CA2308151A1 - Biphenyl derivatives as pharmaceuticals - Google Patents
Biphenyl derivatives as pharmaceuticals Download PDFInfo
- Publication number
- CA2308151A1 CA2308151A1 CA002308151A CA2308151A CA2308151A1 CA 2308151 A1 CA2308151 A1 CA 2308151A1 CA 002308151 A CA002308151 A CA 002308151A CA 2308151 A CA2308151 A CA 2308151A CA 2308151 A1 CA2308151 A1 CA 2308151A1
- Authority
- CA
- Canada
- Prior art keywords
- methoxy
- compound
- formula
- biphenyl
- free base
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000003814 drug Substances 0.000 title claims abstract description 7
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 70
- 239000012458 free base Substances 0.000 claims description 29
- 239000002253 acid Substances 0.000 claims description 21
- 150000003839 salts Chemical group 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 9
- 210000004556 brain Anatomy 0.000 claims description 7
- 206010015037 epilepsy Diseases 0.000 claims description 7
- 208000014674 injury Diseases 0.000 claims description 7
- 230000008733 trauma Effects 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 150000002431 hydrogen Chemical group 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000001589 carboacyl group Chemical group 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- WZWAGNASFYMVNX-UHFFFAOYSA-N 3-[2-methoxy-5-[4-(trifluoromethyl)phenyl]phenyl]-1-methylpiperidine Chemical compound COC1=CC=C(C=2C=CC(=CC=2)C(F)(F)F)C=C1C1CCCN(C)C1 WZWAGNASFYMVNX-UHFFFAOYSA-N 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000008024 pharmaceutical diluent Substances 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical group OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 2
- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 4
- SSJXIUAHEKJCMH-WDSKDSINSA-N (1s,2s)-cyclohexane-1,2-diamine Chemical compound N[C@H]1CCCC[C@@H]1N SSJXIUAHEKJCMH-WDSKDSINSA-N 0.000 claims 1
- YBFOLXIGOMIICM-UHFFFAOYSA-N 3-[2-methoxy-5-[4-(trifluoromethyl)phenyl]phenyl]-1-propylpiperidine Chemical compound C1N(CCC)CCCC1C1=CC(C=2C=CC(=CC=2)C(F)(F)F)=CC=C1OC YBFOLXIGOMIICM-UHFFFAOYSA-N 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 58
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
- 239000000203 mixture Substances 0.000 description 34
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- 239000003921 oil Substances 0.000 description 31
- 235000019198 oils Nutrition 0.000 description 31
- 239000000243 solution Substances 0.000 description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- 235000019439 ethyl acetate Nutrition 0.000 description 21
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 229960001866 silicon dioxide Drugs 0.000 description 18
- 239000012267 brine Substances 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 229940093499 ethyl acetate Drugs 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 10
- 239000013078 crystal Substances 0.000 description 10
- 239000012362 glacial acetic acid Substances 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- FWWOWPGPERBCNJ-UHFFFAOYSA-N 2-hydroxy-4-(2-hydroxyethoxy)-4-oxobutanoic acid Chemical compound OCCOC(=O)CC(O)C(O)=O FWWOWPGPERBCNJ-UHFFFAOYSA-N 0.000 description 9
- 229910017974 NH40H Inorganic materials 0.000 description 9
- 229910021529 ammonia Inorganic materials 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 8
- HTFXWAOSQODIBI-UHFFFAOYSA-N 2-benzyl-1,3-dihydropyrrolo[3,4-c]pyridine Chemical compound C1C2=CC=NC=C2CN1CC1=CC=CC=C1 HTFXWAOSQODIBI-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 230000003287 optical effect Effects 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- VBAHFEPKESUPDE-UHFFFAOYSA-N 2-methoxyamphetamine Chemical compound COC1=CC=CC=C1CC(C)N VBAHFEPKESUPDE-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- 208000006011 Stroke Diseases 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 101150041968 CDC13 gene Proteins 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- -1 piperidino, piperazinyl Chemical group 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 238000006824 Eschweiler-Clarke methylation reaction Methods 0.000 description 4
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000001632 sodium acetate Substances 0.000 description 4
- 235000017281 sodium acetate Nutrition 0.000 description 4
- MKVBOOXXOLQOHN-UHFFFAOYSA-N 1-(2-methoxyphenyl)-n,n-dimethylpropan-2-amine Chemical compound COC1=CC=CC=C1CC(C)N(C)C MKVBOOXXOLQOHN-UHFFFAOYSA-N 0.000 description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- 208000002381 Brain Hypoxia Diseases 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- NUOXSJGIRWCWNR-UHFFFAOYSA-N decane-3,5-dione Chemical compound CCCCCC(=O)CC(=O)CC NUOXSJGIRWCWNR-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-M fumarate(1-) Chemical compound OC(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-M 0.000 description 3
- 229930195712 glutamate Natural products 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- YTEROTYXILFWNI-UHFFFAOYSA-N 1-(2-methoxyphenyl)butan-2-amine Chemical compound CCC(N)CC1=CC=CC=C1OC YTEROTYXILFWNI-UHFFFAOYSA-N 0.000 description 2
- MZMHWEHHKKBAKU-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-n,n-dimethylpropan-2-amine Chemical compound COC1=CC=C(Br)C=C1CC(C)N(C)C MZMHWEHHKKBAKU-UHFFFAOYSA-N 0.000 description 2
- WIDZSVXMBTVJPQ-UHFFFAOYSA-N 1-[2-methoxy-5-[4-(trifluoromethyl)phenyl]phenyl]propan-2-amine hydrochloride Chemical compound Cl.COc1ccc(cc1CC(C)N)-c1ccc(cc1)C(F)(F)F WIDZSVXMBTVJPQ-UHFFFAOYSA-N 0.000 description 2
- OFYVONMDKJKATB-FPLPWBNLSA-N 1-methoxy-2-[(z)-2-nitroprop-1-enyl]benzene Chemical compound COC1=CC=CC=C1\C=C(\C)[N+]([O-])=O OFYVONMDKJKATB-FPLPWBNLSA-N 0.000 description 2
- PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 2
- VFQBJSIARXYLCL-UHFFFAOYSA-N 2-[2-methoxy-5-[4-(trifluoromethyl)phenyl]phenyl]ethanamine Chemical compound C1=C(CCN)C(OC)=CC=C1C1=CC=C(C(F)(F)F)C=C1 VFQBJSIARXYLCL-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
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- 241001465754 Metazoa Species 0.000 description 2
- 208000035544 Nonketotic hyperglycinaemia Diseases 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FVECELJHCSPHKY-UHFFFAOYSA-N Veratridine Natural products C1=C(OC)C(OC)=CC=C1C(=O)OC1C2(O)OC34CC5(O)C(CN6C(CCC(C)C6)C6(C)O)C6(O)C(O)CC5(O)C4CCC2C3(C)CC1 FVECELJHCSPHKY-UHFFFAOYSA-N 0.000 description 2
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- 238000004296 chiral HPLC Methods 0.000 description 2
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- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
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- 238000002425 crystallisation Methods 0.000 description 2
- VRTOYNNAQUDMNG-UHFFFAOYSA-N ethyl 3-(2-methoxyphenyl)pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CCC1C1=CC=CC=C1OC VRTOYNNAQUDMNG-UHFFFAOYSA-N 0.000 description 2
- BZOLCSHUPLJTJK-UHFFFAOYSA-N ethyl 3-(5-bromo-2-methoxyphenyl)pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CCC1C1=CC(Br)=CC=C1OC BZOLCSHUPLJTJK-UHFFFAOYSA-N 0.000 description 2
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- 208000028867 ischemia Diseases 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 210000003657 middle cerebral artery Anatomy 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- XTEGVFVZDVNBPF-UHFFFAOYSA-N naphthalene-1,5-disulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1S(O)(=O)=O XTEGVFVZDVNBPF-UHFFFAOYSA-N 0.000 description 2
- 230000003961 neuronal insult Effects 0.000 description 2
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 2
- FVECELJHCSPHKY-JLSHOZRYSA-N veratridine Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)O[C@@H]1[C@@]2(O)O[C@]34C[C@@]5(O)[C@H](CN6[C@@H](CC[C@H](C)C6)[C@@]6(C)O)[C@]6(O)[C@@H](O)C[C@@]5(O)[C@@H]4CC[C@H]2[C@]3(C)CC1 FVECELJHCSPHKY-JLSHOZRYSA-N 0.000 description 2
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
- C07C211/29—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
- C07C217/60—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9723133.6A GB9723133D0 (en) | 1997-11-03 | 1997-11-03 | Organic compounds |
| GBGB9723134.4A GB9723134D0 (en) | 1997-11-03 | 1997-11-03 | Organic compounds |
| GB9723134.4 | 1997-11-03 | ||
| GB9723133.6 | 1997-11-03 | ||
| PCT/EP1998/006880 WO1999023073A1 (en) | 1997-11-03 | 1998-10-30 | Biphenyl derivatives as pharmaceuticals |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2308151A1 true CA2308151A1 (en) | 1999-05-14 |
Family
ID=26312535
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002308151A Abandoned CA2308151A1 (en) | 1997-11-03 | 1998-10-30 | Biphenyl derivatives as pharmaceuticals |
Country Status (18)
| Country | Link |
|---|---|
| EP (1) | EP1037876A1 (no) |
| JP (1) | JP2001521923A (no) |
| KR (1) | KR20010031699A (no) |
| CN (1) | CN1278249A (no) |
| AR (1) | AR016148A1 (no) |
| AU (1) | AU740448B2 (no) |
| BR (1) | BR9813897A (no) |
| CA (1) | CA2308151A1 (no) |
| CO (1) | CO5011067A1 (no) |
| ID (1) | ID24413A (no) |
| IL (1) | IL135580A0 (no) |
| NO (1) | NO20002321L (no) |
| NZ (1) | NZ503815A (no) |
| PE (1) | PE123599A1 (no) |
| PL (1) | PL339922A1 (no) |
| SK (1) | SK6412000A3 (no) |
| TR (1) | TR200001122T2 (no) |
| WO (1) | WO1999023073A1 (no) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6858592B2 (en) | 2001-06-29 | 2005-02-22 | Genzyme Corporation | Aryl boronic acids for treating obesity |
| US7041280B2 (en) | 2001-06-29 | 2006-05-09 | Genzyme Corporation | Aryl boronate functionalized polymers for treating obesity |
| TW200840566A (en) * | 2006-12-22 | 2008-10-16 | Esteve Labor Dr | Heterocyclyl-substituted-ethylamino-phenyl derivatives, their preparation and use as medicaments |
| US8575364B2 (en) * | 2008-10-30 | 2013-11-05 | Janssen Pharmaceutica Nv | Modulators of serotonin receptor |
| US8642583B2 (en) | 2008-10-30 | 2014-02-04 | Janssen Pharmaceutica Nv | Serotonin receptor modulators |
| DE102009015697A1 (de) | 2009-03-31 | 2010-10-07 | Markus Dr. Heinrich | Verfahren zur Arylierung von ringsubstituierten Phenolen und Phenylethern |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2114122A (en) * | 1938-04-12 | Alcohols and process fob making | ||
| DE674968C (de) * | 1935-01-15 | 1939-04-26 | Roehm & Haas Company | Verfahren zur Herstellung von phenolartigen Aralkylaminoalkoholen |
| US2040039A (en) * | 1935-02-26 | 1936-05-05 | Rohm & Haas | Phenolic morpholines |
| US2485550A (en) * | 1946-06-25 | 1949-10-25 | Hoffmann La Roche | Quaternary salts of carbamic acid esters of tertiary-hydroxybenzyl-amines |
| US2493710A (en) * | 1947-03-21 | 1950-01-03 | Hoffmann La Roche | Carbamic acid esters |
| US2872477A (en) * | 1957-04-05 | 1959-02-03 | Dow Chemical Co | alpha-(dialkylamino)-6-phenyl-o-cresol esters |
| JPS5328150A (en) * | 1976-08-25 | 1978-03-16 | Sugai Chemical Ind Co Ltd | Novel orthophenyl phenol derivative process for preparing same |
| CN1029227C (zh) * | 1989-02-08 | 1995-07-05 | 大制药株式会社 | 苯衍生物的制备方法 |
| US5428037A (en) * | 1993-04-09 | 1995-06-27 | Syntex Pharmaceuticals, Ltd. | Heterocyclic derivatives in the treatment of Ischaemia and related diseases |
| JPH072655A (ja) * | 1993-06-18 | 1995-01-06 | Otsuka Pharmaceut Co Ltd | 末梢神経変性修復又は保護剤 |
| ES2169102T3 (es) * | 1994-10-14 | 2002-07-01 | Merck Patent Gmbh | (r)-(-)-2-(5-(4-fluorfenil)-3-piridilmetilaminometil)-cromano como agente activo sobre el sistema nervioso central. |
| WO1996016058A1 (en) * | 1994-11-23 | 1996-05-30 | Neurogen Corporation | Aminomethyl aryl compounds; dopamine receptor subtype selective ligands |
| IL116249A (en) * | 1994-12-12 | 2003-07-06 | Pfizer | Nk-1 receptor antagonists for the treatment of neuronal damage and stroke |
| DE19637237A1 (de) * | 1996-09-13 | 1998-03-19 | Merck Patent Gmbh | Piperazin-Derivate |
-
1998
- 1998-10-29 CO CO98063635A patent/CO5011067A1/es unknown
- 1998-10-30 WO PCT/EP1998/006880 patent/WO1999023073A1/en not_active Ceased
- 1998-10-30 BR BR9813897-9A patent/BR9813897A/pt not_active IP Right Cessation
- 1998-10-30 AR ARP980105469A patent/AR016148A1/es not_active Application Discontinuation
- 1998-10-30 CN CN98810761A patent/CN1278249A/zh active Pending
- 1998-10-30 CA CA002308151A patent/CA2308151A1/en not_active Abandoned
- 1998-10-30 ID IDW20000790A patent/ID24413A/id unknown
- 1998-10-30 IL IL13558098A patent/IL135580A0/xx unknown
- 1998-10-30 NZ NZ503815A patent/NZ503815A/en unknown
- 1998-10-30 JP JP2000518948A patent/JP2001521923A/ja active Pending
- 1998-10-30 EP EP98958884A patent/EP1037876A1/en not_active Withdrawn
- 1998-10-30 TR TR2000/01122T patent/TR200001122T2/xx unknown
- 1998-10-30 AU AU14872/99A patent/AU740448B2/en not_active Ceased
- 1998-10-30 SK SK641-2000A patent/SK6412000A3/sk unknown
- 1998-10-30 KR KR1020007004762A patent/KR20010031699A/ko not_active Ceased
- 1998-10-30 PL PL98339922A patent/PL339922A1/xx unknown
- 1998-11-02 PE PE1998001034A patent/PE123599A1/es not_active Application Discontinuation
-
2000
- 2000-05-02 NO NO20002321A patent/NO20002321L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| NZ503815A (en) | 2002-05-31 |
| SK6412000A3 (en) | 2000-09-12 |
| CO5011067A1 (es) | 2001-02-28 |
| KR20010031699A (ko) | 2001-04-16 |
| PL339922A1 (en) | 2001-01-15 |
| TR200001122T2 (tr) | 2000-08-21 |
| AU1487299A (en) | 1999-05-24 |
| WO1999023073A1 (en) | 1999-05-14 |
| JP2001521923A (ja) | 2001-11-13 |
| EP1037876A1 (en) | 2000-09-27 |
| AU740448B2 (en) | 2001-11-01 |
| NO20002321D0 (no) | 2000-05-02 |
| ID24413A (id) | 2000-07-20 |
| PE123599A1 (es) | 1999-12-20 |
| BR9813897A (pt) | 2000-09-26 |
| NO20002321L (no) | 2000-05-02 |
| IL135580A0 (en) | 2001-05-20 |
| AR016148A1 (es) | 2001-06-20 |
| CN1278249A (zh) | 2000-12-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |