NO300040B1 - N-(aryloksyalkyl)heteroaryl-8-azabicyklo(3.2.1.)oktaner, anvendelse av forbindelsene for fremstilling av et medikament og en farmasöytisk sammensetning - Google Patents
N-(aryloksyalkyl)heteroaryl-8-azabicyklo(3.2.1.)oktaner, anvendelse av forbindelsene for fremstilling av et medikament og en farmasöytisk sammensetning Download PDFInfo
- Publication number
- NO300040B1 NO300040B1 NO920438A NO920438A NO300040B1 NO 300040 B1 NO300040 B1 NO 300040B1 NO 920438 A NO920438 A NO 920438A NO 920438 A NO920438 A NO 920438A NO 300040 B1 NO300040 B1 NO 300040B1
- Authority
- NO
- Norway
- Prior art keywords
- azabicyclo
- mixture
- ethanone
- compound
- octan
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 76
- 229940079593 drug Drugs 0.000 title claims description 6
- 239000003814 drug Substances 0.000 title claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title description 18
- 125000005160 aryl oxy alkyl group Chemical group 0.000 title 1
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 239000002253 acid Substances 0.000 claims abstract description 10
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
- 150000002367 halogens Chemical group 0.000 claims abstract description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 230000000561 anti-psychotic effect Effects 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 5
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 239000000935 antidepressant agent Substances 0.000 claims description 4
- 229940005513 antidepressants Drugs 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 230000001430 anti-depressive effect Effects 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 229910052731 fluorine Chemical group 0.000 claims description 2
- 239000011737 fluorine Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- IWMCTNRCGBXFTN-UHFFFAOYSA-N 1-[4-[2-[3-(1,2-benzoxazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl]ethoxy]-3-methoxyphenyl]ethanone Chemical group COC1=CC(C(C)=O)=CC=C1OCCN1C2CCC1CC(C=1C3=CC=CC=C3ON=1)C2 IWMCTNRCGBXFTN-UHFFFAOYSA-N 0.000 claims 1
- MHDSPQALHVBVDZ-UHFFFAOYSA-N 1-[4-[4-[3-(2h-indazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl]butoxy]-3-methoxyphenyl]ethanone Chemical group COC1=CC(C(C)=O)=CC=C1OCCCCN1C2CCC1CC(C=1C3=CC=CC=C3NN=1)C2 MHDSPQALHVBVDZ-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 73
- -1 loweralkylamino Chemical group 0.000 abstract description 20
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 abstract description 12
- 229940076279 serotonin Drugs 0.000 abstract description 5
- 239000000164 antipsychotic agent Substances 0.000 abstract description 3
- 239000003112 inhibitor Substances 0.000 abstract description 3
- 230000003287 optical effect Effects 0.000 abstract description 2
- 150000002431 hydrogen Chemical group 0.000 abstract 3
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 2
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 69
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 51
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 48
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 46
- 239000000047 product Substances 0.000 description 44
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- 239000003921 oil Substances 0.000 description 40
- 238000010992 reflux Methods 0.000 description 40
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- 238000004458 analytical method Methods 0.000 description 27
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 25
- 239000002904 solvent Substances 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 229910000027 potassium carbonate Inorganic materials 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 19
- 238000004128 high performance liquid chromatography Methods 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 238000010828 elution Methods 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 15
- 229910052799 carbon Inorganic materials 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 13
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 12
- 239000012267 brine Substances 0.000 description 11
- PQSOLLURQXDZSZ-UHFFFAOYSA-N n,n-diethylethanamine;ethyl acetate;methanol Chemical compound OC.CCOC(C)=O.CCN(CC)CC PQSOLLURQXDZSZ-UHFFFAOYSA-N 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 239000000843 powder Substances 0.000 description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
- 239000001530 fumaric acid Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 238000003556 assay Methods 0.000 description 7
- 239000006260 foam Substances 0.000 description 7
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 6
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
- GIMIJKJIXKGENB-TYYBGVCCSA-N acetaldehyde (E)-but-2-enedioic acid Chemical compound CC=O.OC(=O)\C=C\C(O)=O GIMIJKJIXKGENB-TYYBGVCCSA-N 0.000 description 6
- 229960004046 apomorphine Drugs 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- QQXLDOJGLXJCSE-KNVOCYPGSA-N tropinone Chemical compound C1C(=O)C[C@H]2CC[C@@H]1N2C QQXLDOJGLXJCSE-KNVOCYPGSA-N 0.000 description 6
- YTKHVPNCKIMSCK-UHFFFAOYSA-N 1-[4-(2-chloroethoxy)-3-methoxyphenyl]ethanone Chemical compound COC1=CC(C(C)=O)=CC=C1OCCCl YTKHVPNCKIMSCK-UHFFFAOYSA-N 0.000 description 5
- GRLLEUJTVGLTQN-UHFFFAOYSA-N 1-[4-(4-bromobutoxy)-3-methoxyphenyl]ethanone Chemical compound COC1=CC(C(C)=O)=CC=C1OCCCCBr GRLLEUJTVGLTQN-UHFFFAOYSA-N 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- PQLFROTZSIMBKR-UHFFFAOYSA-N ethenyl carbonochloridate Chemical compound ClC(=O)OC=C PQLFROTZSIMBKR-UHFFFAOYSA-N 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- RBBVSSYQKVBALO-UHFFFAOYSA-N 1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethanone Chemical compound COC1=CC(C(C)=O)=CC=C1OCCCCl RBBVSSYQKVBALO-UHFFFAOYSA-N 0.000 description 4
- BMXNJHYCBZOMHT-UHFFFAOYSA-N 3-(8-azabicyclo[3.2.1]octan-3-yl)-1,2-benzothiazole Chemical compound C1=CC=C2C(C3CC4CCC(C3)N4)=NSC2=C1 BMXNJHYCBZOMHT-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 230000009194 climbing Effects 0.000 description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 4
- CJTOXKYNDFVEMF-UHFFFAOYSA-N (2-fluorophenyl)-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)methanone Chemical compound CN1C(C2)CCC1CC2C(=O)C1=CC=CC=C1F CJTOXKYNDFVEMF-UHFFFAOYSA-N 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 3
- IEULZFLCNZRGPX-UHFFFAOYSA-N 3-(8-azabicyclo[3.2.1]octan-3-yl)-1,2-benzoxazole Chemical compound C1=CC=C2C(C3CC4CCC(C3)N4)=NOC2=C1 IEULZFLCNZRGPX-UHFFFAOYSA-N 0.000 description 3
- YDWKEJUASAXXSI-UHFFFAOYSA-N 3-(8-azabicyclo[3.2.1]octan-3-yl)-2h-indazole Chemical compound C1=CC=C2C(C3CC4CCC(C3)N4)=NNC2=C1 YDWKEJUASAXXSI-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
- 239000005695 Ammonium acetate Substances 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- QQXLDOJGLXJCSE-UHFFFAOYSA-N N-methylnortropinone Natural products C1C(=O)CC2CCC1N2C QQXLDOJGLXJCSE-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 235000019257 ammonium acetate Nutrition 0.000 description 3
- 229940043376 ammonium acetate Drugs 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- WGXZDYPGLJYBJW-UHFFFAOYSA-N chloroform;propan-2-ol Chemical compound CC(C)O.ClC(Cl)Cl WGXZDYPGLJYBJW-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 3
- UDTCCMWTWUBDCL-UHFFFAOYSA-N (2,4-difluorophenyl)-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)methanone Chemical compound CN1C(C2)CCC1CC2C(=O)C1=CC=C(F)C=C1F UDTCCMWTWUBDCL-UHFFFAOYSA-N 0.000 description 2
- FMCAFXHLMUOIGG-JTJHWIPRSA-N (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-JTJHWIPRSA-N 0.000 description 2
- FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 2
- GSGCGPNPIGTTBH-UHFFFAOYSA-N 1-[4-[2-[3-(6-fluoro-1,2-benzoxazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl]propoxy]-2-methoxyphenyl]ethanone Chemical compound C1=C(C(C)=O)C(OC)=CC(OCC(C)N2C3CCC2CC(C3)C=2C3=CC=C(F)C=C3ON=2)=C1 GSGCGPNPIGTTBH-UHFFFAOYSA-N 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 2
- ITQSDIUULPOEQY-UHFFFAOYSA-N 3-(8-azabicyclo[3.2.1]octan-3-yl)-6-fluoro-2h-indazole Chemical compound C1C(N2)CCC2CC1C1=NNC2=CC(F)=CC=C21 ITQSDIUULPOEQY-UHFFFAOYSA-N 0.000 description 2
- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 2
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical class CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 150000002473 indoazoles Chemical class 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- AGJSNMGHAVDLRQ-IWFBPKFRSA-N methyl (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-IWFBPKFRSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000000862 serotonergic effect Effects 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- WGWFSHZGBLCTMI-WLHGVMLRSA-N (e)-but-2-enedioic acid;1-[4-[4-[3-(2h-indazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl]butoxy]-3-methoxyphenyl]ethanone Chemical compound OC(=O)\C=C\C(O)=O.COC1=CC(C(C)=O)=CC=C1OCCCCN1C2CCC1CC(C=1C3=CC=CC=C3NN=1)C2 WGWFSHZGBLCTMI-WLHGVMLRSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical class C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 description 1
- BSCXOIPRVSWFFT-UHFFFAOYSA-N 1-(dimethoxymethyl)-2,4-difluorobenzene Chemical compound COC(OC)C1=CC=C(F)C=C1F BSCXOIPRVSWFFT-UHFFFAOYSA-N 0.000 description 1
- GHRDHBIBFZLUJM-UHFFFAOYSA-N 1-(dimethoxymethyl)-2-fluorobenzene Chemical compound COC(OC)C1=CC=CC=C1F GHRDHBIBFZLUJM-UHFFFAOYSA-N 0.000 description 1
- SGUGPTQZOYTZDH-UHFFFAOYSA-N 1-[3-bromo-4-[2-[3-(6-fluoro-1,2-benzoxazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl]propoxy]phenyl]ethanone Chemical compound C1C(C=2C3=CC=C(F)C=C3ON=2)CC2CCC1N2C(C)COC1=CC=C(C(C)=O)C=C1Br SGUGPTQZOYTZDH-UHFFFAOYSA-N 0.000 description 1
- XWSNFZLPHWJTNK-WLHGVMLRSA-N 1-[4-[2-[3-(1,2-benzoxazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl]ethoxy]-3-methoxyphenyl]ethanone;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.COC1=CC(C(C)=O)=CC=C1OCCN1C2CCC1CC(C=1C3=CC=CC=C3ON=1)C2 XWSNFZLPHWJTNK-WLHGVMLRSA-N 0.000 description 1
- UDOABSHIKVZEOS-UHFFFAOYSA-N 1-[4-[2-[3-(2h-indazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl]ethoxy]-3-methoxyphenyl]ethanone Chemical compound COC1=CC(C(C)=O)=CC=C1OCCN1C2CCC1CC(C=1C3=CC=CC=C3NN=1)C2 UDOABSHIKVZEOS-UHFFFAOYSA-N 0.000 description 1
- FBTHBTVRWKNIMF-UHFFFAOYSA-N 1-[4-[2-[3-(6-chloro-1,2-benzoxazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl]propoxy]-3-methoxyphenyl]ethanone Chemical compound COC1=CC(C(C)=O)=CC=C1OCC(C)N1C2CCC1CC(C=1C3=CC=C(Cl)C=C3ON=1)C2 FBTHBTVRWKNIMF-UHFFFAOYSA-N 0.000 description 1
- HYWWNXFMJRXKSL-UHFFFAOYSA-N 1-[4-[2-[3-(6-fluoro-1,2-benzoxazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl]propoxy]-3-methylsulfanylphenyl]ethanone Chemical compound CSC1=CC(C(C)=O)=CC=C1OCC(C)N1C2CCC1CC(C=1C3=CC=C(F)C=C3ON=1)C2 HYWWNXFMJRXKSL-UHFFFAOYSA-N 0.000 description 1
- BRDCNEWRZLSHLA-UHFFFAOYSA-N 1-[4-[2-[3-(6-fluoro-1,2-benzoxazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl]propoxy]phenyl]ethanone Chemical compound C1C(C=2C3=CC=C(F)C=C3ON=2)CC2CCC1N2C(C)COC1=CC=C(C(C)=O)C=C1 BRDCNEWRZLSHLA-UHFFFAOYSA-N 0.000 description 1
- KIZDHLHLAJMQHH-WLHGVMLRSA-N 1-[4-[3-[3-(1,2-benzoxazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl]propoxy]-3-methoxyphenyl]ethanone;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.COC1=CC(C(C)=O)=CC=C1OCCCN1C2CCC1CC(C=1C3=CC=CC=C3ON=1)C2 KIZDHLHLAJMQHH-WLHGVMLRSA-N 0.000 description 1
- CTWLZTDJZYPJEU-UHFFFAOYSA-N 1-[4-[3-[3-(2h-indazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl]propoxy]-3-methoxyphenyl]ethanone Chemical compound COC1=CC(C(C)=O)=CC=C1OCCCN1C2CCC1CC(C=1C3=CC=CC=C3NN=1)C2 CTWLZTDJZYPJEU-UHFFFAOYSA-N 0.000 description 1
- BRBQCDXSUROAKK-UHFFFAOYSA-N 1-[4-[3-[3-(6-fluoro-1,2-benzoxazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl]propoxy]-3-methoxyphenyl]ethanone;hydrochloride Chemical compound Cl.COC1=CC(C(C)=O)=CC=C1OCCCN1C2CCC1CC(C=1C3=CC=C(F)C=C3ON=1)C2 BRBQCDXSUROAKK-UHFFFAOYSA-N 0.000 description 1
- CXLJEJVDMYKYSR-UHFFFAOYSA-N 1-[4-[3-[3-(6-fluoro-2h-indazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl]propoxy]-3-methoxyphenyl]ethanone Chemical compound COC1=CC(C(C)=O)=CC=C1OCCCN1C2CCC1CC(C=1C3=CC=C(F)C=C3NN=1)C2 CXLJEJVDMYKYSR-UHFFFAOYSA-N 0.000 description 1
- UEUKGNZEBYYSTD-UHFFFAOYSA-N 1-[4-[4-[3-(1,2-benzothiazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl]butoxy]-3-methoxyphenyl]ethanone;hydrochloride Chemical compound Cl.COC1=CC(C(C)=O)=CC=C1OCCCCN1C2CCC1CC(C=1C3=CC=CC=C3SN=1)C2 UEUKGNZEBYYSTD-UHFFFAOYSA-N 0.000 description 1
- VALXPSGQZKFETL-UHFFFAOYSA-N 1-[4-[4-[3-(1,2-benzoxazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl]butoxy]-3-methoxyphenyl]ethanone;hydrochloride Chemical compound Cl.COC1=CC(C(C)=O)=CC=C1OCCCCN1C2CCC1CC(C=1C3=CC=CC=C3ON=1)C2 VALXPSGQZKFETL-UHFFFAOYSA-N 0.000 description 1
- VTFPYTZFDOUOJU-UHFFFAOYSA-N 1-[4-[4-[3-(6-fluoro-2h-indazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl]butoxy]-3-methoxyphenyl]ethanone Chemical compound COC1=CC(C(C)=O)=CC=C1OCCCCN1C2CCC1CC(C=1C3=CC=C(F)C=C3NN=1)C2 VTFPYTZFDOUOJU-UHFFFAOYSA-N 0.000 description 1
- GOXLTJHFDOOIGV-UHFFFAOYSA-N 1-[diethoxyphosphoryl(methoxy)methyl]-2,4-difluorobenzene Chemical compound CCOP(=O)(OCC)C(OC)C1=CC=C(F)C=C1F GOXLTJHFDOOIGV-UHFFFAOYSA-N 0.000 description 1
- LIZHZAYTRQGJOW-UHFFFAOYSA-N 1-[diethoxyphosphoryl(methoxy)methyl]-2-fluorobenzene Chemical compound CCOP(=O)(OCC)C(OC)C1=CC=CC=C1F LIZHZAYTRQGJOW-UHFFFAOYSA-N 0.000 description 1
- JPKTXPPKLGWWTQ-UHFFFAOYSA-N 3-(8-azabicyclo[3.2.1]octan-3-yl)-1,2-benzoxazole;hydrochloride Chemical compound Cl.C1=CC=C2C(C3CC4CCC(C3)N4)=NOC2=C1 JPKTXPPKLGWWTQ-UHFFFAOYSA-N 0.000 description 1
- DRHUSFNYWPYFMR-UHFFFAOYSA-N 3-(8-azabicyclo[3.2.1]octan-3-yl)-6-fluoro-1,2-benzoxazole Chemical compound C1C(N2)CCC2CC1C1=NOC2=CC(F)=CC=C21 DRHUSFNYWPYFMR-UHFFFAOYSA-N 0.000 description 1
- BUOLPEFFRQDNCZ-UHFFFAOYSA-N 3-(8-azabicyclo[3.2.1]octan-3-yl)-6-fluoro-1,2-benzoxazole;hydrochloride Chemical compound Cl.C1C(N2)CCC2CC1C1=NOC2=CC(F)=CC=C21 BUOLPEFFRQDNCZ-UHFFFAOYSA-N 0.000 description 1
- WNCGJHRCFWDXBQ-UHFFFAOYSA-N 3-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-1,2-benzothiazole Chemical compound C1=CC=C2C(C3CC4CCC(C3)N4C)=NSC2=C1 WNCGJHRCFWDXBQ-UHFFFAOYSA-N 0.000 description 1
- VFHGZDMDFICPPU-UHFFFAOYSA-N 3-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-1,2-benzothiazole;hydrochloride Chemical compound Cl.C1=CC=C2C(C3CC4CCC(C3)N4C)=NSC2=C1 VFHGZDMDFICPPU-UHFFFAOYSA-N 0.000 description 1
- PWLAVUNCVMVRBU-UHFFFAOYSA-N 3-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-1,2-benzoxazole Chemical compound C1=CC=C2C(C3CC4CCC(C3)N4C)=NOC2=C1 PWLAVUNCVMVRBU-UHFFFAOYSA-N 0.000 description 1
- VVEJCYNZIQKTDR-UHFFFAOYSA-N 3-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-1,2-benzoxazole;hydrate;hydrochloride Chemical compound O.Cl.C1=CC=C2C(C3CC4CCC(C3)N4C)=NOC2=C1 VVEJCYNZIQKTDR-UHFFFAOYSA-N 0.000 description 1
- XXWMRFTXIWEDPG-UHFFFAOYSA-N 3-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-2h-indazole Chemical compound C1=CC=C2C(C3CC4CCC(C3)N4C)=NNC2=C1 XXWMRFTXIWEDPG-UHFFFAOYSA-N 0.000 description 1
- SFSKUQOTKMJEFB-UHFFFAOYSA-N 3-(8-methyl-8-azabicyclo[3.2.1]octan-5-yl)-2h-indazole Chemical compound C1=CC=C2C(C34CCC(CCC4)N3C)=NNC2=C1 SFSKUQOTKMJEFB-UHFFFAOYSA-N 0.000 description 1
- WUKQSQFQMNKTAE-UHFFFAOYSA-N 6-fluoro-3-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-1,2-benzoxazole Chemical compound FC1=CC=C2C(C3CC4CCC(C3)N4C)=NOC2=C1 WUKQSQFQMNKTAE-UHFFFAOYSA-N 0.000 description 1
- AFABIKRUOVDMBH-UHFFFAOYSA-N 6-fluoro-3-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-1,2-benzoxazole;hydrochloride Chemical compound Cl.FC1=CC=C2C(C3CC4CCC(C3)N4C)=NOC2=C1 AFABIKRUOVDMBH-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- NIFBNIANYCOETB-UHFFFAOYSA-N 8-methyl-n-(2-phenylethyl)-8-azabicyclo[3.2.1]octan-3-amine Chemical compound CN1C(C2)CCC1CC2NCCC1=CC=CC=C1 NIFBNIANYCOETB-UHFFFAOYSA-N 0.000 description 1
- LPMXVESGRSUGHW-UHFFFAOYSA-N Acolongiflorosid K Natural products OC1C(O)C(O)C(C)OC1OC1CC2(O)CCC3C4(O)CCC(C=5COC(=O)C=5)C4(C)CC(O)C3C2(CO)C(O)C1 LPMXVESGRSUGHW-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- HUQWKRVOWXSRFZ-UHFFFAOYSA-N ClCCCOC1=C(C=C(C=C1)CC(=O)C1=CC=CC=C1)OC Chemical compound ClCCCOC1=C(C=C(C=C1)CC(=O)C1=CC=CC=C1)OC HUQWKRVOWXSRFZ-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241001492222 Epicoccum Species 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 229910017976 MgO 4 Inorganic materials 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- LPMXVESGRSUGHW-GHYGWZAOSA-N Ouabain Natural products O([C@@H]1[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O1)[C@H]1C[C@@H](O)[C@@]2(CO)[C@@](O)(C1)CC[C@H]1[C@]3(O)[C@@](C)([C@H](C4=CC(=O)OC4)CC3)C[C@@H](O)[C@H]21 LPMXVESGRSUGHW-GHYGWZAOSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 244000166550 Strophanthus gratus Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- 229920001615 Tragacanth Polymers 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 150000008316 benzisoxazoles Chemical class 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000012649 demethylating agent Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- YKWNUSJLICDQEO-UHFFFAOYSA-N ethoxyethane;propan-2-ol Chemical compound CC(C)O.CCOCC YKWNUSJLICDQEO-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- WTDFFADXONGQOM-UHFFFAOYSA-N formaldehyde;hydrochloride Chemical compound Cl.O=C WTDFFADXONGQOM-UHFFFAOYSA-N 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 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
- 239000011976 maleic acid Substances 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 229940087646 methanolamine Drugs 0.000 description 1
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 description 1
- AGJSNMGHAVDLRQ-HUUJSLGLSA-N methyl (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-HUUJSLGLSA-N 0.000 description 1
- KWKAKUADMBZCLK-UHFFFAOYSA-N methyl heptene Natural products CCCCCCC=C KWKAKUADMBZCLK-UHFFFAOYSA-N 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- KCRVMZHBQUDJQK-UHFFFAOYSA-N n-[(2-fluorophenyl)-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)methylidene]hydroxylamine Chemical compound CN1C(C2)CCC1CC2C(=NO)C1=CC=CC=C1F KCRVMZHBQUDJQK-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- ZHVULPDNOFUIML-UHFFFAOYSA-N octane;hydrochloride Chemical compound Cl.CCCCCCCC ZHVULPDNOFUIML-UHFFFAOYSA-N 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- LPMXVESGRSUGHW-HBYQJFLCSA-N ouabain Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C[C@@]2(O)CC[C@H]3[C@@]4(O)CC[C@H](C=5COC(=O)C=5)[C@@]4(C)C[C@@H](O)[C@@H]3[C@@]2(CO)[C@H](O)C1 LPMXVESGRSUGHW-HBYQJFLCSA-N 0.000 description 1
- 229960003343 ouabain Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000013275 serotonin uptake Effects 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000003568 synaptosome Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical class C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- 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
- A61P25/24—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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US65014491A | 1991-02-04 | 1991-02-04 |
Publications (3)
Publication Number | Publication Date |
---|---|
NO920438D0 NO920438D0 (no) | 1992-02-03 |
NO920438L NO920438L (no) | 1992-08-05 |
NO300040B1 true NO300040B1 (no) | 1997-03-24 |
Family
ID=24607667
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO920438A NO300040B1 (no) | 1991-02-04 | 1992-02-03 | N-(aryloksyalkyl)heteroaryl-8-azabicyklo(3.2.1.)oktaner, anvendelse av forbindelsene for fremstilling av et medikament og en farmasöytisk sammensetning |
Country Status (21)
Country | Link |
---|---|
EP (1) | EP0498331B1 (es) |
JP (1) | JPH089613B2 (es) |
KR (1) | KR100222774B1 (es) |
AT (1) | ATE138377T1 (es) |
AU (1) | AU641842B2 (es) |
CA (1) | CA2060573C (es) |
CZ (1) | CZ284754B6 (es) |
DE (1) | DE69210849T2 (es) |
DK (1) | DK0498331T3 (es) |
ES (1) | ES2089255T3 (es) |
FI (1) | FI111367B (es) |
GR (1) | GR3020094T3 (es) |
HU (2) | HU217616B (es) |
IE (1) | IE74905B1 (es) |
IL (1) | IL100861A (es) |
MX (1) | MX9200471A (es) |
NO (1) | NO300040B1 (es) |
NZ (1) | NZ241481A (es) |
PL (1) | PL169092B1 (es) |
RU (1) | RU2075479C1 (es) |
ZA (1) | ZA92753B (es) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9510459D0 (en) | 1995-05-24 | 1995-07-19 | Zeneca Ltd | Bicyclic amines |
TR199800628T2 (xx) * | 1995-10-13 | 1998-07-21 | Neurosearch A/S | 8-Azabisiklo$3.2.1]okt-2-en t�revleri, bunlar�n haz�rlanmas� ve kullan�m�. |
ES2218676T3 (es) * | 1996-05-13 | 2004-11-16 | Syngenta Limited | Aminas biciclicas como insecticidas. |
GB9623944D0 (en) * | 1996-11-15 | 1997-01-08 | Zeneca Ltd | Bicyclic amine derivatives |
GB9624114D0 (en) * | 1996-11-20 | 1997-01-08 | Zeneca Ltd | Pesticidal bicyclic amine derivatives |
GB9624611D0 (en) * | 1996-11-26 | 1997-01-15 | Zeneca Ltd | Bicyclic amine compounds |
EP0944627B1 (en) | 1996-11-26 | 2004-02-18 | Syngenta Limited | 8-azabicyclo 3.2.1]octane-, 8-azabicyclo 3.2.1]oct-6-ene-, 9-azabicyclo 3.3.1]nonane-, 9-aza-3-oxabicyclo 3.3.1]nonane- and 9-aza-3-thiabicyclo 3.3.1]nonane derivatives, their preparation and their use as insecticides |
CZ298824B6 (cs) | 1997-05-30 | 2008-02-20 | Neurosearch A/S | Deriváty 8-azabicyklo[3.2.1]okt-2-enu, zpusob jejich prípravy a jejich použití |
US6251893B1 (en) * | 1998-06-15 | 2001-06-26 | Nps Allelix Corp. | Bicyclic piperidine and piperazine compounds having 5-HT6 receptor affinity |
AU1930901A (en) * | 1999-12-20 | 2001-07-03 | Eli Lilly And Company | Azabicyclo(3.2.1)octane derivatives |
AU2049501A (en) * | 1999-12-20 | 2001-07-03 | Eli Lilly And Company | Benzofuran derivatives |
WO2002066469A2 (en) * | 2001-02-16 | 2002-08-29 | Aventis Pharmaceuticals Inc. | Novel heterocyclic amide derivatives and their use as dopamine d3 receptor ligands |
US7247643B2 (en) * | 2003-02-12 | 2007-07-24 | Neurosearch A/S | 8-aza-bicyclo (3.2.1) octane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2548666A1 (fr) * | 1983-07-08 | 1985-01-11 | Delalande Sa | Nouveaux derives du nor-tropane et du granatane, leur procede de preparation et leur application en therapeutique |
DE3850742T2 (de) * | 1987-11-04 | 1994-10-27 | Beecham Group Plc | Neue 4-Oxobenzotriazine und 4-Oxochinazoline. |
-
1992
- 1992-01-31 FI FI920435A patent/FI111367B/fi active
- 1992-01-31 NZ NZ241481A patent/NZ241481A/en unknown
- 1992-02-01 KR KR1019920001588A patent/KR100222774B1/ko not_active IP Right Cessation
- 1992-02-03 IL IL10086192A patent/IL100861A/xx not_active IP Right Cessation
- 1992-02-03 ES ES92101706T patent/ES2089255T3/es not_active Expired - Lifetime
- 1992-02-03 IE IE920349A patent/IE74905B1/en not_active IP Right Cessation
- 1992-02-03 AT AT92101706T patent/ATE138377T1/de not_active IP Right Cessation
- 1992-02-03 CA CA002060573A patent/CA2060573C/en not_active Expired - Fee Related
- 1992-02-03 HU HU9203977A patent/HU217616B/hu not_active IP Right Cessation
- 1992-02-03 RU SU925010691A patent/RU2075479C1/ru active
- 1992-02-03 PL PL92293363A patent/PL169092B1/pl unknown
- 1992-02-03 AU AU10605/92A patent/AU641842B2/en not_active Ceased
- 1992-02-03 MX MX9200471A patent/MX9200471A/es not_active IP Right Cessation
- 1992-02-03 HU HU9200321A patent/HU207863B/hu not_active IP Right Cessation
- 1992-02-03 DE DE69210849T patent/DE69210849T2/de not_active Expired - Fee Related
- 1992-02-03 JP JP4017668A patent/JPH089613B2/ja not_active Expired - Fee Related
- 1992-02-03 EP EP92101706A patent/EP0498331B1/en not_active Expired - Lifetime
- 1992-02-03 DK DK92101706.7T patent/DK0498331T3/da active
- 1992-02-03 CZ CS92297A patent/CZ284754B6/cs not_active IP Right Cessation
- 1992-02-03 ZA ZA92753A patent/ZA92753B/xx unknown
- 1992-02-03 NO NO920438A patent/NO300040B1/no unknown
-
1996
- 1996-05-30 GR GR960401453T patent/GR3020094T3/el unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6001847A (en) | Chemical compounds | |
US6433175B1 (en) | Pyrroloindoles, pyridoindoles and azepinoindoles as 5-ht2c agonists | |
TW413679B (en) | Lactam derivatives useful as psychotherapeutic agents and pharmaceutical compositions containing them | |
US9763952B2 (en) | Dihydro-benzo-oxazine and dihydro-pyrido-oxazine derivatives | |
TWI385175B (zh) | 作為β-分泌酶調節劑之螺旋-三環化合物及其使用方法 | |
CA3076150A1 (en) | Selective p2x3 modulators | |
SK94096A3 (en) | Tetracyclic derivatives, process of preparation, their use and pharmaceutical compositions containing them | |
US6365598B1 (en) | Pyrroloquinolines for treatment of obesity | |
JP6626454B2 (ja) | Trpa1モジュレーター | |
NO300040B1 (no) | N-(aryloksyalkyl)heteroaryl-8-azabicyklo(3.2.1.)oktaner, anvendelse av forbindelsene for fremstilling av et medikament og en farmasöytisk sammensetning | |
TW200811170A (en) | Urea derivatives of tropane, their preparation and their therapeutic application | |
TW201130816A (en) | New CCR2 receptor antagonists and uses thereof | |
US11014882B2 (en) | 3-phosphoglycerate dehydrogenase inhibitors and uses thereof | |
US8324214B2 (en) | 1,3-dihydro-2H-pyrrolo[3,2-bpyridin-2-one derivatives, preparation thereof and therapeutic uses thereof | |
EA003400B1 (ru) | Азабициклические лиганды рецепторов 5нт1 | |
NO823557L (no) | 6-fluor-3-(3-(1-heterocyklo)propyl)-1,2-benzisoksazoler, fremgangsmaate til deres fremstilling, farmasoeytiske blandinger inneholdende disse og deres bruk som legemidler | |
US5234931A (en) | Heteroaryl-8-azabicyclo[3.2.1]octanes as antipsychotic agents, 5-HT3 receptor antagonists and inhibitors of the reuptake of serotonin | |
KR19990022265A (ko) | 항정신병제로서의 피리딘이미닐-1,2-벤즈이속사졸 및-벤즈이소티아졸 | |
US5340936A (en) | 8-azabicyclo[3.2.1]octane methanone and corresponding oximes | |
US5334599A (en) | Heteroaryl-8-azabicyclo[3,2,1]octanes as antipsychotic agents, 5-HT3 receptor antagonists and inhibitors of the reuptake of serotonin | |
US20150148377A1 (en) | Quinoline Derivatives |