CA2236357C - 5-phenyl-3-(piperidin-4-yl)-1,3,4-oxadiazol-2(3h)-one derivatives for use as 5-ht4 or h3 receptor ligands - Google Patents
5-phenyl-3-(piperidin-4-yl)-1,3,4-oxadiazol-2(3h)-one derivatives for use as 5-ht4 or h3 receptor ligands Download PDFInfo
- Publication number
- CA2236357C CA2236357C CA002236357A CA2236357A CA2236357C CA 2236357 C CA2236357 C CA 2236357C CA 002236357 A CA002236357 A CA 002236357A CA 2236357 A CA2236357 A CA 2236357A CA 2236357 C CA2236357 C CA 2236357C
- Authority
- CA
- Canada
- Prior art keywords
- group
- piperidin
- chloro
- dihydro
- dimethylamino
- 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 - Fee Related
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- 239000003446 ligand Substances 0.000 title description 5
- RJIHZTHWMPTLQL-UHFFFAOYSA-N 5-phenyl-3-piperidin-4-yl-1,3,4-oxadiazol-2-one Chemical class O=C1OC(C=2C=CC=CC=2)=NN1C1CCNCC1 RJIHZTHWMPTLQL-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 88
- -1 2,3-dihydro-1H-inden-1-yl Chemical group 0.000 claims abstract description 57
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 19
- 125000005843 halogen group Chemical group 0.000 claims abstract description 10
- 239000001257 hydrogen Substances 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 125000003277 amino group Chemical group 0.000 claims abstract description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 3
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 72
- 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
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Chemical compound CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 claims description 9
- 238000002360 preparation method Methods 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
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- 239000012458 free base Substances 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
- 108091005482 5-HT4 receptors Proteins 0.000 abstract description 6
- 102000004384 Histamine H3 receptors Human genes 0.000 abstract description 4
- 108090000981 Histamine H3 receptors Proteins 0.000 abstract description 4
- 125000000217 alkyl group Chemical group 0.000 abstract description 4
- 210000000748 cardiovascular system Anatomy 0.000 abstract description 3
- 210000003169 central nervous system Anatomy 0.000 abstract description 3
- 210000005095 gastrointestinal system Anatomy 0.000 abstract 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 abstract description 3
- 210000000056 organ Anatomy 0.000 abstract description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 abstract description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
- 125000003342 alkenyl group Chemical group 0.000 abstract 1
- 230000002485 urinary effect Effects 0.000 abstract 1
- 238000002844 melting Methods 0.000 description 44
- 230000008018 melting Effects 0.000 description 44
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- 230000002829 reductive effect Effects 0.000 description 37
- 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 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 29
- 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 24
- 238000001914 filtration Methods 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000002244 precipitate Substances 0.000 description 18
- 239000007787 solid Substances 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 239000000725 suspension Substances 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 238000003760 magnetic stirring Methods 0.000 description 11
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 238000010828 elution Methods 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 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
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 230000011514 reflex Effects 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- RDTNHKAOMIMKAR-UHFFFAOYSA-N 5-(6-chloro-3,4-dihydro-2h-chromen-8-yl)-3-piperidin-4-yl-1,3,4-oxadiazol-2-one;hydrochloride Chemical compound Cl.C=1C(Cl)=CC=2CCCOC=2C=1C(OC1=O)=NN1C1CCNCC1 RDTNHKAOMIMKAR-UHFFFAOYSA-N 0.000 description 4
- 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
- 230000036506 anxiety Effects 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-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
- 239000000010 aprotic solvent Substances 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 229940076279 serotonin Drugs 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
- 230000009870 specific binding Effects 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- RLKMOPWWGZKHOP-UHFFFAOYSA-N 1-butylpiperidin-4-ol Chemical compound CCCCN1CCC(O)CC1 RLKMOPWWGZKHOP-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
- HQDKULCXUILIJK-UHFFFAOYSA-N 5-(4-amino-5-chloro-2-methoxyphenyl)-3-(1-methylpiperidin-4-yl)-1,3,4-oxadiazol-2-one;hydrochloride Chemical compound Cl.COC1=CC(N)=C(Cl)C=C1C(OC1=O)=NN1C1CCN(C)CC1 HQDKULCXUILIJK-UHFFFAOYSA-N 0.000 description 2
- SXNDHILBPJENQA-UHFFFAOYSA-N 5-(5-amino-6-chloro-2,3-dihydro-1,4-benzodioxin-8-yl)-3-(1-butylpiperidin-4-yl)-1,3,4-oxadiazol-2-one;hydrochloride Chemical compound Cl.C1CN(CCCC)CCC1N1C(=O)OC(C=2C=3OCCOC=3C(N)=C(Cl)C=2)=N1 SXNDHILBPJENQA-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
- YLUSJQXFXOEXCI-UHFFFAOYSA-N 5-(5-chloro-2,3-dihydro-1-benzofuran-7-yl)-3-piperidin-4-yl-1,3,4-oxadiazol-2-one;hydrochloride Chemical compound Cl.C=1C(Cl)=CC=2CCOC=2C=1C(OC1=O)=NN1C1CCNCC1 YLUSJQXFXOEXCI-UHFFFAOYSA-N 0.000 description 2
- 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 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
- 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
- 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 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
- 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
- 208000024827 Alzheimer disease Diseases 0.000 description 2
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- 241000700198 Cavia Species 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 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 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
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
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- 208000028017 Psychotic disease Diseases 0.000 description 2
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
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- 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 2
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- 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
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- 235000019341 magnesium sulphate Nutrition 0.000 description 2
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- 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
- 230000003387 muscular Effects 0.000 description 2
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- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
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- 238000013222 sprague-dawley male rat Methods 0.000 description 2
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
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- 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 (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| 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 |
| 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 |
| FR95/13252 | 1995-11-09 | ||
| FR95/13253 | 1995-11-09 | ||
| FR96/02663 | 1996-03-04 | ||
| 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 |
|---|---|
| CA2236357A1 CA2236357A1 (en) | 1997-05-15 |
| CA2236357C true CA2236357C (en) | 2006-10-17 |
Family
ID=27253120
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002236357A Expired - Fee Related CA2236357C (en) | 1995-11-09 | 1996-11-05 | 5-phenyl-3-(piperidin-4-yl)-1,3,4-oxadiazol-2(3h)-one derivatives for use as 5-ht4 or h3 receptor ligands |
Country Status (29)
| Country | Link |
|---|---|
| US (1) | US5929089A (OSRAM) |
| EP (1) | EP0863897B1 (OSRAM) |
| JP (1) | JP4263240B2 (OSRAM) |
| CN (1) | CN1077891C (OSRAM) |
| AR (1) | AR004708A1 (OSRAM) |
| AT (1) | ATE181328T1 (OSRAM) |
| AU (1) | AU707325B2 (OSRAM) |
| BG (1) | BG63463B1 (OSRAM) |
| BR (1) | BR9611311A (OSRAM) |
| CA (1) | CA2236357C (OSRAM) |
| CO (1) | CO4770968A1 (OSRAM) |
| CZ (1) | CZ287268B6 (OSRAM) |
| DE (1) | DE69602970T2 (OSRAM) |
| EE (1) | EE03487B1 (OSRAM) |
| ES (1) | ES2135934T3 (OSRAM) |
| GR (1) | GR3030823T3 (OSRAM) |
| HU (1) | HUP0001168A3 (OSRAM) |
| IL (1) | IL124364A (OSRAM) |
| MX (1) | MX9803696A (OSRAM) |
| NO (1) | NO309606B1 (OSRAM) |
| NZ (1) | NZ321626A (OSRAM) |
| PL (1) | PL186204B1 (OSRAM) |
| RU (1) | RU2167160C2 (OSRAM) |
| SI (1) | SI0863897T1 (OSRAM) |
| SK (1) | SK282335B6 (OSRAM) |
| TR (1) | TR199800827T2 (OSRAM) |
| TW (1) | TW371303B (OSRAM) |
| UA (1) | UA50748C2 (OSRAM) |
| WO (1) | WO1997017345A1 (OSRAM) |
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 |
| EP0980370A1 (fr) * | 1997-05-06 | 2000-02-23 | Sanofi-Synthelabo | Derives de 5-phenyl-1,3,4-oxadiazol-2(3h)-one et leur utilisation comme ligands 5-ht4 |
| 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 |
| ATE310566T1 (de) | 1998-09-18 | 2005-12-15 | Alcon Mfg Ltd | 5ht2-agoniste zur behandlung des glaukoms |
| CN1461216A (zh) * | 1999-04-28 | 2003-12-10 | 呼吸器有限公司 | 用作治疗有关支气管收缩的机能障碍的药物的化合物 |
| AU5861900A (en) * | 1999-06-15 | 2001-01-02 | Respiratorius Ab | Receptor agonists and antagonists |
| WO2002012224A2 (en) * | 2000-08-08 | 2002-02-14 | Ortho Mcneil Pharmaceutical, Inc. | Bicyclic compounds as h3 receptor ligands |
| WO2002012214A2 (en) * | 2000-08-08 | 2002-02-14 | Ortho Mcneil Pharmaceutical Inc. | Non-imidazole aryloxyalkylamines as h3 receptor ligands |
| CA2419036A1 (en) | 2000-08-08 | 2002-02-14 | Ortho-Mcneil Pharmaceutical, Inc. | Non-imidazole aryloxypiperidines as h3 receptor ligands |
| US7208497B2 (en) | 2001-07-02 | 2007-04-24 | Novo Nordisk A/S | Substituted piperazines and diazepanes |
| WO2003004480A2 (en) | 2001-07-02 | 2003-01-16 | Novo Nordisk A/S | Substituted piperazine and diazepanes as histamine h3 receptor agonists |
| EP1434765B1 (en) * | 2001-09-14 | 2009-12-02 | High Point Pharmaceuticals, LLC | Substituted piperidines with selective binding to histamine h3-receptor |
| 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 |
| JP4619655B2 (ja) | 2001-09-14 | 2011-01-26 | ハイ・ポイント・ファーマスーティカルズ、エルエルシー | 新規アミノアゼチジン、−ピロリジンおよび−ピペリジン誘導体 |
| US7064135B2 (en) | 2001-10-12 | 2006-06-20 | Novo Nordisk Inc. | Substituted piperidines |
| 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 |
| US7005448B2 (en) | 2001-12-14 | 2006-02-28 | Alcon, Inc. | Aminoalkyl-benzofuran-5-ol compounds for the treatment of glaucoma |
| 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 |
| AU2005254800B2 (en) | 2004-06-15 | 2010-12-09 | Pfizer Inc. | Benzimidazolone carboxylic acid derivatives |
| US7737163B2 (en) | 2004-06-15 | 2010-06-15 | Pfizer Inc. | Benzimidazolone carboxylic acid derivatives |
| BRPI0613564A2 (pt) | 2005-07-04 | 2011-01-18 | Novo Nordisk As | compostos, seus usos na preparação de composições farmacêuticas e composições farmacêuticas compreendendo os mesmos |
| PL1959951T3 (pl) * | 2005-12-01 | 2010-06-30 | Hoffmann La Roche | Heteroarylo-podstawione pochodne piperydyny jako inhibitory l-cpt1 |
| AU2007267197B2 (en) * | 2006-05-29 | 2011-12-01 | High Point Pharmaceuticals, Llc | 3- (1, 3-Benzodioxol-5-yl) -6- (4-cyclopropylpiperazin-1-yl) -pyridazine, its salts and solvates and its use as histamine H3 receptor antagonist |
| EP2014656A3 (en) * | 2007-06-11 | 2011-08-24 | High Point Pharmaceuticals, LLC | New heteocyclic h3 antagonists |
| MX337721B (es) * | 2011-09-19 | 2016-03-16 | Suven Life Sciences Ltd | Compuestos de heteroarilo como ligandos del receptor 5-ht4. |
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 |
| WO1993003725A1 (en) * | 1991-08-20 | 1993-03-04 | Smithkline Beecham Plc | 5-ht4 receptor antagonists |
| DK0604494T3 (da) * | 1991-09-12 | 1999-11-29 | Smithkline Beecham Plc | 5-HT4-receptorantagonister |
| AU667874B2 (en) * | 1992-02-06 | 1996-04-18 | Smithkline Beecham Plc | Benzopyran, benzothiopyran and benzofuran derivatives as 5-HT4 antagonists |
| 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 CZ CZ19981421A patent/CZ287268B6/cs not_active IP Right Cessation
- 1996-11-05 ES ES96937390T patent/ES2135934T3/es not_active Expired - Lifetime
- 1996-11-05 AU AU75001/96A patent/AU707325B2/en not_active Ceased
- 1996-11-05 JP JP51791797A patent/JP4263240B2/ja not_active Expired - Fee Related
- 1996-11-05 EE EE9800155A patent/EE03487B1/xx not_active IP Right Cessation
- 1996-11-05 BR BR9611311A patent/BR9611311A/pt not_active IP Right Cessation
- 1996-11-05 UA UA98031589A patent/UA50748C2/uk unknown
- 1996-11-05 CN CN96198208A patent/CN1077891C/zh not_active Expired - Fee Related
- 1996-11-05 CA CA002236357A patent/CA2236357C/en not_active Expired - Fee Related
- 1996-11-05 SK SK599-98A patent/SK282335B6/sk not_active IP Right Cessation
- 1996-11-05 AT AT96937390T patent/ATE181328T1/de active
- 1996-11-05 RU RU98110976/04A patent/RU2167160C2/ru not_active IP Right Cessation
- 1996-11-05 WO PCT/FR1996/001730 patent/WO1997017345A1/fr not_active Ceased
- 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 HU HU0001168A patent/HUP0001168A3/hu unknown
- 1996-11-05 TR TR1998/00827T patent/TR199800827T2/xx unknown
- 1996-11-05 NZ NZ321626A patent/NZ321626A/xx not_active IP Right Cessation
- 1996-11-05 DE DE69602970T patent/DE69602970T2/de not_active Expired - Lifetime
- 1996-11-05 US US09/068,390 patent/US5929089A/en not_active Expired - Lifetime
- 1996-11-05 PL PL96326671A patent/PL186204B1/pl not_active IP Right Cessation
- 1996-11-05 IL IL12436496A patent/IL124364A/xx not_active IP Right Cessation
- 1996-11-07 TW TW085113594A patent/TW371303B/zh not_active IP Right Cessation
- 1996-11-08 CO CO96059097A patent/CO4770968A1/es unknown
- 1996-11-08 AR ARP960105098A patent/AR004708A1/es active IP Right Grant
-
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
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Legal Events
| Date | Code | Title | Description |
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| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20141105 |