FI93114B - Förfarande för framställning av som läkemedel användbara (aza)naftalensultamderivat - Google Patents
Förfarande för framställning av som läkemedel användbara (aza)naftalensultamderivat Download PDFInfo
- Publication number
- FI93114B FI93114B FI893297A FI893297A FI93114B FI 93114 B FI93114 B FI 93114B FI 893297 A FI893297 A FI 893297A FI 893297 A FI893297 A FI 893297A FI 93114 B FI93114 B FI 93114B
- Authority
- FI
- Finland
- Prior art keywords
- radical
- substituted
- formula
- dioxide
- hydroxy
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 36
- 238000002360 preparation method Methods 0.000 title claims description 8
- 239000003814 drug Substances 0.000 title claims description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 title 2
- -1 bis (4-fluorophenyl) methylene Chemical group 0.000 claims description 229
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 64
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 62
- 150000001875 compounds Chemical class 0.000 claims description 52
- 125000005843 halogen group Chemical group 0.000 claims description 38
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 33
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 17
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 11
- 239000011707 mineral Substances 0.000 claims description 11
- KZKRRZFCAYOXQE-UHFFFAOYSA-N 1$l^{2}-azinane Chemical compound C1CC[N]CC1 KZKRRZFCAYOXQE-UHFFFAOYSA-N 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 9
- 150000007524 organic acids Chemical class 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical compound O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 3
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical group [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 2
- 230000002152 alkylating effect Effects 0.000 claims 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 165
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 165
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 162
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 147
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 139
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 136
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 126
- 239000000203 mixture Substances 0.000 description 124
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 99
- 238000009835 boiling Methods 0.000 description 77
- 229910052786 argon Inorganic materials 0.000 description 68
- 239000000377 silicon dioxide Substances 0.000 description 68
- 239000003480 eluent Substances 0.000 description 64
- 238000010992 reflux Methods 0.000 description 59
- 238000003818 flash chromatography Methods 0.000 description 55
- 238000000746 purification Methods 0.000 description 48
- 238000001953 recrystallisation Methods 0.000 description 46
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 239000000243 solution Substances 0.000 description 44
- 238000003756 stirring Methods 0.000 description 40
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- 239000003921 oil Substances 0.000 description 38
- 235000019198 oils Nutrition 0.000 description 38
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
- 239000011541 reaction mixture Substances 0.000 description 36
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 238000002844 melting Methods 0.000 description 21
- 230000008018 melting Effects 0.000 description 21
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000012153 distilled water Substances 0.000 description 17
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 17
- 235000019341 magnesium sulphate Nutrition 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 17
- 239000012043 crude product Substances 0.000 description 16
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 15
- 239000006185 dispersion Substances 0.000 description 15
- 239000012312 sodium hydride Substances 0.000 description 15
- 229910000104 sodium hydride Inorganic materials 0.000 description 15
- 239000002904 solvent Substances 0.000 description 14
- 239000004264 Petrolatum Substances 0.000 description 13
- 229940066842 petrolatum Drugs 0.000 description 13
- 235000019271 petrolatum Nutrition 0.000 description 13
- 150000003254 radicals Chemical class 0.000 description 13
- 239000002244 precipitate Substances 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 8
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- 235000009518 sodium iodide Nutrition 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- 230000031709 bromination Effects 0.000 description 6
- 238000005893 bromination reaction Methods 0.000 description 6
- 239000012442 inert solvent Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 5
- 150000008041 alkali metal carbonates Chemical class 0.000 description 5
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 5
- 150000008046 alkali metal hydrides Chemical class 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- XYKSABPYIZPLRX-UHFFFAOYSA-N benzo[e][1,2]benzothiazole Chemical compound C1=CC=CC2=C3C=NSC3=CC=C21 XYKSABPYIZPLRX-UHFFFAOYSA-N 0.000 description 5
- 230000026030 halogenation Effects 0.000 description 5
- 238000005658 halogenation reaction Methods 0.000 description 5
- AVJKDKWRVSSJPK-UHFFFAOYSA-N 1-(4-fluorophenyl)piperazine Chemical compound C1=CC(F)=CC=C1N1CCNCC1 AVJKDKWRVSSJPK-UHFFFAOYSA-N 0.000 description 4
- CIRSPTXGPFAXRE-UHFFFAOYSA-N 3-(1,2,3,6-tetrahydropyridin-4-yl)-1h-indole Chemical compound C1NCCC(C=2C3=CC=CC=C3NC=2)=C1 CIRSPTXGPFAXRE-UHFFFAOYSA-N 0.000 description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
- JAYGEXFKJUWRML-UHFFFAOYSA-N 4-bromo-5-nitroisoquinoline Chemical compound N1=CC(Br)=C2C([N+](=O)[O-])=CC=CC2=C1 JAYGEXFKJUWRML-UHFFFAOYSA-N 0.000 description 4
- RJLUYBOSXJNQBN-UHFFFAOYSA-N 4-bromoisoquinolin-5-amine Chemical compound N1=CC(Br)=C2C(N)=CC=CC2=C1 RJLUYBOSXJNQBN-UHFFFAOYSA-N 0.000 description 4
- BFZIPXDGEFRLML-UHFFFAOYSA-N 4-bromoisoquinoline-5-sulfonamide Chemical compound N1=CC(Br)=C2C(S(=O)(=O)N)=CC=CC2=C1 BFZIPXDGEFRLML-UHFFFAOYSA-N 0.000 description 4
- DETHFQYKUHNJRY-UHFFFAOYSA-N 4-bromoisoquinoline-5-sulfonyl chloride Chemical compound N1=CC(Br)=C2C(S(=O)(=O)Cl)=CC=CC2=C1 DETHFQYKUHNJRY-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- RZAAXGSFUPZABT-UHFFFAOYSA-N BrOBr.OC1=CC=C(C=C1)N1CCNCC1 Chemical compound BrOBr.OC1=CC=C(C=C1)N1CCNCC1 RZAAXGSFUPZABT-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 4
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 4
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 239000012429 reaction media Substances 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 3
- ABERUOJGWHYBJL-UHFFFAOYSA-N (4-fluorophenyl)-piperidin-4-ylmethanone Chemical compound C1=CC(F)=CC=C1C(=O)C1CCNCC1 ABERUOJGWHYBJL-UHFFFAOYSA-N 0.000 description 3
- VODHXHSRIUDUHP-UHFFFAOYSA-N 1-(4-bromobutan-2-yl)-4-(4-fluorophenyl)piperazine Chemical compound C1CN(C(CCBr)C)CCN1C1=CC=C(F)C=C1 VODHXHSRIUDUHP-UHFFFAOYSA-N 0.000 description 3
- ZVWPDURJKLPNAL-UHFFFAOYSA-N 3-bromobutan-1-ol Chemical compound CC(Br)CCO ZVWPDURJKLPNAL-UHFFFAOYSA-N 0.000 description 3
- FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 description 3
- MEFDFYOJQUOHCR-UHFFFAOYSA-N 4-(4-methylphenyl)piperidin-4-ol Chemical compound C1=CC(C)=CC=C1C1(O)CCNCC1 MEFDFYOJQUOHCR-UHFFFAOYSA-N 0.000 description 3
- OMPXTQYWYRWWPH-UHFFFAOYSA-N 4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1NCCC(C=2C=CC=CC=2)=C1 OMPXTQYWYRWWPH-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 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 3
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000006210 lotion Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 229940076279 serotonin Drugs 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000001119 stannous chloride Substances 0.000 description 3
- 235000011150 stannous chloride Nutrition 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- UVWJFYASSBGLMW-UHFFFAOYSA-N 1-(3-chloropropyl)-4-phenyl-3,6-dihydro-2h-pyridine Chemical compound C1N(CCCCl)CCC(C=2C=CC=CC=2)=C1 UVWJFYASSBGLMW-UHFFFAOYSA-N 0.000 description 2
- AZGNTLLAVWZVIQ-UHFFFAOYSA-N 1-benzyl-4-(4-methylphenyl)piperidin-4-ol Chemical compound C1=CC(C)=CC=C1C1(O)CCN(CC=2C=CC=CC=2)CC1 AZGNTLLAVWZVIQ-UHFFFAOYSA-N 0.000 description 2
- IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 description 2
- ZBTMRBYMKUEVEU-UHFFFAOYSA-N 1-bromo-4-methylbenzene Chemical compound CC1=CC=C(Br)C=C1 ZBTMRBYMKUEVEU-UHFFFAOYSA-N 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- QIWSFPPCACOCJR-UHFFFAOYSA-N 3-[4-(4-fluorophenyl)piperazin-1-yl]butan-1-ol Chemical compound C1CN(C(CCO)C)CCN1C1=CC=C(F)C=C1 QIWSFPPCACOCJR-UHFFFAOYSA-N 0.000 description 2
- ZDFQBFVFCPABKQ-UHFFFAOYSA-N 3-piperazin-1-yl-1,2-benzoxazole Chemical compound C1CNCCN1C1=NOC2=CC=CC=C12 ZDFQBFVFCPABKQ-UHFFFAOYSA-N 0.000 description 2
- BYNBAMHAURJNTR-UHFFFAOYSA-N 3-piperidin-4-yl-1h-benzimidazol-2-one Chemical compound O=C1NC2=CC=CC=C2N1C1CCNCC1 BYNBAMHAURJNTR-UHFFFAOYSA-N 0.000 description 2
- KAIRZPVWWIMPFT-UHFFFAOYSA-N 3-piperidin-4-yl-1h-indole Chemical compound C1CNCCC1C1=CNC2=CC=CC=C12 KAIRZPVWWIMPFT-UHFFFAOYSA-N 0.000 description 2
- VHBVKKWTZYRNHX-UHFFFAOYSA-N 4,4-diphenylpiperidine;hydrochloride Chemical compound Cl.C1CNCCC1(C=1C=CC=CC=1)C1=CC=CC=C1 VHBVKKWTZYRNHX-UHFFFAOYSA-N 0.000 description 2
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- 239000004299 sodium benzoate Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
- C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/06—Peri-condensed systems
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- Pulmonology (AREA)
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Claims (3)
1. Förfarande för framställning av föreningar med formeln (I), vilka är användbara som läkemedel, 5 02S-N-R6 — R1 Γιι^Ι—R2 ίο (I) r4 H3 där Ri är 15 en 1,2,3,6-tetrahydropyrid-l-ylradikal, som i ställning 4 är substltuerad med (a) en fenylradikal, (b) en fenylradikal, som är substituerad med en halogenatom eller en alkyl-, hydroxi- eller alkoxiradikal, (c) en in-dol-3-ylradikal, (d) en indol-3-ylradikal, som i kväveato-20 men är substituerad med en alkyl- eller alkylkarbonylradi-kal och/eller i ställning 5 med en klor- eller fluoratom eller (e) en 5-hydroxi-indol-3-ylradikal, en piperazin-l-ylradikal, som i ställning 4 är substituerad med (a) en fenylradikal, (b) en fenylradikal, . 25 som är substituerad med en alkoxi-, alkyl-, hydroxi-, nit ro- eller aminoradikal eller en halogenatom, (c) en 1,2-bensoisotiazol-3-ylradikal, (d) en 1,2-bensoisooxazol-3-ylradikal eller (e) en pyrid-2-ylradikal, en piperidinoradikal, som i ställning 4 är substi-30 tuerad med (a) en fenylradikal, (b) en fenylradikal, som är substituerad med en halogenatom eller en hydroxi-, alkyl- eller alkoxiradikal, (c) tvä fenylradikaler, (d) en bis(4-fluorfenyl)metylenradikal, (e) en 4-fluorbensoylra-dikal, (f) en 2-oxobensoimidazolin-l-ylradikal, (g) en 2-35 oxobensoimidazolin-2-ylradikal, som i ställning 3 är substituerad med en alkylkarbonyl- eller bensoylradikal, (h) 93114 72 en hydroxiradikal eller en fenylradikal, som eventuellt är substituerad med en alkyl-, alkoxi- eller hydroxiradikal eller en halogenatom, (i) en indol-3-ylradikal, (j) en indol-3-ylradikal, som i kväveatomen är substituerad med 5 en alkyl- eller alkylkarbonylradikal och/eller i ställning 5 med en klor- eller fluoratom eller (k) en 5-hydroxiin-dol-3-ylradikal, (1) R2 och R3f vilka är identiska med varandra, är väteatomer eller halogenatomer och R4 är en väteatom, eller
10 R2 och R4 är väteatomer och R3 är en halogenatom eller en acetylaminoradikal, eller R2 och R3 är väteatomer och R4 är en halogenatom, och R5 är en grupp -CH=, eller (2) R2, R3 och R4 är väteatomer, och R5 är en kväve- 15 atom, R6 är en alkylenkedja med 2-4 kolatomer eller en propylenkedja, som i ställning 1 eller 3 är substituerad med en alkylradikal eller i ställning 2 med en alkyl-, alkoxi-, hydroxi-, dialkylamino-, piperidino-, morfolino-20 eller tiomorfolinoradikal, förutsatt, att dä R6 är en propylenradikal, som i ställning 2 är substituerad med en dialkylamino-, piperidino-, morfolino- eller tiomorfolinoradikal, kan R2 ej vara en radikal, som innehäller en hydroxiradikal, 25 varvid alkyl- och alkoxiradikalerna samt alkyl- och alkoxidelarna innehäller 1-4 kolatomer i en rak eller förgrenad kedja, och salter därav med mineralsyror och organiska syror, kännetecknat därav, att:
30 A - för framställning av föreningar med formeln (I), med undantag av sädana, i vilka R6 är en propylenradi-‘ kai, som i ställning 2 är substituerad med en dialkylami no-, piperidino-, morfolino- eller tiomorfolinoradikal, och/eller R2 är en 4-aminofenylpiperazin-l-ylradikal, om-35 sätts ett halogenderivat, som har formeln: 93114 73 02S- N-Re-Hal ΑΛ-R2
5 YY5 R4 R3 10 där Hal är en halogenatom och R2, R3, R4, R5 och R6 beteck-nar sanuna som ovan, förutom att R6 ej är en dialkylami-no-, piperidino-, morfolino- eller tiomorfolinoradikal, med en förening, som har formeln:
15 HR1 (III) där Rj betecknar sanuna som ovan, förutom att den ej kan vara en 4-aminofenylpiperazin-l-ylradikal, produkten iso-leras och eventuellt omvandlas till ett salt med en mine-20 ralsyra eller en organisk syra, B - för framställning av sädana föreningar med formeln I, där R5 är en grupp =CH-, R2, R3 och R4 är väteatomer, eller R2 och R4 är väteatomer och R3 är en halogenatom, el-. 25 ler R2 och R3 är väteatomer och R4 är en halogenatom, eller R2 och R3 är halogenatomer och R4 är en väteatom, eller R5 är en kväveatom och R2, R3 och R4 är väteatomer, och R6 är en alkylenradikal med 2-4 kolatomer eller en 30 propylenradikal, som i ställning 2 är substituerad med en hydroxi-, alkyl- eller alkoxiradikal, förutom sädana, i vilka Rx är en 4-aminofenylpipera-zin-l-ylradikal, omsätts en förening, som har formeln: 74
95 I 14 02S-NH - R2 v jL (IV^ = \Λ/5 R4 R3 där R2, R3, R4 och R5 betecknar sanuna som ovan, raed ett sä-10 dant derivat, som har formeln: Hal-Rg-Rj^ (X) där Rx och R6 betecknar samma som ovan, produkten isoleras 15 och eventuellt omvandlas till ett salt med en mineralsyra eller en organisk syra, C - för framställning av sädana föreningar med formeln I, där R6 är en propylenradikal, som i ställning 2 är substituerad med en alkoxiradikal, förutom sädana, i vilka 20 R1 är en 1,2,3,6-tetrahydropyrid-l-ylradikal, som i ställning 4 är substituerad med en hydroxifenylradikal, en in-dol-3-ylradikal, som i ställning 5 är substituerad med en hydroxiradikal, en piperazin-l-ylradikal, som i ställning 4 är substituerad med en amino- eller hydroxifenylradikal, . 25 eller en piperidinoradikal, som i ställning 4 är substi- tuerad med en 2-oxo-bensimidazolin-l-yl- eller hydroxifenylradikal, med en hydroxiradikal och en fenylradikal, som eventuellt är substituerad med en hydroxiradikal, eller med en indol-3-ylradikal, som eventuellt i ställning 5 är 30 substituerad med en hydroxiradikal, alkyleras motsvarande förening med formeln (I), där R6 är en propylenradikal, som i ställning 2 är substituerad med en hydroxiradikal, produkten isoleras och eventuellt omvandlas tili ett sait med en mineralsyra eller en orga-35 nisk syra. 93114 75 D - för framställning av sädana föreningar med for-meln I, där R6 är en propylenradikal, som i ställning 2 är substituerad med en dialkylamino-, piperidino-. morfolino-eller tiomorfolinoradikal, omsätts ett derivat, som har 5 formeln: 02S- N - CH2- CH- CH2 - Rl i^yS-*2 l 10 Vt 5 R4 r3 15 där Rx, R2, R3, R4 och R5 är definierade pä samma sätt som i formeln I, för erhällande av ett derivat, som har formeln: H-Rg (XII) 20 där R8 är en dialkylamino-, piperidino-, morfolino- eller tiomorfolinoradikal, produkten isoleras och eventuellt omvandlas tili ett sait med en mineralsyra eller en orga-nisk syra, E - för framställning av sädana föreningar med for-25 mein I, där R6 är en propylenradikal, som i ställning 3 är substituerad med en metylradikal, förutom sädana, i vilka R3 är en acetylaminoradikal och/eller R3 är en substituent, som innehäller en hydroxiradikal, omsätts ett derivat, som har formeln: 30 O2S- NH ΛΛ— «2 I (IV)
35 II R4 R3 ϊό I I 4 76 där R2, R3, R4 och R5 betecknar sanuna som i formeln I, för-utom att R3 ej kan vara en acetylaminoradikal, med ett de-rivat, som har formeln:
5 Br-CH2-CH2-(j:H-R1 (XIII) CH3 där R3 betecknar samma som i formeln I, förutsatt, att den ej innehäller en hydroxlradikal, produkten isoleras och 10 eventuellt omvandlas till ett salt med en mineralsyra el-ler en organisk syra, F - för framställning av sädana föreningar med formeln I, där R3 är en 1,2,3,6-tetrahydropyrid-l-ylradikal, som i ställning 4 är substituerad med en indol-3-ylradi-15 kai, som i kväveatomen är substituerad med en alkyl- eller alkylkarbonylradikal, eller en piperidinoradikal, som i ställning 4 är substituerad med en 2-oxobensimidazolin-l-ylradikal, som i ställning 3 är substituerad med en alkyl-karbonyl- eller bensoylradikal, eller med en indol-3-ylra-20 dikal, som i kväveatomen är substituerad med en alkyl-eller alkylkarbonylradikal, förutom sädana, i vilka R6 är en propylenradikal, som i ställning 2 är substituerad med en hydroxiradikal, omsätts ett derivat, som har formeln: 25 Hal-Rg (XV) där Hai är en halogenatom, och R9 är en alkyl-, alkylkarbo-nyl- eller bensoylradikal, med motsvarande derivat med 30 formeln I, där R: är en 1,2,3,6-tetrahydropyrid-l-ylradi-; kai, som i ställning 4 är substituerad med en indol-3-yl- radikal, eller en piperidinoradikal, som i ställning 4 är substituerad med en 2-oxobensimidazolin-l-yl- eller indol- 3-ylradikal, produkten isoleras och eventuellt omvandlas 35 tili ett sait med en mineralsyra eller en organisk syra, 93114 77 G- för framställning av sädana föreningar med for-meln I, där Rx är en 1,2,3,6-tetrahydropyrid-l-ylradikal, som i ställning 4 är substituerad med en halogenfenylradi-kal, dehydrateras motsvarande förening med formeln I, där 5 Rj är en 1,2,3,6-tetrahydropyrid-l-ylradikal, som i ställning 4 är substituerad med en hydroxiradikal och en halo-genfenylradikal, produkten isoleras och eventuellt omvand-las tili ett sait med en mineralsyra eller en organisk syra,
10 H - för framställning av sädana föreningar med for meln I, där Rx är en 4-aminofenylpiperazin-l-ylradikal, reduceras motsvarande förening med formeln I, där R2 är en 4-nitrofenylpiperazin-l-ylradikal, produkten isoleras och eventuellt omvandlas tili ett sait med en mineralsyra el-15 ler en organisk syra.
2. Förfarande enligt patentkravet 1, känne- t e c k n a t därav, att halogenatomerna är klor- och bromatomer.
3. Förfarande enligt patentkravet 1, känne-20 tecknat därav, att man framställer föreningar med formeln I, där R: är en 1,2,3,6-tetrahydropyrid-l-ylradikal, som i ställning 4 är substituerad med en halogenfe-nylradikal, en fenylradikal eller en indol-3-ylradikal, som i kväveatomen är substituerad med en alkyl- eller al-25 kylkarbonylradikal, en piperazin-l-ylradikal, som i ställ ning 4 är substituerad med en pyrid-2-yl-, 1,2-bensisotia-zol-3-yl- eller fenylradikal, som är substituerad med en halogenatom eller en hydroxi-, amino- eller alkylradikal, eller en piperidinoradikal, som i ställning 4 är substi-30 tuerad med en fenyl- eller N-alkyl-indol-3-ylradikal.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8809218 | 1988-07-07 | ||
| FR8809218A FR2633928B1 (fr) | 1988-07-07 | 1988-07-07 | Derives de (aza)naphtalenesultame, leurs procedes de preparation et les medicaments les contenant |
| FR8902167 | 1989-02-20 | ||
| FR8902167A FR2643265B1 (fr) | 1989-02-20 | 1989-02-20 | Derives de (aza)naphto(1,8-cd)isothiazole dioxyde-1,1 leurs procedes de preparation et les medicaments les contenant |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI893297A0 FI893297A0 (sv) | 1989-07-06 |
| FI893297A7 FI893297A7 (sv) | 1990-01-08 |
| FI93114B true FI93114B (sv) | 1994-11-15 |
| FI93114C FI93114C (sv) | 1995-02-27 |
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| Application Number | Title | Priority Date | Filing Date |
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| FI893297A FI93114C (sv) | 1988-07-07 | 1989-07-06 | Förfarande för framställning av som läkemedel användbara (aza)naftalensultamderivat |
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| EP (1) | EP0350403B1 (sv) |
| JP (1) | JP2763791B2 (sv) |
| KR (1) | KR0138908B1 (sv) |
| AU (1) | AU620114B2 (sv) |
| CA (1) | CA1326483C (sv) |
| DE (1) | DE68904364T2 (sv) |
| DK (1) | DK335489A (sv) |
| ES (1) | ES2054057T3 (sv) |
| FI (1) | FI93114C (sv) |
| GR (1) | GR3006775T3 (sv) |
| HU (1) | HU210833B (sv) |
| IE (1) | IE62364B1 (sv) |
| IL (1) | IL90858A (sv) |
| NO (1) | NO179007C (sv) |
| NZ (1) | NZ229856A (sv) |
| PT (1) | PT91098B (sv) |
| TW (1) | TW197440B (sv) |
Families Citing this family (21)
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| EP0429341A3 (en) * | 1989-11-20 | 1991-11-13 | Rhone-Poulenc Sante | Heterocyclic derivatives, their preparation and pharmaceuticals containing them |
| FR2663635A2 (fr) * | 1989-12-26 | 1991-12-27 | Rhone Poulenc Sante | Derives heterocycliques, leur preparation et les medicaments les contenant. |
| FR2656306A1 (fr) * | 1989-12-26 | 1991-06-28 | Rhone Poulenc Sante | Derives heterocycliques, leur preparation et les medicaments les contenant. |
| FR2662696A2 (fr) * | 1989-12-13 | 1991-12-06 | Rhone Poulenc Sante | Antagonistes de la serotonine, leur preparation et medicaments les contenant. |
| FR2661177A1 (fr) * | 1990-04-23 | 1991-10-25 | Rhone Poulenc Sante | Derives du naphtosultame antagonistes de la serotonine, leur preparation et les medicaments les contenant. |
| FR2675801A1 (fr) * | 1991-04-24 | 1992-10-30 | Rhone Poulenc Rorer Sa | Piperidines, leur preparation et les medicaments les contenant. |
| FR2675800A1 (fr) * | 1991-04-26 | 1992-10-30 | Rhone Poulenc Rorer Sa | Derives heterocycliques antiserotonines leur preparation et les medicaments les contenant. |
| US5202321A (en) * | 1991-06-13 | 1993-04-13 | Merck Frosst Canada, Inc. | Thiopyrano[2,3,4-c,d]indoles as inhibitors of leukotriene biosynthesis |
| FR2687575A1 (fr) * | 1992-02-24 | 1993-08-27 | Rhone Poulenc Rorer Sa | Application du [[(fluoro-4 phenyl)-4 piperazinyl-1]-3 propyl]-2 2h naphto [1,8-cd] isothiazole dioxyde-1,1 pour obtenir un medicament anorexigene. |
| US6001827A (en) * | 1993-12-24 | 1999-12-14 | Suntory Limited | Benzothiazine derivative |
| CN1058492C (zh) * | 1993-12-24 | 2000-11-15 | 三得利株式会社 | 苯并噻嗪衍生物 |
| US5874429A (en) * | 1993-12-24 | 1999-02-23 | Suntory Limited | Benzothiazine derivative |
| GB9416571D0 (en) * | 1994-08-16 | 1994-10-12 | Battelle Memorial Institute | Novel alkylamino derivatives as sigma 2 selective ligands |
| SE9902765D0 (sv) * | 1999-07-21 | 1999-07-21 | Astra Pharma Prod | Novel compounds |
| US6521630B1 (en) | 1999-08-31 | 2003-02-18 | Pfizer Inc. | Tetrahydroquinazoline-2,4-diones and therapeutic uses thereof |
| GB2362381A (en) * | 2000-05-18 | 2001-11-21 | Lilly Co Eli | Pharmaceutically active indolyl-piperidines |
| US6844338B2 (en) | 2000-05-18 | 2005-01-18 | Eli Lilly And Company | Piperidyindoles as serotonin receptor ligands |
| WO2006090783A1 (ja) * | 2005-02-25 | 2006-08-31 | Kowa Co., Ltd. | ４－フルオロイソキノリン－５－スルホニルハライド又はその塩の製造方法 |
| WO2008105442A1 (ja) | 2007-02-28 | 2008-09-04 | Asahi Kasei Pharma Corporation | スルホンアミド誘導体 |
| AU2013288265B2 (en) | 2012-07-09 | 2017-04-06 | Lupin Limited | Tetrahydroquinazolinone derivatives as PARP inhibitors |
| CN108299411B (zh) * | 2017-01-13 | 2021-02-05 | 中国人民解放军军事医学科学院毒物药物研究所 | 4,4-二苯基哌啶类化合物或其可药用盐、药物组合物及用途 |
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|---|---|---|---|---|
| BE755589A (fr) * | 1969-09-03 | 1971-03-02 | Janssen Pharmaceutica Nv | Benzimidazoolcarbamaten |
| DE2139084C3 (de) * | 1971-08-04 | 1979-03-01 | Byk Gulden Lomberg Chemische Fabrik Gmbh, 7750 Konstanz | Verfahren zur Herstellung von 4,4-Diphenyl-piperidinen |
| US4110449A (en) * | 1977-05-23 | 1978-08-29 | E. R. Squibb & Sons, Inc. | 2-substituted benzisothiazol-3-ones |
| US4485107A (en) * | 1982-11-01 | 1984-11-27 | Janssen Pharmaceutica N.V. | [[Bis(aryl)methylene]-1-piperidinyl]alkyl-pyrimidinones |
| JPS59229556A (ja) * | 1983-06-13 | 1984-12-24 | Konishiroku Photo Ind Co Ltd | 熱現像カラ−感光要素 |
| IE58370B1 (en) * | 1985-04-10 | 1993-09-08 | Lundbeck & Co As H | Indole derivatives |
| GB8510840D0 (en) * | 1985-04-29 | 1985-06-05 | Allied Corp | Electrical connectors |
-
1989
- 1989-07-03 IL IL9085889A patent/IL90858A/en not_active IP Right Cessation
- 1989-07-06 ES ES89401948T patent/ES2054057T3/es not_active Expired - Lifetime
- 1989-07-06 DE DE8989401948T patent/DE68904364T2/de not_active Expired - Fee Related
- 1989-07-06 CA CA000604956A patent/CA1326483C/fr not_active Expired - Fee Related
- 1989-07-06 US US07/375,934 patent/US5021420A/en not_active Expired - Fee Related
- 1989-07-06 IE IE218989A patent/IE62364B1/en not_active IP Right Cessation
- 1989-07-06 NO NO892808A patent/NO179007C/no not_active IP Right Cessation
- 1989-07-06 TW TW078105229A patent/TW197440B/zh active
- 1989-07-06 HU HU893433A patent/HU210833B/hu not_active IP Right Cessation
- 1989-07-06 AU AU37906/89A patent/AU620114B2/en not_active Ceased
- 1989-07-06 FI FI893297A patent/FI93114C/sv not_active IP Right Cessation
- 1989-07-06 DK DK335489A patent/DK335489A/da not_active Application Discontinuation
- 1989-07-06 KR KR1019890009655A patent/KR0138908B1/ko not_active Expired - Fee Related
- 1989-07-06 NZ NZ229856A patent/NZ229856A/xx unknown
- 1989-07-06 EP EP89401948A patent/EP0350403B1/fr not_active Expired - Lifetime
- 1989-07-07 PT PT91098A patent/PT91098B/pt not_active IP Right Cessation
- 1989-07-07 JP JP1174356A patent/JP2763791B2/ja not_active Expired - Lifetime
-
1990
- 1990-11-06 US US07/609,506 patent/US5036075A/en not_active Expired - Fee Related
-
1993
- 1993-01-14 GR GR920402400T patent/GR3006775T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL90858A (en) | 1994-08-26 |
| HUT56098A (en) | 1991-07-29 |
| ES2054057T3 (es) | 1994-08-01 |
| DK335489D0 (da) | 1989-07-06 |
| JP2763791B2 (ja) | 1998-06-11 |
| IL90858A0 (en) | 1990-02-09 |
| PT91098A (pt) | 1990-02-08 |
| FI93114C (sv) | 1995-02-27 |
| NO892808L (no) | 1990-01-08 |
| NO179007C (no) | 1996-07-17 |
| IE892189L (en) | 1990-01-07 |
| EP0350403B1 (fr) | 1993-01-13 |
| DE68904364D1 (de) | 1993-02-25 |
| AU3790689A (en) | 1990-01-11 |
| NO179007B (no) | 1996-04-09 |
| NZ229856A (en) | 1990-08-28 |
| JPH0267274A (ja) | 1990-03-07 |
| HU210833B (en) | 1995-08-28 |
| US5036075A (en) | 1991-07-30 |
| NO892808D0 (no) | 1989-07-06 |
| KR900001707A (ko) | 1990-02-27 |
| FI893297A7 (sv) | 1990-01-08 |
| KR0138908B1 (ko) | 1998-05-15 |
| US5021420A (en) | 1991-06-04 |
| FI893297A0 (sv) | 1989-07-06 |
| DK335489A (da) | 1990-01-08 |
| CA1326483C (fr) | 1994-01-25 |
| AU620114B2 (en) | 1992-02-13 |
| PT91098B (pt) | 1994-12-30 |
| DE68904364T2 (de) | 1993-07-15 |
| TW197440B (sv) | 1993-01-01 |
| EP0350403A1 (fr) | 1990-01-10 |
| GR3006775T3 (sv) | 1993-06-30 |
| IE62364B1 (en) | 1995-01-25 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| BB | Publication of examined application | ||
| MM | Patent lapsed |
Owner name: RHONE-POULENC SANTE |