DE69602970T2 - 5-(phenyl)-3-(4-piperidinyl)-1,3,4-oxadiazol-2(3h)-on-derivate verwendbar als 5-ht4- oder h3-rezeptorliganden - Google Patents
5-(phenyl)-3-(4-piperidinyl)-1,3,4-oxadiazol-2(3h)-on-derivate verwendbar als 5-ht4- oder h3-rezeptorligandenInfo
- Publication number
- DE69602970T2 DE69602970T2 DE69602970T DE69602970T DE69602970T2 DE 69602970 T2 DE69602970 T2 DE 69602970T2 DE 69602970 T DE69602970 T DE 69602970T DE 69602970 T DE69602970 T DE 69602970T DE 69602970 T2 DE69602970 T2 DE 69602970T2
- Authority
- DE
- Germany
- Prior art keywords
- group
- piperidin
- dihydro
- compound
- chloro
- 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.)
- Expired - Lifetime
Links
- -1 4-PIPERIDINYL Chemical class 0.000 title claims description 57
- 239000003446 ligand Substances 0.000 title description 4
- 102000005962 receptors Human genes 0.000 title description 4
- 108020003175 receptors Proteins 0.000 title description 4
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 90
- 239000000203 mixture Substances 0.000 claims description 68
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 10
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Chemical compound CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 claims description 9
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 7
- 239000012458 free base Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000012876 carrier material Substances 0.000 claims description 2
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical compound C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 238000006268 reductive amination reaction Methods 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 1
- 230000003287 optical effect Effects 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
- 230000008018 melting Effects 0.000 description 44
- 238000002844 melting Methods 0.000 description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- 230000002829 reductive effect Effects 0.000 description 38
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- 238000003756 stirring Methods 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 238000001914 filtration Methods 0.000 description 24
- 239000002904 solvent Substances 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000002244 precipitate Substances 0.000 description 17
- 239000007787 solid Substances 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- 239000012074 organic phase Substances 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 208000035475 disorder Diseases 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 10
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 5
- LDECUSDQMXVUMP-UHFFFAOYSA-N benzyl 3-[6-[[2-(butylamino)-1-[3-methoxycarbonyl-4-(2-methoxy-2-oxoethoxy)phenyl]-2-oxoethyl]-hexylamino]-6-oxohexyl]-4-methyl-2-oxo-6-(4-phenylphenyl)-1,6-dihydropyrimidine-5-carboxylate Chemical compound O=C1NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)C(C(=O)OCC=2C=CC=CC=2)=C(C)N1CCCCCC(=O)N(CCCCCC)C(C(=O)NCCCC)C1=CC=C(OCC(=O)OC)C(C(=O)OC)=C1 LDECUSDQMXVUMP-UHFFFAOYSA-N 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 208000019901 Anxiety disease Diseases 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 230000036506 anxiety Effects 0.000 description 4
- 239000000010 aprotic solvent Substances 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 229940076279 serotonin Drugs 0.000 description 4
- 230000009870 specific binding Effects 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- RLKMOPWWGZKHOP-UHFFFAOYSA-N 1-butylpiperidin-4-ol Chemical compound CCCCN1CCC(O)CC1 RLKMOPWWGZKHOP-UHFFFAOYSA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 3
- KLPBRQIQIHTCRI-UHFFFAOYSA-N 4-amino-5-chloro-2-(cyclopropylmethoxy)benzoic acid Chemical compound C1=C(Cl)C(N)=CC(OCC2CC2)=C1C(O)=O KLPBRQIQIHTCRI-UHFFFAOYSA-N 0.000 description 3
- ABQHXSZKQQZAML-UHFFFAOYSA-N 5-(4-amino-5-chloro-2-methoxyphenyl)-3-piperidin-4-yl-1,3,4-oxadiazol-2-one Chemical compound COC1=CC(N)=C(Cl)C=C1C(OC1=O)=NN1C1CCNCC1 ABQHXSZKQQZAML-UHFFFAOYSA-N 0.000 description 3
- NUSGHOZCGBGOGB-UHFFFAOYSA-N 5-(5-chloro-2,3-dihydro-1-benzofuran-7-yl)-3-piperidin-4-yl-1,3,4-oxadiazol-2-one Chemical compound C=1C(Cl)=CC=2CCOC=2C=1C(OC1=O)=NN1C1CCNCC1 NUSGHOZCGBGOGB-UHFFFAOYSA-N 0.000 description 3
- AYWZMFWXMUZADG-UHFFFAOYSA-N 5-(5-chloro-2,3-dihydro-1-benzofuran-7-yl)-3h-1,3,4-oxadiazol-2-one Chemical compound C=1C(Cl)=CC=2CCOC=2C=1C1=NNC(=O)O1 AYWZMFWXMUZADG-UHFFFAOYSA-N 0.000 description 3
- 108091005482 5-HT4 receptors Proteins 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- ZNJHFNUEQDVFCJ-UHFFFAOYSA-M sodium;2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid;hydroxide Chemical compound [OH-].[Na+].OCCN1CCN(CCS(O)(=O)=O)CC1 ZNJHFNUEQDVFCJ-UHFFFAOYSA-M 0.000 description 3
- PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- BAUWRHPMUVYFOD-UHFFFAOYSA-N 1-methylpiperidin-4-ol Chemical compound CN1CCC(O)CC1 BAUWRHPMUVYFOD-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- RVEATKYEARPWRE-UHFFFAOYSA-N 4-amino-5-chloro-2-methoxybenzoic acid Chemical compound COC1=CC(N)=C(Cl)C=C1C(O)=O RVEATKYEARPWRE-UHFFFAOYSA-N 0.000 description 2
- WNMCTSHHWRPDNQ-UHFFFAOYSA-N 5-(4-amino-5-chloro-2-methoxyphenyl)-3-(1-methylpiperidin-4-yl)-1,3,4-oxadiazol-2-one Chemical compound COC1=CC(N)=C(Cl)C=C1C(OC1=O)=NN1C1CCN(C)CC1 WNMCTSHHWRPDNQ-UHFFFAOYSA-N 0.000 description 2
- IVAVPGIRMLIZIK-UHFFFAOYSA-N 5-(4-amino-5-chloro-2-methoxyphenyl)-3-[1-(2-phenylethyl)piperidin-4-yl]-1,3,4-oxadiazol-2-one Chemical compound COC1=CC(N)=C(Cl)C=C1C(OC1=O)=NN1C1CCN(CCC=2C=CC=CC=2)CC1 IVAVPGIRMLIZIK-UHFFFAOYSA-N 0.000 description 2
- BQNIHLDTULCIEK-UHFFFAOYSA-N 5-(5-amino-6-chloro-2,3-dihydro-1,4-benzodioxin-8-yl)-3-[1-(4,4,4-trifluorobutyl)piperidin-4-yl]-1,3,4-oxadiazol-2-one Chemical compound C1=2OCCOC=2C(N)=C(Cl)C=C1C(OC1=O)=NN1C1CCN(CCCC(F)(F)F)CC1 BQNIHLDTULCIEK-UHFFFAOYSA-N 0.000 description 2
- WLWMWCGUHCKKOH-UHFFFAOYSA-N 5-(5-amino-6-chloro-2,3-dihydro-1,4-benzodioxin-8-yl)-3-piperidin-4-yl-1,3,4-oxadiazol-2-one Chemical compound C1=2OCCOC=2C(N)=C(Cl)C=C1C(OC1=O)=NN1C1CCNCC1 WLWMWCGUHCKKOH-UHFFFAOYSA-N 0.000 description 2
- VWMNFPMZOBFURK-UHFFFAOYSA-N 5-(6-chloro-3,4-dihydro-2h-chromen-8-yl)-3h-1,3,4-oxadiazol-2-one Chemical compound C=1C(Cl)=CC=2CCCOC=2C=1C1=NNC(=O)O1 VWMNFPMZOBFURK-UHFFFAOYSA-N 0.000 description 2
- UJRRAIJFGCLEBS-UHFFFAOYSA-N 5-[4-amino-5-chloro-2-(cyclopropylmethoxy)phenyl]-3h-1,3,4-oxadiazol-2-one Chemical compound N=1NC(=O)OC=1C=1C=C(Cl)C(N)=CC=1OCC1CC1 UJRRAIJFGCLEBS-UHFFFAOYSA-N 0.000 description 2
- KGEWUGWPCVDMCP-UHFFFAOYSA-N 5-amino-6-chloro-2,3-dihydro-1,4-benzodioxine-8-carboxylic acid Chemical compound O1CCOC2=C1C(C(O)=O)=CC(Cl)=C2N KGEWUGWPCVDMCP-UHFFFAOYSA-N 0.000 description 2
- JVKROPCXEGJZRU-UHFFFAOYSA-N 5-chloro-1-[4-(dimethylamino)piperidin-1-yl]pentan-1-one Chemical compound CN(C)C1CCN(C(=O)CCCCCl)CC1 JVKROPCXEGJZRU-UHFFFAOYSA-N 0.000 description 2
- HIDAFWCPNYVJAD-UHFFFAOYSA-N 6-chloro-3,4-dihydro-2h-chromene-8-carboxylic acid Chemical compound C1CCOC2=C1C=C(Cl)C=C2C(=O)O HIDAFWCPNYVJAD-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 102000004384 Histamine H3 receptors Human genes 0.000 description 2
- 108090000981 Histamine H3 receptors Proteins 0.000 description 2
- 206010026749 Mania Diseases 0.000 description 2
- QKDDJDBFONZGBW-UHFFFAOYSA-N N-Cyclohexy-4-(imidazol-4-yl)-1-piperidinecarbothioamide Chemical compound C1CC(C=2NC=NC=2)CCN1C(=S)NC1CCCCC1 QKDDJDBFONZGBW-UHFFFAOYSA-N 0.000 description 2
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010039966 Senile dementia Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- IJVDIVLXNQKIPE-UHFFFAOYSA-N benzyl n-[6-chloro-8-(5-oxo-4-piperidin-4-yl-1,3,4-oxadiazol-2-yl)-2,3-dihydro-1,4-benzodioxin-5-yl]carbamate Chemical compound C=12OCCOC2=C(NC(=O)OCC=2C=CC=CC=2)C(Cl)=CC=1C(OC1=O)=NN1C1CCNCC1 IJVDIVLXNQKIPE-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 2
- 229960004484 carbachol Drugs 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 210000000748 cardiovascular system Anatomy 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000003238 esophagus Anatomy 0.000 description 2
- HLKRRQKWCIYCOW-UHFFFAOYSA-N ethyl 5-amino-2,3-dihydro-1,4-benzodioxine-8-carboxylate Chemical compound O1CCOC2=C1C(N)=CC=C2C(=O)OCC HLKRRQKWCIYCOW-UHFFFAOYSA-N 0.000 description 2
- DEIOKFOOELDPJF-UHFFFAOYSA-N ethyl 5-amino-6-chloro-2,3-dihydro-1,4-benzodioxine-8-carboxylate Chemical compound O1CCOC2=C1C(N)=C(Cl)C=C2C(=O)OCC DEIOKFOOELDPJF-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- CLPRZDRHQSJNJT-UHFFFAOYSA-N methyl 4-amino-5-chloro-2-(cyclopropylmethoxy)benzoate Chemical compound COC(=O)C1=CC(Cl)=C(N)C=C1OCC1CC1 CLPRZDRHQSJNJT-UHFFFAOYSA-N 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 238000013222 sprague-dawley male rat Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 2
- 210000001635 urinary tract Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- IKSNDOVDVVPSMA-UHFFFAOYSA-N 1-(bromomethyl)-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(CBr)C=C1 IKSNDOVDVVPSMA-UHFFFAOYSA-N 0.000 description 1
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
- GZCJYYAZHWTDPB-UHFFFAOYSA-N 3-(1-butylpiperidin-4-yl)-5-(5-chloro-2,3-dihydro-1-benzofuran-7-yl)-1,3,4-oxadiazol-2-one Chemical compound C1CN(CCCC)CCC1N1C(=O)OC(C=2C=3OCCC=3C=C(Cl)C=2)=N1 GZCJYYAZHWTDPB-UHFFFAOYSA-N 0.000 description 1
- WTSXVIMLKCKWIW-UHFFFAOYSA-N 3h-1,3,4-oxadiazol-2-one Chemical compound O=C1NN=CO1 WTSXVIMLKCKWIW-UHFFFAOYSA-N 0.000 description 1
- DBCAQXHNJOFNGC-UHFFFAOYSA-N 4-bromo-1,1,1-trifluorobutane Chemical compound FC(F)(F)CCCBr DBCAQXHNJOFNGC-UHFFFAOYSA-N 0.000 description 1
- ASEQRNMSKNNTSN-UHFFFAOYSA-N 4-chloro-1-[4-(dimethylamino)piperidin-1-yl]butan-1-one Chemical compound CN(C)C1CCN(C(=O)CCCCl)CC1 ASEQRNMSKNNTSN-UHFFFAOYSA-N 0.000 description 1
- MZLXFFYMEYFKIT-UHFFFAOYSA-N 5-(5-amino-6-chloro-2,3-dihydro-1,4-benzodioxin-8-yl)-3-[1-[[4-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-1,3,4-oxadiazol-2-one Chemical compound C1=2OCCOC=2C(N)=C(Cl)C=C1C(OC1=O)=NN1C(CC1)CCN1CC1=CC=C(C(F)(F)F)C=C1 MZLXFFYMEYFKIT-UHFFFAOYSA-N 0.000 description 1
- LKYLYFSTNNVQNS-UHFFFAOYSA-N 5-amino-2,3-dihydro-1,4-benzodioxine-8-carboxylic acid Chemical compound O1CCOC2=C1C(C(O)=O)=CC=C2N LKYLYFSTNNVQNS-UHFFFAOYSA-N 0.000 description 1
- POUGGJABXBLKJV-UHFFFAOYSA-N 5-chloro-2,3-dihydro-1-benzofuran-7-carbohydrazide Chemical compound NNC(=O)C1=CC(Cl)=CC2=C1OCC2 POUGGJABXBLKJV-UHFFFAOYSA-N 0.000 description 1
- SGPAPRPKRANLEF-UHFFFAOYSA-N 5-chloro-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound OC(=O)C1=CC(Cl)=CC2=C1OCC2 SGPAPRPKRANLEF-UHFFFAOYSA-N 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 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 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 208000032841 Bulimia Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- LAJHAXGOMYTCIB-UHFFFAOYSA-N C1CN(C)CCC1N1C(=O)OC(C=2C=3OCCOC=3C(NC(=O)OCC=3C=CC=CC=3)=C(Cl)C=2)=N1 Chemical compound C1CN(C)CCC1N1C(=O)OC(C=2C=3OCCOC=3C(NC(=O)OCC=3C=CC=CC=3)=C(Cl)C=2)=N1 LAJHAXGOMYTCIB-UHFFFAOYSA-N 0.000 description 1
- 206010007270 Carcinoid syndrome Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 206010008631 Cholera Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000030814 Eating disease Diseases 0.000 description 1
- 206010053155 Epigastric discomfort Diseases 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- MOZPSIXKYJUTKI-UHFFFAOYSA-N GR 113808 Chemical compound C12=CC=CC=C2N(C)C=C1C(=O)OCC1CCN(CCNS(C)(=O)=O)CC1 MOZPSIXKYJUTKI-UHFFFAOYSA-N 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 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 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010033864 Paranoia Diseases 0.000 description 1
- 208000027099 Paranoid disease Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 206010046555 Urinary retention Diseases 0.000 description 1
- MOZPSIXKYJUTKI-RLXJOQACSA-N [1-[2-(methanesulfonamido)ethyl]piperidin-4-yl]methyl 1-(tritritiomethyl)indole-3-carboxylate Chemical compound C12=CC=CC=C2N(C([3H])([3H])[3H])C=C1C(=O)OCC1CCN(CCNS(C)(=O)=O)CC1 MOZPSIXKYJUTKI-RLXJOQACSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000000454 anti-cipatory effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- KUGFSPPRBJULDP-UHFFFAOYSA-N benzyl n-[2-chloro-5-methoxy-4-(2-oxo-3h-1,3,4-oxadiazol-5-yl)phenyl]carbamate Chemical compound ClC=1C=C(C=2OC(=O)NN=2)C(OC)=CC=1NC(=O)OCC1=CC=CC=C1 KUGFSPPRBJULDP-UHFFFAOYSA-N 0.000 description 1
- LENDSNXCLUCERI-UHFFFAOYSA-N benzyl n-[2-chloro-5-methoxy-4-(5-oxo-4-piperidin-4-yl-1,3,4-oxadiazol-2-yl)phenyl]carbamate Chemical compound ClC=1C=C(C=2OC(=O)N(C3CCNCC3)N=2)C(OC)=CC=1NC(=O)OCC1=CC=CC=C1 LENDSNXCLUCERI-UHFFFAOYSA-N 0.000 description 1
- YLPNUUCSFYZZER-UHFFFAOYSA-N benzyl n-[6-chloro-8-(2-oxo-3h-1,3,4-oxadiazol-5-yl)-2,3-dihydro-1,4-benzodioxin-5-yl]carbamate Chemical compound C=12OCCOC2=C(NC(=O)OCC=2C=CC=CC=2)C(Cl)=CC=1C1=NNC(=O)O1 YLPNUUCSFYZZER-UHFFFAOYSA-N 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- UUWSLBWDFJMSFP-UHFFFAOYSA-N bromomethylcyclohexane Chemical compound BrCC1CCCCC1 UUWSLBWDFJMSFP-UHFFFAOYSA-N 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- UBAZGMLMVVQSCD-UHFFFAOYSA-N carbon dioxide;molecular oxygen Chemical compound O=O.O=C=O UBAZGMLMVVQSCD-UHFFFAOYSA-N 0.000 description 1
- JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 235000014632 disordered eating Nutrition 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 206010013990 dysuria Diseases 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 206010016766 flatulence Diseases 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000000742 histaminergic effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- UMJJFEIKYGFCAT-UHFFFAOYSA-N indan-2-one Chemical compound C1=CC=C2CC(=O)CC2=C1 UMJJFEIKYGFCAT-UHFFFAOYSA-N 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 210000003750 lower gastrointestinal tract Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical group CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- ZWKNURNGLFWTBX-UHFFFAOYSA-N methyl 3-amino-5-chloro-2-methoxybenzoate Chemical compound COC(=O)C1=CC(Cl)=CC(N)=C1OC ZWKNURNGLFWTBX-UHFFFAOYSA-N 0.000 description 1
- VPUNONJHQKLMEF-UHFFFAOYSA-N methyl 5-chloro-2,3-dihydro-1-benzofuran-7-carboxylate Chemical compound COC(=O)C1=CC(Cl)=CC2=C1OCC2 VPUNONJHQKLMEF-UHFFFAOYSA-N 0.000 description 1
- XURXSJHLMYVRDF-UHFFFAOYSA-N methyl 6-chloro-3,4-dihydro-2h-chromene-8-carboxylate Chemical compound C1CCOC2=C1C=C(Cl)C=C2C(=O)OC XURXSJHLMYVRDF-UHFFFAOYSA-N 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 230000005801 respiratory difficulty Effects 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000001932 seasonal effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000000862 serotonergic effect Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- OTNVGWMVOULBFZ-UHFFFAOYSA-N sodium;hydrochloride Chemical compound [Na].Cl OTNVGWMVOULBFZ-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- UDIULSPBXRJHEO-UHFFFAOYSA-N tert-butyl 4-[5-(5-chloro-2,3-dihydro-1-benzofuran-7-yl)-2-oxo-1,3,4-oxadiazol-3-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1C(=O)OC(C=2C=3OCCC=3C=C(Cl)C=2)=N1 UDIULSPBXRJHEO-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary 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
-
- 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
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Ophthalmology & Optometry (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9513253A FR2741070B1 (fr) | 1995-11-09 | 1995-11-09 | Derives de 5-phenyl-3-(piperidin-4-yl)-1,3,4-oxadiazol-2(3h) -one, leur preparation et leur application en therapeutique |
| FR9513252A FR2741069B1 (fr) | 1995-11-09 | 1995-11-09 | Derives de 5-phenyl-3-(piperidin-4-yl)-1,3,4-oxadiazol-2(3h) -one, leur preparation et leur application en therapeutique |
| FR9602663A FR2745574B1 (fr) | 1996-03-04 | 1996-03-04 | Derives de 5-phenyl-3-(piperidin-4-yl)-1, 3, 4-oxadiazol-2 (3h)-one, leur preparation et leur application en therapeutique |
| PCT/FR1996/001730 WO1997017345A1 (fr) | 1995-11-09 | 1996-11-05 | Derives de 5-phenyl-3-(piperidin-4-yl)-1,3,4-oxadiazol-2(3h)-one, utiles comme ligands des recepteurs 5-ht4 ou h¿3? |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69602970D1 DE69602970D1 (de) | 1999-07-22 |
| DE69602970T2 true DE69602970T2 (de) | 2000-01-20 |
Family
ID=27253120
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69602970T Expired - Lifetime DE69602970T2 (de) | 1995-11-09 | 1996-11-05 | 5-(phenyl)-3-(4-piperidinyl)-1,3,4-oxadiazol-2(3h)-on-derivate verwendbar als 5-ht4- oder h3-rezeptorliganden |
Country Status (29)
| Country | Link |
|---|---|
| US (1) | US5929089A (enExample) |
| EP (1) | EP0863897B1 (enExample) |
| JP (1) | JP4263240B2 (enExample) |
| CN (1) | CN1077891C (enExample) |
| AR (1) | AR004708A1 (enExample) |
| AT (1) | ATE181328T1 (enExample) |
| AU (1) | AU707325B2 (enExample) |
| BG (1) | BG63463B1 (enExample) |
| BR (1) | BR9611311A (enExample) |
| CA (1) | CA2236357C (enExample) |
| CO (1) | CO4770968A1 (enExample) |
| CZ (1) | CZ287268B6 (enExample) |
| DE (1) | DE69602970T2 (enExample) |
| EE (1) | EE03487B1 (enExample) |
| ES (1) | ES2135934T3 (enExample) |
| GR (1) | GR3030823T3 (enExample) |
| HU (1) | HUP0001168A3 (enExample) |
| IL (1) | IL124364A (enExample) |
| MX (1) | MX9803696A (enExample) |
| NO (1) | NO309606B1 (enExample) |
| NZ (1) | NZ321626A (enExample) |
| PL (1) | PL186204B1 (enExample) |
| RU (1) | RU2167160C2 (enExample) |
| SI (1) | SI0863897T1 (enExample) |
| SK (1) | SK282335B6 (enExample) |
| TR (1) | TR199800827T2 (enExample) |
| TW (1) | TW371303B (enExample) |
| UA (1) | UA50748C2 (enExample) |
| WO (1) | WO1997017345A1 (enExample) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW467902B (en) * | 1996-07-31 | 2001-12-11 | Bristol Myers Squibb Co | Diphenyl heterocycles as potassium channel modulators |
| FR2762316B1 (fr) * | 1997-04-18 | 1999-12-17 | Sanofi Synthelabo | Derives de 5-aryl-3-(8-azabicyclo[3.2.1] octan-3-yl)-1,3,4- oxadiazol-2(3h)-one, leur preparation et leur application en therapeutique |
| JP2002504896A (ja) * | 1997-05-06 | 2002-02-12 | サノフィ−サンテラボ | ５−フェニル−１，３，４−オキサジアゾール−２（３ｈ）−オン誘導体およびそれらの５−ｈｔ４リガンドとしての使用 |
| FR2763068B1 (fr) * | 1997-05-06 | 1999-06-04 | Synthelabo | Derives de 3-(pyrrolidin-3-yl)-1,3,4-oxadiazol-2(3h)-one, leur preparation et leur application en therapeutique |
| GB9715816D0 (en) * | 1997-07-25 | 1997-10-01 | Black James Foundation | Histamine H receptor ligands |
| US6960579B1 (en) | 1998-05-19 | 2005-11-01 | Alcon Manufacturing, Ltd. | Serotonergic 5HT7 receptor compounds for treating ocular and CNS disorders |
| EP1112106B1 (en) | 1998-09-18 | 2005-11-23 | Alcon Manufacturing Ltd. | Serotonergic 5ht2 agonists for treating glaucoma |
| JP2002542287A (ja) * | 1999-04-28 | 2002-12-10 | レスピラトリウス アクチボラゲット | 医 薬 |
| CN1355698A (zh) * | 1999-06-15 | 2002-06-26 | 呼吸器有限公司 | 可用作治疗有关支气管收缩的机能障碍的药物的化合物 |
| PT1313721E (pt) | 2000-08-08 | 2006-06-30 | Ortho Mcneil Pharm Inc | Ariloxialquilaminas nao imidazoles como ligandos de receptor h3 |
| AU8112101A (en) | 2000-08-08 | 2002-02-18 | Ortho Mcneil Pharm Inc | Non-imidazole aryloxypiperidines |
| PT1311499E (pt) | 2000-08-08 | 2006-07-31 | Ortho Mcneil Pharm Inc | Compostos biciclicos como ligandos do receptor h3 |
| JP2005502623A (ja) | 2001-07-02 | 2005-01-27 | ノボ ノルディスク アクティーゼルスカブ | 置換ピペラジンおよびジアゼパン |
| US7208497B2 (en) | 2001-07-02 | 2007-04-24 | Novo Nordisk A/S | Substituted piperazines and diazepanes |
| US20030186963A1 (en) | 2001-09-14 | 2003-10-02 | Dorwald Florencio Zaragoza | Substituted piperidines |
| US6673829B2 (en) | 2001-09-14 | 2004-01-06 | Novo Nordisk A/S | Aminoazetidine,-pyrrolidine and -piperidine derivatives |
| EP1434765B1 (en) * | 2001-09-14 | 2009-12-02 | High Point Pharmaceuticals, LLC | Substituted piperidines with selective binding to histamine h3-receptor |
| WO2003024928A2 (en) | 2001-09-14 | 2003-03-27 | Novo Nordisk A/S | Novel aminoazetidine, -pyrrolidine and -piperidine derivatives |
| EP1444219A1 (en) | 2001-10-12 | 2004-08-11 | Novo Nordisk A/S | Substituted piperidines and their use for the treatment of diseases related to the histamine h3 receptor |
| US7064135B2 (en) | 2001-10-12 | 2006-06-20 | Novo Nordisk Inc. | Substituted piperidines |
| JP2005511764A (ja) | 2001-12-14 | 2005-04-28 | アルコン，インコーポレイテッド | 緑内障の処置のためのアミノアルキルベンゾフラン−５−オール化合物 |
| US20030236259A1 (en) * | 2002-02-05 | 2003-12-25 | Rolf Hohlweg | Novel aryl- and heteroarylpiperazines |
| GB0211230D0 (en) * | 2002-05-16 | 2002-06-26 | Medinnova Sf | Treatment of heart failure |
| US7332508B2 (en) | 2002-12-18 | 2008-02-19 | Novo Nordisk A/S | Substituted homopiperidine, piperidine or pyrrolidine derivatives |
| GB0325956D0 (en) * | 2003-11-06 | 2003-12-10 | Addex Pharmaceuticals Sa | Novel compounds |
| BRPI0512046A (pt) | 2004-06-15 | 2008-02-06 | Pfizer | derivados de ácido benzimidazolona carboxìlico |
| US7737163B2 (en) | 2004-06-15 | 2010-06-15 | Pfizer Inc. | Benzimidazolone carboxylic acid derivatives |
| MX2007015675A (es) | 2005-07-04 | 2008-02-20 | Novo Nordisk As | Antagonistas del receptor de histamina h3. |
| CN101321525B (zh) * | 2005-12-01 | 2013-01-30 | 霍夫曼-拉罗奇有限公司 | 作为l-cpt1抑制剂的杂芳基取代的哌啶衍生物 |
| KR20090040259A (ko) | 2006-05-29 | 2009-04-23 | 하이 포인트 파마슈티칼스, 엘엘씨 | 3-(1,3-벤조디옥솔-5-일)-6-(4-시클로프로필피페라진-1-일)-피리다진, 그것의 염과 용매화합물 및 그것의 히스타민 ｈ3 수용체 안타고니스트로서의 용도 |
| EP2014656A3 (en) | 2007-06-11 | 2011-08-24 | High Point Pharmaceuticals, LLC | New heteocyclic h3 antagonists |
| ME02107B (me) | 2011-09-19 | 2015-10-20 | Heteroaril jedinjenja kao ligandi 5-ht4 receptora |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5055476A (en) * | 1990-08-13 | 1991-10-08 | Hoechst-Roussel Pharmaceuticals Incorporated | 3-(1,2-benzisoxazol-3-yl)-4-pyridinamines and derivatives |
| AU2435092A (en) * | 1991-08-20 | 1993-03-16 | Smithkline Beecham Plc | 5-ht4 receptor antagonists |
| FI941178L (fi) * | 1991-09-12 | 1994-03-11 | Smithkline Beecham Plc | 5-HT4-reseptoriantagonisteja |
| NZ246915A (en) * | 1992-02-06 | 1996-05-28 | Smithkline Beecham Plc | Benzopyran, benzothiopyran and benzofuran derivatives, preparation and pharmaceutical compositions thereof |
| GB9219163D0 (en) * | 1992-09-10 | 1992-10-28 | Smithkline Beecham Plc | Pharmaceuticals |
| JPH06157518A (ja) * | 1992-11-27 | 1994-06-03 | Yamanouchi Pharmaceut Co Ltd | 新規なオキサジアゾール誘導体又はその塩 |
-
1996
- 1996-11-05 BR BR9611311A patent/BR9611311A/pt not_active IP Right Cessation
- 1996-11-05 WO PCT/FR1996/001730 patent/WO1997017345A1/fr not_active Ceased
- 1996-11-05 DE DE69602970T patent/DE69602970T2/de not_active Expired - Lifetime
- 1996-11-05 JP JP51791797A patent/JP4263240B2/ja not_active Expired - Fee Related
- 1996-11-05 ES ES96937390T patent/ES2135934T3/es not_active Expired - Lifetime
- 1996-11-05 RU RU98110976/04A patent/RU2167160C2/ru not_active IP Right Cessation
- 1996-11-05 CZ CZ19981421A patent/CZ287268B6/cs not_active IP Right Cessation
- 1996-11-05 AU AU75001/96A patent/AU707325B2/en not_active Ceased
- 1996-11-05 IL IL12436496A patent/IL124364A/xx not_active IP Right Cessation
- 1996-11-05 PL PL96326671A patent/PL186204B1/pl not_active IP Right Cessation
- 1996-11-05 HU HU0001168A patent/HUP0001168A3/hu unknown
- 1996-11-05 SI SI9630092T patent/SI0863897T1/xx not_active IP Right Cessation
- 1996-11-05 EP EP96937390A patent/EP0863897B1/fr not_active Expired - Lifetime
- 1996-11-05 US US09/068,390 patent/US5929089A/en not_active Expired - Lifetime
- 1996-11-05 CA CA002236357A patent/CA2236357C/en not_active Expired - Fee Related
- 1996-11-05 AT AT96937390T patent/ATE181328T1/de active
- 1996-11-05 SK SK599-98A patent/SK282335B6/sk not_active IP Right Cessation
- 1996-11-05 CN CN96198208A patent/CN1077891C/zh not_active Expired - Fee Related
- 1996-11-05 EE EE9800155A patent/EE03487B1/xx not_active IP Right Cessation
- 1996-11-05 NZ NZ321626A patent/NZ321626A/xx not_active IP Right Cessation
- 1996-11-05 TR TR1998/00827T patent/TR199800827T2/xx unknown
- 1996-11-05 UA UA98031589A patent/UA50748C2/uk unknown
- 1996-11-07 TW TW085113594A patent/TW371303B/zh not_active IP Right Cessation
- 1996-11-08 AR ARP960105098A patent/AR004708A1/es active IP Right Grant
- 1996-11-08 CO CO96059097A patent/CO4770968A1/es unknown
-
1998
- 1998-04-28 BG BG102412A patent/BG63463B1/bg unknown
- 1998-05-07 NO NO982092A patent/NO309606B1/no not_active IP Right Cessation
- 1998-05-08 MX MX9803696A patent/MX9803696A/es unknown
-
1999
- 1999-07-20 GR GR990401913T patent/GR3030823T3/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69602970T2 (de) | 5-(phenyl)-3-(4-piperidinyl)-1,3,4-oxadiazol-2(3h)-on-derivate verwendbar als 5-ht4- oder h3-rezeptorliganden | |
| DE69614270T2 (de) | 5-azabicyclo(3.1.0.)hexylalkyl-2-piperidone und - glutarimide als neurokinin receptor antagonisten. | |
| DE69522355T2 (de) | Neue N-(3,4-Dichlorphenyl-propyl)-piperidin-Derivate als selektive humane NK3-Rezeptorantagonisten | |
| DE69326160T2 (de) | 4-carboxamidopiperidinderivate, zwischenprodukte und verwendung als neurokinin antagonisten | |
| DE69323375T2 (de) | Quartäre basische Amide als Antagonisten von Tachykininen | |
| DE69225500T2 (de) | Chinazolinone als mittel gegen angina | |
| DE69410784T2 (de) | Azacyclische verbindungen, sie enthaltende zusammensetzungen und ihre verwendung als tachykinin antagoniste | |
| DE3782785T2 (de) | Piperidinderivate, ihre herstellung und ihre verwendung. | |
| DE69224196T2 (de) | 3-aminopiperidine derivate und verwandete stickstoff enthaltende heterocyclische verbindungen | |
| JP4488891B2 (ja) | Ｎ−［フェニル（ピペリジン−２−イル）メチル］ベンズアミド誘導体、その製造法、およびその治療用途 | |
| DE69506510T2 (de) | Piperidinderivate, verwendbar als Neurokinin-Rezeptor-Antagonisten | |
| DE69128236T2 (de) | N-Acyl-2,3-benzodiazepin-Derivate, diese enthaltende pharmazeutische Zusammensetzungen und Verfahren zu ihrer Herstellung | |
| DE3885357T2 (de) | Anellierte Indolderivate. | |
| DE60309057T2 (de) | Azabicycloderivate als antagonisten des muscarinischen rezeptors | |
| AU2010297263B2 (en) | Substituted N-phenyl-1-(4-pyridinyl)-1H-pyrazol-3-amines | |
| IE59056B1 (en) | 4-benzyl-1-(2h)-phthalazinone derivatives | |
| DE69712084T2 (de) | Aminothiazole derivate, ihre herstellung und sie enthaltenden pharmazeutischen zusammensetzungen | |
| DE69806141T2 (de) | Indazoleamid-verbindungen als serotoninergene mittel | |
| EA016948B1 (ru) | Модуляторы никотиновых ацетилхолиновых рецепторов | |
| DE69323667T2 (de) | 4-substituierte 1,2,4-Triazolderivate | |
| DE69630717T2 (de) | 1-acyl-3-phenyl-3-(3-piperidinopropyl)piperidinderivate als für den menschlichen nk3-rezeptor selektive antagonisten | |
| DE19952147A1 (de) | Neue Cyclopropane, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung | |
| DE69722281T2 (de) | 3-Aza-piperidon- (Tetrahydropyrimidin-2-on) und 3-Oxa-piperidon (1,3-Oxazin-2-on) Derivate, deren Herstellung und deren Verwendung als Tachykinin/Neurokinin Antagonisten | |
| DE69801905T2 (de) | 5-aryl-3-(8-azabicyclo[3.2.1]oct-3-yl)-1,3,4-oxadiazol-2(3h)-one derivate als 5-ht4 rezeptor liganden | |
| NZ245260A (en) | Piperidine derivatives, preparation and pharmaceutical compositions thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8327 | Change in the person/name/address of the patent owner |
Owner name: SANOFI-SYNTHELABO, PARIS, FR |
|
| 8364 | No opposition during term of opposition | ||
| 8327 | Change in the person/name/address of the patent owner |
Owner name: SANOFI-AVENTIS, PARIS, FR |
|
| R082 | Change of representative |
Ref document number: 863897 Country of ref document: EP Representative=s name: TER MEER STEINMEISTER & PARTNER GBR PATENTANWA, DE |