SK18292001A3 - Bispidínové zlúčeniny užitočné pri liečbe srdcových arytmií - Google Patents

Bispidínové zlúčeniny užitočné pri liečbe srdcových arytmií Download PDF

Info

Publication number: SK18292001A3
Authority: SK; Slovakia
Prior art keywords: formula; compound; alkyl; compounds; optionally substituted
Prior art date: 1999-06-16

Application number

SK1829-2001A

Other languages

English (en)

Slovak (sk)

Inventor

Magnus BJ�RSNE

Marianne Frantsi

Kurt-J�Rgen Hoffmann

Bengt Ohlsson

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 SK18292001A3 publication Critical patent/SK18292001A3/sk

Links

206010003119 arrhythmia Diseases 0.000 title claims abstract description 24
238000011282 treatment Methods 0.000 title claims abstract description 15
PTPQJKANBKHDPM-UHFFFAOYSA-N 3,7-diazabicyclo[3.3.1]nonane Chemical class C1NCC2CNCC1C2 PTPQJKANBKHDPM-UHFFFAOYSA-N 0.000 title claims description 18
150000001875 compounds Chemical class 0.000 claims abstract description 280
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 91
238000000034 method Methods 0.000 claims description 44
-1 substituted Chemical class 0.000 claims description 39
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
125000001424 substituent group Chemical group 0.000 claims description 29
238000006243 chemical reaction Methods 0.000 claims description 27
229910052799 carbon Inorganic materials 0.000 claims description 25
125000003545 alkoxy group Chemical group 0.000 claims description 22
229910052757 nitrogen Inorganic materials 0.000 claims description 22
229910052739 hydrogen Inorganic materials 0.000 claims description 21
125000004093 cyano group Chemical group *C#N 0.000 claims description 18
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
229910052760 oxygen Inorganic materials 0.000 claims description 17
125000002947 alkylene group Chemical group 0.000 claims description 16
229910052736 halogen Inorganic materials 0.000 claims description 11
150000002367 halogens Chemical class 0.000 claims description 11
230000009467 reduction Effects 0.000 claims description 11
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
239000001301 oxygen Substances 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 9
125000005842 heteroatom Chemical group 0.000 claims description 9
238000002360 preparation method Methods 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
125000003118 aryl group Chemical group 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
125000005843 halogen group Chemical group 0.000 claims description 7
230000008569 process Effects 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
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 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 6
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
229910052740 iodine Inorganic materials 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 3
YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 claims description 2
239000004480 active ingredient Substances 0.000 claims description 2
239000002671 adjuvant Substances 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
230000001590 oxidative effect Effects 0.000 claims description 2
150000001721 carbon Chemical group 0.000 claims 2
230000002152 alkylating effect Effects 0.000 claims 1
125000004430 oxygen atom Chemical group O* 0.000 claims 1
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 28
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
239000003960 organic solvent Substances 0.000 description 24
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 23
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 20
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
238000010992 reflux Methods 0.000 description 14
239000002904 solvent Substances 0.000 description 14
230000000694 effects Effects 0.000 description 13
238000005481 NMR spectroscopy Methods 0.000 description 12
239000002585 base Substances 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 11
239000000203 mixture Substances 0.000 description 11
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
125000004432 carbon atom Chemical group C* 0.000 description 9
125000006239 protecting group Chemical group 0.000 description 9
238000012360 testing method Methods 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
238000002474 experimental method Methods 0.000 description 7
125000002883 imidazolyl group Chemical group 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
239000000243 solution Substances 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
HQRYXGZGNUPUIK-RUSYTGNQSA-N tert-butyl 3-[(2s)-3-(4-cyanophenoxy)-2-hydroxypropyl]-2,4-dimethyl-3,7-diazabicyclo[3.3.1]nonane-7-carboxylate Chemical compound C([C@@H](O)CN1C(C)C2CC(CN(C2)C(=O)OC(C)(C)C)C1C)OC1=CC=C(C#N)C=C1 HQRYXGZGNUPUIK-RUSYTGNQSA-N 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
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 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000003416 antiarrhythmic agent Substances 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
239000003638 chemical reducing agent Substances 0.000 description 6
239000000460 chlorine Substances 0.000 description 6
125000004122 cyclic group Chemical group 0.000 description 6
229940079593 drug Drugs 0.000 description 6
238000004128 high performance liquid chromatography Methods 0.000 description 6
AOELDAGSFOHVFW-UHFFFAOYSA-N 3,7-dibenzyl-3,7-diazabicyclo[3.3.1]nonane Chemical compound C=1C=CC=CC=1CN(C1)CC(C2)CC1CN2CC1=CC=CC=C1 AOELDAGSFOHVFW-UHFFFAOYSA-N 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-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
NAJRJYSDTWRVKY-UHFFFAOYSA-N 7-benzyl-2,4-dimethyl-3,7-diazabicyclo[3.3.1]nonane Chemical compound CC1NC(C)C(C2)CC1CN2CC1=CC=CC=C1 NAJRJYSDTWRVKY-UHFFFAOYSA-N 0.000 description 4
125000005233 alkylalcohol group Chemical group 0.000 description 4
239000012298 atmosphere Substances 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
230000000747 cardiac effect Effects 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
125000000524 functional group Chemical group 0.000 description 4
239000007789 gas Substances 0.000 description 4
BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 4
230000002336 repolarization Effects 0.000 description 4
150000003839 salts Chemical class 0.000 description 4
239000012279 sodium borohydride Substances 0.000 description 4
229910000033 sodium borohydride Inorganic materials 0.000 description 4
239000000126 substance Substances 0.000 description 4
238000004809 thin layer chromatography Methods 0.000 description 4
230000002861 ventricular Effects 0.000 description 4
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 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
238000004587 chromatography analysis Methods 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
239000007822 coupling agent Substances 0.000 description 3
231100000673 dose–response relationship Toxicity 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
239000007800 oxidant agent Substances 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
239000000377 silicon dioxide Substances 0.000 description 3
239000007858 starting material Substances 0.000 description 3
230000000638 stimulation Effects 0.000 description 3
HQRYXGZGNUPUIK-UHFFFAOYSA-N tert-butyl 3-[3-(4-cyanophenoxy)-2-hydroxypropyl]-2,4-dimethyl-3,7-diazabicyclo[3.3.1]nonane-7-carboxylate Chemical compound CC1C(CN(C2)C(=O)OC(C)(C)C)CC2C(C)N1CC(O)COC1=CC=C(C#N)C=C1 HQRYXGZGNUPUIK-UHFFFAOYSA-N 0.000 description 3
NUNHMCLGQOSQQW-UHFFFAOYSA-N tert-butyl 7-benzyl-2,4-dimethyl-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound CC1N(C(=O)OC(C)(C)C)C(C)C(C2)CC1CN2CC1=CC=CC=C1 NUNHMCLGQOSQQW-UHFFFAOYSA-N 0.000 description 3
JFLCCGFMLBSXBA-UHFFFAOYSA-N tert-butyl 7-benzyl-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC(C2)CC1CN2CC1=CC=CC=C1 JFLCCGFMLBSXBA-UHFFFAOYSA-N 0.000 description 3
YYUADVVEJKUGRU-UHFFFAOYSA-N tert-butyl 7-benzyl-4-methyl-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)C(C)C(C2)CC1CN2CC1=CC=CC=C1 YYUADVVEJKUGRU-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 2
JVNQIVFIOMMCFT-UHFFFAOYSA-N 3-benzyl-6-methyl-3,7-diazabicyclo[3.3.1]nonane Chemical compound CC1NCC(C2)CC1CN2CC1=CC=CC=C1 JVNQIVFIOMMCFT-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
WREXVDPOLDOXJL-UHFFFAOYSA-N 4-(oxiran-2-ylmethoxy)benzonitrile Chemical compound C1=CC(C#N)=CC=C1OCC1OC1 WREXVDPOLDOXJL-UHFFFAOYSA-N 0.000 description 2
ASVNRQFCHFLEPS-MNZRSNTBSA-N 4-[(2s)-3-(7-benzyl-2,4-dimethyl-3,7-diazabicyclo[3.3.1]nonan-3-yl)-2-hydroxypropoxy]benzonitrile Chemical compound CC1N(C[C@H](O)COC=2C=CC(=CC=2)C#N)C(C)C(C2)CC1CN2CC1=CC=CC=C1 ASVNRQFCHFLEPS-MNZRSNTBSA-N 0.000 description 2
NEHZDZNYHKMYAQ-UHFFFAOYSA-N 4-[3-(2,4-dimethyl-3,7-diazabicyclo[3.3.1]nonan-3-yl)-2-hydroxypropoxy]benzonitrile Chemical compound CC1C(C2)CNCC2C(C)N1CC(O)COC1=CC=C(C#N)C=C1 NEHZDZNYHKMYAQ-UHFFFAOYSA-N 0.000 description 2
ASVNRQFCHFLEPS-UHFFFAOYSA-N 4-[3-(7-benzyl-2,4-dimethyl-3,7-diazabicyclo[3.3.1]nonan-3-yl)-2-hydroxypropoxy]benzonitrile Chemical compound CC1N(CC(O)COC=2C=CC(=CC=2)C#N)C(C)C(C2)CC1CN2CC1=CC=CC=C1 ASVNRQFCHFLEPS-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
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
241000700198 Cavia Species 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-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
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
208000018452 Torsade de pointes Diseases 0.000 description 2
208000002363 Torsades de Pointes Diseases 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
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
239000003795 chemical substances by application Substances 0.000 description 2
230000008878 coupling Effects 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
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
238000010265 fast atom bombardment Methods 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
208000019622 heart disease Diseases 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
125000004356 hydroxy functional group Chemical group O* 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-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
230000003287 optical effect Effects 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
239000002243 precursor Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
238000000926 separation method Methods 0.000 description 2
239000011734 sodium Substances 0.000 description 2
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
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 2
ONCQIRSOYJPZNU-UHFFFAOYSA-N tert-butyl 3-[3-(4-cyanophenoxy)-2-hydroxypropyl]-4-methyl-3,7-diazabicyclo[3.3.1]nonane-7-carboxylate Chemical compound CC1C(CN(C2)C(=O)OC(C)(C)C)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 ONCQIRSOYJPZNU-UHFFFAOYSA-N 0.000 description 2
VMQUBAOCJHKHNF-UHFFFAOYSA-N tert-butyl 7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-2,4-dimethyl-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound CC1N(C(=O)OC(C)(C)C)C(C)C(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 VMQUBAOCJHKHNF-UHFFFAOYSA-N 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
BRLQWZUYTZBJKN-VKHMYHEASA-N (-)-Epichlorohydrin Chemical compound ClC[C@H]1CO1 BRLQWZUYTZBJKN-VKHMYHEASA-N 0.000 description 1
DLNAKYFPFYUBDR-UHFFFAOYSA-N (4-aminophenyl)-(7-benzyl-3,7-diazabicyclo[3.3.1]nonan-3-yl)methanone Chemical compound C1=CC(N)=CC=C1C(=O)N1CC(CN(CC=2C=CC=CC=2)C2)CC2C1 DLNAKYFPFYUBDR-UHFFFAOYSA-N 0.000 description 1
DLNAKYFPFYUBDR-HDICACEKSA-N (4-aminophenyl)-[(1s,5r)-7-benzyl-3,7-diazabicyclo[3.3.1]nonan-3-yl]methanone Chemical compound C1=CC(N)=CC=C1C(=O)N1C[C@@H](CN(CC=2C=CC=CC=2)C2)C[C@@H]2C1 DLNAKYFPFYUBDR-HDICACEKSA-N 0.000 description 1
BKXNECYZQMFRLG-UHFFFAOYSA-N (4-imidazol-1-ylphenyl)-(7-propan-2-yl-3,7-diazabicyclo[3.3.1]nonan-3-yl)methanone Chemical compound C1N(C(C)C)CC(C2)CC1CN2C(=O)C(C=C1)=CC=C1N1C=CN=C1 BKXNECYZQMFRLG-UHFFFAOYSA-N 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 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
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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
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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
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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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Hospice & Palliative Care (AREA)
Hematology (AREA)
Diabetes (AREA)
Epidemiology (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

SK1829-2001A 1999-06-16 2000-06-15 Bispidínové zlúčeniny užitočné pri liečbe srdcových arytmií SK18292001A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
SE9902269A SE9902269D0 (sv)	1999-06-16	1999-06-16	Pharmaceutically active compounds
PCT/SE2000/001252 WO2000076998A1 (en)	1999-06-16	2000-06-15	New bispidine compounds useful in the treatment of cardiac arrhythmias

Publications (1)

Publication Number	Publication Date
SK18292001A3 true SK18292001A3 (sk)	2002-12-03

Family

ID=20416101

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1829-2001A SK18292001A3 (sk)	1999-06-16	2000-06-15	Bispidínové zlúčeniny užitočné pri liečbe srdcových arytmií

Country Status (28)

Country	Link
EP (1)	EP1192156B1 (is)
JP (1)	JP2003502327A (is)
KR (1)	KR20020042534A (is)
CN (1)	CN1187351C (is)
AR (1)	AR024392A1 (is)
AT (1)	ATE259809T1 (is)
AU (1)	AU762040B2 (is)
BR (1)	BR0011667A (is)
CA (1)	CA2377395A1 (is)
CZ (1)	CZ20014493A3 (is)
DE (1)	DE60008377T2 (is)
DK (1)	DK1192156T3 (is)
EE (1)	EE200100679A (is)
ES (1)	ES2214291T3 (is)
HK (1)	HK1045689A1 (is)
HU (1)	HUP0300244A3 (is)
IL (1)	IL146751A0 (is)
IS (1)	IS6200A (is)
MX (1)	MXPA01012926A (is)
NO (1)	NO20016120L (is)
NZ (1)	NZ516014A (is)
PL (1)	PL353155A1 (is)
PT (1)	PT1192156E (is)
SE (1)	SE9902269D0 (is)
SK (1)	SK18292001A3 (is)
TR (1)	TR200103635T2 (is)
WO (1)	WO2000076998A1 (is)
ZA (1)	ZA200109798B (is)

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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

Family Cites Families (5)

* Cited by examiner, † Cited by third party
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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
SE9704709D0 (sv) *	1997-12-17	1997-12-17	Astra Ab	Pharmaceutically active compounds

1999
- 1999-06-16 SE SE9902269A patent/SE9902269D0/xx unknown
2000
- 2000-06-15 CN CNB008116075A patent/CN1187351C/zh not_active Expired - Fee Related
- 2000-06-15 SK SK1829-2001A patent/SK18292001A3/sk unknown
- 2000-06-15 EE EEP200100679A patent/EE200100679A/xx unknown
- 2000-06-15 DK DK00946588T patent/DK1192156T3/da active
- 2000-06-15 EP EP00946588A patent/EP1192156B1/en not_active Expired - Lifetime
- 2000-06-15 HU HU0300244A patent/HUP0300244A3/hu unknown
- 2000-06-15 CZ CZ20014493A patent/CZ20014493A3/cs unknown
- 2000-06-15 TR TR2001/03635T patent/TR200103635T2/xx unknown
- 2000-06-15 AT AT00946588T patent/ATE259809T1/de not_active IP Right Cessation
- 2000-06-15 PL PL00353155A patent/PL353155A1/xx not_active Application Discontinuation
- 2000-06-15 CA CA002377395A patent/CA2377395A1/en not_active Abandoned
- 2000-06-15 MX MXPA01012926A patent/MXPA01012926A/es active IP Right Grant
- 2000-06-15 PT PT00946588T patent/PT1192156E/pt unknown
- 2000-06-15 AU AU60323/00A patent/AU762040B2/en not_active Ceased
- 2000-06-15 ES ES00946588T patent/ES2214291T3/es not_active Expired - Lifetime
- 2000-06-15 WO PCT/SE2000/001252 patent/WO2000076998A1/en not_active Ceased
- 2000-06-15 IL IL14675100A patent/IL146751A0/xx unknown
- 2000-06-15 DE DE60008377T patent/DE60008377T2/de not_active Expired - Fee Related
- 2000-06-15 NZ NZ516014A patent/NZ516014A/xx unknown
- 2000-06-15 BR BR0011667-0A patent/BR0011667A/pt not_active IP Right Cessation
- 2000-06-15 KR KR1020017016167A patent/KR20020042534A/ko not_active Withdrawn
- 2000-06-15 JP JP2001503856A patent/JP2003502327A/ja active Pending
- 2000-06-15 HK HK02107114.4A patent/HK1045689A1/zh unknown
- 2000-06-16 AR ARP000103016A patent/AR024392A1/es unknown
- 2000-12-14 IS IS6200A patent/IS6200A/is unknown
2001
- 2001-11-28 ZA ZA200109798A patent/ZA200109798B/en unknown
- 2001-12-14 NO NO20016120A patent/NO20016120L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
TR200103635T2 (tr)	2002-04-22
DE60008377T2 (de)	2004-12-09
HUP0300244A2 (hu)	2003-06-28
NZ516014A (en)	2003-06-30
EP1192156B1 (en)	2004-02-18
WO2000076998A1 (en)	2000-12-21
CZ20014493A3 (cs)	2002-05-15
DK1192156T3 (da)	2004-05-17
IL146751A0 (en)	2002-07-25
CN1370165A (zh)	2002-09-18
CA2377395A1 (en)	2000-12-21
EE200100679A (et)	2003-02-17
NO20016120D0 (no)	2001-12-14
AR024392A1 (es)	2002-10-02
NO20016120L (no)	2002-02-18
SE9902269D0 (sv)	1999-06-16
PT1192156E (pt)	2004-06-30
AU6032300A (en)	2001-01-02
AU762040B2 (en)	2003-06-19
JP2003502327A (ja)	2003-01-21
HUP0300244A3 (en)	2003-12-29
MXPA01012926A (es)	2002-07-30
DE60008377D1 (de)	2004-03-25
WO2000076998B1 (en)	2001-03-08
IS6200A (is)	2001-12-14
ES2214291T3 (es)	2004-09-16
ZA200109798B (en)	2003-02-28
KR20020042534A (ko)	2002-06-05
ATE259809T1 (de)	2004-03-15
CN1187351C (zh)	2005-02-02
PL353155A1 (en)	2003-10-20
BR0011667A (pt)	2002-04-02
HK1045689A1 (zh)	2002-12-06
EP1192156A1 (en)	2002-04-03

Publication	Publication Date	Title
EP1047695B1 (en)	2004-03-17	Novel bispidine antiarrhythmic compounds
US7012074B2 (en)	2006-03-14	3,8-Diazabicyclo[3.2.1]octanes and their use in the treatment of cardiac arrhythmias
SK18292001A3 (sk)	2002-12-03	Bispidínové zlúčeniny užitočné pri liečbe srdcových arytmií
US6887881B1 (en)	2005-05-03	Bispidine compounds useful in the treatment of cardiac arrythmias
AU761576B2 (en)	2003-06-05	New bispidine compounds useful in the treatment of cardiac arrhythmias
EP1192155B1 (en)	2003-04-02	New bispidine compounds useful in the treatment of cardiac arrhythmias
US20040229900A1 (en)	2004-11-18	Bispidine compounds useful in the treatment of cardiac arrythmias
SK42003A3 (en)	2003-07-01	New bispidine compounds and their use in the treatment of cardiac arrhythmias
US20050004113A1 (en)	2005-01-06	New bispidine compounds useful in the treatment of cardiac arrhythmias
US20030212095A1 (en)	2003-11-13	New bispidine compounds and their use in the treatment of cardiac arrhythmias
CZ20002222A3 (cs)	2000-11-15	Nové bispidinové sloučeniny s antiarytmickým účinkem