SK18282001A3 - Bispidínové zlúčeniny užitočné pri liečbe srdcových arytmií - Google Patents

Bispidínové zlúčeniny užitočné pri liečbe srdcových arytmií Download PDF

Info

Publication number: SK18282001A3
Authority: SK; Slovakia
Prior art keywords: formula; compound; alkyl; compounds; groups
Prior art date: 1999-06-16

Application number

SK1828-2001A

Other languages

English (en)

Slovak (sk)

Inventor

Annika BJ�RE

Magnus BJ�RSNE

Torbj�rn HALVARSSON

Kurt-J�Rgen Hoffmann

Bertil Samuelsson

Gert Strandlund

Original Assignee

Astrazeneca Ab

Priority date (The priority date 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 date listed.)

1999-06-16

Filing date

2000-06-15

Publication date

2002-12-03

2000-06-15 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2002-12-03 Publication of SK18282001A3 publication Critical patent/SK18282001A3/sk

Links

206010003119 arrhythmia Diseases 0.000 title claims abstract description 25
238000011282 treatment Methods 0.000 title claims abstract description 16
PTPQJKANBKHDPM-UHFFFAOYSA-N 3,7-diazabicyclo[3.3.1]nonane Chemical class C1NCC2CNCC1C2 PTPQJKANBKHDPM-UHFFFAOYSA-N 0.000 title claims description 14
150000001875 compounds Chemical class 0.000 claims abstract description 292
230000006793 arrhythmia Effects 0.000 claims abstract description 15
238000011321 prophylaxis Methods 0.000 claims abstract description 7
230000001746 atrial effect Effects 0.000 claims abstract description 5
206010047281 Ventricular arrhythmia Diseases 0.000 claims abstract description 4
206010003130 Arrhythmia supraventricular Diseases 0.000 claims abstract description 3
125000000217 alkyl group Chemical group 0.000 claims description 87
-1 substituted Chemical class 0.000 claims description 54
238000000034 method Methods 0.000 claims description 39
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 31
229910052799 carbon Inorganic materials 0.000 claims description 30
125000001424 substituent group Chemical group 0.000 claims description 26
229910052739 hydrogen Inorganic materials 0.000 claims description 23
238000006243 chemical reaction Methods 0.000 claims description 21
125000004093 cyano group Chemical group *C#N 0.000 claims description 20
229910052757 nitrogen Inorganic materials 0.000 claims description 20
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
125000003545 alkoxy group Chemical group 0.000 claims description 18
125000002947 alkylene group Chemical group 0.000 claims description 16
229910052760 oxygen Inorganic materials 0.000 claims description 13
230000009467 reduction Effects 0.000 claims description 13
125000004432 carbon atom Chemical group C* 0.000 claims description 12
125000003118 aryl group Chemical group 0.000 claims description 11
238000002360 preparation method Methods 0.000 claims description 10
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
239000003814 drug Substances 0.000 claims description 9
125000005843 halogen group Chemical group 0.000 claims description 9
125000005842 heteroatom Chemical group 0.000 claims description 9
239000001301 oxygen Substances 0.000 claims description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
229910052717 sulfur Inorganic materials 0.000 claims description 9
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 8
150000002367 halogens Chemical class 0.000 claims description 8
125000000623 heterocyclic group Chemical group 0.000 claims description 8
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
239000011593 sulfur Substances 0.000 claims description 7
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 6
230000008569 process Effects 0.000 claims description 6
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
150000001204 N-oxides Chemical class 0.000 claims description 4
229910052794 bromium Inorganic materials 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 claims description 3
125000005037 alkyl phenyl group Chemical group 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
229910052740 iodine Inorganic materials 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
239000004480 active ingredient Substances 0.000 claims description 2
239000002671 adjuvant Substances 0.000 claims description 2
230000029936 alkylation Effects 0.000 claims description 2
238000005804 alkylation reaction Methods 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
230000001590 oxidative effect Effects 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 60
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 52
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 41
239000000243 solution Substances 0.000 description 38
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 32
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
238000005481 NMR spectroscopy Methods 0.000 description 26
239000002904 solvent Substances 0.000 description 26
239000000203 mixture Substances 0.000 description 25
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 23
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
239000011541 reaction mixture Substances 0.000 description 23
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
239000003960 organic solvent Substances 0.000 description 20
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 18
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
DMUXSGAKEXSNGN-UHFFFAOYSA-N 2-ethyloctanoic acid Chemical compound CCCCCCC(CC)C(O)=O DMUXSGAKEXSNGN-UHFFFAOYSA-N 0.000 description 17
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
239000000460 chlorine Substances 0.000 description 17
235000019439 ethyl acetate Nutrition 0.000 description 17
239000012044 organic layer Substances 0.000 description 17
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 15
238000004440 column chromatography Methods 0.000 description 13
230000000694 effects Effects 0.000 description 13
238000010992 reflux Methods 0.000 description 13
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
239000002585 base Substances 0.000 description 9
125000006239 protecting group Chemical group 0.000 description 9
239000011734 sodium Substances 0.000 description 9
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
238000000262 chemical ionisation mass spectrometry Methods 0.000 description 8
239000003638 chemical reducing agent Substances 0.000 description 8
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 8
238000004128 high performance liquid chromatography Methods 0.000 description 8
238000012360 testing method Methods 0.000 description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
238000002474 experimental method Methods 0.000 description 7
125000002883 imidazolyl group Chemical group 0.000 description 7
239000012279 sodium borohydride Substances 0.000 description 7
229910000033 sodium borohydride Inorganic materials 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
QTHDSOKMOPEDTQ-YZVRCSRASA-N tert-butyl 7-[(2s)-3-(4-cyanophenoxy)-2-hydroxypropyl]-9-hydroxy-9-methyl-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C([C@@H](O)CN1CC2CN(CC(C1)C2(C)O)C(=O)OC(C)(C)C)OC1=CC=C(C#N)C=C1 QTHDSOKMOPEDTQ-YZVRCSRASA-N 0.000 description 7
238000004809 thin layer chromatography Methods 0.000 description 7
239000003416 antiarrhythmic agent Substances 0.000 description 6
239000012298 atmosphere Substances 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
229940079593 drug Drugs 0.000 description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
239000000377 silicon dioxide Substances 0.000 description 6
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
229960000583 acetic acid Drugs 0.000 description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
125000004122 cyclic group Chemical group 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
238000000746 purification Methods 0.000 description 5
239000007858 starting material Substances 0.000 description 5
NQYURYJVMCRCCN-UHFFFAOYSA-N tert-butyl 7-benzyl-9-hydroxy-9-methyl-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1C(C2(C)O)CN(C(=O)OC(C)(C)C)CC2CN1CC1=CC=CC=C1 NQYURYJVMCRCCN-UHFFFAOYSA-N 0.000 description 5
125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 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
229930040373 Paraformaldehyde Natural products 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
125000005233 alkylalcohol group Chemical group 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
239000012267 brine Substances 0.000 description 4
230000000747 cardiac effect Effects 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
238000001914 filtration Methods 0.000 description 4
125000000524 functional group Chemical group 0.000 description 4
239000007789 gas Substances 0.000 description 4
SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 4
229960004592 isopropanol Drugs 0.000 description 4
229910052763 palladium Inorganic materials 0.000 description 4
229920002866 paraformaldehyde Polymers 0.000 description 4
230000002336 repolarization Effects 0.000 description 4
150000003839 salts Chemical class 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
238000003756 stirring Methods 0.000 description 4
239000000126 substance Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
230000002861 ventricular Effects 0.000 description 4
KPUYNELHBVOTER-UHFFFAOYSA-N 3,7-dibenzyl-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonan-9-ol Chemical compound C1C(C)(C2O)CN(CC=3C=CC=CC=3)CC2(C)CN1CC1=CC=CC=C1 KPUYNELHBVOTER-UHFFFAOYSA-N 0.000 description 3
VDPCIZXWEQHOJC-UHFFFAOYSA-N 3,7-dibenzyl-3,7-diazabicyclo[3.3.1]nonan-9-one Chemical compound C1C(CN(CC=2C=CC=CC=2)C2)C(=O)C2CN1CC1=CC=CC=C1 VDPCIZXWEQHOJC-UHFFFAOYSA-N 0.000 description 3
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 3
WREXVDPOLDOXJL-UHFFFAOYSA-N 4-(oxiran-2-ylmethoxy)benzonitrile Chemical compound C1=CC(C#N)=CC=C1OCC1OC1 WREXVDPOLDOXJL-UHFFFAOYSA-N 0.000 description 3
239000012359 Methanesulfonyl chloride Substances 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
239000002253 acid Substances 0.000 description 3
125000004429 atom Chemical group 0.000 description 3
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
ITLORZVALDCNOW-UHFFFAOYSA-N benzyl 2-[(4-cyanophenoxy)methyl]aziridine-1-carboxylate Chemical compound C1C(COC=2C=CC(=CC=2)C#N)N1C(=O)OCC1=CC=CC=C1 ITLORZVALDCNOW-UHFFFAOYSA-N 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
231100000673 dose–response relationship Toxicity 0.000 description 3
PHPCORSGSHAUHI-UHFFFAOYSA-N ethyl 7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1C(C2O)CN(C(=O)OCC)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 PHPCORSGSHAUHI-UHFFFAOYSA-N 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
239000007800 oxidant agent Substances 0.000 description 3
230000003647 oxidation Effects 0.000 description 3
238000007254 oxidation reaction Methods 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
230000033764 rhythmic process Effects 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
239000007787 solid Substances 0.000 description 3
238000001228 spectrum Methods 0.000 description 3
230000000638 stimulation Effects 0.000 description 3
UTRMIIQBNOZLDV-UHFFFAOYSA-N tert-butyl 7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1C(C2O)CN(C(=O)OC(C)(C)C)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 UTRMIIQBNOZLDV-UHFFFAOYSA-N 0.000 description 3
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
AJADMCRWRSKHBJ-UHFFFAOYSA-N 3,7-dibenzyl-9-methyl-3,7-diazabicyclo[3.3.1]nonan-9-ol Chemical compound C1C(CN(CC=2C=CC=CC=2)C2)C(C)(O)C2CN1CC1=CC=CC=C1 AJADMCRWRSKHBJ-UHFFFAOYSA-N 0.000 description 2
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
NRTKUYGHEKNAOU-UHFFFAOYSA-N 3-benzyl-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonan-9-ol Chemical compound C1C(C)(C2O)CNCC2(C)CN1CC1=CC=CC=C1 NRTKUYGHEKNAOU-UHFFFAOYSA-N 0.000 description 2
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-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
HRPASSWJHQAQCT-UHFFFAOYSA-N 4-(3-hydroxypropylamino)benzonitrile Chemical compound OCCCNC1=CC=C(C#N)C=C1 HRPASSWJHQAQCT-UHFFFAOYSA-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
229960000549 4-dimethylaminophenol Drugs 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
239000005711 Benzoic acid Substances 0.000 description 2
241000700198 Cavia Species 0.000 description 2
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
229910010082 LiAlH Inorganic materials 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
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 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
208000018452 Torsade de pointes Diseases 0.000 description 2
208000002363 Torsades de Pointes Diseases 0.000 description 2
MNHDBZDKDFCZTC-UHFFFAOYSA-N [1-(4-cyanophenoxy)-3-(phenylmethoxycarbonylamino)propan-2-yl] methanesulfonate Chemical compound C=1C=C(C#N)C=CC=1OCC(OS(=O)(=O)C)CNC(=O)OCC1=CC=CC=C1 MNHDBZDKDFCZTC-UHFFFAOYSA-N 0.000 description 2
230000036982 action potential Effects 0.000 description 2
230000003213 activating effect Effects 0.000 description 2
230000004913 activation Effects 0.000 description 2
238000003556 assay Methods 0.000 description 2
230000008901 benefit Effects 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
230000036772 blood pressure Effects 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
230000008878 coupling Effects 0.000 description 2
239000007822 coupling agent Substances 0.000 description 2
238000010168 coupling process Methods 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
230000001186 cumulative effect Effects 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
LUBGFMZTGFXIIN-UHFFFAOYSA-N ethyl 4-oxopiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(=O)CC1 LUBGFMZTGFXIIN-UHFFFAOYSA-N 0.000 description 2
230000001747 exhibiting effect Effects 0.000 description 2
238000010265 fast atom bombardment Methods 0.000 description 2
208000019622 heart disease Diseases 0.000 description 2
125000004356 hydroxy functional group Chemical group O* 0.000 description 2
OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 2
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
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125000004434 sulfur atom Chemical group 0.000 description 1
230000001629 suppression Effects 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
230000035488 systolic blood pressure Effects 0.000 description 1
239000008399 tap water Substances 0.000 description 1
235000020679 tap water Nutrition 0.000 description 1
238000003419 tautomerization reaction Methods 0.000 description 1
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
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 1
APPONRMXPXKTQH-UHFFFAOYSA-N tert-butyl 7-[3-(4-cyanoanilino)propyl]-9-hydroxy-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1C(C)(C2O)CN(C(=O)OC(C)(C)C)CC2(C)CN1CCCNC1=CC=C(C#N)C=C1 APPONRMXPXKTQH-UHFFFAOYSA-N 0.000 description 1
OKMKFCJXAKMFAI-UHFFFAOYSA-N tert-butyl 7-[3-(4-cyanoanilino)propyl]-9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1C(C2O)CN(C(=O)OC(C)(C)C)CC2CN1CCCNC1=CC=C(C#N)C=C1 OKMKFCJXAKMFAI-UHFFFAOYSA-N 0.000 description 1
NOSHVVATLOCOAN-UHFFFAOYSA-N tert-butyl 7-[3-(4-cyanophenoxy)-2-(phenylmethoxycarbonylamino)propyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC(C2)CC1CN2CC(NC(=O)OCC=1C=CC=CC=1)COC1=CC=C(C#N)C=C1 NOSHVVATLOCOAN-UHFFFAOYSA-N 0.000 description 1
PFLURNNMZRZJOU-UHFFFAOYSA-N tert-butyl 9-hydroxy-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1NCC2(C)CN(C(=O)OC(C)(C)C)CC1(C)C2O PFLURNNMZRZJOU-UHFFFAOYSA-N 0.000 description 1
VRSHRTOFXJXWQZ-UHFFFAOYSA-N tert-butyl 9-hydroxy-9-methyl-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1NCC2CN(C(=O)OC(C)(C)C)CC1C2(C)O VRSHRTOFXJXWQZ-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
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(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
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000000335 thiazolyl 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
CMQCNTNASCDNGR-UHFFFAOYSA-N toluene;hydrate Chemical compound O.CC1=CC=CC=C1 CMQCNTNASCDNGR-UHFFFAOYSA-N 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
125000001425 triazolyl 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
210000003462 vein Anatomy 0.000 description 1
238000005303 weighing Methods 0.000 description 1
235000014101 wine Nutrition 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
- 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)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Hydrogenated Pyridines (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

SK1828-2001A 1999-06-16 2000-06-15 Bispidínové zlúčeniny užitočné pri liečbe srdcových arytmií SK18282001A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
SE9902270A SE9902270D0 (sv)	1999-06-16	1999-06-16	Pharmaceutically active compounds
PCT/SE2000/001253 WO2000076999A1 (fr)	1999-06-16	2000-06-15	Nouveaux composes de bispidine utiles dans le traitement des arythmies cardiaques

Publications (1)

Publication Number	Publication Date
SK18282001A3 true SK18282001A3 (sk)	2002-12-03

Family

ID=20416102

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1828-2001A SK18282001A3 (sk)	1999-06-16	2000-06-15	Bispidínové zlúčeniny užitočné pri liečbe srdcových arytmií

Country Status (29)

Country	Link
US (1)	US6887881B1 (fr)
EP (1)	EP1192154B1 (fr)
JP (1)	JP2003502328A (fr)
KR (1)	KR20020010711A (fr)
CN (1)	CN1187350C (fr)
AR (1)	AR024393A1 (fr)
AT (1)	ATE261965T1 (fr)
AU (1)	AU762244B2 (fr)
BR (1)	BR0011673A (fr)
CA (1)	CA2384339A1 (fr)
CZ (1)	CZ20014494A3 (fr)
DE (1)	DE60009069T2 (fr)
DK (1)	DK1192154T3 (fr)
EE (1)	EE200100674A (fr)
ES (1)	ES2216912T3 (fr)
HK (1)	HK1045690A1 (fr)
HU (1)	HUP0202929A3 (fr)
IL (1)	IL146752A0 (fr)
IS (1)	IS6199A (fr)
MX (1)	MXPA01012925A (fr)
NO (1)	NO20016127L (fr)
NZ (1)	NZ516015A (fr)
PL (1)	PL353794A1 (fr)
PT (1)	PT1192154E (fr)
SE (1)	SE9902270D0 (fr)
SK (1)	SK18282001A3 (fr)
TR (1)	TR200103659T2 (fr)
WO (1)	WO2000076999A1 (fr)
ZA (1)	ZA200109800B (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SE9903759D0 (sv) *	1999-10-18	1999-10-18	Astra Ab	Pharmaceutically active 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
RU2228934C1 (ru) *	2003-05-20	2004-05-20	ООО "Исследовательский институт химического разнообразия"	Замещенные 3,7-диазобицикло[3.3.1]нонаны, фокусированная библиотека и комбинаторная библиотека
IN2013DE02892A (fr)	2013-09-30	2015-04-03	Council Scient Ind Res

Family Cites Families (20)

* Cited by examiner, † Cited by third party
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
ATA237287A (de)	1987-09-21	1993-02-15	Vaillant Gmbh	Steuerung der temperatur des heizmediums einer umlaufheizung
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
DE4402931A1 (de)	1994-02-01	1995-08-03	Kali Chemie Pharma Gmbh	Neue 3-Phenylsulfonyl-3,7-diazabicyclo[3,3,1] nonan-Verbindungen enthaltende Arzneimittel
JP2000500454A (ja)	1995-11-13	2000-01-18	スミスクライン・ビーチャム・コーポレイション	血液調節化合物
SE9602263D0 (sv) *	1996-06-07	1996-06-07	Astra Ab	New amino acid derivatives
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
GB9823103D0 (en) *	1998-10-23	1998-12-16	Pfizer Ltd	Pharmaceutically active compounds
TR200102911T2 (tr)	1999-04-09	2002-01-21	Astrazeneca Ab	Adamantan türevleri.
SE9901875D0 (sv)	1999-05-25	1999-05-25	Astra Pharma Prod	Novel compounds
SE9902271D0 (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
SE9903759D0 (sv) *	1999-10-18	1999-10-18	Astra Ab	Pharmaceutically active compounds
SE0002603D0 (sv) *	2000-07-07	2000-07-07	Astrazeneca Ab	New compounds

1999
- 1999-06-16 SE SE9902270A patent/SE9902270D0/xx unknown
2000
- 2000-06-15 SK SK1828-2001A patent/SK18282001A3/sk unknown
- 2000-06-15 DE DE60009069T patent/DE60009069T2/de not_active Expired - Fee Related
- 2000-06-15 HK HK02107115.3A patent/HK1045690A1/zh unknown
- 2000-06-15 EP EP00944526A patent/EP1192154B1/fr not_active Expired - Lifetime
- 2000-06-15 PL PL00353794A patent/PL353794A1/xx not_active Application Discontinuation
- 2000-06-15 MX MXPA01012925A patent/MXPA01012925A/es unknown
- 2000-06-15 TR TR2001/03659T patent/TR200103659T2/xx unknown
- 2000-06-15 HU HU0202929A patent/HUP0202929A3/hu unknown
- 2000-06-15 IL IL14675200A patent/IL146752A0/xx unknown
- 2000-06-15 AU AU58611/00A patent/AU762244B2/en not_active Ceased
- 2000-06-15 CN CNB008116008A patent/CN1187350C/zh not_active Expired - Fee Related
- 2000-06-15 ES ES00944526T patent/ES2216912T3/es not_active Expired - Lifetime
- 2000-06-15 US US09/623,709 patent/US6887881B1/en not_active Expired - Fee Related
- 2000-06-15 KR KR1020017016165A patent/KR20020010711A/ko not_active Withdrawn
- 2000-06-15 NZ NZ516015A patent/NZ516015A/xx unknown
- 2000-06-15 EE EEP200100674A patent/EE200100674A/xx unknown
- 2000-06-15 CZ CZ20014494A patent/CZ20014494A3/cs unknown
- 2000-06-15 DK DK00944526T patent/DK1192154T3/da active
- 2000-06-15 CA CA002384339A patent/CA2384339A1/fr not_active Abandoned
- 2000-06-15 WO PCT/SE2000/001253 patent/WO2000076999A1/fr not_active Ceased
- 2000-06-15 BR BR0011673-4A patent/BR0011673A/pt not_active IP Right Cessation
- 2000-06-15 AT AT00944526T patent/ATE261965T1/de not_active IP Right Cessation
- 2000-06-15 PT PT00944526T patent/PT1192154E/pt unknown
- 2000-06-15 JP JP2001503857A patent/JP2003502328A/ja active Pending
- 2000-06-16 AR ARP000103017A patent/AR024393A1/es unknown
2001
- 2001-11-28 ZA ZA200109800A patent/ZA200109800B/en unknown
- 2001-12-14 NO NO20016127A patent/NO20016127L/no not_active Application Discontinuation
- 2001-12-14 IS IS6199A patent/IS6199A/is unknown

Also Published As

Publication number	Publication date
EP1192154A1 (fr)	2002-04-03
AR024393A1 (es)	2002-10-02
DE60009069D1 (de)	2004-04-22
EE200100674A (et)	2003-02-17
PT1192154E (pt)	2004-07-30
DE60009069T2 (de)	2004-10-14
CN1370164A (zh)	2002-09-18
BR0011673A (pt)	2002-03-12
SE9902270D0 (sv)	1999-06-16
IL146752A0 (en)	2002-07-25
IS6199A (is)	2001-12-14
EP1192154B1 (fr)	2004-03-17
ATE261965T1 (de)	2004-04-15
AU762244B2 (en)	2003-06-19
CZ20014494A3 (cs)	2002-05-15
MXPA01012925A (es)	2002-07-30
KR20020010711A (ko)	2002-02-04
ZA200109800B (en)	2003-02-28
HUP0202929A2 (hu)	2003-02-28
TR200103659T2 (tr)	2002-04-22
HK1045690A1 (zh)	2002-12-06
CN1187350C (zh)	2005-02-02
NZ516015A (en)	2003-06-30
DK1192154T3 (da)	2004-06-28
CA2384339A1 (fr)	2000-12-21
US6887881B1 (en)	2005-05-03
NO20016127L (no)	2002-02-12
WO2000076999A1 (fr)	2000-12-21
JP2003502328A (ja)	2003-01-21
PL353794A1 (en)	2003-12-01
AU5861100A (en)	2001-01-02
HUP0202929A3 (en)	2003-04-28
NO20016127D0 (no)	2001-12-14
ES2216912T3 (es)	2004-11-01

Publication	Publication Date	Title
EP1047695B1 (fr)	2004-03-17	Nouveaux composes de bispidine antiarythmiques
US7012074B2 (en)	2006-03-14	3,8-Diazabicyclo[3.2.1]octanes and their use in the treatment of cardiac arrhythmias
SK18282001A3 (sk)	2002-12-03	Bispidínové zlúčeniny užitočné pri liečbe srdcových arytmií
AU761576B2 (en)	2003-06-05	New bispidine compounds useful in the treatment of cardiac arrhythmias
SK42003A3 (en)	2003-07-01	New bispidine compounds and their use in the treatment of cardiac arrhythmias
SK18292001A3 (sk)	2002-12-03	Bispidínové zlúčeniny užitočné pri liečbe srdcových arytmií
US20040229900A1 (en)	2004-11-18	Bispidine compounds useful in the treatment of cardiac arrythmias
EP1192155B1 (fr)	2003-04-02	Composes de bispidine pouvant etre utilises pour le traitement de l'arythmie cardiaque
US20050004113A1 (en)	2005-01-06	New bispidine compounds useful in the treatment of cardiac arrhythmias
CZ20002222A3 (cs)	2000-11-15	Nové bispidinové sloučeniny s antiarytmickým účinkem