SK17212000A3 - Benzofuránové deriváty, farmaceutické kompozície ich obsahujúce a spôsob prípravy aktívnej zložky - Google Patents
Benzofuránové deriváty, farmaceutické kompozície ich obsahujúce a spôsob prípravy aktívnej zložky Download PDFInfo
- Publication number
- SK17212000A3 SK17212000A3 SK1721-2000A SK17212000A SK17212000A3 SK 17212000 A3 SK17212000 A3 SK 17212000A3 SK 17212000 A SK17212000 A SK 17212000A SK 17212000 A3 SK17212000 A3 SK 17212000A3
- Authority
- SK
- Slovakia
- Prior art keywords
- group
- alkyl
- dimethyl
- formula
- benzofuran
- Prior art date
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- 150000001907 coumarones Chemical class 0.000 title claims abstract description 45
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 23
- 238000000034 method Methods 0.000 title claims description 31
- 239000004480 active ingredient Substances 0.000 title claims description 14
- 238000002360 preparation method Methods 0.000 title claims description 14
- 230000008569 process Effects 0.000 title claims description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 205
- -1 biphenylyl Chemical group 0.000 claims description 161
- 239000011541 reaction mixture Substances 0.000 claims description 94
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 88
- 125000000217 alkyl group Chemical group 0.000 claims description 80
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 58
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 56
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
- 150000003839 salts Chemical class 0.000 claims description 48
- 239000002253 acid Substances 0.000 claims description 44
- 125000000623 heterocyclic group Chemical group 0.000 claims description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims description 38
- 125000003545 alkoxy group Chemical group 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 37
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 35
- 229910052736 halogen Inorganic materials 0.000 claims description 30
- 150000002367 halogens Chemical class 0.000 claims description 30
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 29
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 28
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 23
- 150000002118 epoxides Chemical class 0.000 claims description 21
- 125000004434 sulfur atom Chemical group 0.000 claims description 21
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- 125000005843 halogen group Chemical group 0.000 claims description 18
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 16
- 150000004820 halides Chemical class 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- 229920006395 saturated elastomer Polymers 0.000 claims description 15
- 150000003335 secondary amines Chemical class 0.000 claims description 15
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 14
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 14
- 125000001624 naphthyl group Chemical group 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 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 13
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- 230000003293 cardioprotective effect Effects 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
- 150000002576 ketones Chemical class 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 5
- 208000015114 central nervous system disease Diseases 0.000 claims description 5
- SWRPGPAAUAZTIK-UHFFFAOYSA-N 1-[3-[(2,2-dimethyl-3H-1-benzofuran-7-yl)oxy]-2-hydroxypropyl]-4-(4-methoxyphenyl)piperidin-4-ol Chemical compound C1=CC(OC)=CC=C1C1(O)CCN(CC(O)COC=2C=3OC(C)(C)CC=3C=CC=2)CC1 SWRPGPAAUAZTIK-UHFFFAOYSA-N 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
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- WRPXQDHQEWBGLY-UHFFFAOYSA-N 1-[3-[(2,2-dimethyl-3H-1-benzofuran-7-yl)oxy]-2-hydroxypropyl]-4-(4-fluorophenyl)piperidin-4-ol Chemical compound C=12OC(C)(C)CC2=CC=CC=1OCC(O)CN(CC1)CCC1(O)C1=CC=C(F)C=C1 WRPXQDHQEWBGLY-UHFFFAOYSA-N 0.000 claims description 3
- ICIUOUQQXQBRMQ-UHFFFAOYSA-N C=12OC(C)(C)CC2=CC=CC=1OCC(O)CN(CC1)CCC1C1=CC=CC(C(F)(F)F)=C1 Chemical compound C=12OC(C)(C)CC2=CC=CC=1OCC(O)CN(CC1)CCC1C1=CC=CC(C(F)(F)F)=C1 ICIUOUQQXQBRMQ-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 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
- QYKOPJAWPVMOHC-UHFFFAOYSA-N 1-[(2,2-dimethyl-3H-1-benzofuran-7-yl)oxy]-3-[4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]propan-2-ol Chemical compound CC1(OC2=C(C1)C=CC=C2OCC(CN2CCC(=CC2)C2=CC(=CC=C2)C(F)(F)F)O)C QYKOPJAWPVMOHC-UHFFFAOYSA-N 0.000 claims description 2
- LNKSMUDGSHOECN-UHFFFAOYSA-N 1-[(2,2-dimethyl-3h-1-benzofuran-7-yl)oxy]-3-(4-pyridin-2-ylpiperazin-1-yl)propan-2-ol Chemical compound C=12OC(C)(C)CC2=CC=CC=1OCC(O)CN(CC1)CCN1C1=CC=CC=N1 LNKSMUDGSHOECN-UHFFFAOYSA-N 0.000 claims description 2
- UZBPBTXOCVBZGJ-UHFFFAOYSA-N 1-[3-[(2,2-dimethyl-3H-1-benzofuran-7-yl)oxy]-2-hydroxypropyl]-4-(3-methoxyphenyl)piperidin-4-ol Chemical compound COC1=CC=CC(C2(O)CCN(CC(O)COC=3C=4OC(C)(C)CC=4C=CC=3)CC2)=C1 UZBPBTXOCVBZGJ-UHFFFAOYSA-N 0.000 claims description 2
- AVFZFLZDMUTOPU-UHFFFAOYSA-N 1-[3-[(2,2-dimethyl-3H-1-benzofuran-7-yl)oxy]-2-hydroxypropyl]-4-(6-methoxynaphthalen-2-yl)piperidin-4-ol Chemical compound C1=CC2=CC(OC)=CC=C2C=C1C(CC1)(O)CCN1CC(O)COC1=CC=CC2=C1OC(C)(C)C2 AVFZFLZDMUTOPU-UHFFFAOYSA-N 0.000 claims description 2
- UJMGZPCKYHBCKU-UHFFFAOYSA-N 2,2-dimethyl-2,3-dihydrobenzofuran Chemical compound C1=CC=C2OC(C)(C)CC2=C1 UJMGZPCKYHBCKU-UHFFFAOYSA-N 0.000 claims description 2
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 2
- FDVQVNVOYONXJC-UHFFFAOYSA-N C=12OC(C)(C)CC2=CC=CC=1OCC(O)CN(CC1)CCC1(O)C1=CC=CC(C(F)(F)F)=C1 Chemical compound C=12OC(C)(C)CC2=CC=CC=1OCC(O)CN(CC1)CCC1(O)C1=CC=CC(C(F)(F)F)=C1 FDVQVNVOYONXJC-UHFFFAOYSA-N 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 208000019622 heart disease Diseases 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 17
- SQICWBWPSSWYJX-UHFFFAOYSA-N 1-[(2,2-dimethyl-3H-1-benzofuran-7-yl)oxy]-3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-2-ol Chemical compound COC1=CC=CC=C1N1CCN(CC(O)COC=2C=3OC(C)(C)CC=3C=CC=2)CC1 SQICWBWPSSWYJX-UHFFFAOYSA-N 0.000 claims 2
- VWWDIMITLFLXFP-UHFFFAOYSA-N CC1(CC2=C(O1)C(=CC=C2)OCC(CN3CCN(CC3)C4=CC(=CC=C4)OC)O)C Chemical compound CC1(CC2=C(O1)C(=CC=C2)OCC(CN3CCN(CC3)C4=CC(=CC=C4)OC)O)C VWWDIMITLFLXFP-UHFFFAOYSA-N 0.000 claims 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 2
- 208000012902 Nervous system disease Diseases 0.000 claims 1
- 235000010290 biphenyl Nutrition 0.000 claims 1
- 239000004305 biphenyl Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000011777 magnesium Substances 0.000 claims 1
- 229910052749 magnesium Inorganic materials 0.000 claims 1
- 239000013543 active substance Substances 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 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 191
- 239000000243 solution Substances 0.000 description 135
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 131
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 120
- 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 96
- 239000000203 mixture Substances 0.000 description 78
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 68
- 239000013078 crystal Substances 0.000 description 66
- 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 63
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 58
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 58
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 53
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 51
- 239000002904 solvent Substances 0.000 description 50
- 238000009835 boiling Methods 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 44
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- 239000012074 organic phase Substances 0.000 description 40
- 238000001816 cooling Methods 0.000 description 37
- 239000000047 product Substances 0.000 description 37
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- 238000010992 reflux Methods 0.000 description 29
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- 239000012071 phase Substances 0.000 description 25
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 24
- 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
- 238000012360 testing method Methods 0.000 description 22
- 229910052938 sodium sulfate Inorganic materials 0.000 description 21
- 235000011152 sodium sulphate Nutrition 0.000 description 21
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 17
- 239000002585 base Substances 0.000 description 16
- 238000001953 recrystallisation Methods 0.000 description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
- 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 10
- 230000000694 effects Effects 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
- 229960002495 buspirone Drugs 0.000 description 9
- HAKSOKWVNPZVNM-UHFFFAOYSA-N 1,2,3,4-tetrahydropyridine;hydrochloride Chemical compound Cl.C1CNC=CC1 HAKSOKWVNPZVNM-UHFFFAOYSA-N 0.000 description 8
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 150000007529 inorganic bases Chemical class 0.000 description 7
- 208000028867 ischemia Diseases 0.000 description 7
- 150000007530 organic bases Chemical class 0.000 description 7
- 150000005622 tetraalkylammonium hydroxides Chemical class 0.000 description 7
- LCQCZZFNKWBHQP-UHFFFAOYSA-N 1-(4-benzhydrylpiperazin-1-yl)-3-[(2,2-dimethyl-3h-1-benzofuran-7-yl)oxy]propan-2-ol Chemical compound C=12OC(C)(C)CC2=CC=CC=1OCC(O)CN(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 LCQCZZFNKWBHQP-UHFFFAOYSA-N 0.000 description 6
- 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 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
- 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
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 6
- 230000000949 anxiolytic effect Effects 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 239000003444 phase transfer catalyst Substances 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 238000005292 vacuum distillation Methods 0.000 description 6
- 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 5
- 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 5
- BGKWESNOOOHUEX-UHFFFAOYSA-N 7-(3-bromopropoxy)-2,2-dimethyl-3h-1-benzofuran Chemical compound C1=CC(OCCCBr)=C2OC(C)(C)CC2=C1 BGKWESNOOOHUEX-UHFFFAOYSA-N 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
- 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 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
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- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
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- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- BQFUGPFWKLLNLZ-UHFFFAOYSA-N 1-[(2,2-dimethyl-3H-1-benzofuran-7-yl)oxy]-3-[4-(4-fluorophenyl)piperazin-1-yl]propan-2-ol Chemical compound C=12OC(C)(C)CC2=CC=CC=1OCC(O)CN(CC1)CCN1C1=CC=C(F)C=C1 BQFUGPFWKLLNLZ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 4
- UMCYQVPPIICEGV-UHFFFAOYSA-N 4-(4-chlorophenyl)-1-[3-[(2,2-dimethyl-3H-1-benzofuran-7-yl)oxy]-2-hydroxypropyl]piperidin-4-ol Chemical compound C=12OC(C)(C)CC2=CC=CC=1OCC(O)CN(CC1)CCC1(O)C1=CC=C(Cl)C=C1 UMCYQVPPIICEGV-UHFFFAOYSA-N 0.000 description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 4
- ASXGJMSKWNBENU-UHFFFAOYSA-N 8-OH-DPAT Chemical compound C1=CC(O)=C2CC(N(CCC)CCC)CCC2=C1 ASXGJMSKWNBENU-UHFFFAOYSA-N 0.000 description 4
- LKEYJHBFGJREKX-UHFFFAOYSA-N CC1(CC2=C(O1)C(=CC=C2)OCC(CN3CCN(CC3)C4=CC=C(C=C4)Cl)O)C Chemical compound CC1(CC2=C(O1)C(=CC=C2)OCC(CN3CCN(CC3)C4=CC=C(C=C4)Cl)O)C LKEYJHBFGJREKX-UHFFFAOYSA-N 0.000 description 4
- BNVRJBZHCLZCOP-UHFFFAOYSA-N Cl.COc1ccc(cc1)C1=CCN(CCCOc2cccc3CC(C)(C)Oc23)CC1 Chemical compound Cl.COc1ccc(cc1)C1=CCN(CCCOc2cccc3CC(C)(C)Oc23)CC1 BNVRJBZHCLZCOP-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
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 4
- 150000001340 alkali metals Chemical class 0.000 description 4
- 150000004792 aryl magnesium halides Chemical class 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 230000008602 contraction Effects 0.000 description 4
- 238000010908 decantation Methods 0.000 description 4
- NWVNXDKZIQLBNM-UHFFFAOYSA-N diphenylmethylpiperazine Chemical compound C1CNCCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 NWVNXDKZIQLBNM-UHFFFAOYSA-N 0.000 description 4
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000002023 wood Substances 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 (3)
| 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 |
| 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 (1)
| Publication Number | Publication Date |
|---|---|
| SK17212000A3 true SK17212000A3 (sk) | 2001-05-10 |
Family
ID=89996544
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1721-2000A SK17212000A3 (sk) | 1998-05-14 | 1999-05-13 | Benzofuránové deriváty, farmaceutické kompozície ich obsahujúce a spôsob prípravy aktívnej zložky |
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 |
|---|---|
| AU753706B2 (en) | 2002-10-24 |
| 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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