JP2002508375A - 新規なビスピジン抗不整脈性化合物 - Google Patents
新規なビスピジン抗不整脈性化合物Info
- Publication number
- JP2002508375A JP2002508375A JP2000539024A JP2000539024A JP2002508375A JP 2002508375 A JP2002508375 A JP 2002508375A JP 2000539024 A JP2000539024 A JP 2000539024A JP 2000539024 A JP2000539024 A JP 2000539024A JP 2002508375 A JP2002508375 A JP 2002508375A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- diazabicyclo
- mmol
- nonane
- 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.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims description 331
- PTPQJKANBKHDPM-UHFFFAOYSA-N 3,7-diazabicyclo[3.3.1]nonane Chemical compound C1NCC2CNCC1C2 PTPQJKANBKHDPM-UHFFFAOYSA-N 0.000 title claims description 11
- 239000003416 antiarrhythmic agent Substances 0.000 title description 11
- 230000003288 anthiarrhythmic effect Effects 0.000 title description 2
- 206010003119 arrhythmia Diseases 0.000 claims abstract description 24
- 230000006793 arrhythmia Effects 0.000 claims abstract description 17
- 230000002265 prevention Effects 0.000 claims abstract description 6
- 206010047281 Ventricular arrhythmia Diseases 0.000 claims abstract description 4
- 230000001746 atrial effect Effects 0.000 claims abstract description 4
- 206010003130 Arrhythmia supraventricular Diseases 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 89
- 238000006243 chemical reaction Methods 0.000 claims description 38
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 36
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 34
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000002947 alkylene group Chemical group 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 230000009467 reduction Effects 0.000 claims description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 150000007524 organic acids Chemical class 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 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 5
- 230000003647 oxidation Effects 0.000 claims description 4
- 238000007254 oxidation reaction Methods 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- FUFZNHHSSMCXCZ-UHFFFAOYSA-N 5-piperidin-4-yl-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C1=CC=CC(C=2N=C(ON=2)C2CCNCC2)=C1 FUFZNHHSSMCXCZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims 1
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical class O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims 1
- 150000003863 ammonium salts Chemical class 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 130
- 238000005481 NMR spectroscopy Methods 0.000 description 120
- -1 alkyl quaternary ammonium salt Chemical class 0.000 description 94
- 239000011541 reaction mixture Substances 0.000 description 89
- 239000000243 solution Substances 0.000 description 77
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 52
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 47
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 44
- 239000012044 organic layer Substances 0.000 description 43
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
- 238000004440 column chromatography Methods 0.000 description 38
- DMUXSGAKEXSNGN-UHFFFAOYSA-N 2-ethyloctanoic acid Chemical compound CCCCCCC(CC)C(O)=O DMUXSGAKEXSNGN-UHFFFAOYSA-N 0.000 description 32
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 26
- 235000019439 ethyl acetate Nutrition 0.000 description 24
- 239000007787 solid Substances 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 21
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 20
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
- 238000000262 chemical ionisation mass spectrometry Methods 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
- 239000003960 organic solvent Substances 0.000 description 17
- 239000000706 filtrate Substances 0.000 description 16
- 239000011734 sodium Substances 0.000 description 16
- 238000000746 purification Methods 0.000 description 15
- 230000000694 effects Effects 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- 239000003921 oil Substances 0.000 description 13
- 235000019198 oils Nutrition 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 125000006239 protecting group Chemical group 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 238000007796 conventional method Methods 0.000 description 9
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- ZFVNQMTWYYKBES-UHFFFAOYSA-N tert-butyl 3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1NCC2CN(C(=O)OC(C)(C)C)CC1C2 ZFVNQMTWYYKBES-UHFFFAOYSA-N 0.000 description 8
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000003638 chemical reducing agent Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- WREXVDPOLDOXJL-UHFFFAOYSA-N 4-(oxiran-2-ylmethoxy)benzonitrile Chemical compound C1=CC(C#N)=CC=C1OCC1OC1 WREXVDPOLDOXJL-UHFFFAOYSA-N 0.000 description 5
- CVNOWLNNPYYEOH-UHFFFAOYSA-N 4-cyanophenol Chemical compound OC1=CC=C(C#N)C=C1 CVNOWLNNPYYEOH-UHFFFAOYSA-N 0.000 description 5
- 229930040373 Paraformaldehyde Natural products 0.000 description 5
- 125000005233 alkylalcohol group Chemical group 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 229920002866 paraformaldehyde Polymers 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- KAAITWOSDOCHEH-UHFFFAOYSA-N 3-benzyl-3,7-diazabicyclo[3.3.1]nonane Chemical compound C1C(C2)CNCC2CN1CC1=CC=CC=C1 KAAITWOSDOCHEH-UHFFFAOYSA-N 0.000 description 4
- ICGLPKIVTVWCFT-UHFFFAOYSA-N 4-methylbenzenesulfonohydrazide Chemical compound CC1=CC=C(S(=O)(=O)NN)C=C1 ICGLPKIVTVWCFT-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 4
- ACFIXJIJDZMPPO-NNYOXOHSSA-N NADPH Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 125000002015 acyclic group Chemical group 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 150000007942 carboxylates Chemical class 0.000 description 4
- 230000000747 cardiac effect Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 230000002336 repolarization Effects 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- QQZUTVCAQZLTTH-UHFFFAOYSA-N 2-(4-cyanophenyl)ethyl methanesulfonate Chemical compound CS(=O)(=O)OCCC1=CC=C(C#N)C=C1 QQZUTVCAQZLTTH-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- IVKAPFWKLFIYCG-UHFFFAOYSA-N 4-(2-bromoethoxy)benzonitrile Chemical compound BrCCOC1=CC=C(C#N)C=C1 IVKAPFWKLFIYCG-UHFFFAOYSA-N 0.000 description 3
- DLQGGZNCJPLPQJ-UHFFFAOYSA-N 4-[3-(3,7-diazabicyclo[3.3.1]nonan-3-yl)-2-hydroxypropoxy]benzonitrile Chemical compound C1C(C2)CNCC2CN1CC(O)COC1=CC=C(C#N)C=C1 DLQGGZNCJPLPQJ-UHFFFAOYSA-N 0.000 description 3
- HQSCPPCMBMFJJN-UHFFFAOYSA-N 4-bromobenzonitrile Chemical compound BrC1=CC=C(C#N)C=C1 HQSCPPCMBMFJJN-UHFFFAOYSA-N 0.000 description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 3
- 229910000831 Steel Inorganic materials 0.000 description 3
- 208000018452 Torsade de pointes Diseases 0.000 description 3
- 208000002363 Torsades de Pointes Diseases 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 230000033764 rhythmic process Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000010959 steel Substances 0.000 description 3
- XWOXYNYCGOBIOZ-UHFFFAOYSA-N tert-butyl 7-[3-(4-cyanoanilino)-3-oxopropyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC(C2)CC1CN2CCC(=O)NC1=CC=C(C#N)C=C1 XWOXYNYCGOBIOZ-UHFFFAOYSA-N 0.000 description 3
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical compound CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- UBDJWOLNWDABFT-UHFFFAOYSA-N 2-cyanopropan-2-yl 7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C#N)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 UBDJWOLNWDABFT-UHFFFAOYSA-N 0.000 description 2
- XCAFUVXBLCWDMX-UHFFFAOYSA-N 2-cyanopropan-2-yl carbonochloridate Chemical compound N#CC(C)(C)OC(Cl)=O XCAFUVXBLCWDMX-UHFFFAOYSA-N 0.000 description 2
- BJSBDAPLFVODIY-UHFFFAOYSA-N 3,7-diazabicyclo[3.3.1]nonane-3-carboxylic acid Chemical compound C1NCC2CN(C(=O)O)CC1C2 BJSBDAPLFVODIY-UHFFFAOYSA-N 0.000 description 2
- UDCHLXJYCUCIAT-UHFFFAOYSA-N 3-chloro-n-(4-cyanophenyl)propanamide Chemical compound ClCCC(=O)NC1=CC=C(C#N)C=C1 UDCHLXJYCUCIAT-UHFFFAOYSA-N 0.000 description 2
- LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
- UDZJFMWGZYXJMG-UHFFFAOYSA-N 4-(3-amino-2-hydroxypropoxy)benzonitrile Chemical compound NCC(O)COC1=CC=C(C#N)C=C1 UDZJFMWGZYXJMG-UHFFFAOYSA-N 0.000 description 2
- PFJMSQJCWVZVCA-UHFFFAOYSA-N 4-(3-chloropropoxy)-3-hydroxybenzonitrile Chemical compound OC1=CC(C#N)=CC=C1OCCCCl PFJMSQJCWVZVCA-UHFFFAOYSA-N 0.000 description 2
- YAJULWYXWDVOSC-LLVKDONJSA-N 4-[[(2s)-2-methyloxiran-2-yl]methoxy]benzonitrile Chemical compound C=1C=C(C#N)C=CC=1OC[C@]1(C)CO1 YAJULWYXWDVOSC-LLVKDONJSA-N 0.000 description 2
- WREXVDPOLDOXJL-SNVBAGLBSA-N 4-[[(2s)-oxiran-2-yl]methoxy]benzonitrile Chemical compound C1=CC(C#N)=CC=C1OC[C@H]1OC1 WREXVDPOLDOXJL-SNVBAGLBSA-N 0.000 description 2
- WTTADDGUHFYGEH-UHFFFAOYSA-N 4-hydroxy-3-methylbenzonitrile Chemical compound CC1=CC(C#N)=CC=C1O WTTADDGUHFYGEH-UHFFFAOYSA-N 0.000 description 2
- VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 2
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- KJGZMWSLYGZISQ-UHFFFAOYSA-N cyclopentyl 7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1C(CN(C2)C(=O)OC3CCCC3)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 KJGZMWSLYGZISQ-UHFFFAOYSA-N 0.000 description 1
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- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
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- MQYQOVYIJOLTNX-UHFFFAOYSA-N dichloromethane;n,n-dimethylformamide Chemical group ClCCl.CN(C)C=O MQYQOVYIJOLTNX-UHFFFAOYSA-N 0.000 description 1
- XNMQEEKYCVKGBD-UHFFFAOYSA-N dimethylacetylene Natural products CC#CC XNMQEEKYCVKGBD-UHFFFAOYSA-N 0.000 description 1
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- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
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- FJYDBKPPGRZSOZ-UHFFFAOYSA-N methyl 5-bromo-2-hydroxybenzoate Chemical compound COC(=O)C1=CC(Br)=CC=C1O FJYDBKPPGRZSOZ-UHFFFAOYSA-N 0.000 description 1
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- ZNYWVNPHYPYAQX-UHFFFAOYSA-N methyl 7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 ZNYWVNPHYPYAQX-UHFFFAOYSA-N 0.000 description 1
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- 229920006391 phthalonitrile polymer Polymers 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000003823 potassium efflux Effects 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
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- HOIZGDHPXHNRDL-UHFFFAOYSA-N propan-2-yl 7-[2-(4-cyanophenyl)ethyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC(C)C)CC(C2)CC1CN2CCC1=CC=C(C#N)C=C1 HOIZGDHPXHNRDL-UHFFFAOYSA-N 0.000 description 1
- HKRKLFPCCDKHMZ-UHFFFAOYSA-N propan-2-yl 7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC(C)C)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 HKRKLFPCCDKHMZ-UHFFFAOYSA-N 0.000 description 1
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- QQKDTTWZXHEGAQ-UHFFFAOYSA-N propyl carbonochloridate Chemical compound CCCOC(Cl)=O QQKDTTWZXHEGAQ-UHFFFAOYSA-N 0.000 description 1
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- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
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- 239000012312 sodium hydride Substances 0.000 description 1
- 239000012418 sodium perborate tetrahydrate Substances 0.000 description 1
- IBDSNZLUHYKHQP-UHFFFAOYSA-N sodium;3-oxidodioxaborirane;tetrahydrate Chemical compound O.O.O.O.[Na+].[O-]B1OO1 IBDSNZLUHYKHQP-UHFFFAOYSA-N 0.000 description 1
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- 235000020679 tap water Nutrition 0.000 description 1
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- CTIRHWCPXYGDGF-HDICACEKSA-N tedisamil Chemical compound [H][C@]12CN(CC3CC3)C[C@]([H])(CN(CC3CC3)C1)C21CCCC1 CTIRHWCPXYGDGF-HDICACEKSA-N 0.000 description 1
- 229960002926 tedisamil Drugs 0.000 description 1
- XFMNPKVLBYQCGA-UHFFFAOYSA-N tert-butyl 11-benzyl-2,5-dioxa-7,11-diazatricyclo[7.3.1.01,6]tridecane-7-carboxylate Chemical compound C1C2(C3)OCCOC2N(C(=O)OC(C)(C)C)CC3CN1CC1=CC=CC=C1 XFMNPKVLBYQCGA-UHFFFAOYSA-N 0.000 description 1
- YLCNNLXOWZPZGU-UHFFFAOYSA-N tert-butyl 3-[3-(4-cyanoanilino)propyl]-3-oxido-7-aza-3-azoniabicyclo[3.3.1]nonane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC(C2)CC1C[N+]2([O-])CCCNC1=CC=C(C#N)C=C1 YLCNNLXOWZPZGU-UHFFFAOYSA-N 0.000 description 1
- BZBQPVOESSZXAZ-UHFFFAOYSA-N tert-butyl 3-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3-oxido-7-aza-3-azoniabicyclo[3.3.1]nonane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC(C2)CC1C[N+]2([O-])CC(O)COC1=CC=C(C#N)C=C1 BZBQPVOESSZXAZ-UHFFFAOYSA-N 0.000 description 1
- SRSAXELYVDOIHW-UHFFFAOYSA-N tert-butyl 3-[3-(4-cyanophenoxy)propyl]-3-oxido-7-aza-3-azoniabicyclo[3.3.1]nonane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC(C2)CC1C[N+]2([O-])CCCOC1=CC=C(C#N)C=C1 SRSAXELYVDOIHW-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- SXYBIHCNKOWWMM-UHFFFAOYSA-N tert-butyl 7-[2-[(4-cyanophenoxy)methyl]-2,3-dihydroxypropyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC(C2)CC1CN2CC(O)(CO)COC1=CC=C(C#N)C=C1 SXYBIHCNKOWWMM-UHFFFAOYSA-N 0.000 description 1
- ZNGTXJWRNDJAOF-UHFFFAOYSA-N tert-butyl 7-[2-[(4-cyanophenyl)methylamino]ethyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC(C2)CC1CN2CCNCC1=CC=C(C#N)C=C1 ZNGTXJWRNDJAOF-UHFFFAOYSA-N 0.000 description 1
- HZVIOWQTIBGKJS-UHFFFAOYSA-N tert-butyl 7-[2-[2-(4-cyanophenoxy)ethoxy]ethyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC(C2)CC1CN2CCOCCOC1=CC=C(C#N)C=C1 HZVIOWQTIBGKJS-UHFFFAOYSA-N 0.000 description 1
- GFGSUMCQJDPASZ-UHFFFAOYSA-N tert-butyl 7-[2-hydroxy-3-[4-(methanesulfonamido)phenoxy]propyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC(C2)CC1CN2CC(O)COC1=CC=C(NS(C)(=O)=O)C=C1 GFGSUMCQJDPASZ-UHFFFAOYSA-N 0.000 description 1
- KLPSYNAGFYAODP-UHFFFAOYSA-N tert-butyl 7-[3-(4-aminophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC(C2)CC1CN2CC(O)COC1=CC=C(N)C=C1 KLPSYNAGFYAODP-UHFFFAOYSA-N 0.000 description 1
- MYQWVYSNDALFEK-UHFFFAOYSA-N tert-butyl 7-[3-(4-cyano-2-nitrophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1[N+]([O-])=O MYQWVYSNDALFEK-UHFFFAOYSA-N 0.000 description 1
- WVRIWANQMCSATC-UHFFFAOYSA-N tert-butyl 7-[3-(4-cyanoanilino)propyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC(C2)CC1CN2CCCNC1=CC=C(C#N)C=C1 WVRIWANQMCSATC-UHFFFAOYSA-N 0.000 description 1
- NDMJFOYBVBPJOK-UHFFFAOYSA-N tert-butyl 7-[3-(4-tert-butylphenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC(C2)CC1CN2CC(O)COC1=CC=C(C(C)(C)C)C=C1 NDMJFOYBVBPJOK-UHFFFAOYSA-N 0.000 description 1
- KYEIRQMTIBRSBG-UHFFFAOYSA-N tert-butyl 7-[4-(4-cyanophenoxy)-2-hydroxybutyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC(C2)CC1CN2CC(O)CCOC1=CC=C(C#N)C=C1 KYEIRQMTIBRSBG-UHFFFAOYSA-N 0.000 description 1
- RJIMESJARPVDDO-UHFFFAOYSA-N tert-butyl 7-[4-(4-cyanophenyl)-4-hydroxybutyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC(C2)CC1CN2CCCC(O)C1=CC=C(C#N)C=C1 RJIMESJARPVDDO-UHFFFAOYSA-N 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 210000001186 vagus nerve Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9704709A SE9704709D0 (sv) | 1997-12-17 | 1997-12-17 | Pharmaceutically active compounds |
| SE9704709-6 | 1997-12-17 | ||
| PCT/SE1998/002276 WO1999031100A1 (en) | 1997-12-17 | 1998-12-10 | Novel bispidine antiarrhythmic compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002508375A true JP2002508375A (ja) | 2002-03-19 |
| JP2002508375A5 JP2002508375A5 (enExample) | 2006-02-02 |
Family
ID=20409426
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000539024A Pending JP2002508375A (ja) | 1997-12-17 | 1998-12-10 | 新規なビスピジン抗不整脈性化合物 |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US6291475B1 (enExample) |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007530541A (ja) * | 2004-03-22 | 2007-11-01 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | グルココルチコイドミメチックスとしてのα−トリフルオロメチルアルコール又はアミン |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9803517D0 (sv) * | 1998-10-15 | 1998-10-15 | Astra Ab | Pharmaceutical preparation |
| 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 |
| SE9902269D0 (sv) * | 1999-06-16 | 1999-06-16 | Astra Ab | Pharmaceutically active compounds |
| US20040229900A1 (en) * | 1999-06-16 | 2004-11-18 | Astrazeneca Ab | Bispidine compounds useful in the treatment of cardiac arrythmias |
| SE9902271D0 (sv) * | 1999-06-16 | 1999-06-16 | Astra Ab | Pharmaceutically active compounds |
| SE9902270D0 (sv) * | 1999-06-16 | 1999-06-16 | Astra Ab | Pharmaceutically active compounds |
| US20050004113A1 (en) * | 1999-06-16 | 2005-01-06 | Astrazeneca Ab | New bispidine compounds useful in the treatment of cardiac arrhythmias |
| SE9902268D0 (sv) * | 1999-06-16 | 1999-06-16 | Astra Ab | Pharmaceutically active compounds |
| US7038054B1 (en) * | 1999-09-03 | 2006-05-02 | Pharmacopeia Drug Discovery, Inc. | Diazabicyclononane scaffold for combinatorial synthesis |
| SE9903759D0 (sv) * | 1999-10-18 | 1999-10-18 | Astra Ab | Pharmaceutically active compounds |
| EP1274710B1 (en) | 1999-12-14 | 2005-02-23 | NeuroSearch A/S | Novel heteroaryl-diazabicycloalkanes |
| SE9904765D0 (sv) | 1999-12-23 | 1999-12-23 | Astra Ab | Pharmaceutically-useful compounds |
| AR030302A1 (es) * | 2000-07-07 | 2003-08-20 | Astrazeneca Ab | Compuestos de bispidina, formulacion farmaceutica, uso para la fabricacion de medicamentos, proceso para la preparacion de estos compuestos y compuestos intermediarios |
| SE0002603D0 (sv) * | 2000-07-07 | 2000-07-07 | Astrazeneca Ab | New compounds |
| US6808924B1 (en) | 2000-07-11 | 2004-10-26 | Claudia Lanari | Mouse mammary tumor lines expressing estrogen and progesterone receptors |
| AR030756A1 (es) | 2000-10-02 | 2003-09-03 | Astrazeneca Ab | Compuesto de oxabispidina util en el tratamiento de arritmias cardiacas |
| SE0003795D0 (sv) | 2000-10-20 | 2000-10-20 | Astrazeneca Ab | Pharmaceutically useful compounds |
| SE0100326D0 (sv) | 2001-02-02 | 2001-02-02 | Astrazeneca Ab | New compounds |
| TWI259836B (en) * | 2001-04-12 | 2006-08-11 | Astrazeneca Ab | Modified release formulation suitable for antiarrhythmic compounds |
| SE0101329D0 (sv) * | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | Pharmaceutical formulation |
| SE0101327D0 (sv) * | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | New crystalline forms |
| SE0101324D0 (sv) * | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | New process |
| DE60203007T2 (de) * | 2001-06-01 | 2005-07-07 | Neurosearch A/S | Heteroaryl-diazabicycloalkanderivaten als cns-modulatoren |
| TW200418468A (en) * | 2002-11-18 | 2004-10-01 | Solvay Pharm Gmbh | Liquid pharmaceutical formulations containing 3,7-diazabicyclo[3,3,1]nonane compounds and method of treatments relating to anti-arrhytmic events |
| 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 |
| CN102485725B (zh) * | 2010-12-02 | 2015-07-22 | 武汉药明康德新药开发有限公司 | 一种双氮杂环桥环类药物模板及其制备方法和应用 |
| WO2012172043A1 (en) | 2011-06-15 | 2012-12-20 | Laboratoire Biodim | Purine derivatives and their use as pharmaceuticals for prevention or treatment of bacterial infections |
| CN102875550B (zh) * | 2011-07-12 | 2016-01-06 | 常州合全药业有限公司 | 1,3,7-三取代-3,7-二氮杂双环[3,3,1]壬烷衍生物及制备方法 |
| CN104151277A (zh) * | 2014-06-30 | 2014-11-19 | 北京万全德众医药生物技术有限公司 | 盐酸决奈达隆一种氧化杂质的制备方法 |
| CN113683585B (zh) * | 2021-09-26 | 2023-07-11 | 齐鲁工业大学 | 一种含环氧基邻苯二甲腈单体的制备方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2428792A1 (de) | 1974-06-14 | 1976-01-02 | Knoll Ag | Neue antiarrhythmika |
| DE3112055A1 (de) | 1981-03-27 | 1982-10-07 | Basf Ag, 6700 Ludwigshafen | Bispidinderivate, ihre herstellung und diese enthaltende arzneimittel |
| DE3234697A1 (de) | 1982-09-18 | 1984-03-22 | Kali-Chemie Pharma Gmbh, 3000 Hannover | Neue diazabicyclo-(3,3,1)-nonane |
| PT88381B (pt) * | 1987-09-09 | 1995-07-06 | Kali Chemie Pharma Gmbh | Processo para a preparacao de novos compostos 3,7-diazabiciclo{3,3,1} nonano, e de composicoes farmaceuticas que contem estes compostos |
| DE3732094A1 (de) * | 1987-09-24 | 1989-04-06 | Basf Ag | Bispidinderivate als klasse iii-antiarrhythmika |
| 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 |
| 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 |
| FR2713081B1 (fr) | 1993-11-29 | 1996-01-12 | Celsa Lg | Filtre sanguin perfectionné à deux séries de pattes en pétales. |
-
1997
- 1997-12-17 SE SE9704709A patent/SE9704709D0/xx unknown
-
1998
- 1998-12-04 ZA ZA9811130A patent/ZA9811130B/xx unknown
- 1998-12-10 NZ NZ504909A patent/NZ504909A/en unknown
- 1998-12-10 HU HU0102307A patent/HUP0102307A3/hu unknown
- 1998-12-10 CN CN98813573A patent/CN1284956A/zh active Pending
- 1998-12-10 EE EEP200000365A patent/EE200000365A/xx unknown
- 1998-12-10 PT PT98962796T patent/PT1047695E/pt unknown
- 1998-12-10 AT AT98962796T patent/ATE261964T1/de not_active IP Right Cessation
- 1998-12-10 DE DE69822513T patent/DE69822513T2/de not_active Expired - Fee Related
- 1998-12-10 EP EP98962796A patent/EP1047695B1/en not_active Expired - Lifetime
- 1998-12-10 DK DK98962796T patent/DK1047695T3/da active
- 1998-12-10 ID IDW20001081A patent/ID24638A/id unknown
- 1998-12-10 BR BR9813668-2A patent/BR9813668A/pt not_active IP Right Cessation
- 1998-12-10 CA CA002314490A patent/CA2314490A1/en not_active Abandoned
- 1998-12-10 SK SK781-2000A patent/SK7812000A3/sk unknown
- 1998-12-10 TR TR2000/01757T patent/TR200001757T2/xx unknown
- 1998-12-10 JP JP2000539024A patent/JP2002508375A/ja active Pending
- 1998-12-10 PL PL98341388A patent/PL341388A1/xx unknown
- 1998-12-10 ES ES98962796T patent/ES2216337T3/es not_active Expired - Lifetime
- 1998-12-10 WO PCT/SE1998/002276 patent/WO1999031100A1/en not_active Ceased
- 1998-12-10 IL IL13637498A patent/IL136374A0/xx unknown
- 1998-12-10 US US09/214,756 patent/US6291475B1/en not_active Expired - Fee Related
- 1998-12-10 AU AU17953/99A patent/AU1795399A/en not_active Abandoned
- 1998-12-10 KR KR1020007006585A patent/KR20010024723A/ko not_active Withdrawn
- 1998-12-10 SI SI9830633T patent/SI1047695T1/xx unknown
- 1998-12-16 AR ARP980106399A patent/AR017217A1/es unknown
-
2000
- 2000-06-02 IS IS5522A patent/IS5522A/is unknown
- 2000-06-16 NO NO20003137A patent/NO20003137L/no not_active Application Discontinuation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007530541A (ja) * | 2004-03-22 | 2007-11-01 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | グルココルチコイドミメチックスとしてのα−トリフルオロメチルアルコール又はアミン |
Also Published As
| Publication number | Publication date |
|---|---|
| US6291475B1 (en) | 2001-09-18 |
| NO20003137D0 (no) | 2000-06-16 |
| HUP0102307A2 (hu) | 2001-12-28 |
| PT1047695E (pt) | 2004-07-30 |
| SE9704709D0 (sv) | 1997-12-17 |
| AR017217A1 (es) | 2001-08-22 |
| CN1284956A (zh) | 2001-02-21 |
| WO1999031100A1 (en) | 1999-06-24 |
| AU1795399A (en) | 1999-07-05 |
| ID24638A (id) | 2000-07-27 |
| CA2314490A1 (en) | 1999-06-24 |
| ES2216337T3 (es) | 2004-10-16 |
| TR200001757T2 (tr) | 2000-09-21 |
| IL136374A0 (en) | 2001-06-14 |
| ATE261964T1 (de) | 2004-04-15 |
| EE200000365A (et) | 2001-10-15 |
| SK7812000A3 (en) | 2001-05-10 |
| SI1047695T1 (en) | 2004-08-31 |
| DE69822513D1 (de) | 2004-04-22 |
| HUP0102307A3 (en) | 2002-02-28 |
| DE69822513T2 (de) | 2005-03-10 |
| BR9813668A (pt) | 2000-10-17 |
| NO20003137L (no) | 2000-08-17 |
| EP1047695A1 (en) | 2000-11-02 |
| PL341388A1 (en) | 2001-04-09 |
| NZ504909A (en) | 2001-11-30 |
| KR20010024723A (ko) | 2001-03-26 |
| ZA9811130B (en) | 1999-06-17 |
| EP1047695B1 (en) | 2004-03-17 |
| DK1047695T3 (da) | 2004-06-28 |
| IS5522A (is) | 2000-06-02 |
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