SK42003A3 - New bispidine compounds and their use in the treatment of cardiac arrhythmias - Google Patents
New bispidine compounds and their use in the treatment of cardiac arrhythmias Download PDFInfo
- Publication number
- SK42003A3 SK42003A3 SK4-2003A SK42003A SK42003A3 SK 42003 A3 SK42003 A3 SK 42003A3 SK 42003 A SK42003 A SK 42003A SK 42003 A3 SK42003 A3 SK 42003A3
- Authority
- SK
- Slovakia
- Prior art keywords
- formula
- group
- compound
- alkyl
- het
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- 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 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 375
- 230000006793 arrhythmia Effects 0.000 claims abstract description 14
- 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
- 238000011321 prophylaxis Methods 0.000 claims abstract 5
- -1 4-cyanophenoxy Chemical group 0.000 claims description 178
- 125000000217 alkyl group Chemical group 0.000 claims description 146
- 125000004432 carbon atom Chemical group C* 0.000 claims description 136
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 110
- 125000003118 aryl group Chemical group 0.000 claims description 82
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 73
- 229910052739 hydrogen Inorganic materials 0.000 claims description 71
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 71
- 239000001257 hydrogen Substances 0.000 claims description 70
- 125000001424 substituent group Chemical group 0.000 claims description 66
- 125000002947 alkylene group Chemical group 0.000 claims description 57
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 53
- 238000006243 chemical reaction Methods 0.000 claims description 43
- 229910052736 halogen Inorganic materials 0.000 claims description 38
- 150000002367 halogens Chemical class 0.000 claims description 38
- 125000004043 oxo group Chemical group O=* 0.000 claims description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 31
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 29
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 238000002360 preparation method Methods 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 17
- 230000009467 reduction Effects 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 14
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- MNLAVFKVRUQAKW-UHFFFAOYSA-N VR nerve agent Chemical compound CCN(CC)CCSP(C)(=O)OCC(C)C MNLAVFKVRUQAKW-UHFFFAOYSA-N 0.000 claims description 11
- 150000001721 carbon Chemical group 0.000 claims description 11
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 claims description 5
- 239000007800 oxidant agent Substances 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- IVRMZWNICZWHMI-UHFFFAOYSA-N Azide Chemical compound [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 230000001590 oxidative effect Effects 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 230000029936 alkylation Effects 0.000 claims description 2
- 238000005804 alkylation reaction Methods 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 230000002140 halogenating effect Effects 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- XAHVPYNDLCTDTE-UHFFFAOYSA-N dipentyl oxalate Chemical compound CCCCCOC(=O)C(=O)OCCCCC XAHVPYNDLCTDTE-UHFFFAOYSA-N 0.000 claims 2
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 210000003918 fraction a Anatomy 0.000 claims 1
- 239000012634 fragment Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims 1
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 257
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 239000000203 mixture Substances 0.000 description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 34
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 31
- 150000002431 hydrogen Chemical class 0.000 description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 239000002904 solvent Substances 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 21
- 125000004126 inden-3-yl group Chemical group [H]C1=C(*)C2=C([H])C([H])=C([H])C([H])=C2C1([H])[H] 0.000 description 21
- 239000003960 organic solvent Substances 0.000 description 20
- 238000012360 testing method Methods 0.000 description 18
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 17
- 238000009835 boiling Methods 0.000 description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 16
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
- 125000003277 amino group Chemical group 0.000 description 14
- 239000002585 base Substances 0.000 description 13
- 235000019439 ethyl acetate Nutrition 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- HQMRIBYCTLBDAK-UHFFFAOYSA-M bis(2-methylpropyl)alumanylium;chloride Chemical compound CC(C)C[Al](Cl)CC(C)C HQMRIBYCTLBDAK-UHFFFAOYSA-M 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 125000006239 protecting group Chemical group 0.000 description 12
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 12
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 239000003638 chemical reducing agent Substances 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-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 8
- 241001465754 Metazoa Species 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 8
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 7
- 230000000747 cardiac effect Effects 0.000 description 7
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
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- 125000004122 cyclic group Chemical group 0.000 description 5
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
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- 238000003786 synthesis reaction Methods 0.000 description 5
- ICGLPKIVTVWCFT-UHFFFAOYSA-N 4-methylbenzenesulfonohydrazide Chemical compound CC1=CC=C(S(=O)(=O)NN)C=C1 ICGLPKIVTVWCFT-UHFFFAOYSA-N 0.000 description 4
- VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 4
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- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
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- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 4
- 125000000524 functional group Chemical group 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
- 238000005259 measurement Methods 0.000 description 4
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- 238000004809 thin layer chromatography Methods 0.000 description 4
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- YLCFJVJPLFZWLT-UHFFFAOYSA-N 7-benzyl-3-butylsulfonyl-3,7-diazabicyclo[3.3.1]nonane Chemical compound C1N(S(=O)(=O)CCCC)CC(C2)CC1CN2CC1=CC=CC=C1 YLCFJVJPLFZWLT-UHFFFAOYSA-N 0.000 description 2
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- GQQRBQODEBCJEA-UHFFFAOYSA-N n-cyano-7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-n'-[(5-hydroxy-1,3,3-trimethylcyclohexyl)methyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboximidamide Chemical compound C1C(C)(C)CC(O)CC1(C)CNC(=NC#N)N1CC(CN(CC(O)COC=2C=CC(=CC=2)C#N)C2)CC2C1 GQQRBQODEBCJEA-UHFFFAOYSA-N 0.000 description 1
- KWAAFLGNDPAQGD-UHFFFAOYSA-N n-cyano-7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-n'-[2-(3,4-dimethoxyphenyl)ethyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboximidamide Chemical compound C1=C(OC)C(OC)=CC=C1CCNC(=NC#N)N1CC(CN(CC(O)COC=2C=CC(=CC=2)C#N)C2)CC2C1 KWAAFLGNDPAQGD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- AKWFJDXCMPOIQD-UHFFFAOYSA-N nonane-3-sulfonamide Chemical compound C(C)C(CCCCCC)S(=O)(=O)N AKWFJDXCMPOIQD-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- VRHXFFHQKBSNDK-UHFFFAOYSA-N o-ethyl 7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonane-3-carbothioate Chemical compound C1N(C(=S)OCC)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 VRHXFFHQKBSNDK-UHFFFAOYSA-N 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 125000001484 phenothiazinyl group Chemical class C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- DUCAQWPRDCMWIH-UHFFFAOYSA-N phenyl n-cyano-7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboximidate Chemical compound C1C(CN(C2)C(OC=3C=CC=CC=3)=NC#N)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 DUCAQWPRDCMWIH-UHFFFAOYSA-N 0.000 description 1
- UXOFXTUCXRNLFA-UHFFFAOYSA-N phenyl-(7-propan-2-yl-3,7-diazabicyclo[3.3.1]nonan-3-yl)methanone Chemical compound C1N(C(C)C)CC(C2)CC1CN2C(=O)C1=CC=CC=C1 UXOFXTUCXRNLFA-UHFFFAOYSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 229960001922 sodium perborate Drugs 0.000 description 1
- YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000035488 systolic blood pressure Effects 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
- YLUDLEMVKBUVDC-UHFFFAOYSA-N tert-butyl 2-[2-(4-cyanophenoxy)ethyl]aziridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC1CCOC1=CC=C(C#N)C=C1 YLUDLEMVKBUVDC-UHFFFAOYSA-N 0.000 description 1
- FFDOXSIZJSGXOQ-UHFFFAOYSA-N tert-butyl 7-[3-(4-cyanophenoxy)-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 FFDOXSIZJSGXOQ-UHFFFAOYSA-N 0.000 description 1
- MYOHDFYCJARIJO-UHFFFAOYSA-N tert-butyl n-[2-[3-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethyl]carbamate Chemical compound C1N(CCNC(=O)OC(C)(C)C)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 MYOHDFYCJARIJO-UHFFFAOYSA-N 0.000 description 1
- IUVINUVWJBACBQ-UHFFFAOYSA-N tert-butyl n-[4-(4-cyanophenoxy)-2-hydroxybutyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC(O)CCOC1=CC=C(C#N)C=C1 IUVINUVWJBACBQ-UHFFFAOYSA-N 0.000 description 1
- OSTGEMHVUNCMFA-UHFFFAOYSA-N tert-butyl n-[4-[7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-4-oxobutan-2-yl]carbamate Chemical compound C1N(C(=O)CC(C)NC(=O)OC(C)(C)C)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 OSTGEMHVUNCMFA-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
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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
- 239000012588 trypsin Substances 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 229940102001 zinc bromide Drugs 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
- A61P9/06—Antiarrhythmics
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0002603A SE0002603D0 (sv) | 2000-07-07 | 2000-07-07 | New compounds |
| SE0002788A SE0002788D0 (sv) | 2000-07-27 | 2000-07-27 | New compounds |
| PCT/SE2001/001544 WO2002004446A1 (en) | 2000-07-07 | 2001-07-04 | New bispidine compounds and their use in the treatment of cardiac arrhythmias |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK42003A3 true SK42003A3 (en) | 2003-07-01 |
Family
ID=26655177
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK4-2003A SK42003A3 (en) | 2000-07-07 | 2001-07-04 | New bispidine compounds and their use in the treatment of cardiac arrhythmias |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP1301510A1 (cs) |
| JP (1) | JP2004502772A (cs) |
| KR (1) | KR20030014426A (cs) |
| CN (1) | CN1440407A (cs) |
| AR (1) | AR030302A1 (cs) |
| AU (1) | AU2001271161A1 (cs) |
| BR (1) | BR0112267A (cs) |
| CA (1) | CA2412848A1 (cs) |
| CZ (1) | CZ200332A3 (cs) |
| EE (1) | EE200300013A (cs) |
| HU (1) | HUP0301304A2 (cs) |
| IL (1) | IL153485A0 (cs) |
| IS (1) | IS6660A (cs) |
| MX (1) | MXPA02012942A (cs) |
| NO (1) | NO20030057L (cs) |
| NZ (1) | NZ523540A (cs) |
| PL (1) | PL360474A1 (cs) |
| RU (1) | RU2002134450A (cs) |
| SK (1) | SK42003A3 (cs) |
| WO (1) | WO2002004446A1 (cs) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004103991A1 (en) * | 2003-05-20 | 2004-12-02 | 'chemical Diversity Research Institute', Ltd. | 2-substituted piperidines, focused library and a pharmaceutical compound |
| US7399765B2 (en) | 2003-09-19 | 2008-07-15 | Abbott Laboratories | Substituted diazabicycloalkane derivatives |
| SE0302775D0 (sv) * | 2003-10-20 | 2003-10-20 | Astrazeneca Ab | Chemical compound and assay |
| RU2472793C1 (ru) * | 2011-07-20 | 2013-01-20 | Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Московский государственный университет тонких химических технологий имени М.В. Ломоносова" (МИТХТ им.М.В.Ломоносова) | 1,5-бис[(трет-бутиламино)метил]-n,n'-ди-трет-бутилбиспидин-9-она и способ его получения |
| CN116444556A (zh) * | 2023-03-24 | 2023-07-18 | 苏州威迈芯材半导体有限公司 | 一种有机硅中间体4-苯甲腈基氧烷基三烷氧基硅烷的制备方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| DE4402933A1 (de) * | 1994-02-01 | 1995-08-03 | Kali Chemie Pharma Gmbh | Neue 3-Benzoyl-3,7-diazabicyclo[3,3,1] nonan-Verbindungen enthaltende Arzneimittel |
| SE9704709D0 (sv) * | 1997-12-17 | 1997-12-17 | Astra Ab | Pharmaceutically active compounds |
| SE9902271D0 (sv) * | 1999-06-16 | 1999-06-16 | Astra Ab | Pharmaceutically active compounds |
| SE9902268D0 (sv) * | 1999-06-16 | 1999-06-16 | Astra Ab | Pharmaceutically active compounds |
| SE9902269D0 (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 |
-
2001
- 2001-06-28 AR ARP010103085A patent/AR030302A1/es not_active Application Discontinuation
- 2001-07-04 EE EEP200300013A patent/EE200300013A/xx unknown
- 2001-07-04 MX MXPA02012942A patent/MXPA02012942A/es unknown
- 2001-07-04 CZ CZ200332A patent/CZ200332A3/cs unknown
- 2001-07-04 SK SK4-2003A patent/SK42003A3/sk unknown
- 2001-07-04 BR BR0112267-3A patent/BR0112267A/pt not_active IP Right Cessation
- 2001-07-04 KR KR10-2003-7000248A patent/KR20030014426A/ko not_active Withdrawn
- 2001-07-04 NZ NZ523540A patent/NZ523540A/en unknown
- 2001-07-04 JP JP2002509311A patent/JP2004502772A/ja active Pending
- 2001-07-04 EP EP01950132A patent/EP1301510A1/en not_active Withdrawn
- 2001-07-04 CN CN01812475A patent/CN1440407A/zh active Pending
- 2001-07-04 CA CA002412848A patent/CA2412848A1/en not_active Abandoned
- 2001-07-04 AU AU2001271161A patent/AU2001271161A1/en not_active Abandoned
- 2001-07-04 HU HU0301304A patent/HUP0301304A2/hu unknown
- 2001-07-04 PL PL36047401A patent/PL360474A1/xx not_active Application Discontinuation
- 2001-07-04 IL IL15348501A patent/IL153485A0/xx unknown
- 2001-07-04 RU RU2002134450/04A patent/RU2002134450A/ru not_active Application Discontinuation
- 2001-07-04 WO PCT/SE2001/001544 patent/WO2002004446A1/en not_active Ceased
-
2002
- 2002-12-19 IS IS6660A patent/IS6660A/is unknown
-
2003
- 2003-01-06 NO NO20030057A patent/NO20030057L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| KR20030014426A (ko) | 2003-02-17 |
| NZ523540A (en) | 2004-07-30 |
| WO2002004446A1 (en) | 2002-01-17 |
| CA2412848A1 (en) | 2002-01-17 |
| EE200300013A (et) | 2004-10-15 |
| JP2004502772A (ja) | 2004-01-29 |
| AU2001271161A1 (en) | 2002-01-21 |
| CZ200332A3 (cs) | 2003-04-16 |
| HUP0301304A2 (hu) | 2003-08-28 |
| IL153485A0 (en) | 2003-07-06 |
| NO20030057D0 (no) | 2003-01-06 |
| MXPA02012942A (es) | 2003-10-06 |
| EP1301510A1 (en) | 2003-04-16 |
| BR0112267A (pt) | 2003-05-20 |
| PL360474A1 (en) | 2004-09-06 |
| CN1440407A (zh) | 2003-09-03 |
| AR030302A1 (es) | 2003-08-20 |
| RU2002134450A (ru) | 2004-07-10 |
| IS6660A (is) | 2002-12-19 |
| NO20030057L (no) | 2003-01-31 |
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