AU753706B2 - Benzofuran derivatives, pharmaceutical composition containing the same, and a process for the preparation of the active ingredient - Google Patents
Benzofuran derivatives, pharmaceutical composition containing the same, and a process for the preparation of the active ingredient Download PDFInfo
- Publication number
- AU753706B2 AU753706B2 AU40529/99A AU4052999A AU753706B2 AU 753706 B2 AU753706 B2 AU 753706B2 AU 40529/99 A AU40529/99 A AU 40529/99A AU 4052999 A AU4052999 A AU 4052999A AU 753706 B2 AU753706 B2 AU 753706B2
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- Australia
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- dimethyl
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- 150000001907 coumarones Chemical class 0.000 title claims description 43
- 238000000034 method Methods 0.000 title claims description 33
- 238000002360 preparation method Methods 0.000 title claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 26
- 239000004480 active ingredient Substances 0.000 title claims description 17
- 230000008569 process Effects 0.000 title claims description 17
- 150000001875 compounds Chemical class 0.000 claims description 184
- 239000011541 reaction mixture Substances 0.000 claims description 95
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 94
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 92
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 84
- -1 biphenylyl group Chemical group 0.000 claims description 72
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 49
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 48
- 150000003839 salts Chemical class 0.000 claims description 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 44
- 125000005843 halogen group Chemical group 0.000 claims description 42
- 239000002253 acid Substances 0.000 claims description 40
- 238000006243 chemical reaction Methods 0.000 claims description 38
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- 125000000623 heterocyclic group Chemical group 0.000 claims description 30
- 125000003545 alkoxy group Chemical group 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 24
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 23
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 22
- 150000002118 epoxides Chemical class 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 150000004820 halides Chemical class 0.000 claims description 17
- 229920006395 saturated elastomer Polymers 0.000 claims description 17
- 150000003335 secondary amines Chemical class 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 125000004434 sulfur atom Chemical group 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 11
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 11
- 208000028867 ischemia Diseases 0.000 claims description 11
- 125000001624 naphthyl group Chemical group 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 9
- 150000002576 ketones Chemical class 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 210000004165 myocardium Anatomy 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 7
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 150000004792 aryl magnesium halides Chemical class 0.000 claims description 5
- 230000006735 deficit Effects 0.000 claims description 5
- 230000010410 reperfusion Effects 0.000 claims description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- VNZLQLYBRIOLFZ-UHFFFAOYSA-N 1-(2-methoxyphenyl)piperazine Chemical compound COC1=CC=CC=C1N1CCNCC1 VNZLQLYBRIOLFZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 241000894007 species Species 0.000 claims description 3
- VHFVKMTVMIZMIK-UHFFFAOYSA-N 1-(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCNCC2)=C1 VHFVKMTVMIZMIK-UHFFFAOYSA-N 0.000 claims description 2
- 239000012050 conventional carrier Substances 0.000 claims description 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims 2
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- DMCVVFIWYIKAEJ-UHFFFAOYSA-N 4-phenylpiperidine-4-carbonitrile Chemical compound C=1C=CC=CC=1C1(C#N)CCNCC1 DMCVVFIWYIKAEJ-UHFFFAOYSA-N 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 1
- 101100534223 Caenorhabditis elegans src-1 gene Proteins 0.000 claims 1
- 235000009917 Crataegus X brevipes Nutrition 0.000 claims 1
- 235000013204 Crataegus X haemacarpa Nutrition 0.000 claims 1
- 235000009685 Crataegus X maligna Nutrition 0.000 claims 1
- 235000009444 Crataegus X rubrocarnea Nutrition 0.000 claims 1
- 235000009486 Crataegus bullatus Nutrition 0.000 claims 1
- 235000017181 Crataegus chrysocarpa Nutrition 0.000 claims 1
- 235000009682 Crataegus limnophila Nutrition 0.000 claims 1
- 235000004423 Crataegus monogyna Nutrition 0.000 claims 1
- 240000000171 Crataegus monogyna Species 0.000 claims 1
- 235000002313 Crataegus paludosa Nutrition 0.000 claims 1
- 235000009840 Crataegus x incaedua Nutrition 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- NWVNXDKZIQLBNM-UHFFFAOYSA-N diphenylmethylpiperazine Chemical compound C1CNCCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 NWVNXDKZIQLBNM-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 309
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 196
- 239000000243 solution Substances 0.000 description 149
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 129
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 117
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 99
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
- 229960004592 isopropanol Drugs 0.000 description 77
- 239000000203 mixture Substances 0.000 description 75
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 70
- 239000013078 crystal Substances 0.000 description 68
- GZBGWGUQAIPVIP-UHFFFAOYSA-N 2,2-dimethyl-7-(oxiran-2-ylmethoxy)-3h-1-benzofuran Chemical compound C=12OC(C)(C)CC2=CC=CC=1OCC1CO1 GZBGWGUQAIPVIP-UHFFFAOYSA-N 0.000 description 59
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 59
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 59
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 51
- 239000002904 solvent Substances 0.000 description 51
- 239000000047 product Substances 0.000 description 42
- 239000012074 organic phase Substances 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- 238000001816 cooling Methods 0.000 description 38
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 32
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 27
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- 239000012071 phase Substances 0.000 description 26
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 238000012360 testing method Methods 0.000 description 21
- 238000005192 partition Methods 0.000 description 20
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 238000003756 stirring Methods 0.000 description 17
- 239000002585 base Substances 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 238000001953 recrystallisation Methods 0.000 description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
- 230000003293 cardioprotective effect Effects 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- QWCRAEMEVRGPNT-UHFFFAOYSA-N buspirone Chemical compound C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 QWCRAEMEVRGPNT-UHFFFAOYSA-N 0.000 description 9
- 229960002495 buspirone Drugs 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 150000007530 organic bases Chemical class 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 7
- 150000005622 tetraalkylammonium hydroxides Chemical class 0.000 description 7
- ROLMZTIHUMKEAI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzonitrile Chemical compound OC1=CC(F)=C(F)C=C1C#N ROLMZTIHUMKEAI-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 241001465754 Metazoa Species 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 230000000949 anxiolytic effect Effects 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- CVVIJWRCGSYCMB-UHFFFAOYSA-N hydron;piperazine;dichloride Chemical compound Cl.Cl.C1CNCCN1 CVVIJWRCGSYCMB-UHFFFAOYSA-N 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- 150000007529 inorganic bases Chemical class 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 238000005292 vacuum distillation Methods 0.000 description 6
- HAKSOKWVNPZVNM-UHFFFAOYSA-N 1,2,3,4-tetrahydropyridine;hydrochloride Chemical compound Cl.C1CNC=CC1 HAKSOKWVNPZVNM-UHFFFAOYSA-N 0.000 description 5
- WJGPNUBJBMCRQH-UHFFFAOYSA-N 2,2-dimethyl-2,3-dihydro-1-benzofuran-7-ol Chemical compound C1=CC(O)=C2OC(C)(C)CC2=C1 WJGPNUBJBMCRQH-UHFFFAOYSA-N 0.000 description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 5
- RGFHJSYBDBNFMX-UHFFFAOYSA-N 4-(4-methoxyphenyl)piperidin-4-ol Chemical compound C1=CC(OC)=CC=C1C1(O)CCNCC1 RGFHJSYBDBNFMX-UHFFFAOYSA-N 0.000 description 5
- TVZCRIROJQEVOT-CABCVRRESA-N Cromakalim Chemical compound N1([C@@H]2C3=CC(=CC=C3OC([C@H]2O)(C)C)C#N)CCCC1=O TVZCRIROJQEVOT-CABCVRRESA-N 0.000 description 5
- 150000005325 alkali earth metal hydroxides Chemical class 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 150000001340 alkali metals Chemical class 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- 239000003444 phase transfer catalyst Substances 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- TZGCBLLTLSJJBB-UHFFFAOYSA-N 5-bromo-2,2-dimethyl-7-(oxiran-2-ylmethoxy)-3h-1-benzofuran Chemical compound C=12OC(C)(C)CC2=CC(Br)=CC=1OCC1CO1 TZGCBLLTLSJJBB-UHFFFAOYSA-N 0.000 description 4
- NPPQSCRMBWNHMW-UHFFFAOYSA-N Meprobamate Chemical compound NC(=O)OCC(C)(CCC)COC(N)=O NPPQSCRMBWNHMW-UHFFFAOYSA-N 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- 206010062575 Muscle contracture Diseases 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 208000006111 contracture Diseases 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 239000000155 melt Substances 0.000 description 4
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 125000005270 trialkylamine group Chemical group 0.000 description 4
- LKMZGTIBHBYUOW-UHFFFAOYSA-N (2,2-dimethyl-3h-1-benzofuran-7-yl) acetate Chemical compound CC(=O)OC1=CC=CC2=C1OC(C)(C)C2 LKMZGTIBHBYUOW-UHFFFAOYSA-N 0.000 description 3
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 3
- BIOFUDSSNYHMCZ-UHFFFAOYSA-N 2,2-dimethyl-5-nitro-7-(oxiran-2-ylmethoxy)-3h-1-benzofuran Chemical compound C=12OC(C)(C)CC2=CC([N+]([O-])=O)=CC=1OCC1CO1 BIOFUDSSNYHMCZ-UHFFFAOYSA-N 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
- RJFISGALWPADNA-UHFFFAOYSA-N 4-[3-(trifluoromethyl)phenyl]-1,2,3,6-tetrahydropyridine;hydrochloride Chemical compound Cl.FC(F)(F)C1=CC=CC(C=2CCNCC=2)=C1 RJFISGALWPADNA-UHFFFAOYSA-N 0.000 description 3
- ILKPZCKFWLTEBQ-UHFFFAOYSA-N 4-[3-(trifluoromethyl)phenyl]piperidin-4-ol Chemical compound C=1C=CC(C(F)(F)F)=CC=1C1(O)CCNCC1 ILKPZCKFWLTEBQ-UHFFFAOYSA-N 0.000 description 3
- ASXGJMSKWNBENU-UHFFFAOYSA-N 8-OH-DPAT Chemical compound C1=CC(O)=C2CC(N(CCC)CCC)CCC2=C1 ASXGJMSKWNBENU-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- FKPSBYZGRQJIMO-UHFFFAOYSA-M benzyl(triethyl)azanium;hydroxide Chemical compound [OH-].CC[N+](CC)(CC)CC1=CC=CC=C1 FKPSBYZGRQJIMO-UHFFFAOYSA-M 0.000 description 3
- KXHPPCXNWTUNSB-UHFFFAOYSA-M benzyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC1=CC=CC=C1 KXHPPCXNWTUNSB-UHFFFAOYSA-M 0.000 description 3
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 208000015114 central nervous system disease Diseases 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000010908 decantation Methods 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 230000002140 halogenating effect Effects 0.000 description 3
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 3
- 210000005240 left ventricle Anatomy 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229960004815 meprobamate Drugs 0.000 description 3
- 125000003386 piperidinyl group Chemical group 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- 239000013558 reference substance Substances 0.000 description 3
- 229940076279 serotonin Drugs 0.000 description 3
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
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- 210000005153 frontal cortex Anatomy 0.000 description 1
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- TVFIYRKPCACCNL-UHFFFAOYSA-N furan-2-carboxamide Chemical class NC(=O)C1=CC=CO1 TVFIYRKPCACCNL-UHFFFAOYSA-N 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
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- 229920000669 heparin Polymers 0.000 description 1
- 229940077716 histamine h2 receptor antagonists for peptic ulcer and gord Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
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- 125000002346 iodo group Chemical group I* 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000007786 learning performance Effects 0.000 description 1
- 210000005246 left atrium Anatomy 0.000 description 1
- 238000005567 liquid scintillation counting Methods 0.000 description 1
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 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
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
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- 230000007334 memory performance Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
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- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 230000003680 myocardial damage Effects 0.000 description 1
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- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
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- 231100000252 nontoxic Toxicity 0.000 description 1
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- 238000007254 oxidation reaction Methods 0.000 description 1
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- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- NCCBCEHAGCSKEA-UHFFFAOYSA-N pentaiodo-$l^{5}-phosphane Chemical compound IP(I)(I)(I)I NCCBCEHAGCSKEA-UHFFFAOYSA-N 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- GZRKXKUVVPSREJ-UHFFFAOYSA-N pyridinylpiperazine Chemical compound C1CNCCN1C1=CC=CC=N1 GZRKXKUVVPSREJ-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- DGQOCLATAPFASR-UHFFFAOYSA-N tetrahydroxy-1,4-benzoquinone Chemical compound OC1=C(O)C(=O)C(O)=C(O)C1=O DGQOCLATAPFASR-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- 230000035922 thirst Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229960002415 trichloroethylene Drugs 0.000 description 1
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- 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
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9801086A HUP9801086A3 (en) | 1998-05-14 | 1998-05-14 | Benzofurane derivatives, pharmaceutical compositions containing them as active ingredient process for producing the active ingredient and intermediates of them |
| HU9801085A HUP9801085A3 (en) | 1998-05-14 | 1998-05-14 | Piperazinyl-alkyl-benzofurane derivatives, pharmaceutical compositions containing them as active ingredient and process for producing the active ingredient |
| HU9801085 | 1998-05-14 | ||
| HU9801086 | 1998-05-14 | ||
| PCT/HU1999/000038 WO1999058527A2 (fr) | 1998-05-14 | 1999-05-13 | Derives de benzofuranne, composition pharmaceutique renfermant ces derives et procede de preparation du principe actif |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU4052999A AU4052999A (en) | 1999-11-29 |
| AU753706B2 true AU753706B2 (en) | 2002-10-24 |
Family
ID=89996544
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU40529/99A Ceased AU753706B2 (en) | 1998-05-14 | 1999-05-13 | Benzofuran derivatives, pharmaceutical composition containing the same, and a process for the preparation of the active ingredient |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP1077973A2 (fr) |
| JP (1) | JP2002514643A (fr) |
| KR (1) | KR20010043618A (fr) |
| AU (1) | AU753706B2 (fr) |
| CA (1) | CA2332275A1 (fr) |
| HR (1) | HRP20000750A2 (fr) |
| PL (1) | PL345309A1 (fr) |
| SK (1) | SK17212000A3 (fr) |
| WO (1) | WO1999058527A2 (fr) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001046177A1 (fr) * | 1999-12-20 | 2001-06-28 | Eli Lilly And Company | Derives de benzofuranne |
| WO2001046186A1 (fr) * | 1999-12-20 | 2001-06-28 | Eli Lilly And Company | Derives de benzofuranne |
| FR2845992B1 (fr) * | 2002-10-16 | 2005-02-04 | Pf Medicament | Derives de 3-(cyclopenten-1yl)-benzyl-ou3-(cyclopenten-1yl)- heteroarylmethyl-amines et leur utilisation a titre de medicaments pour le traitement de la schizophrenie |
| JP2008530221A (ja) * | 2005-02-17 | 2008-08-07 | バイエル・クロツプサイエンス・アクチエンゲゼルシヤフト | （二置換プロペニル）フェニルアルキル置換ジヒドロベンゾフランを調製するための改善された方法 |
| HU230761B1 (hu) * | 2007-05-30 | 2018-03-28 | Egis Gyógyszergyár Nyilvánosan Működő Részvénytársaság | Új, szelektív 5HT6-receptorgátló benzofurán-származékok és eljárás előállításukra |
| HU230729B1 (hu) * | 2007-05-30 | 2017-12-28 | Egis Gyógyszergyár Nyilvánosan Működő Részvénytársaság | Új, szelektív 5HT7-receptorgátló benzofurán-származékok és eljárás előállításukra |
| GB201312499D0 (en) * | 2013-07-12 | 2013-08-28 | Isis Innovation | Therapeutic compounds |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH474511A (fr) * | 1966-06-24 | 1969-06-30 | F. Hoffmann-La Roche & Co. Aktiengesellschaft | |
| DE2235597A1 (de) * | 1972-07-20 | 1974-01-31 | Boehringer Mannheim Gmbh | 1-eckige klammer auf 3-(5,6,7,8tetrahydronaphth-1-yl-oxy) -propyl eckige klammer zu -piperazin-derivate und verfahren zu ihrer herstellung |
| FR2353291A1 (fr) * | 1976-05-31 | 1977-12-30 | Parcor | Nouveaux derives du benzofuranne |
| US4110536A (en) * | 1977-04-18 | 1978-08-29 | Miles Laboratories, Inc. | Derivatives of 5-(indol-3-yl)hydantoin |
| US4612309A (en) * | 1984-10-23 | 1986-09-16 | William H. Rorer, Inc. | Antisecretory bicyclic benzo-oxy heterocyclic ethers and thioethers |
| US4966907A (en) * | 1988-08-12 | 1990-10-30 | Merck & Co., Inc. | 6-substituted 5-hydroxy-2,3-dihydrobenzofurans as inhibitors of leukotriene biosynthesis |
| GB9005014D0 (en) * | 1990-03-06 | 1990-05-02 | Janssen Pharmaceutica Nv | N.(4.piperidinyl)(dihydrobenzofuran or dihydro.2h.benzopyran)carboxamide derivatives |
| FR2681319B1 (fr) * | 1991-09-12 | 1995-02-17 | Synthelabo | Derives de 1-(phenoxyalkyl)piperidine, leur preparation et leur application en therapeutique. |
| CZ289031B6 (cs) * | 1994-09-27 | 2001-10-17 | Janssen Pharmaceutica N. V. | Deriváty N-substituovaných piperidinylových bicyklických benzoátů |
| TW490465B (en) * | 1994-11-24 | 2002-06-11 | Janssen Pharmaceutica Nv | Enterokinetic benzamide, the preparation process and the pharmaceutical compositions thereof |
| GB9507882D0 (en) * | 1995-04-18 | 1995-05-31 | Pharmacia Spa | Substituted dihydrobenzofuran derivatives as 5-ht4 agonists |
| ZA9610745B (en) * | 1995-12-22 | 1997-06-24 | Warner Lambert Co | 4-Subsituted piperidine analogs and their use as subtype selective nmda receptor antagonists |
| NZ330263A (en) * | 1996-02-15 | 1999-06-29 | Janssen Pharmaceutica Nv | Esters of 3-hydroxy-piperidinemethanol derivatives to improve gastric emptying |
-
1999
- 1999-05-13 WO PCT/HU1999/000038 patent/WO1999058527A2/fr not_active Application Discontinuation
- 1999-05-13 JP JP2000548331A patent/JP2002514643A/ja active Pending
- 1999-05-13 EP EP99923772A patent/EP1077973A2/fr not_active Withdrawn
- 1999-05-13 CA CA002332275A patent/CA2332275A1/fr not_active Abandoned
- 1999-05-13 SK SK1721-2000A patent/SK17212000A3/sk unknown
- 1999-05-13 KR KR1020007012773A patent/KR20010043618A/ko not_active Application Discontinuation
- 1999-05-13 PL PL99345309A patent/PL345309A1/xx unknown
- 1999-05-13 AU AU40529/99A patent/AU753706B2/en not_active Ceased
-
2000
- 2000-11-03 HR HR20000750A patent/HRP20000750A2/hr not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| SK17212000A3 (sk) | 2001-05-10 |
| AU4052999A (en) | 1999-11-29 |
| KR20010043618A (ko) | 2001-05-25 |
| WO1999058527A2 (fr) | 1999-11-18 |
| JP2002514643A (ja) | 2002-05-21 |
| WO1999058527A3 (fr) | 2000-01-27 |
| CA2332275A1 (fr) | 1999-11-18 |
| HRP20000750A2 (en) | 2001-06-30 |
| EP1077973A2 (fr) | 2001-02-28 |
| PL345309A1 (en) | 2001-12-03 |
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