LV12593B - HETEROCYCLIC COMPOUNDS FOR TREATMENT OF CNS AND HEART AND HOSPITAL SYSTEM DISTRIBUTION - Google Patents
HETEROCYCLIC COMPOUNDS FOR TREATMENT OF CNS AND HEART AND HOSPITAL SYSTEM DISTRIBUTION Download PDFInfo
- Publication number
- LV12593B LV12593B LVP-00-100A LV000100A LV12593B LV 12593 B LV12593 B LV 12593B LV 000100 A LV000100 A LV 000100A LV 12593 B LV12593 B LV 12593B
- Authority
- LV
- Latvia
- Prior art keywords
- ethyl
- piperazine
- isochroman
- methoxyphenyl
- het
- Prior art date
Links
- 238000011282 treatment Methods 0.000 title description 17
- 208000024172 Cardiovascular disease Diseases 0.000 title description 6
- 150000002391 heterocyclic compounds Chemical class 0.000 title 1
- -1 aromatic bicyclic amines Chemical class 0.000 claims abstract description 181
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 233
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 166
- 125000000217 alkyl group Chemical group 0.000 claims description 52
- 229910052799 carbon Inorganic materials 0.000 claims description 42
- 150000003839 salts Chemical class 0.000 claims description 41
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 18
- HEBMCVBCEDMUOF-UHFFFAOYSA-N isochromane Chemical compound C1=CC=C2COCCC2=C1 HEBMCVBCEDMUOF-UHFFFAOYSA-N 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- XWPHCXHSCHILFV-UHFFFAOYSA-N 1-[2-(6-bromo-3,4-dihydro-1h-isochromen-1-yl)ethyl]-4-(3,4-dichlorophenyl)piperazine Chemical compound C1=C(Cl)C(Cl)=CC=C1N1CCN(CCC2C3=CC=C(Br)C=C3CCO2)CC1 XWPHCXHSCHILFV-UHFFFAOYSA-N 0.000 claims description 10
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 5
- SHJOWWBWZGRHLF-UHFFFAOYSA-N 1-[1-(3,4-dihydro-1h-isochromen-1-yl)-2-methylpropan-2-yl]-4-(2-methoxyphenyl)piperazine Chemical compound COC1=CC=CC=C1N1CCN(C(C)(C)CC2C3=CC=CC=C3CCO2)CC1 SHJOWWBWZGRHLF-UHFFFAOYSA-N 0.000 claims description 3
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 claims description 3
- 239000012965 benzophenone Substances 0.000 claims description 3
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 3
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 3
- NWLFULOZPXDHRN-UHFFFAOYSA-N 1-(3-chlorophenyl)-4-[2-(3,4-dihydro-1h-isochromen-1-yl)ethyl]piperazine Chemical compound ClC1=CC=CC(N2CCN(CCC3C4=CC=CC=C4CCO3)CC2)=C1 NWLFULOZPXDHRN-UHFFFAOYSA-N 0.000 claims description 2
- JXRQHKXEZIPBIV-UHFFFAOYSA-N 1-[2-(3,4-dihydro-1h-isochromen-1-yl)ethyl]-4-(4-ethoxyphenyl)piperazine Chemical compound C1=CC(OCC)=CC=C1N1CCN(CCC2C3=CC=CC=C3CCO2)CC1 JXRQHKXEZIPBIV-UHFFFAOYSA-N 0.000 claims description 2
- AHTMVIGBCFJKEL-UHFFFAOYSA-N 1-[2-(3,4-dihydro-1h-isochromen-1-yl)ethyl]-4-(4-propan-2-yloxyphenyl)piperazine Chemical compound C1=CC(OC(C)C)=CC=C1N1CCN(CCC2C3=CC=CC=C3CCO2)CC1 AHTMVIGBCFJKEL-UHFFFAOYSA-N 0.000 claims description 2
- TVKPGNSYNGCMHF-UHFFFAOYSA-N 4-[4-[2-(6-fluoro-3,4-dihydro-1h-isochromen-1-yl)ethyl]piperazin-1-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1CCN(CCC2C3=CC=C(F)C=C3CCO2)CC1 TVKPGNSYNGCMHF-UHFFFAOYSA-N 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 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 description 2
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 claims description 2
- 125000004250 isochroman-1-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])([H])OC2([H])* 0.000 claims 20
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 15
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 9
- IAUNACXRZSWWJT-UHFFFAOYSA-N 1-[2-(3,4-dihydro-1h-isochromen-1-yl)ethyl]-4-(4-methoxyphenyl)piperazine Chemical compound C1=CC(OC)=CC=C1N1CCN(CCC2C3=CC=CC=C3CCO2)CC1 IAUNACXRZSWWJT-UHFFFAOYSA-N 0.000 claims 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 2
- FQMQAPOVPMCSRI-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)-4-[2-(3,4-dihydro-1h-isochromen-1-yl)ethyl]piperazine Chemical compound C1=C(Cl)C(Cl)=CC=C1N1CCN(CCC2C3=CC=CC=C3CCO2)CC1 FQMQAPOVPMCSRI-UHFFFAOYSA-N 0.000 claims 1
- TYBOIFXSTWOXGD-UHFFFAOYSA-N 1-(4-chlorophenyl)-4-[2-(3,4-dihydro-1h-isochromen-1-yl)ethyl]piperazine Chemical compound C1=CC(Cl)=CC=C1N1CCN(CCC2C3=CC=CC=C3CCO2)CC1 TYBOIFXSTWOXGD-UHFFFAOYSA-N 0.000 claims 1
- LLOOZAFAYJVQKK-UHFFFAOYSA-N 1-(4-methoxyphenyl)-4-[2-(1,3,4,5-tetrahydro-2-benzoxepin-1-yl)ethyl]piperazine Chemical compound C1=CC(OC)=CC=C1N1CCN(CCC2C3=CC=CC=C3CCCO2)CC1 LLOOZAFAYJVQKK-UHFFFAOYSA-N 0.000 claims 1
- JGJTWCFWPIEDML-UHFFFAOYSA-N 1-[2-(2,3,4,4a,6,10b-hexahydro-1h-benzo[c]chromen-6-yl)ethyl]-4-(4-fluorophenyl)piperazine Chemical compound C1=CC(F)=CC=C1N1CCN(CCC2C3=CC=CC=C3C3CCCCC3O2)CC1 JGJTWCFWPIEDML-UHFFFAOYSA-N 0.000 claims 1
- UKOCGOXTVCIACM-UHFFFAOYSA-N 1-[2-(3,4-dihydro-1H-2-benzopyran-1-yl)ethyl]-4-(4-fluorophenyl)piperazine Chemical compound C1=CC(F)=CC=C1N1CCN(CCC2C3=CC=CC=C3CCO2)CC1 UKOCGOXTVCIACM-UHFFFAOYSA-N 0.000 claims 1
- GFDZUHLCNNXHJV-UHFFFAOYSA-N 1-[2-(3,4-dihydro-1h-isochromen-1-yl)ethyl]-4-(2-methoxyphenyl)piperazine Chemical compound COC1=CC=CC=C1N1CCN(CCC2C3=CC=CC=C3CCO2)CC1 GFDZUHLCNNXHJV-UHFFFAOYSA-N 0.000 claims 1
- OHBQZWSNQDHHNE-UHFFFAOYSA-N 1-[2-(3,4-dihydro-1h-isochromen-1-yl)ethyl]-4-(2-methylphenyl)piperazine Chemical compound CC1=CC=CC=C1N1CCN(CCC2C3=CC=CC=C3CCO2)CC1 OHBQZWSNQDHHNE-UHFFFAOYSA-N 0.000 claims 1
- ACAZWUHJRGNNFL-UHFFFAOYSA-N 1-[2-(3,4-dihydro-1h-isochromen-1-yl)ethyl]-4-(3-methoxyphenyl)piperazine Chemical compound COC1=CC=CC(N2CCN(CCC3C4=CC=CC=C4CCO3)CC2)=C1 ACAZWUHJRGNNFL-UHFFFAOYSA-N 0.000 claims 1
- ITYINGUJRDFDQJ-UHFFFAOYSA-N 1-[2-(3,4-dihydro-1h-isochromen-1-yl)ethyl]-4-(4-methylphenyl)piperazine Chemical compound C1=CC(C)=CC=C1N1CCN(CCC2C3=CC=CC=C3CCO2)CC1 ITYINGUJRDFDQJ-UHFFFAOYSA-N 0.000 claims 1
- MJGWYWCQTPTHLL-UHFFFAOYSA-N 1-[2-(3,4-dihydro-1h-isochromen-1-yl)ethyl]-4-phenylpiperidine Chemical compound O1CCC2=CC=CC=C2C1CCN(CC1)CCC1C1=CC=CC=C1 MJGWYWCQTPTHLL-UHFFFAOYSA-N 0.000 claims 1
- FYOHISLGJUTCND-UHFFFAOYSA-N 1-[2-(3,4-dihydro-1h-isochromen-1-yl)ethyl]piperazine Chemical compound O1CCC2=CC=CC=C2C1CCN1CCNCC1 FYOHISLGJUTCND-UHFFFAOYSA-N 0.000 claims 1
- FXRVAILYOCGMKX-UHFFFAOYSA-N 1-[2-(6-chloro-3,4-dihydro-1h-isochromen-1-yl)ethyl]-4-(4-methoxyphenyl)piperazine Chemical compound C1=CC(OC)=CC=C1N1CCN(CCC2C3=CC=C(Cl)C=C3CCO2)CC1 FXRVAILYOCGMKX-UHFFFAOYSA-N 0.000 claims 1
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 claims 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 1
- RNADZIJPXOABLO-IXFSTUDKSA-N 4-[(3r,5s)-4-[2-[(1s)-3,4-dihydro-1h-isochromen-1-yl]ethyl]-3,5-dimethylpiperazin-1-yl]benzenesulfonamide Chemical compound C([C@@H](N([C@H](C)C1)CC[C@H]2C3=CC=CC=C3CCO2)C)N1C1=CC=C(S(N)(=O)=O)C=C1 RNADZIJPXOABLO-IXFSTUDKSA-N 0.000 claims 1
- BECDFKNOBZYKDM-QFIPXVFZSA-N 4-[4-[2-[(1s)-3,4-dihydro-1h-isochromen-1-yl]ethyl]-1,4-diazepan-1-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1CCN(CC[C@H]2C3=CC=CC=C3CCO2)CCC1 BECDFKNOBZYKDM-QFIPXVFZSA-N 0.000 claims 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims 1
- 241001077660 Molo Species 0.000 claims 1
- WLQDZIODBKZAOY-UHFFFAOYSA-N N-[1-[2-(3,4-dihydro-1H-isochromen-1-yl)ethyl]piperidin-4-yl]-3-ethoxy-N-methylpyridin-2-amine methanesulfonic acid Chemical compound CS(O)(=O)=O.CCOC1=CC=CN=C1N(C)C1CCN(CCC2C3=CC=CC=C3CCO2)CC1 WLQDZIODBKZAOY-UHFFFAOYSA-N 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 230000001052 transient effect Effects 0.000 claims 1
- 239000000164 antipsychotic agent Substances 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 454
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 317
- 150000001875 compounds Chemical class 0.000 description 201
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 188
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 186
- 239000000203 mixture Substances 0.000 description 166
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 149
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 117
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 115
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 104
- 238000000034 method Methods 0.000 description 89
- 230000002829 reductive effect Effects 0.000 description 86
- 229960005141 piperazine Drugs 0.000 description 80
- 239000002253 acid Substances 0.000 description 71
- 239000012074 organic phase Substances 0.000 description 70
- 239000002480 mineral oil Substances 0.000 description 69
- 229940042472 mineral oil Drugs 0.000 description 69
- 235000010446 mineral oil Nutrition 0.000 description 69
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 68
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 62
- 239000000741 silica gel Substances 0.000 description 62
- 229910002027 silica gel Inorganic materials 0.000 description 62
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 60
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 56
- 239000011780 sodium chloride Substances 0.000 description 55
- 235000011167 hydrochloric acid Nutrition 0.000 description 54
- 229960000443 hydrochloric acid Drugs 0.000 description 54
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 52
- 235000019341 magnesium sulphate Nutrition 0.000 description 52
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 51
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 51
- 238000006243 chemical reaction Methods 0.000 description 49
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
- GJLPPLXUSQQWIS-UHFFFAOYSA-N 1-[2-(3,4-dihydro-1h-isochromen-1-yl)ethyl]-4-[3-(trifluoromethyl)phenyl]piperazine;dihydrochloride Chemical compound Cl.Cl.FC(F)(F)C1=CC=CC(N2CCN(CCC3C4=CC=CC=C4CCO3)CC2)=C1 GJLPPLXUSQQWIS-UHFFFAOYSA-N 0.000 description 42
- 150000002148 esters Chemical class 0.000 description 40
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 38
- 239000002904 solvent Substances 0.000 description 38
- 239000000243 solution Substances 0.000 description 37
- 125000001424 substituent group Chemical group 0.000 description 34
- 125000002619 bicyclic group Chemical group 0.000 description 33
- 125000001246 bromo group Chemical group Br* 0.000 description 33
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 30
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 229940073584 methylene chloride Drugs 0.000 description 27
- 238000003756 stirring Methods 0.000 description 27
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 26
- 125000003118 aryl group Chemical group 0.000 description 26
- 235000017557 sodium bicarbonate Nutrition 0.000 description 26
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 26
- 229960001407 sodium bicarbonate Drugs 0.000 description 26
- 239000007787 solid Substances 0.000 description 26
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 25
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 239000012458 free base Substances 0.000 description 23
- 239000002585 base Substances 0.000 description 22
- 125000001309 chloro group Chemical group Cl* 0.000 description 22
- 229920006395 saturated elastomer Polymers 0.000 description 22
- 150000001408 amides Chemical class 0.000 description 21
- 230000000875 corresponding effect Effects 0.000 description 20
- UAHRYAPHTHSBPR-UHFFFAOYSA-N n-[[1-[2-(3,4-dihydro-1h-isochromen-1-yl)ethyl]piperidin-4-yl]methyl]-3-ethoxypyridin-2-amine;methanesulfonic acid Chemical compound CS(O)(=O)=O.CCOC1=CC=CN=C1NCC1CCN(CCC2C3=CC=CC=C3CCO2)CC1 UAHRYAPHTHSBPR-UHFFFAOYSA-N 0.000 description 20
- 235000011121 sodium hydroxide Nutrition 0.000 description 20
- 229940083608 sodium hydroxide Drugs 0.000 description 20
- 239000000463 material Substances 0.000 description 19
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 19
- 239000000047 product Substances 0.000 description 18
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 17
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
- 150000001721 carbon Chemical group 0.000 description 16
- 239000012280 lithium aluminium hydride Substances 0.000 description 16
- 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 15
- 239000012071 phase Substances 0.000 description 15
- 239000011734 sodium Substances 0.000 description 15
- 229910052708 sodium Inorganic materials 0.000 description 15
- 229910052938 sodium sulfate Inorganic materials 0.000 description 15
- 235000011152 sodium sulphate Nutrition 0.000 description 15
- CTZWEXAQFFYMQD-UHFFFAOYSA-N 2-(3,4-dihydro-1h-isochromen-1-yl)acetic acid Chemical compound C1=CC=C2C(CC(=O)O)OCCC2=C1 CTZWEXAQFFYMQD-UHFFFAOYSA-N 0.000 description 14
- 150000001412 amines Chemical class 0.000 description 14
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 14
- 239000000126 substance Substances 0.000 description 14
- 238000004809 thin layer chromatography Methods 0.000 description 14
- UBXIECYGXFARTC-UHFFFAOYSA-N 1-(2-chlorophenyl)piperazine;dihydrochloride Chemical compound Cl.Cl.ClC1=CC=CC=C1N1CCNCC1 UBXIECYGXFARTC-UHFFFAOYSA-N 0.000 description 13
- AVJKDKWRVSSJPK-UHFFFAOYSA-N 1-(4-fluorophenyl)piperazine Chemical compound C1=CC(F)=CC=C1N1CCNCC1 AVJKDKWRVSSJPK-UHFFFAOYSA-N 0.000 description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 13
- 238000001816 cooling Methods 0.000 description 13
- 229940086542 triethylamine Drugs 0.000 description 13
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 12
- 238000004128 high performance liquid chromatography Methods 0.000 description 12
- 229940098779 methanesulfonic acid Drugs 0.000 description 12
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Classifications
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
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- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- 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
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
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- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
- C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/76—Benzo[c]pyrans
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- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
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- C07D311/78—Ring systems having three or more relevant rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
- C07D313/02—Seven-membered rings
- C07D313/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D313/08—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with one six-membered ring
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- 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
- C07D405/06—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 carbon chain containing only aliphatic carbon atoms
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- 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
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
- C07F7/0814—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring said ring is substituted at a C ring atom by Si
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Anesthesiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Ventilation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US17521893A | 1993-12-28 | 1993-12-28 | |
US27997494A | 1994-07-25 | 1994-07-25 |
Publications (2)
Publication Number | Publication Date |
---|---|
LV12593A LV12593A (en) | 2000-12-20 |
LV12593B true LV12593B (en) | 2001-04-20 |
Family
ID=26870999
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
LVP-00-100A LV12593B (en) | 1993-12-28 | 2000-07-28 | HETEROCYCLIC COMPOUNDS FOR TREATMENT OF CNS AND HEART AND HOSPITAL SYSTEM DISTRIBUTION |
Country Status (17)
Country | Link |
---|---|
US (2) | US5877317A (de) |
EP (1) | EP0737189B1 (de) |
JP (1) | JP3773255B2 (de) |
CN (1) | CN1046507C (de) |
AT (1) | ATE182590T1 (de) |
AU (1) | AU684874B2 (de) |
CA (1) | CA2176722A1 (de) |
DE (1) | DE69419778T2 (de) |
DK (1) | DK0737189T3 (de) |
ES (1) | ES2133714T3 (de) |
GR (1) | GR3031585T3 (de) |
IL (1) | IL111940A (de) |
LV (1) | LV12593B (de) |
MY (1) | MY115431A (de) |
NZ (1) | NZ277373A (de) |
TW (1) | TW419475B (de) |
WO (1) | WO1995018118A1 (de) |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2225282A1 (en) * | 1995-06-30 | 1997-01-23 | Pharmacia & Upjohn Company | 1,6-disubstituted isochromans for treatment of migraine headaches |
FR2737724B1 (fr) * | 1995-08-09 | 1997-09-05 | Synthelabo | Derives de 1-[2-(2,3-dihydro-1h-inden-1-yl)ethyl]-4- (naphtalen-1-yl) piperazine, leur preparation et leur application en therapeutique |
US6342533B1 (en) | 1998-12-01 | 2002-01-29 | Sepracor, Inc. | Derivatives of (−)-venlafaxine and methods of preparing and using the same |
AR021509A1 (es) * | 1998-12-08 | 2002-07-24 | Lundbeck & Co As H | Derivados de benzofurano, su preparacion y uso |
KR20010081071A (ko) | 1998-12-08 | 2001-08-25 | 피터슨 존 메이달 | 벤조푸란 유도체, 그것들의 제조 및 사용 |
ES2305606T3 (es) * | 1999-04-06 | 2008-11-01 | Sepracor Inc. | Succinato de o-desmetilvenlafaxina. |
IL154378A0 (en) * | 2000-08-16 | 2003-09-17 | Upjohn Co | Compounds for the treatment of addictive disorders |
GB2370270A (en) * | 2000-12-20 | 2002-06-26 | Lilly Co Eli | Pharmaceutical compounds |
US7335660B2 (en) | 2001-12-19 | 2008-02-26 | Eli Lilly And Company | Isochroman compounds for treatment of CNS disorders |
GB0130339D0 (en) * | 2001-12-19 | 2002-02-06 | Lilly Co Eli | Isochroman compounds |
JP5231707B2 (ja) * | 2004-03-31 | 2013-07-10 | 大日本印刷株式会社 | フェノール置換環状アミンの新規アシル化法 |
US7541355B2 (en) * | 2005-05-23 | 2009-06-02 | Vela Acquisition Corporation | Conversion process for 2,3-benzodiazepine enantiomers |
JP2009500420A (ja) * | 2005-07-06 | 2009-01-08 | セプラコア インコーポレーテッド | エスゾピクロン及びo−デスメチルベンラファキシンの組み合わせ、並びに閉経期並びに気分、不安、及び認知障害の治療方法 |
JO2769B1 (en) | 2005-10-26 | 2014-03-15 | جانسين فارماسوتيكا ان. في | Rapid decomposition of physiologically antagonistic agents of the 2-dopamine receptor |
JO2849B1 (en) | 2007-02-13 | 2015-03-15 | جانسين فارماسوتيكا ان. في | Dopamine 2 receptor antagonists are rapidly hydrolyzed |
AU2008240729B2 (en) | 2007-04-23 | 2012-08-23 | Janssen Pharmaceutica N.V. | Thia(dia)zoles as fast dissociating dopamine 2 receptor antagonists |
DK2148873T3 (da) | 2007-04-23 | 2012-11-26 | Janssen Pharmaceutica Nv | 4-alkoxypyridazinderivater som hurtigt dissocierende dopamin 2- receptorantagonister |
ES2622161T3 (es) | 2008-07-31 | 2017-07-05 | Janssen Pharmaceutica, N.V. | Piridinas sustituidas con piperazin-1-il-trifluorometilo como antagonistas del receptor de la dopamina 2 de disociación rápida |
TW201422590A (zh) | 2012-09-07 | 2014-06-16 | Abbvie Inc | 雜環核激素受體調節劑 |
EP2935284A4 (de) | 2012-12-21 | 2016-04-27 | Abbvie Inc | Heterocyclische nuklearhormonrezeptormodulatoren |
US11192913B2 (en) * | 2020-01-09 | 2021-12-07 | The United States of America, as represented The Secretary of Agriculture | C-glycoside amine derivatives and methods of making |
Family Cites Families (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1143702A (de) * | 1965-03-18 | |||
US3549656A (en) * | 1967-12-28 | 1970-12-22 | Kefalas As | Antidepressant 1 - aminoalkyl - thiophthalanes and acid addition salts thereof |
US4130646A (en) * | 1975-07-25 | 1978-12-19 | E. R. Squibb & Sons, Inc. | 1,2,3,4-Tetrahydro-2-((4-(phenyl)-1-piperazinyl)methyl)-1-naphthalenols and derivatives and analogs thereof |
JPS5919549B2 (ja) * | 1976-01-01 | 1984-05-07 | 武田薬品工業株式会社 | 異節環状化合物 |
GB1552004A (en) * | 1976-05-26 | 1979-09-05 | Takeda Chemical Industries Ltd | Isochroman derivatives |
US4153612A (en) * | 1977-10-31 | 1979-05-08 | The Upjohn Company | 2-Benzoxepins |
US4179510A (en) * | 1977-10-31 | 1979-12-18 | The Upjohn Company | Methods of treating psychosis |
US4556656A (en) * | 1978-10-23 | 1985-12-03 | The Upjohn Company | 2-Benzoxepins |
CA1338012C (en) * | 1987-04-27 | 1996-01-30 | John Michael Mccall | Pharmaceutically active amines |
US5120843A (en) * | 1987-04-27 | 1992-06-09 | Upjohn | Pharmaceutically active amines |
FR2618437B1 (fr) * | 1987-07-23 | 1989-11-17 | Rhone Poulenc Sante | Nouveaux derives du benzopyranne, leur preparation et les medicaments qui les contiennent |
US5140040A (en) * | 1988-01-15 | 1992-08-18 | Abbott Laboratories | 1-aminomethyl-1,2,3,4-tetrahydronaphthalenes |
US4994486A (en) * | 1989-05-31 | 1991-02-19 | Abbott Laboratories | Dopaminergic compounds |
US4963568A (en) * | 1989-05-31 | 1990-10-16 | Abbott Laboratories | Dopamine agonists |
JPH03178952A (ja) * | 1989-06-23 | 1991-08-02 | Kyowa Hakko Kogyo Co Ltd | アリールアルキルアミン誘導体 |
US5032598A (en) * | 1989-12-08 | 1991-07-16 | Merck & Co., Inc. | Nitrogens containing heterocyclic compounds as class III antiarrhythmic agents |
US5215989A (en) * | 1989-12-08 | 1993-06-01 | Merck & Co., Inc. | Nitrogen-containing heterocyclic compounds as class III antiarrhythmic agents |
EP0450689A1 (de) * | 1990-04-02 | 1991-10-09 | Akzo Nobel N.V. | Isochromanderivate |
IE73232B1 (en) * | 1990-05-25 | 1997-05-21 | Akzo Nv | Isochromane derivatives |
FR2664592B1 (fr) * | 1990-07-10 | 1994-09-02 | Adir | Nouveaux derives de la piperidine, de la tetrahydropyridine et de la pyrrolidine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
WO1992018089A2 (en) * | 1991-04-09 | 1992-10-29 | The Upjohn Company | Use of steroidal and non-steroidal amines to sensitize multidrug-resistant cells |
FR2687401B1 (fr) * | 1992-02-18 | 1994-05-20 | Meram Laboratoires | Derives de la 1,4-dialkylpiperazine, procedes d'obtention et compositions pharmaceutiques les contenant. |
IT1255178B (it) * | 1992-06-26 | 1995-10-20 | Pierrel Spa | N(eter0)-aril-n(etero)-tetralinalchil piperazine aventi attivita' serotoninergica,dopaminergica e adrenergica |
-
1994
- 1994-11-30 CA CA002176722A patent/CA2176722A1/en not_active Abandoned
- 1994-11-30 JP JP51802595A patent/JP3773255B2/ja not_active Expired - Fee Related
- 1994-11-30 CN CN94194651A patent/CN1046507C/zh not_active Expired - Fee Related
- 1994-11-30 AT AT95903555T patent/ATE182590T1/de not_active IP Right Cessation
- 1994-11-30 NZ NZ277373A patent/NZ277373A/en unknown
- 1994-11-30 ES ES95903555T patent/ES2133714T3/es not_active Expired - Lifetime
- 1994-11-30 AU AU12571/95A patent/AU684874B2/en not_active Ceased
- 1994-11-30 DK DK95903555T patent/DK0737189T3/da active
- 1994-11-30 US US08/663,094 patent/US5877317A/en not_active Expired - Lifetime
- 1994-11-30 EP EP95903555A patent/EP0737189B1/de not_active Expired - Lifetime
- 1994-11-30 WO PCT/US1994/013284 patent/WO1995018118A1/en active IP Right Grant
- 1994-11-30 DE DE69419778T patent/DE69419778T2/de not_active Expired - Fee Related
- 1994-12-09 IL IL11194094A patent/IL111940A/xx not_active IP Right Cessation
- 1994-12-16 TW TW083111775A patent/TW419475B/zh not_active IP Right Cessation
- 1994-12-28 MY MYPI94003542A patent/MY115431A/en unknown
-
1999
- 1999-01-28 US US09/239,007 patent/US6133446A/en not_active Expired - Fee Related
- 1999-10-21 GR GR990402679T patent/GR3031585T3/el unknown
-
2000
- 2000-07-28 LV LVP-00-100A patent/LV12593B/en unknown
Also Published As
Publication number | Publication date |
---|---|
WO1995018118A1 (en) | 1995-07-06 |
US6133446A (en) | 2000-10-17 |
IL111940A (en) | 2000-09-28 |
ATE182590T1 (de) | 1999-08-15 |
TW419475B (en) | 2001-01-21 |
NZ277373A (en) | 1998-07-28 |
DE69419778D1 (de) | 1999-09-02 |
GR3031585T3 (en) | 2000-01-31 |
LV12593A (en) | 2000-12-20 |
EP0737189A1 (de) | 1996-10-16 |
US5877317A (en) | 1999-03-02 |
DE69419778T2 (de) | 1999-12-09 |
CN1046507C (zh) | 1999-11-17 |
IL111940A0 (en) | 1995-03-15 |
CN1139431A (zh) | 1997-01-01 |
MY115431A (en) | 2003-06-30 |
ES2133714T3 (es) | 1999-09-16 |
AU684874B2 (en) | 1998-01-08 |
JPH09507224A (ja) | 1997-07-22 |
JP3773255B2 (ja) | 2006-05-10 |
AU1257195A (en) | 1995-07-17 |
EP0737189B1 (de) | 1999-07-28 |
DK0737189T3 (da) | 2000-03-06 |
CA2176722A1 (en) | 1995-07-06 |
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