalkan-Derivaten zur Verwendung bei der Bekämpfung der Cocainsucht |
| TWI244481B (en) | 1998-12-23 | 2005-12-01 | Pfizer | 3-azabicyclo[3.1.0]hexane derivatives useful in therapy |
| GB9912411D0 (en) | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
| GB9912413D0 (en) | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
| GB9912416D0 (en) | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
| GB9912410D0 (en) | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
| GB9912415D0 (en) | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
| GB9912417D0 (en) | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
| US6784200B2 (en) * | 2000-10-13 | 2004-08-31 | Bristol-Myers Squibb Pharma Company | Bicyclic and tricyclic amines as modulators of chemokine receptor activity |
| US6586446B1 (en) | 1999-10-15 | 2003-07-01 | Bristol-Myers Squibb Company | Bicyclic and tricyclic amines as modulators of chemokine receptor activity |
| GB0015562D0 (en) * | 2000-06-23 | 2000-08-16 | Pfizer Ltd | Heterocycles |
| SE0100326D0 (sv) | 2001-02-02 | 2001-02-02 | Astrazeneca Ab | New compounds |
| CA2440803A1 (en) * | 2001-03-07 | 2002-09-12 | Pfizer Products Inc. | Modulators of chemokine receptor activity |
| MXPA05001726A (es) * | 2002-08-14 | 2005-05-27 | Abbott Lab | Compuestos azabiciclicos son agentes activos del sistema nervioso central. |
| EP1534675B1 (en) * | 2002-08-23 | 2009-02-25 | Ranbaxy Laboratories, Ltd. | Fluoro and sulphonylamino containing 3,6-disubstituted azabicyclo¬3.1.0 hexane derivatives as muscarinic receptor antagonists |
| EP1572648B1 (en) * | 2002-12-10 | 2008-07-09 | Ranbaxy Laboratories, Ltd. | 3,6-disubstituted azabicyclo (3.1.0)-hexane derivatives as muscarinic receptor antagonists |
| FR2866647B1 (fr) * | 2004-02-20 | 2006-10-27 | Servier Lab | Nouveaux derives azabicycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| BRPI0511982A (pt) | 2004-06-09 | 2008-01-22 | Hoffmann La Roche | compostos antiviróticos heterocìclicos |
| GB0507602D0 (en) | 2005-04-14 | 2005-05-18 | Glaxo Group Ltd | Compounds |
| US7665658B2 (en) | 2005-06-07 | 2010-02-23 | First Data Corporation | Dynamic aggregation of payment transactions |
| EP1849772A1 (en) * | 2006-04-28 | 2007-10-31 | Laboratorios Del Dr. Esteve, S.A. | Bicyclic tetrahydropyrrole compounds |
| EP1849771A1 (en) * | 2006-04-28 | 2007-10-31 | Laboratorios Del Dr. Esteve, S.A. | Bicyclic tetrahydropyrrole compounds |
| US8299113B2 (en) | 2006-04-28 | 2012-10-30 | Laboratorios Del Dr. Esteve, S.A. | Bicyclic tetrahydropyrrole compounds |
| GB0625198D0 (en) | 2006-12-18 | 2007-01-24 | Glaxo Group Ltd | Chemical compounds |
| GB0809479D0 (en) * | 2008-05-23 | 2008-07-02 | Glaxo Group Ltd | Novel compounds |
| WO2011140425A1 (en) | 2010-05-06 | 2011-11-10 | Vertex Pharmaceuticals Incorporated | Heterocyclic chromene-spirocyclic piperidine amides as modulators of ion channels |
| WO2012042539A2 (en) * | 2010-09-28 | 2012-04-05 | Panacea Biotec Ltd | Novel bicyclic compounds |
| JP5951625B2 (ja) | 2010-11-24 | 2016-07-13 | ザ・トラスティーズ・オブ・コランビア・ユニバーシティー・イン・ザ・シティー・オブ・ニューヨークＴｈｅ Ｔｒｕｓｔｅｅｓ Ｏｆ Ｃｏｌｕｍｂｉａ Ｕｎｉｖｅｒｓｉｔｙ Ｉｎ Ｔｈｅ Ｃｉｔｙ Ｏｆ Ｎｅｗ Ｙｏｒｋ | 加齢性黄斑変性症およびシュタルガルト病の処置のための非レチノイドｒｂｐ４アンタゴニスト |
| BR112013019211A2 (pt) | 2011-02-02 | 2021-07-06 | Vertex Pharma | amidas de piperidina espirocíclicas de pirrolopirazina como moduladores de canais de íon |
| CA2827311A1 (en) | 2011-02-18 | 2012-08-23 | Vertex Pharmaceuticals Incorporated | Chroman-spirocyclic piperidine amides as modulators of ion channels |
| AU2012229187B2 (en) | 2011-03-14 | 2016-11-10 | Vertex Pharmaceuticals Incorporated | Morpholine-spirocyclic piperidine amides as modulators of ion channels |
| US9333202B2 (en) | 2012-05-01 | 2016-05-10 | The Trustees Of Columbia University In The City Of New York | Non-retinoid antagonists for treatment of age-related macular degeneration and stargardt disease |
| US9944644B2 (en) | 2013-03-14 | 2018-04-17 | The Trustees Of Columbia University In The City Of New York | Octahydropyrrolopyrroles their preparation and use |
| WO2014151959A1 (en) | 2013-03-14 | 2014-09-25 | The Trustees Of Columbia University In The City Of New York | N-alkyl-2-phenoxyethanamines, their preparation and use |
| DK2968304T3 (en) | 2013-03-14 | 2019-01-28 | Univ Columbia | 4-PHENYLPIPERIDINES, THEIR PREPARATION AND USE. |
| EP2968303B1 (en) | 2013-03-14 | 2018-07-04 | The Trustees of Columbia University in the City of New York | Octahydrocyclopentapyrroles, their preparation and use |
| WO2015048507A1 (en) | 2013-09-26 | 2015-04-02 | Mnemosyne Pharmaceuticals, Inc. | Selective octahydro-cyclopenta[c] pyrrole negative modulators of nr2b |
| CN111393434B (zh) | 2014-04-30 | 2022-11-04 | 哥伦比亚大学董事会 | 取代的4-苯基哌啶及其制备和用途 |
| JO3579B1 (ar) | 2014-09-26 | 2020-07-05 | Luc Therapeutics Inc | مُعدِلات تفاغرية سالبة لمستقبل nr2b من المركب n-ألكيل أريل-5-أوكسي أريل-ثامن هيدرو-خماسي الحلقة [c] بيرول |
| HK1250029A1 (zh) | 2015-08-05 | 2018-11-23 | Indivior Uk Limited | 具有双环结构的多巴胺d3受体拮抗剂 |
| EP3495363B1 (en) | 2016-07-28 | 2023-08-23 | Shionogi & Co., Ltd | Nitrogen-containing condensed ring compounds having dopamine d3 receptor antagonistic effect |
| AU2019211806A1 (en) | 2018-01-26 | 2020-07-30 | Shionogi & Co., Ltd. | Condensed cyclic compound having dopamine D3 receptor antagonism |
| KR20200136384A (ko) | 2018-02-05 | 2020-12-07 | 알케르메스, 인코포레이티드 | 통증 치료용 화합물 |
| SG11202104886YA (en) | 2018-11-14 | 2021-06-29 | Janssen Pharmaceutica Nv | Improved synthetic methods of making fused heterocyclic compounds as orexin receptor modulators |
| WO2020243415A2 (en) | 2019-05-31 | 2020-12-03 | Ikena Oncology, Inc. | Tead inhibitors and uses thereof |
| KR20220034739A (ko) | 2019-05-31 | 2022-03-18 | 이케나 온콜로지, 인코포레이티드 | Tead 억제제 및 이의 용도 |
| CN114957087A (zh) * | 2022-04-13 | 2022-08-30 | 湖南复瑞生物医药技术有限责任公司 | 一种帕罗韦德中间体制备方法 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1289845B (de) * | 1958-04-22 | 1969-02-27 | Janssen Pharmaceutica Nv | 4-(4'-Hydroxy-4'-phenylpiperidino)-butyrophenone, deren Saeureadditionssalze sowie Verfahren zu deren Herstellung |
| WO1992018480A1 (de) * | 1991-04-16 | 1992-10-29 | Basf Aktiengesellschaft | 1,3,4-trisubstituierte piperidin-derivate, ihre herstellung und verwendung |
| US5216018A (en) * | 1992-02-14 | 1993-06-01 | Du Pont Merck Pharmaceutical Company | Hydroisoindolines and hydroisoquinolines as psychotropic |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NO154582C (no) * | 1978-10-20 | 1986-11-05 | Ferrosan Ab | Analogifremgangsmaate for fremstilling av terapeutisk aktive difenyl-dibutylpiperazinkarboksamider. |
| US4435419A (en) * | 1981-07-01 | 1984-03-06 | American Cyanamid Company | Method of treating depression using azabicyclohexanes |
| US4605655A (en) * | 1984-03-06 | 1986-08-12 | Bristol-Myers Company | Antipsychotic 1-fluorophenylbutyl-4-(2-pyrimidinyl)piperazine derivatives |
| EP0190472B1 (en) * | 1984-12-21 | 1989-07-12 | Duphar International Research B.V | New pharmaceutical compositions having anti-psychotic properties |
| US5055470A (en) * | 1989-06-01 | 1991-10-08 | Bristol-Myers Squibb Co. | Method of treatment of ischemia in brain |
| US4994460A (en) * | 1989-06-01 | 1991-02-19 | Bristol-Myers Squibb Co. | Agents for treatment of brain ischemia |
| US5532243A (en) * | 1992-02-14 | 1996-07-02 | The Dupont Merck Pharmaceutical Company | Antipsychotic nitrogen-containing bicyclic compounds |
| DE4219973A1 (de) * | 1992-06-19 | 1993-12-23 | Basf Ag | N-substituierte Azabicycloheptan-Derivate, ihre Herstellung und Verwendung |
| DE4243287A1 (de) * | 1992-06-19 | 1993-12-23 | Basf Ag | N-Substituierte Azabicycloheptan-Derivate, ihre Herstellung und Verwendung |
-
1993
- 1993-12-04 DE DE4341403A patent/DE4341403A1/de not_active Withdrawn
-
1994
- 1994-11-26 US US08/656,240 patent/US5703091A/en not_active Expired - Lifetime
- 1994-11-26 EP EP95903284A patent/EP0731802B1/en not_active Expired - Lifetime
- 1994-11-26 ES ES95903284T patent/ES2148476T3/es not_active Expired - Lifetime
- 1994-11-26 JP JP51538295A patent/JP3935201B2/ja not_active Expired - Fee Related
- 1994-11-26 AT AT95903284T patent/ATE194620T1/de active
- 1994-11-26 BR BR9408246A patent/BR9408246A/pt not_active Application Discontinuation
- 1994-11-26 DE DE69425273T patent/DE69425273T2/de not_active Expired - Lifetime
- 1994-11-26 WO PCT/EP1994/003913 patent/WO1995015327A1/en not_active Ceased
- 1994-11-26 AU AU12403/95A patent/AU680583B2/en not_active Ceased
- 1994-12-02 IL IL11186194A patent/IL111861A/xx not_active IP Right Cessation
- 1994-12-05 TW TW083111264A patent/TW285667B/zh active
-
1996
- 1996-06-03 FI FI962324A patent/FI113644B/fi not_active IP Right Cessation
- 1996-06-03 NO NO962286A patent/NO306346B1/no not_active IP Right Cessation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1289845B (de) * | 1958-04-22 | 1969-02-27 | Janssen Pharmaceutica Nv | 4-(4'-Hydroxy-4'-phenylpiperidino)-butyrophenone, deren Saeureadditionssalze sowie Verfahren zu deren Herstellung |
| WO1992018480A1 (de) * | 1991-04-16 | 1992-10-29 | Basf Aktiengesellschaft | 1,3,4-trisubstituierte piperidin-derivate, ihre herstellung und verwendung |
| US5216018A (en) * | 1992-02-14 | 1993-06-01 | Du Pont Merck Pharmaceutical Company | Hydroisoindolines and hydroisoquinolines as psychotropic |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0731802B1 (en) | 2000-07-12 |
| US5703091A (en) | 1997-12-30 |
| TW285667B (enExample) | 1996-09-11 |
| AU1240395A (en) | 1995-06-19 |
| JPH09506346A (ja) | 1997-06-24 |
| IL111861A0 (en) | 1995-03-15 |
| FI962324L (fi) | 1996-06-03 |
| BR9408246A (pt) | 1997-05-27 |
| FI113644B (fi) | 2004-05-31 |
| FI962324A0 (fi) | 1996-06-03 |
| DE4341403A1 (de) | 1995-06-08 |
| NO962286D0 (no) | 1996-06-03 |
| ATE194620T1 (de) | 2000-07-15 |
| DE69425273D1 (de) | 2000-08-17 |
| ES2148476T3 (es) | 2000-10-16 |
| DE69425273T2 (de) | 2001-01-18 |
| NO962286L (no) | 1996-06-03 |
| NO306346B1 (no) | 1999-10-25 |
| WO1995015327A1 (en) | 1995-06-08 |
| IL111861A (en) | 1999-08-17 |
| EP0731802A1 (en) | 1996-09-18 |
| JP3935201B2 (ja) | 2007-06-20 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PC | Assignment registered |
Owner name: ABBOTT GMBH AND CO. KG Free format text: FORMER OWNER WAS: BASF AKTIENGESELLSCHAFT |