ZA200202575B - New oxabispidine compounds useful in the treatment of cardiac arrhythmias. - Google Patents
New oxabispidine compounds useful in the treatment of cardiac arrhythmias. Download PDFInfo
- Publication number
- ZA200202575B ZA200202575B ZA200202575A ZA200202575A ZA200202575B ZA 200202575 B ZA200202575 B ZA 200202575B ZA 200202575 A ZA200202575 A ZA 200202575A ZA 200202575 A ZA200202575 A ZA 200202575A ZA 200202575 B ZA200202575 B ZA 200202575B
- Authority
- ZA
- South Africa
- Prior art keywords
- compound
- diazabicyclo
- oxa
- formula
- benzonitrile
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 386
- 206010003119 arrhythmia Diseases 0.000 title claims description 18
- 238000011282 treatment Methods 0.000 title claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 184
- 238000006243 chemical reaction Methods 0.000 claims description 103
- 229910052799 carbon Inorganic materials 0.000 claims description 88
- 125000005843 halogen group Chemical group 0.000 claims description 86
- 125000002947 alkylene group Chemical group 0.000 claims description 77
- 125000003118 aryl group Chemical group 0.000 claims description 71
- 125000001424 substituent group Chemical group 0.000 claims description 66
- 229910052739 hydrogen Inorganic materials 0.000 claims description 60
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 55
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 53
- 238000000034 method Methods 0.000 claims description 50
- 125000003545 alkoxy group Chemical group 0.000 claims description 38
- 125000004432 carbon atom Chemical group C* 0.000 claims description 37
- -1 3-{7-[3-(4-acetyl-1-piperazinyl)propyl]-9-oxa-3,7-diazabicyclo[3.3.1]- non-3-yl}propyl Chemical group 0.000 claims description 31
- 239000002904 solvent Substances 0.000 claims description 31
- 239000002585 base Substances 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- 230000008569 process Effects 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 239000003054 catalyst Substances 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 11
- 230000009467 reduction Effects 0.000 claims description 11
- 230000006793 arrhythmia Effects 0.000 claims description 10
- 125000004104 aryloxy group Chemical group 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 230000003647 oxidation Effects 0.000 claims description 10
- 238000007254 oxidation reaction Methods 0.000 claims description 10
- 239000001301 oxygen Substances 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical group C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 125000001475 halogen functional group Chemical group 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 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 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
- 230000002140 halogenating effect Effects 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical group S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000002346 iodo group Chemical group I* 0.000 claims description 5
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 5
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 5
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 230000002378 acidificating effect Effects 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 239000011593 sulfur Chemical group 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- 206010047281 Ventricular arrhythmia Diseases 0.000 claims description 3
- 230000001746 atrial effect Effects 0.000 claims description 3
- 238000010511 deprotection reaction Methods 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- UAXNXOMKCGKNCI-UHFFFAOYSA-N 1-diphenylphosphanylethyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(C)P(C=1C=CC=CC=1)C1=CC=CC=C1 UAXNXOMKCGKNCI-UHFFFAOYSA-N 0.000 claims description 2
- YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 136
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 24
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 12
- 238000011321 prophylaxis Methods 0.000 claims 7
- LAQPNDIUHRHNCV-UHFFFAOYSA-N isophthalonitrile Chemical compound N#CC1=CC=CC(C#N)=C1 LAQPNDIUHRHNCV-UHFFFAOYSA-N 0.000 claims 3
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 2
- 238000009472 formulation Methods 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 2
- USHQAANQUPSIEV-UHFFFAOYSA-N 2-(4-acetylpiperazin-1-yl)ethyl 7-[2-(4-cyanophenoxy)ethyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1CN(C(=O)C)CCN1CCOC(=O)N1CC(O2)CN(CCOC=3C=CC(=CC=3)C#N)CC2C1 USHQAANQUPSIEV-UHFFFAOYSA-N 0.000 claims 1
- RIURJKDIVNJRIF-UHFFFAOYSA-N 2-[7-[2-(4-cyanophenoxy)ethyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl]-n,n-diethylacetamide Chemical compound C1C(O2)CN(CC(=O)N(CC)CC)CC2CN1CCOC1=CC=C(C#N)C=C1 RIURJKDIVNJRIF-UHFFFAOYSA-N 0.000 claims 1
- SVRLHMUYPADDQO-UHFFFAOYSA-N 2-[7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl]-n-propan-2-ylacetamide Chemical compound C1C(O2)CN(CC(=O)NC(C)C)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 SVRLHMUYPADDQO-UHFFFAOYSA-N 0.000 claims 1
- YZSKKTMJMAPQOW-UHFFFAOYSA-N 2-[7-[3-(4-cyanophenyl)sulfonylpropyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl]-n-propan-2-ylacetamide Chemical compound C1C(O2)CN(CC(=O)NC(C)C)CC2CN1CCCS(=O)(=O)C1=CC=C(C#N)C=C1 YZSKKTMJMAPQOW-UHFFFAOYSA-N 0.000 claims 1
- QUXJOPAIAIISAV-UHFFFAOYSA-N 4-[1-(3,4-dimethoxyphenoxy)-4-[3-(3,3-dimethyl-2-oxobutyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]butyl]benzonitrile Chemical compound C1=C(OC)C(OC)=CC=C1OC(C=1C=CC(=CC=1)C#N)CCCN1CC(O2)CN(CC(=O)C(C)(C)C)CC2C1 QUXJOPAIAIISAV-UHFFFAOYSA-N 0.000 claims 1
- SYJFQACWAVOYBU-UHFFFAOYSA-N 4-[2-(3-butylsulfonyl-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl)ethoxy]benzonitrile Chemical compound C1C(O2)CN(S(=O)(=O)CCCC)CC2CN1CCOC1=CC=C(C#N)C=C1 SYJFQACWAVOYBU-UHFFFAOYSA-N 0.000 claims 1
- RNRJBHDIYOGOKC-UHFFFAOYSA-N 4-[2-[3-(2,2-difluoroethyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethoxy]benzonitrile Chemical compound C1C(O2)CN(CC(F)F)CC2CN1CCOC1=CC=C(C#N)C=C1 RNRJBHDIYOGOKC-UHFFFAOYSA-N 0.000 claims 1
- ZFCLEMPZXCRWKC-UHFFFAOYSA-N 4-[2-[3-(3,3-dimethyl-2-oxobutyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethoxy]benzene-1,3-dicarbonitrile Chemical compound C1C(O2)CN(CC(=O)C(C)(C)C)CC2CN1CCOC1=CC=C(C#N)C=C1C#N ZFCLEMPZXCRWKC-UHFFFAOYSA-N 0.000 claims 1
- RYYDXQOTNIVFHE-UHFFFAOYSA-N 4-[2-[3-(3,3-dimethyl-2-oxobutyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethoxy]benzonitrile Chemical compound C1C(O2)CN(CC(=O)C(C)(C)C)CC2CN1CCOC1=CC=C(C#N)C=C1 RYYDXQOTNIVFHE-UHFFFAOYSA-N 0.000 claims 1
- CYXCSOWXRRGAHX-UHFFFAOYSA-N 4-[2-[3-[(2,4-difluorophenyl)methyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethoxy]benzonitrile Chemical compound FC1=CC(F)=CC=C1CN1CC(O2)CN(CCOC=3C=CC(=CC=3)C#N)CC2C1 CYXCSOWXRRGAHX-UHFFFAOYSA-N 0.000 claims 1
- TZXOTBUVXNBRLH-UHFFFAOYSA-N 4-[2-[3-[(4-fluorophenyl)methyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethoxy]benzonitrile Chemical compound C1=CC(F)=CC=C1CN1CC(O2)CN(CCOC=3C=CC(=CC=3)C#N)CC2C1 TZXOTBUVXNBRLH-UHFFFAOYSA-N 0.000 claims 1
- NVOOJOZGMYNPJV-UHFFFAOYSA-N 4-[2-[3-[1-(2,6-dimethylphenoxy)propan-2-yl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethoxy]benzonitrile Chemical compound C1C(O2)CN(CCOC=3C=CC(=CC=3)C#N)CC2CN1C(C)COC1=C(C)C=CC=C1C NVOOJOZGMYNPJV-UHFFFAOYSA-N 0.000 claims 1
- CSGHHNHUEHTXHP-UHFFFAOYSA-N 4-[2-[3-[2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-oxoethyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethoxy]benzonitrile Chemical compound C=1C=C2OCCOC2=CC=1C(=O)CN(CC(C1)O2)CC2CN1CCOC1=CC=C(C#N)C=C1 CSGHHNHUEHTXHP-UHFFFAOYSA-N 0.000 claims 1
- WZSGYCQVVPFHIO-UHFFFAOYSA-N 4-[2-[3-[2-(4-fluorophenyl)-2-oxoethyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethoxy]benzonitrile Chemical compound C1=CC(F)=CC=C1C(=O)CN1CC(O2)CN(CCOC=3C=CC(=CC=3)C#N)CC2C1 WZSGYCQVVPFHIO-UHFFFAOYSA-N 0.000 claims 1
- KIEDYFNJCNMNLR-UHFFFAOYSA-N 4-[2-[7-(2-phenoxyethyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl]ethoxy]benzonitrile Chemical compound C1=CC(C#N)=CC=C1OCCN1CC(O2)CN(CCOC=3C=CC=CC=3)CC2C1 KIEDYFNJCNMNLR-UHFFFAOYSA-N 0.000 claims 1
- PPQQRFHTPHFIJT-UHFFFAOYSA-N 4-[2-[7-(2-pyrrol-1-ylethyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl]ethoxy]benzonitrile Chemical compound C1=CC(C#N)=CC=C1OCCN1CC(O2)CN(CCN3C=CC=C3)CC2C1 PPQQRFHTPHFIJT-UHFFFAOYSA-N 0.000 claims 1
- OYCWICGIUMJGOV-UHFFFAOYSA-N 4-[2-[7-(3-ethylsulfonylpropyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl]ethoxy]benzonitrile Chemical compound C1C(O2)CN(CCCS(=O)(=O)CC)CC2CN1CCOC1=CC=C(C#N)C=C1 OYCWICGIUMJGOV-UHFFFAOYSA-N 0.000 claims 1
- ZZTDZOBVWCNSSA-UHFFFAOYSA-N 4-[2-[7-[2-(4-methyl-1,3-thiazol-5-yl)ethyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl]ethoxy]benzonitrile Chemical compound N1=CSC(CCN2CC3CN(CCOC=4C=CC(=CC=4)C#N)CC(O3)C2)=C1C ZZTDZOBVWCNSSA-UHFFFAOYSA-N 0.000 claims 1
- BXLKDOXGUJOFFK-UHFFFAOYSA-N 4-[2-[7-[3-(4-acetylpiperazin-1-yl)propyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl]ethoxy]benzonitrile Chemical compound C1CN(C(=O)C)CCN1CCCN1CC(O2)CN(CCOC=3C=CC(=CC=3)C#N)CC2C1 BXLKDOXGUJOFFK-UHFFFAOYSA-N 0.000 claims 1
- ILMYQYNVENUQBH-UHFFFAOYSA-N 4-[2-hydroxy-3-[3-[2-(4-methoxyphenyl)-2-oxoethyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]propoxy]benzonitrile Chemical compound C1=CC(OC)=CC=C1C(=O)CN1CC(O2)CN(CC(O)COC=3C=CC(=CC=3)C#N)CC2C1 ILMYQYNVENUQBH-UHFFFAOYSA-N 0.000 claims 1
- RZGYRHZWYOENKC-UHFFFAOYSA-N 4-[2-hydroxy-3-[7-(oxan-2-ylmethyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl]propoxy]benzonitrile Chemical compound C1C(O2)CN(CC3OCCCC3)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 RZGYRHZWYOENKC-UHFFFAOYSA-N 0.000 claims 1
- MYNBXBKCCVXTON-UHFFFAOYSA-N 4-[3-(3-benzyl-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl)propylamino]benzonitrile Chemical compound C1=CC(C#N)=CC=C1NCCCN1CC(O2)CN(CC=3C=CC=CC=3)CC2C1 MYNBXBKCCVXTON-UHFFFAOYSA-N 0.000 claims 1
- PRAXUAILYHAJER-UHFFFAOYSA-N 4-[3-(3-butylsulfonyl-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl)-2-hydroxypropoxy]benzonitrile Chemical compound C1C(O2)CN(S(=O)(=O)CCCC)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 PRAXUAILYHAJER-UHFFFAOYSA-N 0.000 claims 1
- JAHWBGQNAOVQRH-UHFFFAOYSA-N 4-[3-(3-butylsulfonyl-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl)propylamino]benzonitrile Chemical compound C1C(O2)CN(S(=O)(=O)CCCC)CC2CN1CCCNC1=CC=C(C#N)C=C1 JAHWBGQNAOVQRH-UHFFFAOYSA-N 0.000 claims 1
- ATVCVFPEZAMBTR-UHFFFAOYSA-N 4-[3-[3-(2-hydroxy-3,3-dimethylbutyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylamino]benzonitrile Chemical compound C1C(O2)CN(CC(O)C(C)(C)C)CC2CN1CCCNC1=CC=C(C#N)C=C1 ATVCVFPEZAMBTR-UHFFFAOYSA-N 0.000 claims 1
- NKBKQXVTZGHPAU-UHFFFAOYSA-N 4-[3-[3-(2-pyrrol-1-ylethyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]propoxy]benzonitrile Chemical compound C1=CC(C#N)=CC=C1OCCCN1CC(O2)CN(CCN3C=CC=C3)CC2C1 NKBKQXVTZGHPAU-UHFFFAOYSA-N 0.000 claims 1
- KZOCHEDMAHPYCK-UHFFFAOYSA-N 4-[3-[3-(3,3-dimethyl-2-oxobutyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylamino]benzonitrile Chemical compound C1C(O2)CN(CC(=O)C(C)(C)C)CC2CN1CCCNC1=CC=C(C#N)C=C1 KZOCHEDMAHPYCK-UHFFFAOYSA-N 0.000 claims 1
- BKWHDRQCLHJLJX-UHFFFAOYSA-N 4-[3-[3-(3-ethylsulfonylpropyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylamino]benzonitrile Chemical compound C1C(O2)CN(CCCS(=O)(=O)CC)CC2CN1CCCNC1=CC=C(C#N)C=C1 BKWHDRQCLHJLJX-UHFFFAOYSA-N 0.000 claims 1
- QAGSHMXKZDEBON-UHFFFAOYSA-N 4-[3-[3-(benzenesulfonyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylamino]benzonitrile Chemical compound C=1C=CC=CC=1S(=O)(=O)N(CC(C1)O2)CC2CN1CCCNC1=CC=C(C#N)C=C1 QAGSHMXKZDEBON-UHFFFAOYSA-N 0.000 claims 1
- CRAXQHFQRVIJRK-UHFFFAOYSA-N 4-[3-[3-(imidazo[1,2-a]pyridin-2-ylmethyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]propoxy]benzonitrile Chemical compound C1=CC(C#N)=CC=C1OCCCN1CC(O2)CN(CC=3N=C4C=CC=CN4C=3)CC2C1 CRAXQHFQRVIJRK-UHFFFAOYSA-N 0.000 claims 1
- OLYARRPXIIOBOG-UHFFFAOYSA-N 4-[3-[3-[(2,4-difluorophenyl)methyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylsulfonyl]benzonitrile Chemical compound FC1=CC(F)=CC=C1CN1CC(O2)CN(CCCS(=O)(=O)C=3C=CC(=CC=3)C#N)CC2C1 OLYARRPXIIOBOG-UHFFFAOYSA-N 0.000 claims 1
- UAMZZHYGFAPMTI-UHFFFAOYSA-N 4-[3-[3-[(4-fluorophenyl)methyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylamino]benzonitrile Chemical compound C1=CC(F)=CC=C1CN1CC(O2)CN(CCCNC=3C=CC(=CC=3)C#N)CC2C1 UAMZZHYGFAPMTI-UHFFFAOYSA-N 0.000 claims 1
- TUVXEDHSDAEVGN-UHFFFAOYSA-N 4-[3-[3-[(4-fluorophenyl)methyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylsulfonyl]benzonitrile Chemical compound C1=CC(F)=CC=C1CN1CC(O2)CN(CCCS(=O)(=O)C=3C=CC(=CC=3)C#N)CC2C1 TUVXEDHSDAEVGN-UHFFFAOYSA-N 0.000 claims 1
- CVSUYSPEMPQIJI-UHFFFAOYSA-N 4-[3-[3-[2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-oxoethyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C1C(O2)CN(CC(=O)C=3C=C4OCCOC4=CC=3)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 CVSUYSPEMPQIJI-UHFFFAOYSA-N 0.000 claims 1
- OEYDFULLPBQXOD-UHFFFAOYSA-N 4-[3-[3-[2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-oxoethyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]propoxy]benzonitrile Chemical compound C=1C=C2OCCOC2=CC=1C(=O)CN(CC(C1)O2)CC2CN1CCCOC1=CC=C(C#N)C=C1 OEYDFULLPBQXOD-UHFFFAOYSA-N 0.000 claims 1
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- 239000007822 coupling agent Substances 0.000 description 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
- 150000002009 diols Chemical class 0.000 description 2
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- 150000002148 esters Chemical class 0.000 description 2
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
- 150000002440 hydroxy compounds Chemical class 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine group Chemical group P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
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- 230000002336 repolarization Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
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- 239000012279 sodium borohydride Substances 0.000 description 2
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- 239000012312 sodium hydride Substances 0.000 description 2
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 description 2
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- JXRGUPLJCCDGKG-UHFFFAOYSA-N 4-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(S(Cl)(=O)=O)C=C1 JXRGUPLJCCDGKG-UHFFFAOYSA-N 0.000 description 1
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- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
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- 208000006218 bradycardia Diseases 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 230000011128 cardiac conduction Effects 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
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- 150000004696 coordination complex Chemical class 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
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- OCXGTPDKNBIOTF-UHFFFAOYSA-N dibromo(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Br)(C=1C=CC=CC=1)(Br)C1=CC=CC=C1 OCXGTPDKNBIOTF-UHFFFAOYSA-N 0.000 description 1
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- FBCACJBKVCSUBF-ZLPCBKJTSA-N ethyl 7-[(2s)-3-(4-cyanophenoxy)-2-hydroxypropyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C([C@@H](O)CN1CC2CN(CC(C1)O2)C(=O)OCC)OC1=CC=C(C#N)C=C1 FBCACJBKVCSUBF-ZLPCBKJTSA-N 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- VHHHONWQHHHLTI-UHFFFAOYSA-N hexachloroethane Chemical compound ClC(Cl)(Cl)C(Cl)(Cl)Cl VHHHONWQHHHLTI-UHFFFAOYSA-N 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- MWSPFHZPVVWJCO-UHFFFAOYSA-M hydron;methyl(trioctyl)azanium;sulfate Chemical compound OS([O-])(=O)=O.CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC MWSPFHZPVVWJCO-UHFFFAOYSA-M 0.000 description 1
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- 150000002500 ions Chemical class 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
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- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000010470 malonic ester synthesis reaction Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- OQJBFFCUFALWQL-UHFFFAOYSA-N n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)N=NC(=O)N1CCCCC1 OQJBFFCUFALWQL-UHFFFAOYSA-N 0.000 description 1
- DYUWTXWIYMHBQS-UHFFFAOYSA-N n-prop-2-enylprop-2-en-1-amine Chemical compound C=CCNCC=C DYUWTXWIYMHBQS-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 125000001484 phenothiazinyl group Chemical class C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 229960001922 sodium perborate Drugs 0.000 description 1
- YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 150000004794 vinyl magnesium halides Chemical class 0.000 description 1
- 238000006886 vinylation reaction Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/08—Bridged systems
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Heart & Thoracic Surgery (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Epoxy Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9903759A SE9903759D0 (sv) | 1999-10-18 | 1999-10-18 | Pharmaceutically active compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200202575B true ZA200202575B (en) | 2003-09-23 |
Family
ID=20417401
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200202575A ZA200202575B (en) | 1999-10-18 | 2002-04-02 | New oxabispidine compounds useful in the treatment of cardiac arrhythmias. |
Country Status (41)
| Country | Link |
|---|---|
| US (6) | US6559143B1 (no) |
| EP (2) | EP1235831B1 (no) |
| JP (3) | JP3973906B2 (no) |
| KR (1) | KR100796142B1 (no) |
| CN (2) | CN101265262A (no) |
| AP (1) | AP1536A (no) |
| AR (2) | AR026064A1 (no) |
| AT (1) | ATE292134T1 (no) |
| AU (1) | AU769513B2 (no) |
| BG (1) | BG65785B1 (no) |
| BR (1) | BR0014804A (no) |
| CA (1) | CA2386910A1 (no) |
| CO (1) | CO5271655A1 (no) |
| CU (1) | CU23210A3 (no) |
| CZ (1) | CZ20021328A3 (no) |
| DE (1) | DE60019158T2 (no) |
| DK (1) | DK1235831T3 (no) |
| EA (1) | EA005319B1 (no) |
| EE (1) | EE04854B1 (no) |
| ES (1) | ES2239047T3 (no) |
| HK (1) | HK1049003B (no) |
| HR (1) | HRP20020336B1 (no) |
| HU (1) | HUP0204085A3 (no) |
| IL (5) | IL149108A0 (no) |
| IS (2) | IS2224B (no) |
| MX (1) | MXPA02003848A (no) |
| MY (1) | MY130661A (no) |
| NO (1) | NO327977B1 (no) |
| NZ (2) | NZ531260A (no) |
| OA (1) | OA12067A (no) |
| PL (1) | PL354970A1 (no) |
| PT (1) | PT1235831E (no) |
| RS (1) | RS50760B (no) |
| SE (1) | SE9903759D0 (no) |
| SI (1) | SI1235831T1 (no) |
| SK (1) | SK286723B6 (no) |
| TR (1) | TR200201059T2 (no) |
| TW (1) | TWI283680B (no) |
| UA (1) | UA75052C2 (no) |
| WO (1) | WO2001028992A2 (no) |
| ZA (1) | ZA200202575B (no) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI229674B (en) | 1998-12-04 | 2005-03-21 | Astra Pharma Prod | Novel triazolo[4,5-d]pyrimidine compounds, pharmaceutical composition containing the same, their process for preparation and uses |
| SE9902270D0 (sv) * | 1999-06-16 | 1999-06-16 | Astra Ab | Pharmaceutically active compounds |
| SE9903759D0 (sv) | 1999-10-18 | 1999-10-18 | Astra Ab | Pharmaceutically active compounds |
| AR030756A1 (es) * | 2000-10-02 | 2003-09-03 | Astrazeneca Ab | Compuesto de oxabispidina util en el tratamiento de arritmias cardiacas |
| SE0101329D0 (sv) * | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | Pharmaceutical formulation |
| TWI259836B (en) * | 2001-04-12 | 2006-08-11 | Astrazeneca Ab | Modified release formulation suitable for antiarrhythmic compounds |
| SE0101324D0 (sv) | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | New process |
| SE0101327D0 (sv) * | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | New crystalline forms |
| SE0101323D0 (sv) * | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | New process |
| BR0214225A (pt) * | 2001-11-22 | 2004-09-21 | Astrazeneca Ab | Processos para a preparação e para a formação de um composto, e, composto |
| SE0201373D0 (sv) * | 2002-05-06 | 2002-05-06 | Astrazeneca Ab | Combination therapy |
| SE0201374D0 (sv) * | 2002-05-06 | 2002-05-06 | Astrazeneca Ab | Pharmaceutical combination |
| SE0201662D0 (sv) * | 2002-05-31 | 2002-05-31 | Astrazeneca Ab | Pharmaceutical combination |
| GB0223712D0 (en) * | 2002-10-14 | 2002-11-20 | Astrazeneca Ab | Chemical intermediate |
| SE0401540D0 (sv) * | 2004-06-15 | 2004-06-15 | Astrazeneca Ab | New compounds |
| SE0401539D0 (sv) | 2004-06-15 | 2004-06-15 | Astrazeneca Ab | New compounds |
| AR057064A1 (es) * | 2005-06-13 | 2007-11-14 | Astrazeneca Ab | Compuestos para el tratamiento de arritmias cardiacas, formulacion farmaceutica y preparacion del compuesto |
| AR053901A1 (es) * | 2005-06-20 | 2007-05-23 | Astrazeneca Ab | Formas fisicas de oxabispidinas n,n'- disustituidas |
| WO2006137769A1 (en) * | 2005-06-20 | 2006-12-28 | Astrazeneca Ab | Process for the preparation of 3,7-dihydroxy-1,5-diazacyclooctanes |
| BRPI0611841A2 (pt) * | 2005-06-20 | 2016-08-30 | Astrazeneca Ab | processos para isolar um sal, para preparar um sal, e para a preparação de um composto |
| EP1915380A4 (en) * | 2005-06-20 | 2010-03-17 | Astrazeneca Ab | PROCESS FOR THE SYNTHESIS OF N, N'-DISUBSTITUTED OXABISPIDINES |
| CN1330636C (zh) * | 2005-09-26 | 2007-08-08 | 鲁南制药集团股份有限公司 | 盐酸替罗非班中间体的合成方法 |
| TW200734342A (en) * | 2005-12-15 | 2007-09-16 | Astrazeneca Ab | New compounds for the treatment of cardiac arrhythmias |
| TW201004963A (en) * | 2008-07-03 | 2010-02-01 | Targacept Inc | Derivatives of oxabispidine as neuronal nicotinic acetylcholine receptor ligands |
| GB2495308B (en) * | 2011-10-05 | 2014-09-10 | John Royce | Method and apparatus for cleaning a filter |
| PE20161035A1 (es) | 2013-03-15 | 2016-11-13 | Global Blood Therapeutics Inc | Compuestos y usos de estos para la modulacion de la hemoglobina |
| EA201992707A1 (ru) | 2013-11-18 | 2020-06-30 | Глобал Блад Терапьютикс, Инк. | Соединения и их применения для модуляции гемоглобина |
| US10231970B2 (en) | 2014-09-30 | 2019-03-19 | NV Heterocycles | Methods of producing heteropolycycles via bis-epoxidation |
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| US3196154A (en) * | 1962-05-17 | 1965-07-20 | Sterling Drug Inc | 3-substituted-9-methyl-3, 9-diazabicyclo [3.3.1] nonanes |
| US3503939A (en) | 1967-03-29 | 1970-03-31 | Du Pont | Polyamides from heterocyclic diamines |
| CH488048A (de) | 1969-06-12 | 1970-03-31 | Inventa Ag | Verfahren zur Herstellung von Polyesterfasern mit verbesserter Gummihaftung |
| JPS5772977A (en) * | 1980-10-23 | 1982-05-07 | Dainippon Ink & Chem Inc | Fluorine-containing diepoxy compound and its preparation |
| DE3112055A1 (de) * | 1981-03-27 | 1982-10-07 | Basf Ag, 6700 Ludwigshafen | Bispidinderivate, ihre herstellung und diese enthaltende arzneimittel |
| US4533713A (en) * | 1983-05-06 | 1985-08-06 | Minnesota Mining And Manufacturing Company | Fluoroaliphaticsulfonamides containing oxirane groups and/or N-β-hydroxyalkylene groups |
| FI67320C (fi) * | 1983-05-09 | 1985-03-11 | Partek Ab | Foerfarande och glidgjutanordning foer gjutning av betongstycken |
| JPS6284071A (ja) * | 1985-10-07 | 1987-04-17 | Kanegafuchi Chem Ind Co Ltd | 新規グリシジル化合物及びその製造方法 |
| JPS6284070A (ja) * | 1985-10-07 | 1987-04-17 | Kanegafuchi Chem Ind Co Ltd | 新規なグリシジル化合物及びその製造法 |
| DE3732094A1 (de) | 1987-09-24 | 1989-04-06 | Basf Ag | Bispidinderivate als klasse iii-antiarrhythmika |
| US5140033A (en) | 1989-04-03 | 1992-08-18 | Bayer Aktiengesellschaft | Antibacterial 5-alkylquinolonecarboxylic acids |
| US5110933A (en) | 1989-11-13 | 1992-05-05 | Board Of Regents Of Oklahoma State University | Salts of 3-azabicyclo[3.3.1]nonanes as antiarrhythmic agents, and precursors thereof |
| FR2664270B1 (fr) * | 1990-07-09 | 1994-04-08 | Norsolor Sa | Nouveaux composes (meth)acryliques porteurs de fonction thiocyanate, leur procede de preparation et leur application a l'obtention de nouveaux polymeres. |
| JP2602745B2 (ja) * | 1991-06-26 | 1997-04-23 | 花王株式会社 | フレキシブルディスク用センターハブのピッキング装置 |
| US5468858A (en) * | 1993-10-28 | 1995-11-21 | The Board Of Regents Of Oklahoma State University Physical Sciences | N-alkyl and n-acyl derivatives of 3,7-diazabicyclo-[3.3.1]nonanes and selected salts thereof as multi-class antiarrhythmic agents |
| US5831099A (en) * | 1995-03-10 | 1998-11-03 | The United States Of America As Represented By The Secretary Of The Army | Compounds of 1,5-disubstituted-3,7 diaza bicyclo 3.3.0! octanes and products containing the same |
| SE9704709D0 (sv) * | 1997-12-17 | 1997-12-17 | Astra Ab | Pharmaceutically active compounds |
| SE9803517D0 (sv) * | 1998-10-15 | 1998-10-15 | Astra Ab | Pharmaceutical preparation |
| NZ514477A (en) | 1999-04-09 | 2003-04-29 | Astrazeneca Ab | Adamantane derivatives |
| SE9902270D0 (sv) * | 1999-06-16 | 1999-06-16 | Astra Ab | Pharmaceutically active compounds |
| SE9903759D0 (sv) * | 1999-10-18 | 1999-10-18 | Astra Ab | Pharmaceutically active compounds |
| SE9904765D0 (sv) * | 1999-12-23 | 1999-12-23 | Astra Ab | Pharmaceutically-useful compounds |
| AR030756A1 (es) * | 2000-10-02 | 2003-09-03 | Astrazeneca Ab | Compuesto de oxabispidina util en el tratamiento de arritmias cardiacas |
-
1999
- 1999-10-18 SE SE9903759A patent/SE9903759D0/xx unknown
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2000
- 2000-10-06 TW TW089120910A patent/TWI283680B/zh not_active IP Right Cessation
- 2000-10-13 JP JP2001531792A patent/JP3973906B2/ja not_active Expired - Fee Related
- 2000-10-13 AU AU10691/01A patent/AU769513B2/en not_active Ceased
- 2000-10-13 DE DE60019158T patent/DE60019158T2/de not_active Expired - Lifetime
- 2000-10-13 NZ NZ531260A patent/NZ531260A/en unknown
- 2000-10-13 PT PT00971960T patent/PT1235831E/pt unknown
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- 2000-10-13 UA UA2002043168A patent/UA75052C2/uk unknown
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- 2000-10-13 EE EEP200200203A patent/EE04854B1/xx not_active IP Right Cessation
- 2000-10-13 CN CNA2008100058488A patent/CN101265262A/zh active Pending
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- 2000-10-13 WO PCT/SE2000/001994 patent/WO2001028992A2/en active Application Filing
- 2000-10-13 EP EP00971960A patent/EP1235831B1/en not_active Expired - Lifetime
- 2000-10-13 EP EP05006781A patent/EP1559717A3/en not_active Withdrawn
- 2000-10-13 CN CNB00816231XA patent/CN100379743C/zh not_active Expired - Fee Related
- 2000-10-13 MX MXPA02003848A patent/MXPA02003848A/es active IP Right Grant
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- 2000-10-13 BR BR0014804-0A patent/BR0014804A/pt not_active IP Right Cessation
- 2000-10-13 RS YUP-294/02A patent/RS50760B/sr unknown
- 2000-10-13 AT AT00971960T patent/ATE292134T1/de not_active IP Right Cessation
- 2000-10-13 SK SK506-2002A patent/SK286723B6/sk not_active IP Right Cessation
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- 2000-10-13 ES ES00971960T patent/ES2239047T3/es not_active Expired - Lifetime
- 2000-10-16 US US09/688,251 patent/US6559143B1/en not_active Expired - Fee Related
- 2000-10-16 MY MYPI20004850A patent/MY130661A/en unknown
- 2000-10-17 AR ARP000105452A patent/AR026064A1/es active IP Right Grant
- 2000-10-17 CO CO00078740A patent/CO5271655A1/es not_active Application Discontinuation
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2002
- 2002-04-02 ZA ZA200202575A patent/ZA200202575B/en unknown
- 2002-04-05 BG BG106588A patent/BG65785B1/bg unknown
- 2002-04-11 IL IL149108A patent/IL149108A/en not_active IP Right Cessation
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- 2002-04-16 HR HR20020336A patent/HRP20020336B1/xx not_active IP Right Cessation
- 2002-04-17 IS IS6346A patent/IS2224B/is unknown
- 2002-04-17 NO NO20021811A patent/NO327977B1/no not_active IP Right Cessation
- 2002-12-12 US US10/317,195 patent/US7164017B2/en not_active Expired - Fee Related
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2003
- 2003-02-18 HK HK03101241.2A patent/HK1049003B/zh not_active IP Right Cessation
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- 2006-03-22 US US11/385,861 patent/US20060166980A1/en not_active Abandoned
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- 2006-08-23 JP JP2006226089A patent/JP2006342182A/ja active Pending
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