CA2412848A1 - 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
- CA2412848A1 CA2412848A1 CA002412848A CA2412848A CA2412848A1 CA 2412848 A1 CA2412848 A1 CA 2412848A1 CA 002412848 A CA002412848 A CA 002412848A CA 2412848 A CA2412848 A CA 2412848A CA 2412848 A1 CA2412848 A1 CA 2412848A1
- Authority
- CA
- Canada
- Prior art keywords
- formula
- compound
- alkyl
- optionally substituted
- compounds
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 206010003119 arrhythmia Diseases 0.000 title claims abstract description 25
- 238000011282 treatment Methods 0.000 title claims abstract description 17
- PTPQJKANBKHDPM-UHFFFAOYSA-N 3,7-diazabicyclo[3.3.1]nonane Chemical class C1NCC2CNCC1C2 PTPQJKANBKHDPM-UHFFFAOYSA-N 0.000 title claims description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 377
- 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
- 125000000217 alkyl group Chemical group 0.000 claims description 179
- -1 -OH Chemical group 0.000 claims description 86
- 238000006243 chemical reaction Methods 0.000 claims description 79
- 125000003118 aryl group Chemical group 0.000 claims description 77
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 71
- 125000002947 alkylene group Chemical group 0.000 claims description 68
- 125000001424 substituent group Chemical group 0.000 claims description 66
- 125000005843 halogen group Chemical group 0.000 claims description 58
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 52
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 38
- 239000012634 fragment Substances 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- 230000009467 reduction Effects 0.000 claims description 20
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 150000001721 carbon Chemical group 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 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 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 101100070530 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) het-6 gene Proteins 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 239000007800 oxidant agent Substances 0.000 claims description 5
- 230000003647 oxidation Effects 0.000 claims description 5
- 238000007254 oxidation reaction Methods 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 229910052717 sulfur Chemical group 0.000 claims description 4
- 239000011593 sulfur Chemical group 0.000 claims description 4
- IVRMZWNICZWHMI-UHFFFAOYSA-N Azide Chemical compound [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- 238000010511 deprotection reaction Methods 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- SIHVSPXVPKLFAB-UHFFFAOYSA-N 2-(3-benzyl-3,7-diazabicyclo[3.3.1]nonan-7-yl)ethanol Chemical compound C1N(CCO)CC(C2)CC1CN2CC1=CC=CC=C1 SIHVSPXVPKLFAB-UHFFFAOYSA-N 0.000 claims description 2
- LHUWGMIFIFULPE-UHFFFAOYSA-N 3-benzyl-7-[3-(2-propyl-1,3-dioxolan-2-yl)propyl]-3,7-diazabicyclo[3.3.1]nonane Chemical compound C1C(CN(CC=2C=CC=CC=2)C2)CC2CN1CCCC1(CCC)OCCO1 LHUWGMIFIFULPE-UHFFFAOYSA-N 0.000 claims description 2
- SEOQYNBBMGIYOF-UHFFFAOYSA-N 4-[3-(7-benzyl-4-methyl-3,7-diazabicyclo[3.3.1]nonan-3-yl)-2-hydroxypropoxy]benzonitrile Chemical compound C1N(CC(O)COC=2C=CC(=CC=2)C#N)C(C)C(C2)CC1CN2CC1=CC=CC=C1 SEOQYNBBMGIYOF-UHFFFAOYSA-N 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 claims description 2
- 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
- 230000002140 halogenating effect Effects 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 36
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
- MNLAVFKVRUQAKW-UHFFFAOYSA-N VR nerve agent Chemical compound CCN(CC)CCSP(C)(=O)OCC(C)C MNLAVFKVRUQAKW-UHFFFAOYSA-N 0.000 claims 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- MHCWBLYCXZVTPV-UHFFFAOYSA-N 3-(3-benzyl-3,7-diazabicyclo[3.3.1]nonan-7-yl)-n-phenylpropanamide Chemical compound C=1C=CC=CC=1NC(=O)CCN(C1)CC(C2)CC1CN2CC1=CC=CC=C1 MHCWBLYCXZVTPV-UHFFFAOYSA-N 0.000 claims 1
- 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 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- CUIFDVJEFHYCEM-UHFFFAOYSA-N n-[1-(7-benzyl-3,7-diazabicyclo[3.3.1]nonan-3-yl)-3-(4-cyanophenoxy)propan-2-yl]methanesulfonamide Chemical compound C1C(CN(CC=2C=CC=CC=2)C2)CC2CN1CC(NS(=O)(=O)C)COC1=CC=C(C#N)C=C1 CUIFDVJEFHYCEM-UHFFFAOYSA-N 0.000 claims 1
- 206010003130 Arrhythmia supraventricular Diseases 0.000 abstract description 2
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 145
- 239000000203 mixture Substances 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- 239000003960 organic solvent Substances 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 19
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- 238000010992 reflux Methods 0.000 description 17
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- 239000002585 base Substances 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 11
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- 125000006239 protecting group Chemical group 0.000 description 11
- 239000003638 chemical reducing agent Substances 0.000 description 10
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-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
- 210000004027 cell Anatomy 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- 125000004429 atom Chemical group 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 229960004592 isopropanol Drugs 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 230000008878 coupling Effects 0.000 description 6
- 238000010168 coupling process Methods 0.000 description 6
- 238000005859 coupling reaction Methods 0.000 description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 6
- 210000002950 fibroblast Anatomy 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 5
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 125000005233 alkylalcohol group Chemical group 0.000 description 5
- 239000003416 antiarrhythmic agent Substances 0.000 description 5
- 125000004122 cyclic group Chemical group 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 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
- VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 4
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 230000000747 cardiac effect Effects 0.000 description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 230000002336 repolarization Effects 0.000 description 4
- 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 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 101150041968 CDC13 gene Proteins 0.000 description 3
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 229910010084 LiAlH4 Inorganic materials 0.000 description 3
- 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 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000002565 electrocardiography Methods 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 239000003862 glucocorticoid Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 3
- 125000000842 isoxazolyl group Chemical group 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- JCMDMJYRJNTTMM-UHFFFAOYSA-N n-cyano-7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-n'-[(3,4,5-trimethoxyphenyl)methyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboximidamide Chemical compound COC1=C(OC)C(OC)=CC(CNC(=NC#N)N2CC3CC(CN(CC(O)COC=4C=CC(=CC=4)C#N)C3)C2)=C1 JCMDMJYRJNTTMM-UHFFFAOYSA-N 0.000 description 3
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 125000004193 piperazinyl group Chemical group 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 3
- 230000033764 rhythmic process Effects 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 230000002861 ventricular Effects 0.000 description 3
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 2
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 2
- 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
- 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 2
- CLFSRXWETMSTNT-UHFFFAOYSA-N 3-butylsulfonyl-3,7-diazabicyclo[3.3.1]nonane Chemical compound C1NCC2CN(S(=O)(=O)CCCC)CC1C2 CLFSRXWETMSTNT-UHFFFAOYSA-N 0.000 description 2
- KCEFCHIDTSIDCO-UHFFFAOYSA-N 7-benzyl-3-(2h-tetrazol-5-yl)-3,7-diazabicyclo[3.3.1]nonane Chemical compound C=1C=CC=CC=1CN(C1)CC(C2)CC1CN2C=1N=NNN=1 KCEFCHIDTSIDCO-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000013975 Delayed Rectifier Potassium Channels Human genes 0.000 description 2
- 108010050556 Delayed Rectifier Potassium Channels Proteins 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 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
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 125000002015 acyclic group Chemical group 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 125000005604 azodicarboxylate group Chemical group 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
- HQMRIBYCTLBDAK-UHFFFAOYSA-M bis(2-methylpropyl)alumanylium;chloride Chemical compound CC(C)C[Al](Cl)CC(C)C HQMRIBYCTLBDAK-UHFFFAOYSA-M 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000010265 fast atom bombardment Methods 0.000 description 2
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 210000004731 jugular vein Anatomy 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- OQJBFFCUFALWQL-UHFFFAOYSA-N n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)N=NC(=O)N1CCCCC1 OQJBFFCUFALWQL-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- FZDPFJLGQWGOLW-UHFFFAOYSA-N phenyl n-cyano-n'-[(3,4,5-trimethoxyphenyl)methyl]carbamimidate Chemical compound COC1=C(OC)C(OC)=CC(CNC(OC=2C=CC=CC=2)=NC#N)=C1 FZDPFJLGQWGOLW-UHFFFAOYSA-N 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
- XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine group Chemical group P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 230000011514 reflex Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 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
- FTABKDGWKNKXQJ-UHFFFAOYSA-N (4-chlorophenyl)-(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=C(Cl)C=C1 FTABKDGWKNKXQJ-UHFFFAOYSA-N 0.000 description 1
- JXEMQTADVVTTAR-UHFFFAOYSA-N 1,1'-biphenyl carbamoyl cyanide Chemical compound C(O)(=N)C#N.C1(=CC=CC=C1)C1=CC=CC=C1 JXEMQTADVVTTAR-UHFFFAOYSA-N 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- ZIOSYBIDGDHSIQ-UHFFFAOYSA-N 1-[1-(4-cyanophenoxy)-3-[3-(1,3-thiazol-2-yl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propan-2-yl]-1-methylurea Chemical compound C1C(CN(C2)C=3SC=CN=3)CC2CN1CC(N(C)C(N)=O)COC1=CC=C(C#N)C=C1 ZIOSYBIDGDHSIQ-UHFFFAOYSA-N 0.000 description 1
- ZIMPVFLDSMUXRP-UHFFFAOYSA-N 1-[1-(4-cyanophenoxy)-3-[7-[2-(2-methoxyethoxy)ethyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]propan-2-yl]-1-methylurea Chemical compound C1N(CCOCCOC)CC(C2)CC1CN2CC(N(C)C(N)=O)COC1=CC=C(C#N)C=C1 ZIMPVFLDSMUXRP-UHFFFAOYSA-N 0.000 description 1
- QTCMTFAIZYGFKE-UHFFFAOYSA-N 1-[1-[7-(1-cyanoethyl)-3,7-diazabicyclo[3.3.1]nonan-3-yl]-3-(4-cyanophenoxy)propan-2-yl]-1-methylurea Chemical compound C(#N)C(C)N1CC2CN(CC(C1)C2)CC(COC2=CC=C(C=C2)C#N)N(C(=O)N)C QTCMTFAIZYGFKE-UHFFFAOYSA-N 0.000 description 1
- VNRGEFBSYSHFQX-UHFFFAOYSA-N 1-[1-[7-[3-(4-acetylpiperazin-1-yl)propyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-3-(4-cyanophenoxy)propan-2-yl]-1-methylurea Chemical compound C1C(CN(CCCN2CCN(CC2)C(C)=O)C2)CC2CN1CC(N(C)C(N)=O)COC1=CC=C(C#N)C=C1 VNRGEFBSYSHFQX-UHFFFAOYSA-N 0.000 description 1
- BHRWAPHJPGKSBX-UHFFFAOYSA-N 1-[5-cyano-2-[3-(3-ethylsulfonyl-3,7-diazabicyclo[3.3.1]nonan-7-yl)-2-hydroxypropoxy]phenyl]-1-ethylurea Chemical compound CCN(C(N)=O)C1=CC(C#N)=CC=C1OCC(O)CN1CC(CN(C2)S(=O)(=O)CC)CC2C1 BHRWAPHJPGKSBX-UHFFFAOYSA-N 0.000 description 1
- INOCWMUDPICJEV-UHFFFAOYSA-N 1-benzyl-3,7-diazabicyclo[3.3.1]nonane Chemical compound C(C1=CC=CC=C1)C12CNCC(CNC1)C2 INOCWMUDPICJEV-UHFFFAOYSA-N 0.000 description 1
- ULSAJQMHTGKPIY-UHFFFAOYSA-N 1-chloro-3,3-dimethylbutan-2-one Chemical compound CC(C)(C)C(=O)CCl ULSAJQMHTGKPIY-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- UBPCTSHRJLHULF-UHFFFAOYSA-N 2-[(7-methyl-3,7-diazabicyclo[3.3.1]nonan-3-yl)methyl]-4-methylsulfonyl-2,3-dihydro-1,4-benzoxazine-6-carbonitrile Chemical compound C1N(S(C)(=O)=O)C2=CC(C#N)=CC=C2OC1CN(C1)CC2CC1CN(C)C2 UBPCTSHRJLHULF-UHFFFAOYSA-N 0.000 description 1
- JWTZFEATBIPUMO-UHFFFAOYSA-N 2-[2-[7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]ethyl]-4-nitrobenzamide Chemical compound C(#N)C1=CC=C(OCC(CN2CC3CN(CC(C2)C3)CCC3=C(C(=O)N)C=CC(=C3)[N+](=O)[O-])O)C=C1 JWTZFEATBIPUMO-UHFFFAOYSA-N 0.000 description 1
- UHTQHHLSGVOGQR-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-4-ium-1-yl]ethanesulfonate Chemical compound OCCN1CCN(CCS(O)(=O)=O)CC1.OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 UHTQHHLSGVOGQR-UHFFFAOYSA-N 0.000 description 1
- ISEUJCMZNAPNTR-UHFFFAOYSA-N 2-[7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-2-oxoacetamide Chemical compound C1N(C(=O)C(=O)N)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 ISEUJCMZNAPNTR-UHFFFAOYSA-N 0.000 description 1
- WXMUMIKKOYQQIH-UHFFFAOYSA-N 2-[[3-[(6-cyano-4-methylsulfonyl-2,3-dihydro-1,4-benzoxazin-2-yl)methyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]methyl]-4-methylsulfonyl-2,3-dihydro-1,4-benzoxazine-6-carbonitrile Chemical compound O1C2=CC=C(C#N)C=C2N(S(=O)(=O)C)CC1CN1CC(CN(CC2OC3=CC=C(C=C3N(C2)S(C)(=O)=O)C#N)C2)CC2C1 WXMUMIKKOYQQIH-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- RXNZFHIEDZEUQM-UHFFFAOYSA-N 2-bromo-1,3-thiazole Chemical compound BrC1=NC=CS1 RXNZFHIEDZEUQM-UHFFFAOYSA-N 0.000 description 1
- WJAXXWSZNSFVNG-UHFFFAOYSA-N 2-bromoethanamine;hydron;bromide Chemical compound [Br-].[NH3+]CCBr WJAXXWSZNSFVNG-UHFFFAOYSA-N 0.000 description 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
- HFRRBFCPKQVFQS-UHFFFAOYSA-N 3,7-bis[2-(4-nitrophenyl)ethyl]-3,7-diazabicyclo[3.3.1]nonane Chemical compound C1=CC([N+](=O)[O-])=CC=C1CCN1CC(CN(CCC=2C=CC(=CC=2)[N+]([O-])=O)C2)CC2C1 HFRRBFCPKQVFQS-UHFFFAOYSA-N 0.000 description 1
- OVJDMJSPIVZXDQ-UHFFFAOYSA-N 3,7-diazabicyclo[3.3.1]nonane-3-carboximidamide Chemical compound C1NCC2CN(C(=N)N)CC1C2 OVJDMJSPIVZXDQ-UHFFFAOYSA-N 0.000 description 1
- DFVVIVHHZCJVAT-UHFFFAOYSA-N 3-(2-ethyltetrazol-5-yl)-3,7-diazabicyclo[3.3.1]nonane Chemical compound CCN1N=NC(N2CC3CNCC(C3)C2)=N1 DFVVIVHHZCJVAT-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- WREXVDPOLDOXJL-UHFFFAOYSA-N 4-(oxiran-2-ylmethoxy)benzonitrile Chemical compound C1=CC(C#N)=CC=C1OCC1OC1 WREXVDPOLDOXJL-UHFFFAOYSA-N 0.000 description 1
- QWHRISMVZANXCV-DAWZGUTISA-N 4-[(2r)-2-hydroxy-3-(3-propanoyl-3,7-diazabicyclo[3.3.1]nonan-7-yl)propoxy]benzonitrile Chemical compound C([C@H](O)CN1CC2CC(C1)CN(C2)C(=O)CC)OC1=CC=C(C#N)C=C1 QWHRISMVZANXCV-DAWZGUTISA-N 0.000 description 1
- APSSASZESPLXTH-MQSUGXTHSA-N 4-[(2r)-3-[3-[(2r)-3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C([C@H](O)CN1CC2CC(CN(C[C@@H](O)COC=3C=CC(=CC=3)C#N)C2)C1)OC1=CC=C(C#N)C=C1 APSSASZESPLXTH-MQSUGXTHSA-N 0.000 description 1
- GHISITIBCCYOGE-UHFFFAOYSA-N 4-[1-(3,4-dimethoxyphenoxy)-4-[3-(1,3-thiazol-2-yl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]butyl]benzonitrile Chemical compound C1=C(OC)C(OC)=CC=C1OC(C=1C=CC(=CC=1)C#N)CCCN1CC(CN(C2)C=3SC=CN=3)CC2C1 GHISITIBCCYOGE-UHFFFAOYSA-N 0.000 description 1
- RLINODWQNFOMKB-UHFFFAOYSA-N 4-[1-(3,4-dimethoxyphenoxy)-4-[3-(2-ethyltetrazol-5-yl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]butyl]benzonitrile Chemical compound CCN1N=NC(N2CC3CC(CN(CCCC(OC=4C=C(OC)C(OC)=CC=4)C=4C=CC(=CC=4)C#N)C3)C2)=N1 RLINODWQNFOMKB-UHFFFAOYSA-N 0.000 description 1
- YPWHVAPYJQUZMV-UHFFFAOYSA-N 4-[1-(3,4-dimethoxyphenoxy)-4-[3-(3,3-dimethyl-2-oxobutyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]butyl]benzonitrile Chemical compound C1=C(OC)C(OC)=CC=C1OC(C=1C=CC(=CC=1)C#N)CCCN1CC(CN(CC(=O)C(C)(C)C)C2)CC2C1 YPWHVAPYJQUZMV-UHFFFAOYSA-N 0.000 description 1
- GXXCZZRNFUOXCD-UHFFFAOYSA-N 4-[1-(3,4-dimethoxyphenoxy)-4-[3-(4-oxoheptyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]butyl]benzonitrile Chemical compound C1N(CCCC(=O)CCC)CC(C2)CC1CN2CCCC(C=1C=CC(=CC=1)C#N)OC1=CC=C(OC)C(OC)=C1 GXXCZZRNFUOXCD-UHFFFAOYSA-N 0.000 description 1
- WOEZMCBLXPOFIS-UHFFFAOYSA-N 4-[1-(3,4-dimethoxyphenoxy)-4-[3-[(4-fluorophenyl)methyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]butyl]benzonitrile Chemical compound C1=C(OC)C(OC)=CC=C1OC(C=1C=CC(=CC=1)C#N)CCCN1CC(CN(CC=2C=CC(F)=CC=2)C2)CC2C1 WOEZMCBLXPOFIS-UHFFFAOYSA-N 0.000 description 1
- AECGJPJPARSSPX-UHFFFAOYSA-N 4-[1-(3,4-dimethoxyphenoxy)-4-[3-[2-(2-methoxyethoxy)ethyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]butyl]benzonitrile Chemical compound C1N(CCOCCOC)CC(C2)CC1CN2CCCC(C=1C=CC(=CC=1)C#N)OC1=CC=C(OC)C(OC)=C1 AECGJPJPARSSPX-UHFFFAOYSA-N 0.000 description 1
- YACYIVMLKBDBCL-UHFFFAOYSA-N 4-[1-(3,4-dimethoxyphenoxy)-4-[3-[2-(3,4-dimethoxyphenyl)ethyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]butyl]benzonitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN1CC(CN(CCCC(OC=2C=C(OC)C(OC)=CC=2)C=2C=CC(=CC=2)C#N)C2)CC2C1 YACYIVMLKBDBCL-UHFFFAOYSA-N 0.000 description 1
- PGFLPQKUAKHQIJ-UHFFFAOYSA-N 4-[1-[2-[7-[3-(4-acetylpiperazin-1-yl)propyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-2-oxoethyl]-5-(4-cyanophenyl)pyrazol-4-yl]benzonitrile Chemical compound C1CN(C(=O)C)CCN1CCCN1CC(CN(C2)C(=O)CN3C(=C(C=N3)C=3C=CC(=CC=3)C#N)C=3C=CC(=CC=3)C#N)CC2C1 PGFLPQKUAKHQIJ-UHFFFAOYSA-N 0.000 description 1
- XAHHUPRFWZTTLD-UHFFFAOYSA-N 4-[2-(3-butanoyl-3,7-diazabicyclo[3.3.1]nonan-7-yl)ethoxy]benzonitrile Chemical compound C1N(C(=O)CCC)CC(C2)CC1CN2CCOC1=CC=C(C#N)C=C1 XAHHUPRFWZTTLD-UHFFFAOYSA-N 0.000 description 1
- ORCGMDQFKRRQIE-UHFFFAOYSA-N 4-[2-[3-[2-(4-cyanophenyl)-2-hydroxyethyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]-1-hydroxyethyl]benzonitrile Chemical compound C=1C=C(C#N)C=CC=1C(O)CN(C1)CC(C2)CC1CN2CC(O)C1=CC=C(C#N)C=C1 ORCGMDQFKRRQIE-UHFFFAOYSA-N 0.000 description 1
- ONLMCIVYACQOBS-UHFFFAOYSA-N 4-[2-[7-(3-ethylsulfonylpropyl)-3,7-diazabicyclo[3.3.1]nonan-3-yl]ethoxy]benzonitrile Chemical compound C1N(CCCS(=O)(=O)CC)CC(C2)CC1CN2CCOC1=CC=C(C#N)C=C1 ONLMCIVYACQOBS-UHFFFAOYSA-N 0.000 description 1
- AHQLCFNKWBJDLW-UHFFFAOYSA-N 4-[2-[7-(4-oxoheptyl)-3,7-diazabicyclo[3.3.1]nonan-3-yl]ethoxy]benzonitrile Chemical compound C1N(CCCC(=O)CCC)CC(C2)CC1CN2CCOC1=CC=C(C#N)C=C1 AHQLCFNKWBJDLW-UHFFFAOYSA-N 0.000 description 1
- QXXJAHXFUPJEBB-UHFFFAOYSA-N 4-[2-[7-[2-(2-methoxyethoxy)ethyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]ethoxy]benzonitrile Chemical compound C1N(CCOCCOC)CC(C2)CC1CN2CCOC1=CC=C(C#N)C=C1 QXXJAHXFUPJEBB-UHFFFAOYSA-N 0.000 description 1
- FQJFQMDKQAAUDR-UHFFFAOYSA-N 4-[2-[7-[2-(3,4-dimethoxyphenyl)ethyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]ethoxy]benzonitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN1CC(CN(CCOC=2C=CC(=CC=2)C#N)C2)CC2C1 FQJFQMDKQAAUDR-UHFFFAOYSA-N 0.000 description 1
- FMDUXHXWOYNHTM-UHFFFAOYSA-N 4-[2-[7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]acetyl]benzonitrile Chemical compound C1C(CN(CC(=O)C=2C=CC(=CC=2)C#N)C2)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 FMDUXHXWOYNHTM-UHFFFAOYSA-N 0.000 description 1
- ZPOXBYYAPVPBMC-UHFFFAOYSA-N 4-[2-hydroxy-3-[3-(1-methylimidazol-4-yl)sulfonyl-3,7-diazabicyclo[3.3.1]nonan-7-yl]propoxy]benzonitrile Chemical compound CN1C=NC(S(=O)(=O)N2CC3CC(CN(CC(O)COC=4C=CC(=CC=4)C#N)C3)C2)=C1 ZPOXBYYAPVPBMC-UHFFFAOYSA-N 0.000 description 1
- WFKFXRSNQNOXRK-UHFFFAOYSA-N 4-[2-hydroxy-3-[3-(1-methyltetrazol-5-yl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propoxy]benzonitrile Chemical compound CN1N=NN=C1N1CC(CN(CC(O)COC=2C=CC(=CC=2)C#N)C2)CC2C1 WFKFXRSNQNOXRK-UHFFFAOYSA-N 0.000 description 1
- YDXMICMAZYUOIJ-UHFFFAOYSA-N 4-[2-hydroxy-3-[3-(2,2,2-trifluoroacetyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propoxy]benzonitrile Chemical compound C1C(CN(C2)C(=O)C(F)(F)F)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 YDXMICMAZYUOIJ-UHFFFAOYSA-N 0.000 description 1
- BXMIRCDWVIPXDA-UHFFFAOYSA-N 4-[2-hydroxy-3-[3-(2-methyltetrazol-5-yl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propoxy]benzonitrile Chemical compound CN1N=NC(N2CC3CC(CN(CC(O)COC=4C=CC(=CC=4)C#N)C3)C2)=N1 BXMIRCDWVIPXDA-UHFFFAOYSA-N 0.000 description 1
- FUJTXANDMPRVFG-UHFFFAOYSA-N 4-[2-hydroxy-3-[3-(2-oxobutyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propoxy]benzonitrile Chemical compound C1N(CC(=O)CC)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 FUJTXANDMPRVFG-UHFFFAOYSA-N 0.000 description 1
- KEMVKWUDFMGCQB-UHFFFAOYSA-N 4-[2-hydroxy-3-[3-(4-methylthiadiazole-5-carbonyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propoxy]benzonitrile Chemical compound N1=NSC(C(=O)N2CC3CC(CN(CC(O)COC=4C=CC(=CC=4)C#N)C3)C2)=C1C KEMVKWUDFMGCQB-UHFFFAOYSA-N 0.000 description 1
- RBVHDTDFIYCQBW-UHFFFAOYSA-N 4-[2-hydroxy-3-[3-(5-methyl-1,2-oxazole-3-carbonyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propoxy]benzonitrile Chemical compound O1C(C)=CC(C(=O)N2CC3CC(CN(CC(O)COC=4C=CC(=CC=4)C#N)C3)C2)=N1 RBVHDTDFIYCQBW-UHFFFAOYSA-N 0.000 description 1
- OBKQMBFKRRSORV-UHFFFAOYSA-N 4-[2-hydroxy-3-[3-(5-pyridin-2-ylthiophen-2-yl)sulfonyl-3,7-diazabicyclo[3.3.1]nonan-7-yl]propoxy]benzonitrile Chemical compound C1C(CN(C2)S(=O)(=O)C=3SC(=CC=3)C=3N=CC=CC=3)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 OBKQMBFKRRSORV-UHFFFAOYSA-N 0.000 description 1
- VGMLEJRBLWDQLE-UHFFFAOYSA-N 4-[2-hydroxy-3-[3-(trifluoromethylsulfonyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propoxy]benzonitrile Chemical compound C1C(CN(C2)S(=O)(=O)C(F)(F)F)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 VGMLEJRBLWDQLE-UHFFFAOYSA-N 0.000 description 1
- VZEDRNLJNMUOBX-UHFFFAOYSA-N 4-[2-hydroxy-3-[7-[(2-oxo-1,3-oxazolidin-4-yl)methyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]propoxy]benzonitrile Chemical compound C1C(CN(CC2NC(=O)OC2)C2)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 VZEDRNLJNMUOBX-UHFFFAOYSA-N 0.000 description 1
- QEOXIERVQYVWSF-UHFFFAOYSA-N 4-[2-hydroxy-3-[7-[2-(2-methoxyethoxy)ethyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]propoxy]benzonitrile Chemical compound C1N(CCOCCOC)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 QEOXIERVQYVWSF-UHFFFAOYSA-N 0.000 description 1
- DLQGGZNCJPLPQJ-UHFFFAOYSA-N 4-[3-(3,7-diazabicyclo[3.3.1]nonan-3-yl)-2-hydroxypropoxy]benzonitrile Chemical compound C1C(C2)CNCC2CN1CC(O)COC1=CC=C(C#N)C=C1 DLQGGZNCJPLPQJ-UHFFFAOYSA-N 0.000 description 1
- RTAYLFCDYMAOTB-UHFFFAOYSA-N 4-[3-(3-butanoyl-3,7-diazabicyclo[3.3.1]nonan-7-yl)-2-hydroxypropoxy]benzonitrile Chemical compound C1N(C(=O)CCC)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 RTAYLFCDYMAOTB-UHFFFAOYSA-N 0.000 description 1
- OCYIYDRUDMBLRK-UHFFFAOYSA-N 4-[3-(3-ethylsulfonyl-3,7-diazabicyclo[3.3.1]nonan-7-yl)-2-hydroxypropoxy]benzonitrile Chemical compound C1N(S(=O)(=O)CC)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 OCYIYDRUDMBLRK-UHFFFAOYSA-N 0.000 description 1
- LMMLGLJVLZVFRD-UHFFFAOYSA-N 4-[3-[3-(1,3-dimethyl-2,6-dioxopyrimidin-4-yl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]-2-hydroxypropoxy]benzonitrile Chemical compound O=C1N(C)C(=O)N(C)C(N2CC3CC(CN(CC(O)COC=4C=CC(=CC=4)C#N)C3)C2)=C1 LMMLGLJVLZVFRD-UHFFFAOYSA-N 0.000 description 1
- MXHOKGUVHGCADI-UHFFFAOYSA-N 4-[3-[3-(1,3-thiazol-2-yl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylamino]benzonitrile Chemical compound C1=CC(C#N)=CC=C1NCCCN1CC(CN(C2)C=3SC=CN=3)CC2C1 MXHOKGUVHGCADI-UHFFFAOYSA-N 0.000 description 1
- JQQFOMNBKMZXSY-UHFFFAOYSA-N 4-[3-[3-(1,3-thiazol-2-yl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylsulfonyl]benzonitrile Chemical compound C=1C=C(C#N)C=CC=1S(=O)(=O)CCCN(C1)CC(C2)CC1CN2C1=NC=CS1 JQQFOMNBKMZXSY-UHFFFAOYSA-N 0.000 description 1
- IZZCCSQLKSTHEW-UHFFFAOYSA-N 4-[3-[3-(1-cyanoethyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C1N(C(C#N)C)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 IZZCCSQLKSTHEW-UHFFFAOYSA-N 0.000 description 1
- VHDPCZNZAQIYTJ-UHFFFAOYSA-N 4-[3-[3-(3,3-dimethyl-2-oxobutyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylamino]benzonitrile Chemical compound C1N(CC(=O)C(C)(C)C)CC(C2)CC1CN2CCCNC1=CC=C(C#N)C=C1 VHDPCZNZAQIYTJ-UHFFFAOYSA-N 0.000 description 1
- IRZXIFQGYBTKIT-UHFFFAOYSA-N 4-[3-[3-(3,3-dimethylbutanoyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C1N(C(=O)CC(C)(C)C)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 IRZXIFQGYBTKIT-UHFFFAOYSA-N 0.000 description 1
- VAZIGMDQIHTWCF-UHFFFAOYSA-N 4-[3-[3-(3,5-dimethyl-1,2-oxazole-4-carbonyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]-2-hydroxypropoxy]benzonitrile Chemical compound CC1=NOC(C)=C1C(=O)N1CC(CN(CC(O)COC=2C=CC(=CC=2)C#N)C2)CC2C1 VAZIGMDQIHTWCF-UHFFFAOYSA-N 0.000 description 1
- NTCHQLDNRILTIV-UHFFFAOYSA-N 4-[3-[3-(3-aminobutanoyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C1N(C(=O)CC(N)C)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 NTCHQLDNRILTIV-UHFFFAOYSA-N 0.000 description 1
- ZWBNOGVQYVHHOD-UHFFFAOYSA-N 4-[3-[3-(3-ethylsulfonylpropyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylamino]benzonitrile Chemical compound C1N(CCCS(=O)(=O)CC)CC(C2)CC1CN2CCCNC1=CC=C(C#N)C=C1 ZWBNOGVQYVHHOD-UHFFFAOYSA-N 0.000 description 1
- KIWJOTSJUROCRK-UHFFFAOYSA-N 4-[3-[3-(5-amino-1h-1,2,4-triazol-3-yl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]-2-hydroxypropoxy]benzonitrile Chemical compound NC1=NNC(N2CC3CC(CN(CC(O)COC=4C=CC(=CC=4)C#N)C3)C2)=N1 KIWJOTSJUROCRK-UHFFFAOYSA-N 0.000 description 1
- RBHOSXMTMCYDMP-UHFFFAOYSA-N 4-[3-[3-(cyclopropylmethyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylamino]benzonitrile Chemical compound C1=CC(C#N)=CC=C1NCCCN1CC(CN(CC2CC2)C2)CC2C1 RBHOSXMTMCYDMP-UHFFFAOYSA-N 0.000 description 1
- XZLMANLYUNRIME-UHFFFAOYSA-N 4-[3-[3-(cyclopropylmethyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylsulfonyl]benzonitrile Chemical compound C=1C=C(C#N)C=CC=1S(=O)(=O)CCCN(C1)CC(C2)CC1CN2CC1CC1 XZLMANLYUNRIME-UHFFFAOYSA-N 0.000 description 1
- WKSIROOSLVKOPH-UHFFFAOYSA-N 4-[3-[3-[(4-fluorophenyl)methyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylamino]benzonitrile Chemical compound C1=CC(F)=CC=C1CN1CC(CN(CCCNC=2C=CC(=CC=2)C#N)C2)CC2C1 WKSIROOSLVKOPH-UHFFFAOYSA-N 0.000 description 1
- WKGBFMGQJOASIO-UHFFFAOYSA-N 4-[3-[3-[(4-fluorophenyl)methyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylsulfonyl]benzonitrile Chemical compound C1=CC(F)=CC=C1CN1CC(CN(CCCS(=O)(=O)C=2C=CC(=CC=2)C#N)C2)CC2C1 WKGBFMGQJOASIO-UHFFFAOYSA-N 0.000 description 1
- YOLNYNZVGWJPTJ-UHFFFAOYSA-N 4-[3-[3-[2-(2-methoxyethoxy)ethyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylamino]benzonitrile Chemical compound C1N(CCOCCOC)CC(C2)CC1CN2CCCNC1=CC=C(C#N)C=C1 YOLNYNZVGWJPTJ-UHFFFAOYSA-N 0.000 description 1
- AUANMKCODDURAQ-UHFFFAOYSA-N 4-[3-[3-[2-(2-methoxyethoxy)ethyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylsulfonyl]benzonitrile Chemical compound C1N(CCOCCOC)CC(C2)CC1CN2CCCS(=O)(=O)C1=CC=C(C#N)C=C1 AUANMKCODDURAQ-UHFFFAOYSA-N 0.000 description 1
- GIBFTAWRZKCULJ-UHFFFAOYSA-N 4-[3-[3-[2-(3,4-dimethoxyphenyl)ethyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylamino]benzonitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN1CC(CN(CCCNC=2C=CC(=CC=2)C#N)C2)CC2C1 GIBFTAWRZKCULJ-UHFFFAOYSA-N 0.000 description 1
- CRZUARZDYOTXTI-UHFFFAOYSA-N 4-[3-[3-[2-(3,4-dimethoxyphenyl)ethyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylsulfonyl]benzonitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN1CC(CN(CCCS(=O)(=O)C=2C=CC(=CC=2)C#N)C2)CC2C1 CRZUARZDYOTXTI-UHFFFAOYSA-N 0.000 description 1
- FYLUJQXZSJAFEO-UHFFFAOYSA-N 4-[3-[3-[3-(4-acetylpiperazin-1-yl)propyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylamino]benzonitrile Chemical compound C1CN(C(=O)C)CCN1CCCN1CC(CN(CCCNC=2C=CC(=CC=2)C#N)C2)CC2C1 FYLUJQXZSJAFEO-UHFFFAOYSA-N 0.000 description 1
- APSSASZESPLXTH-UHFFFAOYSA-N 4-[3-[3-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C1C(CN(CC(O)COC=2C=CC(=CC=2)C#N)C2)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 APSSASZESPLXTH-UHFFFAOYSA-N 0.000 description 1
- PTGGDXZVEILOCU-UHFFFAOYSA-N 4-[3-[3-[3-(4-cyanophenoxy)-2-hydroxypropyl]-9,9-bis(propylsulfanyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C1C(CN(CC(O)COC=2C=CC(=CC=2)C#N)C2)C(SCCC)(SCCC)C2CN1CC(O)COC1=CC=C(C#N)C=C1 PTGGDXZVEILOCU-UHFFFAOYSA-N 0.000 description 1
- PRXHVVWDDJHUFU-UHFFFAOYSA-N 4-[3-[7-(3-ethylsulfonylpropyl)-3,7-diazabicyclo[3.3.1]nonan-3-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C1N(CCCS(=O)(=O)CC)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 PRXHVVWDDJHUFU-UHFFFAOYSA-N 0.000 description 1
- HLWWKRLQCRCERA-UHFFFAOYSA-N 4-[3-[7-(cyclopropylmethyl)-3,7-diazabicyclo[3.3.1]nonan-3-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C1C(CN(CC2CC2)C2)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 HLWWKRLQCRCERA-UHFFFAOYSA-N 0.000 description 1
- AVOFRCCGINYEEJ-UHFFFAOYSA-N 4-[3-[7-[(4-fluorophenyl)methyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C1C(CN(CC=2C=CC(F)=CC=2)C2)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 AVOFRCCGINYEEJ-UHFFFAOYSA-N 0.000 description 1
- UXRVIUGAYSKMSK-UHFFFAOYSA-N 4-[3-[7-[2-(3,4-dimethoxyphenyl)ethyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN1CC(CN(CC(O)COC=2C=CC(=CC=2)C#N)C2)CC2C1 UXRVIUGAYSKMSK-UHFFFAOYSA-N 0.000 description 1
- OBSZZBGWASPXGZ-UHFFFAOYSA-N 4-[3-[7-[3-(4-acetylpiperazin-1-yl)propyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C1CN(C(=O)C)CCN1CCCN1CC(CN(CC(O)COC=2C=CC(=CC=2)C#N)C2)CC2C1 OBSZZBGWASPXGZ-UHFFFAOYSA-N 0.000 description 1
- XVUKAFQFXSHXFM-UHFFFAOYSA-N 4-[3-[7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-2,5-dioxa-7,11-diazatricyclo[7.3.1.01,6]tridecan-11-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C1C(C2)CN(CC(O)COC=3C=CC(=CC=3)C#N)C3OCCOC32CN1CC(O)COC1=CC=C(C#N)C=C1 XVUKAFQFXSHXFM-UHFFFAOYSA-N 0.000 description 1
- WDRHATNZZPPJGU-UHFFFAOYSA-N 4-[3-amino-4-(3-butylsulfonyl-3,7-diazabicyclo[3.3.1]nonan-7-yl)butoxy]benzonitrile Chemical compound C1N(S(=O)(=O)CCCC)CC(C2)CC1CN2CC(N)CCOC1=CC=C(C#N)C=C1 WDRHATNZZPPJGU-UHFFFAOYSA-N 0.000 description 1
- NQTGAODGLMLOFS-UHFFFAOYSA-N 4-[4-(3-butanoyl-3,7-diazabicyclo[3.3.1]nonan-7-yl)-1-(3,4-dimethoxyphenoxy)butyl]benzonitrile Chemical compound C1N(C(=O)CCC)CC(C2)CC1CN2CCCC(C=1C=CC(=CC=1)C#N)OC1=CC=C(OC)C(OC)=C1 NQTGAODGLMLOFS-UHFFFAOYSA-N 0.000 description 1
- AEUZIZVNUSJXDQ-UHFFFAOYSA-N 4-[4-(3-butanoyl-3,7-diazabicyclo[3.3.1]nonan-7-yl)butyl]benzonitrile Chemical compound C1N(C(=O)CCC)CC(C2)CC1CN2CCCCC1=CC=C(C#N)C=C1 AEUZIZVNUSJXDQ-UHFFFAOYSA-N 0.000 description 1
- QDJGPGHGOVUSAK-UHFFFAOYSA-N 4-[4-(3-butylsulfonyl-3,7-diazabicyclo[3.3.1]nonan-7-yl)-1-(3,4-dimethoxyphenoxy)butyl]benzonitrile Chemical compound C1N(S(=O)(=O)CCCC)CC(C2)CC1CN2CCCC(C=1C=CC(=CC=1)C#N)OC1=CC=C(OC)C(OC)=C1 QDJGPGHGOVUSAK-UHFFFAOYSA-N 0.000 description 1
- AWVZURFBIKMYEF-UHFFFAOYSA-N 4-[4-[3-(3,3-dimethyl-2-oxobutyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]butyl]benzonitrile Chemical compound C1N(CC(=O)C(C)(C)C)CC(C2)CC1CN2CCCCC1=CC=C(C#N)C=C1 AWVZURFBIKMYEF-UHFFFAOYSA-N 0.000 description 1
- RUHANCNSPGUWMU-UHFFFAOYSA-N 4-[4-[3-(cyclopropylmethyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]-1-(3,4-dimethoxyphenoxy)butyl]benzonitrile Chemical compound C1=C(OC)C(OC)=CC=C1OC(C=1C=CC(=CC=1)C#N)CCCN1CC(CN(CC2CC2)C2)CC2C1 RUHANCNSPGUWMU-UHFFFAOYSA-N 0.000 description 1
- JQPZVIHCDHLRQB-UHFFFAOYSA-N 4-[4-[3-[2-(3,4-dimethoxyphenyl)ethyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]butyl]benzonitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN1CC(CN(CCCCC=2C=CC(=CC=2)C#N)C2)CC2C1 JQPZVIHCDHLRQB-UHFFFAOYSA-N 0.000 description 1
- JMOKMGSDMUYZDX-UHFFFAOYSA-N 4-[5-(4-cyanophenyl)-1-[2-[7-(3-ethylsulfonylpropyl)-3,7-diazabicyclo[3.3.1]nonan-3-yl]-2-oxoethyl]pyrazol-4-yl]benzonitrile Chemical compound C1N(CCCS(=O)(=O)CC)CC(C2)CC1CN2C(=O)CN1N=CC(C=2C=CC(=CC=2)C#N)=C1C1=CC=C(C#N)C=C1 JMOKMGSDMUYZDX-UHFFFAOYSA-N 0.000 description 1
- HJWGLMDYFGRTGV-UHFFFAOYSA-N 4-[5-(4-cyanophenyl)-1-[2-[7-[2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-oxoethyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-2-oxoethyl]pyrazol-4-yl]benzonitrile Chemical compound C1C(CN(CC(=O)C=2C=C3OCCOC3=CC=2)C2)CC2CN1C(=O)CN1N=CC(C=2C=CC(=CC=2)C#N)=C1C1=CC=C(C#N)C=C1 HJWGLMDYFGRTGV-UHFFFAOYSA-N 0.000 description 1
- QVRPFPZKEYSWAC-UHFFFAOYSA-N 4-[5-(4-cyanophenyl)-1-[2-[7-[2-(2-methoxyethoxy)ethyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-2-oxoethyl]pyrazol-4-yl]benzonitrile Chemical compound C1N(CCOCCOC)CC(C2)CC1CN2C(=O)CN1N=CC(C=2C=CC(=CC=2)C#N)=C1C1=CC=C(C#N)C=C1 QVRPFPZKEYSWAC-UHFFFAOYSA-N 0.000 description 1
- XUQLERHVTAWOBQ-UHFFFAOYSA-N 4-[5-(4-cyanophenyl)-1-[2-[7-[2-(3,4-dimethoxyphenyl)ethyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-2-oxoethyl]pyrazol-4-yl]benzonitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN1CC(CN(C2)C(=O)CN3C(=C(C=N3)C=3C=CC(=CC=3)C#N)C=3C=CC(=CC=3)C#N)CC2C1 XUQLERHVTAWOBQ-UHFFFAOYSA-N 0.000 description 1
- JPPHUEREEZVSKS-UHFFFAOYSA-N 4-[5-(4-cyanophenyl)-1-[2-oxo-2-[7-(4-oxoheptyl)-3,7-diazabicyclo[3.3.1]nonan-3-yl]ethyl]pyrazol-4-yl]benzonitrile Chemical compound C1N(CCCC(=O)CCC)CC(C2)CC1CN2C(=O)CN1N=CC(C=2C=CC(=CC=2)C#N)=C1C1=CC=C(C#N)C=C1 JPPHUEREEZVSKS-UHFFFAOYSA-N 0.000 description 1
- YPXAUBNRIJAKHB-UHFFFAOYSA-N 4-[7-[2-(3,4-dimethoxyphenyl)ethyl]-3,7-diazabicyclo[3.3.1]nonane-3-carbonyl]benzonitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN1CC(CN(C2)C(=O)C=3C=CC(=CC=3)C#N)CC2C1 YPXAUBNRIJAKHB-UHFFFAOYSA-N 0.000 description 1
- HQLKKNZDGZUVOT-UHFFFAOYSA-N 4-[[7-(4-oxoheptyl)-3,7-diazabicyclo[3.3.1]nonan-3-yl]sulfonyl]benzonitrile Chemical compound C1N(CCCC(=O)CCC)CC(C2)CC1CN2S(=O)(=O)C1=CC=C(C#N)C=C1 HQLKKNZDGZUVOT-UHFFFAOYSA-N 0.000 description 1
- DMAYBPBPEUFIHJ-UHFFFAOYSA-N 4-bromobut-1-ene Chemical compound BrCCC=C DMAYBPBPEUFIHJ-UHFFFAOYSA-N 0.000 description 1
- BTJIUGUIPKRLHP-UHFFFAOYSA-M 4-nitrophenolate Chemical compound [O-]C1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-M 0.000 description 1
- LHFKPWNSSDDNFE-UHFFFAOYSA-N 7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-n,n-dimethyl-3,7-diazabicyclo[3.3.1]nonane-3-sulfonamide Chemical compound C1N(S(=O)(=O)N(C)C)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 LHFKPWNSSDDNFE-UHFFFAOYSA-N 0.000 description 1
- CGFWWSKNMUPDGW-UHFFFAOYSA-N 7-benzyl-3,7-diazabicyclo[3.3.1]nonane-3-carbonitrile Chemical compound C1N(C#N)CC(C2)CC1CN2CC1=CC=CC=C1 CGFWWSKNMUPDGW-UHFFFAOYSA-N 0.000 description 1
- NDQFHDJESHWKGW-UHFFFAOYSA-N 7-benzyl-3-(2-ethyltetrazol-5-yl)-3,7-diazabicyclo[3.3.1]nonane Chemical compound CCN1N=NC(N2CC3CC(CN(CC=4C=CC=CC=4)C3)C2)=N1 NDQFHDJESHWKGW-UHFFFAOYSA-N 0.000 description 1
- 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 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 101100515516 Arabidopsis thaliana XI-H gene Proteins 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- PEBLRZIQHMTHDQ-UHFFFAOYSA-N C(#N)C1=CC=C(C=C1)O.C(CC=C)OC1=CC=C(C#N)C=C1 Chemical compound C(#N)C1=CC=C(C=C1)O.C(CC=C)OC1=CC=C(C#N)C=C1 PEBLRZIQHMTHDQ-UHFFFAOYSA-N 0.000 description 1
- PZCUTTWXEBEJHE-UHFFFAOYSA-N C(C1=CC=CC=C1)N1CC2CNCC(C1)C2.C(C2=CC=CC=C2)N2CC1CN(CC(C2)C1)C#N Chemical compound C(C1=CC=CC=C1)N1CC2CNCC(C1)C2.C(C2=CC=CC=C2)N2CC1CN(CC(C2)C1)C#N PZCUTTWXEBEJHE-UHFFFAOYSA-N 0.000 description 1
- WSLDEIGMSAAKRK-UHFFFAOYSA-N C(CC=C)OC1=CC=C(C#N)C=C1.O1C(C1)CCOC1=CC=C(C#N)C=C1 Chemical compound C(CC=C)OC1=CC=C(C#N)C=C1.O1C(C1)CCOC1=CC=C(C#N)C=C1 WSLDEIGMSAAKRK-UHFFFAOYSA-N 0.000 description 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 239000002879 Lewis base Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 101100021974 Mus musculus Ltk gene Proteins 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- BZORFPDSXLZWJF-UHFFFAOYSA-N N,N-dimethyl-1,4-phenylenediamine Chemical compound CN(C)C1=CC=C(N)C=C1 BZORFPDSXLZWJF-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- IQCKJAHILNOFPY-UHFFFAOYSA-N O1C(C1)CCOC1=CC=C(C#N)C=C1.NCC(CCOC1=CC=C(C#N)C=C1)O Chemical compound O1C(C1)CCOC1=CC=C(C#N)C=C1.NCC(CCOC1=CC=C(C#N)C=C1)O IQCKJAHILNOFPY-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000004257 Potassium Channel Human genes 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical class [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- IBUGLHHGZLMWBM-UHFFFAOYSA-N [N].C1NCC2CNCC1C2 Chemical compound [N].C1NCC2CNCC1C2 IBUGLHHGZLMWBM-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 1
- 125000005037 alkyl phenyl group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229950005516 ambasilide Drugs 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000001949 anaesthesia Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- UFXKXBXIKWAQKP-UHFFFAOYSA-N bicyclo[3.3.1]nonane-3-carboxamide Chemical compound C1CCC2CC(C(=O)N)CC1C2 UFXKXBXIKWAQKP-UHFFFAOYSA-N 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- PMCPYLGCPSNSLS-FOLVSLTJSA-N bisaramil Chemical compound CCN1C[C@@H]2CN(C)C[C@H](C1)[C@@H]2OC(=O)C1=CC=C(Cl)C=C1 PMCPYLGCPSNSLS-FOLVSLTJSA-N 0.000 description 1
- 229950007885 bisaramil Drugs 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
- 208000006218 bradycardia Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 230000011128 cardiac conduction Effects 0.000 description 1
- 238000007675 cardiac surgery Methods 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- 230000003205 diastolic effect Effects 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 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 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 229960002994 dofetilide Drugs 0.000 description 1
- IXTMWRCNAAVVAI-UHFFFAOYSA-N dofetilide Chemical compound C=1C=C(NS(C)(=O)=O)C=CC=1CCN(C)CCOC1=CC=C(NS(C)(=O)=O)C=C1 IXTMWRCNAAVVAI-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
- 230000001435 haemodynamic effect Effects 0.000 description 1
- 125000005059 halophenyl group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 210000005246 left atrium Anatomy 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- YNTOKMNHRPSGFU-UHFFFAOYSA-N n-Propyl carbamate Chemical compound CCCOC(N)=O YNTOKMNHRPSGFU-UHFFFAOYSA-N 0.000 description 1
- HZOAWRSTMMODKP-UHFFFAOYSA-N n-[4-[[3-[[4-(methanesulfonamido)phenyl]methyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]methyl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1CN1CC(CN(CC=2C=CC(NS(C)(=O)=O)=CC=2)C2)CC2C1 HZOAWRSTMMODKP-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 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
- 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
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 239000002953 phosphate buffered saline 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
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 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
- 125000004497 pyrazol-5-yl group Chemical group N1N=CC=C1* 0.000 description 1
- 125000000719 pyrrolidinyl 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
- 239000000376 reactant Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 238000004007 reversed phase HPLC Methods 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
- 229910000029 sodium carbonate 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
- 241000894007 species Species 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
- 238000010998 test method Methods 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl 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
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation 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
- 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
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 (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0002603-9 | 2000-07-07 | ||
| SE0002603A SE0002603D0 (sv) | 2000-07-07 | 2000-07-07 | New compounds |
| SE0002788-8 | 2000-07-27 | ||
| 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 |
|---|---|
| CA2412848A1 true CA2412848A1 (en) | 2002-01-17 |
Family
ID=26655177
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002412848A Abandoned CA2412848A1 (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 |
| 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 |
| SK42003A3 (en) | 2003-07-01 |
| AR030302A1 (es) | 2003-08-20 |
| RU2002134450A (ru) | 2004-07-10 |
| IS6660A (is) | 2002-12-19 |
| NO20030057L (no) | 2003-01-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1360187B1 (en) | 3,7-diazabicyclo(3.3.0)octanes and their use in the treatment of cardiac arrhythmias | |
| US20040039199A1 (en) | Oxabispidine compound useful in the treatment of cardiac arrhythmias | |
| US7012074B2 (en) | 3,8-Diazabicyclo[3.2.1]octanes and their use in the treatment of cardiac arrhythmias | |
| CA2412848A1 (en) | New bispidine compounds and their use in the treatment of cardiac arrhythmias | |
| US20030212095A1 (en) | New bispidine compounds and their use in the treatment of cardiac arrhythmias | |
| AU761576B2 (en) | New bispidine compounds useful in the treatment of cardiac arrhythmias | |
| EP1192154B1 (en) | Bispidine compounds useful in the treatment of cardiac arrhythmias | |
| US20040229900A1 (en) | Bispidine compounds useful in the treatment of cardiac arrythmias | |
| EP1192156B1 (en) | Bispidine compounds useful in the treatment of cardiac arrhythmias | |
| EP1192155B1 (en) | New bispidine compounds useful in the treatment of cardiac arrhythmias | |
| AU2002226854A1 (en) | 3,7-diazabicyclo[3.30]octanes and their use in the treatment of cardiac arrhythmias |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |