HUP0301304A2 - Új biszpidinvegyületek és felhasználásuk szívritmuszavarok kezelésére és ezeket tartalmazó gyógyszerkészítmények - Google Patents

Info

Publication number

HUP0301304A2

HUP0301304A2 HU0301304A HUP0301304A HUP0301304A2 HU P0301304 A2 HUP0301304 A2 HU P0301304A2 HU 0301304 A HU0301304 A HU 0301304A HU P0301304 A HUP0301304 A HU P0301304A HU P0301304 A2 HUP0301304 A2 HU P0301304A2

Authority

HU

Hungary

Prior art keywords

group

formula

compounds

alkyl

hydrogen atom

Prior art date

2000-07-07

Links

• Espacenet
• Global Dossier
• Discuss

• PTPQJKANBKHDPM-UHFFFAOYSA-N 3,7-diazabicyclo[3.3.1]nonane Chemical class C1NCC2CNCC1C2 PTPQJKANBKHDPM-UHFFFAOYSA-N 0.000 title claims abstract description 21
• 238000002360 preparation method Methods 0.000 title claims description 61
• 238000000034 method Methods 0.000 title claims description 39
• 206010003119 arrhythmia Diseases 0.000 title claims description 18
• 230000008569 process Effects 0.000 title claims description 15
• 150000001875 compounds Chemical class 0.000 claims abstract description 403
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 159
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 127
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 95
• 125000002947 alkylene group Chemical group 0.000 claims abstract description 76
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 55
• 150000002367 halogens Chemical class 0.000 claims abstract description 44
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 43
• -1 nitro- Chemical class 0.000 claims abstract description 40
• 238000004519 manufacturing process Methods 0.000 claims abstract 3
• 125000003118 aryl group Chemical group 0.000 claims description 77
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 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 67
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 64
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 44
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 42
• 125000001424 substituent group Chemical group 0.000 claims description 42
• 239000001257 hydrogen Substances 0.000 claims description 27
• 229910052739 hydrogen Inorganic materials 0.000 claims description 27
• 229910052757 nitrogen Inorganic materials 0.000 claims description 25
• 229910052799 carbon Inorganic materials 0.000 claims description 22
• 230000002829 reductive effect Effects 0.000 claims description 21
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
• 125000005843 halogen group Chemical group 0.000 claims description 16
• 125000004429 atom Chemical group 0.000 claims description 15
• 239000003814 drug Substances 0.000 claims description 15
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 13
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
• 125000003545 alkoxy group Chemical group 0.000 claims description 12
• 150000001721 carbon Chemical group 0.000 claims description 11
• MNLAVFKVRUQAKW-UHFFFAOYSA-N VR nerve agent Chemical compound CCN(CC)CCSP(C)(=O)OCC(C)C MNLAVFKVRUQAKW-UHFFFAOYSA-N 0.000 claims description 8
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
• 230000006793 arrhythmia Effects 0.000 claims description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
• 239000003795 chemical substances by application Substances 0.000 claims description 6
• 125000000623 heterocyclic group Chemical group 0.000 claims description 6
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
• 239000007800 oxidant agent Substances 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• 239000001301 oxygen Substances 0.000 claims description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 230000002265 prevention Effects 0.000 claims description 5
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
• 230000002861 ventricular Effects 0.000 claims description 4
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 3
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
• IVRMZWNICZWHMI-UHFFFAOYSA-N Azide Chemical compound [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 claims description 3
• 206010047281 Ventricular arrhythmia Diseases 0.000 claims description 3
• 239000004480 active ingredient Substances 0.000 claims description 3
• 125000001624 naphthyl group Chemical group 0.000 claims description 3
• 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 2
• 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
• 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 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
• 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 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
• 206010003130 Arrhythmia supraventricular Diseases 0.000 claims description 2
• YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 claims description 2
• 239000002671 adjuvant Substances 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
• 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 description 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
• 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 2
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
• 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 75
• 238000006243 chemical reaction Methods 0.000 description 56
• 239000000203 mixture Substances 0.000 description 52
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
• 239000000243 solution Substances 0.000 description 26
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
• 239000003960 organic solvent Substances 0.000 description 23
• 239000011541 reaction mixture Substances 0.000 description 23
• 239000002904 solvent Substances 0.000 description 23
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
• 238000010992 reflux Methods 0.000 description 16
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
• 239000002585 base Substances 0.000 description 13
• HQMRIBYCTLBDAK-UHFFFAOYSA-M bis(2-methylpropyl)alumanylium;chloride Chemical compound CC(C)C[Al](Cl)CC(C)C HQMRIBYCTLBDAK-UHFFFAOYSA-M 0.000 description 13
• 230000000694 effects Effects 0.000 description 13
• 229910000027 potassium carbonate Inorganic materials 0.000 description 13
• 241001465754 Metazoa Species 0.000 description 12
• 125000003277 amino group Chemical group 0.000 description 12
• 239000003054 catalyst Substances 0.000 description 12
• 238000012360 testing method Methods 0.000 description 12
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 11
• 210000004027 cell Anatomy 0.000 description 10
• 239000003638 chemical reducing agent Substances 0.000 description 10
• 229940079593 drug Drugs 0.000 description 10
• 239000000706 filtrate Substances 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
• 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 9
• 238000004587 chromatography analysis Methods 0.000 description 9
• 229920006395 saturated elastomer Polymers 0.000 description 9
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
• 150000002431 hydrogen Chemical class 0.000 description 8
• 239000000047 product Substances 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• 210000002950 fibroblast Anatomy 0.000 description 7
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• 230000003213 activating effect Effects 0.000 description 6
• 239000003416 antiarrhythmic agent Substances 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 239000003480 eluent Substances 0.000 description 6
• 238000004128 high performance liquid chromatography Methods 0.000 description 6
• 239000000543 intermediate Substances 0.000 description 6
• 230000000144 pharmacologic effect Effects 0.000 description 6
• 150000003839 salts Chemical class 0.000 description 6
• 239000000741 silica gel Substances 0.000 description 6
• 229910002027 silica gel Inorganic materials 0.000 description 6
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
• 230000000747 cardiac effect Effects 0.000 description 5
• 238000007796 conventional method Methods 0.000 description 5
• 238000005859 coupling reaction Methods 0.000 description 5
• 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
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
• 238000002474 experimental method Methods 0.000 description 5
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
• 239000002953 phosphate buffered saline Substances 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 230000009467 reduction Effects 0.000 description 5
• 239000012279 sodium borohydride Substances 0.000 description 5
• 229910000033 sodium borohydride Inorganic materials 0.000 description 5
• 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 4
• VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 4
• 238000004458 analytical method Methods 0.000 description 4
• 239000012298 atmosphere Substances 0.000 description 4
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
• 239000000460 chlorine Substances 0.000 description 4
• 239000007822 coupling agent Substances 0.000 description 4
• 239000003862 glucocorticoid Substances 0.000 description 4
• 210000002216 heart Anatomy 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
• 210000004379 membrane Anatomy 0.000 description 4
• 239000012528 membrane Substances 0.000 description 4
• 150000002829 nitrogen Chemical class 0.000 description 4
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 4
• 230000002336 repolarization Effects 0.000 description 4
• 230000033764 rhythmic process Effects 0.000 description 4
• 125000004434 sulfur atom Chemical group 0.000 description 4
• 238000003786 synthesis reaction Methods 0.000 description 4
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
• 238000004809 thin layer chromatography Methods 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
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
• KAAITWOSDOCHEH-UHFFFAOYSA-N 3-benzyl-3,7-diazabicyclo[3.3.1]nonane Chemical compound C1C(C2)CNCC2CN1CC1=CC=CC=C1 KAAITWOSDOCHEH-UHFFFAOYSA-N 0.000 description 3
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 3
• ICGLPKIVTVWCFT-UHFFFAOYSA-N 4-methylbenzenesulfonohydrazide Chemical compound CC1=CC=C(S(=O)(=O)NN)C=C1 ICGLPKIVTVWCFT-UHFFFAOYSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
• 102000004257 Potassium Channel Human genes 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• 230000015572 biosynthetic process Effects 0.000 description 3
• 230000000903 blocking effect Effects 0.000 description 3
• 229910052794 bromium Inorganic materials 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• 230000008878 coupling Effects 0.000 description 3
• 238000010168 coupling process Methods 0.000 description 3
• 150000002148 esters Chemical class 0.000 description 3
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
• 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• 125000002541 furyl group Chemical group 0.000 description 3
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 3
• 210000004731 jugular vein Anatomy 0.000 description 3
• 239000012280 lithium aluminium hydride Substances 0.000 description 3
• 230000002503 metabolic effect Effects 0.000 description 3
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 3
• 230000003287 optical effect Effects 0.000 description 3
• 150000007524 organic acids Chemical class 0.000 description 3
• 230000001590 oxidative effect Effects 0.000 description 3
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
• 125000004193 piperazinyl group Chemical group 0.000 description 3
• 108020001213 potassium channel Proteins 0.000 description 3
• 239000000651 prodrug Substances 0.000 description 3
• 229940002612 prodrug Drugs 0.000 description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
• 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
• 230000004044 response Effects 0.000 description 3
• 235000017557 sodium bicarbonate Nutrition 0.000 description 3
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
• 238000001228 spectrum Methods 0.000 description 3
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
• 229910052717 sulfur Inorganic materials 0.000 description 3
• 230000009466 transformation Effects 0.000 description 3
• 125000006527 (C1-C5) alkyl group Chemical group 0.000 description 2
• USVVENVKYJZFMW-ONEGZZNKSA-N (e)-carboxyiminocarbamic acid Chemical class OC(=O)\N=N\C(O)=O USVVENVKYJZFMW-ONEGZZNKSA-N 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
• ZQTRICNUAXVYPU-UHFFFAOYSA-N 4-(4-amino-3-hydroxybutoxy)benzonitrile Chemical compound NCC(O)CCOC1=CC=C(C#N)C=C1 ZQTRICNUAXVYPU-UHFFFAOYSA-N 0.000 description 2
• XZGQQCFEIDXEAI-UHFFFAOYSA-N 4-[2-(oxiran-2-yl)ethoxy]benzonitrile Chemical compound C1=CC(C#N)=CC=C1OCCC1OC1 XZGQQCFEIDXEAI-UHFFFAOYSA-N 0.000 description 2
• KRTAVQKUTUYWGI-UHFFFAOYSA-N 4-but-3-enoxybenzonitrile Chemical compound C=CCCOC1=CC=C(C#N)C=C1 KRTAVQKUTUYWGI-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 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 2
• 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
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• WMVNIYRHPVLSHQ-UHFFFAOYSA-N C(C1=CC=CC=C1)N(CC(C1)C2)CC1CN2C1=NNN=N1.N Chemical compound C(C1=CC=CC=C1)N(CC(C1)C2)CC1CN2C1=NNN=N1.N WMVNIYRHPVLSHQ-UHFFFAOYSA-N 0.000 description 2
• 241000700198 Cavia Species 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• 238000006751 Mitsunobu reaction Methods 0.000 description 2
• 150000001204 N-oxides Chemical class 0.000 description 2
• ACFIXJIJDZMPPO-NNYOXOHSSA-N NADPH Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• OSEYODNHHAWAMK-UHFFFAOYSA-N [4-(4-cyanophenoxy)-1-[(2-methylpropan-2-yl)oxycarbonylamino]butan-2-yl] methanesulfonate Chemical compound CC(C)(C)OC(=O)NCC(OS(C)(=O)=O)CCOC1=CC=C(C#N)C=C1 OSEYODNHHAWAMK-UHFFFAOYSA-N 0.000 description 2
• 238000010521 absorption reaction Methods 0.000 description 2
• 239000002253 acid Substances 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 230000036982 action potential Effects 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 230000002411 adverse Effects 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 235000019270 ammonium chloride Nutrition 0.000 description 2
• 235000011114 ammonium hydroxide Nutrition 0.000 description 2
• 230000001746 atrial effect 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
• 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
• 210000001715 carotid artery Anatomy 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 230000001186 cumulative effect Effects 0.000 description 2
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
• MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical class Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 238000001640 fractional crystallisation Methods 0.000 description 2
• 239000007789 gas Substances 0.000 description 2
• 208000019622 heart disease Diseases 0.000 description 2
• 125000005842 heteroatom Chemical group 0.000 description 2
• 125000002883 imidazolyl group Chemical group 0.000 description 2
• 239000012442 inert solvent Substances 0.000 description 2
• 150000002500 ions Chemical class 0.000 description 2
• 125000000842 isoxazolyl group Chemical group 0.000 description 2
• 238000004949 mass spectrometry Methods 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification 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
• 239000012074 organic phase Substances 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
• 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
• 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
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• 125000004076 pyridyl group Chemical group 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
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 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
• 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
• 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 2
• TZRQZPMQUXEZMC-UHFFFAOYSA-N tert-butyl n-(2-bromoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCBr TZRQZPMQUXEZMC-UHFFFAOYSA-N 0.000 description 2
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
• 125000003831 tetrazolyl group Chemical group 0.000 description 2
• 229940124597 therapeutic agent Drugs 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 125000000335 thiazolyl group Chemical group 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 2
• YUPUSBMJCFBHAP-UHFFFAOYSA-N (3,4,5-trimethoxyphenyl)methanamine Chemical compound COC1=CC(CN)=CC(OC)=C1OC YUPUSBMJCFBHAP-UHFFFAOYSA-N 0.000 description 1
• DLNAKYFPFYUBDR-UHFFFAOYSA-N (4-aminophenyl)-(7-benzyl-3,7-diazabicyclo[3.3.1]nonan-3-yl)methanone Chemical compound C1=CC(N)=CC=C1C(=O)N1CC(CN(CC=2C=CC=CC=2)C2)CC2C1 DLNAKYFPFYUBDR-UHFFFAOYSA-N 0.000 description 1
• DLNAKYFPFYUBDR-HDICACEKSA-N (4-aminophenyl)-[(1s,5r)-7-benzyl-3,7-diazabicyclo[3.3.1]nonan-3-yl]methanone Chemical compound C1=CC(N)=CC=C1C(=O)N1C[C@@H](CN(CC=2C=CC=CC=2)C2)C[C@@H]2C1 DLNAKYFPFYUBDR-HDICACEKSA-N 0.000 description 1
• 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
• 125000006552 (C3-C8) cycloalkyl group Chemical group 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
• UZOZMKDUISGBJK-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]-3-methylurea Chemical compound C1C(CN(C2)C=3SC=CN=3)CC2CN1CC(NC(=O)NC)COC1=CC=C(C#N)C=C1 UZOZMKDUISGBJK-UHFFFAOYSA-N 0.000 description 1
• HVBKCSMNWAYBFO-UHFFFAOYSA-N 1-[1-(4-cyanophenoxy)-3-[3-(3,3-dimethyl-2-oxobutyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propan-2-yl]-3-methylurea Chemical compound C1C(CN(CC(=O)C(C)(C)C)C2)CC2CN1CC(NC(=O)NC)COC1=CC=C(C#N)C=C1 HVBKCSMNWAYBFO-UHFFFAOYSA-N 0.000 description 1
• RNAKCZZUJXQOTB-UHFFFAOYSA-N 1-[1-(4-cyanophenoxy)-3-[3-[2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-oxoethyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]propan-2-yl]-3-methylurea Chemical compound C1C(CN(CC(=O)C=2C=C3OCCOC3=CC=2)C2)CC2CN1CC(NC(=O)NC)COC1=CC=C(C#N)C=C1 RNAKCZZUJXQOTB-UHFFFAOYSA-N 0.000 description 1
• GESZKHPIYNFYQH-UHFFFAOYSA-N 1-[1-(4-cyanophenoxy)-3-[7-(cyclopropylmethyl)-3,7-diazabicyclo[3.3.1]nonan-3-yl]propan-2-yl]-3-methylurea Chemical compound C1C(CN(CC2CC2)C2)CC2CN1CC(NC(=O)NC)COC1=CC=C(C#N)C=C1 GESZKHPIYNFYQH-UHFFFAOYSA-N 0.000 description 1
• JHPSOTFCEWMQEV-UHFFFAOYSA-N 1-[1-(4-cyanophenoxy)-3-[7-[2-(3,4-dimethoxyphenyl)ethyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]propan-2-yl]-3-methylurea Chemical compound C1C(CN(CCC=2C=C(OC)C(OC)=CC=2)C2)CC2CN1CC(NC(=O)NC)COC1=CC=C(C#N)C=C1 JHPSOTFCEWMQEV-UHFFFAOYSA-N 0.000 description 1
• TXCWNVXDSXAZDO-UHFFFAOYSA-N 1-[1-[3-(1-cyanoethyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]-3-(4-cyanophenoxy)propan-2-yl]-3-methylurea Chemical compound C1C(CN(C2)C(C)C#N)CC2CN1CC(NC(=O)NC)COC1=CC=C(C#N)C=C1 TXCWNVXDSXAZDO-UHFFFAOYSA-N 0.000 description 1
• LPRLDSCFRXXKEM-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]-3-methylurea Chemical compound C1C(CN(CCCN2CCN(CC2)C(C)=O)C2)CC2CN1CC(NC(=O)NC)COC1=CC=C(C#N)C=C1 LPRLDSCFRXXKEM-UHFFFAOYSA-N 0.000 description 1
• RGENXDQBZBKATQ-UHFFFAOYSA-N 1-[2-[2-amino-3-(7-ethylsulfonyl-3,7-diazabicyclo[3.3.1]nonan-3-yl)propoxy]-5-cyanophenyl]-3-ethylurea Chemical compound CCNC(=O)NC1=CC(C#N)=CC=C1OCC(N)CN1CC(CN(C2)S(=O)(=O)CC)CC2C1 RGENXDQBZBKATQ-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
• 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
• 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
• ZHOVIYASUQUNQT-DAWZGUTISA-N 2-[7-[(2r)-3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-n-ethyl-2-oxoacetamide Chemical compound C([C@H](O)CN1CC2CC(C1)CN(C2)C(=O)C(=O)NCC)OC1=CC=C(C#N)C=C1 ZHOVIYASUQUNQT-DAWZGUTISA-N 0.000 description 1
• ZHOVIYASUQUNQT-ABHNRTSZSA-N 2-[7-[(2s)-3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-n-ethyl-2-oxoacetamide Chemical compound C([C@@H](O)CN1CC2CC(C1)CN(C2)C(=O)C(=O)NCC)OC1=CC=C(C#N)C=C1 ZHOVIYASUQUNQT-ABHNRTSZSA-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
• GOVOCTKWGPMCAE-UHFFFAOYSA-N 2-[7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-n-(2,6-dimethylphenyl)acetamide Chemical compound CC1=CC=CC(C)=C1NC(=O)CN1CC(CN(CC(O)COC=2C=CC(=CC=2)C#N)C2)CC2C1 GOVOCTKWGPMCAE-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
• SBFZGKLZNLCYFM-UHFFFAOYSA-N 3,5-dimethyl-2,3-dihydro-1,2-oxazole Chemical compound CC1NOC(C)=C1 SBFZGKLZNLCYFM-UHFFFAOYSA-N 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
• 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
• 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
• ZWPMOISCXUVIRP-MHJFOBGBSA-N 4-[(2s)-2-amino-3-[3-(3,3-dimethyl-2-oxobutyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propoxy]benzonitrile Chemical compound C([C@@H](N)CN1CC2CC(C1)CN(C2)CC(=O)C(C)(C)C)OC1=CC=C(C#N)C=C1 ZWPMOISCXUVIRP-MHJFOBGBSA-N 0.000 description 1
• QWHRISMVZANXCV-ABHNRTSZSA-N 4-[(2s)-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-ABHNRTSZSA-N 0.000 description 1
• APSSASZESPLXTH-XIGIHCPSSA-N 4-[(2s)-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-XIGIHCPSSA-N 0.000 description 1
• AIIZTRUBKHXJJG-CBGCIVQGSA-N 4-[(2s)-3-[3-[(2s)-2-amino-3-(4-methoxyphenyl)propanoyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N1CC(CN(C[C@H](O)COC=2C=CC(=CC=2)C#N)C2)CC2C1 AIIZTRUBKHXJJG-CBGCIVQGSA-N 0.000 description 1
• FMGLPGITEVDJJY-XSNSTOHYSA-N 4-[(2s)-3-[3-[(2s)-2-amino-3-methylbutanoyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C([C@@H](O)CN1CC2CC(C1)CN(C2)C(=O)[C@@H](N)C(C)C)OC1=CC=C(C#N)C=C1 FMGLPGITEVDJJY-XSNSTOHYSA-N 0.000 description 1
• DPJQOKOTKIHROL-JXMROGBWSA-N 4-[(E)-3-[7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-3-oxoprop-1-enyl]benzonitrile Chemical compound C1C(C2)CN(CC(O)COc3ccc(C#N)cc3)CC1CN2C(=O)\C=C\c1ccc(C#N)cc1 DPJQOKOTKIHROL-JXMROGBWSA-N 0.000 description 1
• HTZFYGVSXOKPIQ-UHFFFAOYSA-N 4-[1-(3,4-dimethoxyphenoxy)-4-[3-(3-ethylsulfonylpropyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]butyl]benzonitrile Chemical compound C1N(CCCS(=O)(=O)CC)CC(C2)CC1CN2CCCC(C=1C=CC(=CC=1)C#N)OC1=CC=C(OC)C(OC)=C1 HTZFYGVSXOKPIQ-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
• 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
• LASJJXLJWPZDGD-UHFFFAOYSA-N 4-[2-(3-butylsulfonyl-3,7-diazabicyclo[3.3.1]nonan-7-yl)ethoxy]benzonitrile Chemical compound C1N(S(=O)(=O)CCCC)CC(C2)CC1CN2CCOC1=CC=C(C#N)C=C1 LASJJXLJWPZDGD-UHFFFAOYSA-N 0.000 description 1
• ZCKXMWGOIVLEED-UHFFFAOYSA-N 4-[2-[3-(1,3-thiazol-2-yl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethoxy]benzonitrile Chemical compound C1=CC(C#N)=CC=C1OCCN1CC(CN(C2)C=3SC=CN=3)CC2C1 ZCKXMWGOIVLEED-UHFFFAOYSA-N 0.000 description 1
• AHFZFNILUKWOLE-UHFFFAOYSA-N 4-[2-[3-(1-cyanoethyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethoxy]benzonitrile Chemical compound C1N(C(C#N)C)CC(C2)CC1CN2CCOC1=CC=C(C#N)C=C1 AHFZFNILUKWOLE-UHFFFAOYSA-N 0.000 description 1
• BNADZJMESNCDFS-UHFFFAOYSA-N 4-[2-[3-(3,3-dimethyl-2-oxobutyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethoxy]benzonitrile Chemical compound C1N(CC(=O)C(C)(C)C)CC(C2)CC1CN2CCOC1=CC=C(C#N)C=C1 BNADZJMESNCDFS-UHFFFAOYSA-N 0.000 description 1
• JHQAWCXMUUVNRU-UHFFFAOYSA-N 4-[2-[3-(cyclopropylmethyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethoxy]benzonitrile Chemical compound C1=CC(C#N)=CC=C1OCCN1CC(CN(CC2CC2)C2)CC2C1 JHQAWCXMUUVNRU-UHFFFAOYSA-N 0.000 description 1
• YNYUDSQXJRNOBV-UHFFFAOYSA-N 4-[2-[3-[(4-fluorophenyl)methyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethoxy]benzonitrile Chemical compound C1=CC(F)=CC=C1CN1CC(CN(CCOC=2C=CC(=CC=2)C#N)C2)CC2C1 YNYUDSQXJRNOBV-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
• JPKITFSBTGGFBM-UHFFFAOYSA-N 4-[2-[3-[2-(4-cyanophenyl)ethyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1CCN1CC(CN(CCC=2C=CC(=CC=2)C#N)C2)CC2C1 JPKITFSBTGGFBM-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
• DJEUWFQTFXXVIC-UHFFFAOYSA-N 4-[2-[7-[3-(4-acetylpiperazin-1-yl)propyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]ethoxy]benzonitrile Chemical compound C1CN(C(=O)C)CCN1CCCN1CC(CN(CCOC=2C=CC(=CC=2)C#N)C2)CC2C1 DJEUWFQTFXXVIC-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
• YNJOLPRIECATMA-UHFFFAOYSA-N 4-[2-hydroxy-3-(3-propan-2-ylsulfonyl-3,7-diazabicyclo[3.3.1]nonan-7-yl)propoxy]benzonitrile Chemical compound C1N(S(=O)(=O)C(C)C)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 YNJOLPRIECATMA-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
• 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
• LWFYPESAVOTMHL-UHFFFAOYSA-N 4-[2-hydroxy-3-[3-(3,3,3-trifluoropropanoyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propoxy]benzonitrile Chemical compound C1C(CN(C2)C(=O)CC(F)(F)F)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 LWFYPESAVOTMHL-UHFFFAOYSA-N 0.000 description 1
• LVVIIODNNZDOGL-UHFFFAOYSA-N 4-[2-hydroxy-3-[3-(3-methylquinolin-8-yl)sulfonyl-3,7-diazabicyclo[3.3.1]nonan-7-yl]propoxy]benzonitrile Chemical compound C=1C=CC2=CC(C)=CN=C2C=1S(=O)(=O)N(C1)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 LVVIIODNNZDOGL-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
• BCBLYTTYBLBHHA-UHFFFAOYSA-N 4-[2-hydroxy-3-[3-[2-hydroxy-3-(2-methyl-1-oxoisoquinolin-4-yl)oxypropyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]propoxy]benzonitrile Chemical compound C12=CC=CC=C2C(=O)N(C)C=C1OCC(O)CN(C1)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 BCBLYTTYBLBHHA-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
• 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
• FXDFOCYWWDANPI-UHFFFAOYSA-N 4-[3-(3-butylsulfonyl-3,7-diazabicyclo[3.3.1]nonan-7-yl)-2-hydroxypropoxy]benzonitrile Chemical compound C1N(S(=O)(=O)CCCC)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 FXDFOCYWWDANPI-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
• LQTJVMKTWRUXTL-UHFFFAOYSA-N 4-[3-(7-benzyl-3,7-diazabicyclo[3.3.1]nonan-3-yl)-2-hydroxypropoxy]benzonitrile Chemical compound C1C(CN(CC=2C=CC=CC=2)C2)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 LQTJVMKTWRUXTL-UHFFFAOYSA-N 0.000 description 1
• SCGQYGCGJGQIQY-UHFFFAOYSA-N 4-[3-[(3,7-dibenzyl-3,7-diazabicyclo[3.3.1]nonan-9-yl)-methylamino]-2-hydroxypropoxy]benzonitrile Chemical compound C1N(CC=2C=CC=CC=2)CC2CN(CC=3C=CC=CC=3)CC1C2N(C)CC(O)COC1=CC=C(C#N)C=C1 SCGQYGCGJGQIQY-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
• 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
• OHCHOYQGSYHXMQ-UHFFFAOYSA-N 4-[3-[3-(2-ethyltetrazol-5-yl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]-2-hydroxypropoxy]benzonitrile Chemical compound CCN1N=NC(N2CC3CC(CN(CC(O)COC=4C=CC(=CC=4)C#N)C3)C2)=N1 OHCHOYQGSYHXMQ-UHFFFAOYSA-N 0.000 description 1
• JHFNQAHHLVOWBN-UHFFFAOYSA-N 4-[3-[3-(2-ethyltetrazol-5-yl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylamino]benzonitrile Chemical compound CCN1N=NC(N2CC3CC(CN(CCCNC=4C=CC(=CC=4)C#N)C3)C2)=N1 JHFNQAHHLVOWBN-UHFFFAOYSA-N 0.000 description 1
• GTWXFNHZTBJSSZ-UHFFFAOYSA-N 4-[3-[3-(3,3-dimethyl-2-oxobutyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylsulfonyl]benzonitrile Chemical compound C1N(CC(=O)C(C)(C)C)CC(C2)CC1CN2CCCS(=O)(=O)C1=CC=C(C#N)C=C1 GTWXFNHZTBJSSZ-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
• IAZMJRYDBDAMEP-UHFFFAOYSA-N 4-[3-[3-(3,4-dimethoxyphenyl)sulfonyl-3,7-diazabicyclo[3.3.1]nonan-7-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C1=C(OC)C(OC)=CC=C1S(=O)(=O)N1CC(CN(CC(O)COC=2C=CC(=CC=2)C#N)C2)CC2C1 IAZMJRYDBDAMEP-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
• FFPIBRZYFHKTNI-UHFFFAOYSA-N 4-[3-[3-(5-tert-butyl-2-methylpyrazole-3-carbonyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]-2-hydroxypropoxy]benzonitrile Chemical compound CN1N=C(C(C)(C)C)C=C1C(=O)N1CC(CN(CC(O)COC=2C=CC(=CC=2)C#N)C2)CC2C1 FFPIBRZYFHKTNI-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
• VMYLXPPKAWBHJZ-UXBLZVDNSA-N 4-[3-[3-[(e)-3-(3,4-dimethoxyphenyl)prop-2-enoyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C1=C(OC)C(OC)=CC=C1\C=C\C(=O)N1CC(CN(CC(O)COC=2C=CC(=CC=2)C#N)C2)CC2C1 VMYLXPPKAWBHJZ-UXBLZVDNSA-N 0.000 description 1
• ZSSQVQPYPGLHDF-UHFFFAOYSA-N 4-[3-[3-[2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-oxoethyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C1C(CN(CC(=O)C=2C=C3OCCOC3=CC=2)C2)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 ZSSQVQPYPGLHDF-UHFFFAOYSA-N 0.000 description 1
• QMFASQZPUMFYOZ-UHFFFAOYSA-N 4-[3-[3-[2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-oxoethyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylamino]benzonitrile Chemical compound C=1C=C2OCCOC2=CC=1C(=O)CN(C1)CC(C2)CC1CN2CCCNC1=CC=C(C#N)C=C1 QMFASQZPUMFYOZ-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
• 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
• CQJPKLOGPCYEFG-UHFFFAOYSA-N 4-[3-[7-(2-aminoethyl)-3,7-diazabicyclo[3.3.1]nonan-3-yl]-2-hydroxypropoxy]benzonitrile Chemical compound C1N(CCN)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 CQJPKLOGPCYEFG-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
• YRWBXULPLFYGBI-UHFFFAOYSA-N 4-[3-[7-(3-ethylsulfonylpropyl)-3,7-diazabicyclo[3.3.1]nonan-3-yl]propylsulfonyl]benzonitrile Chemical compound C1N(CCCS(=O)(=O)CC)CC(C2)CC1CN2CCCS(=O)(=O)C1=CC=C(C#N)C=C1 YRWBXULPLFYGBI-UHFFFAOYSA-N 0.000 description 1
• WLSNROQDCHJEHX-UHFFFAOYSA-N 4-[3-[7-(cyclopropylmethyl)-3,7-diazabicyclo[3.3.1]nonan-3-yl]-2-hydroxypropoxy]-n,n-dimethylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N(C)C)=CC=C1OCC(O)CN1CC(CN(CC2CC2)C2)CC2C1 WLSNROQDCHJEHX-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
• KUOGCSDFQAZXFS-UHFFFAOYSA-N 4-[3-[7-[3-(4-acetylpiperazin-1-yl)propyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-2-hydroxypropoxy]-n,n-dimethylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N(C)C)=CC=C1OCC(O)CN1CC(CN(CCCN2CCN(CC2)C(C)=O)C2)CC2C1 KUOGCSDFQAZXFS-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
• 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
• NFQBNCWYJJVJMW-UHFFFAOYSA-N 4-[4-[3-(1-cyanoethyl)-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(C2)C(C)C#N)CC2C1 NFQBNCWYJJVJMW-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
• 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
• 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
• LIJRFBYDYPFCCV-UHFFFAOYSA-N 4-acetamido-n-[2-[3-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethyl]benzamide Chemical compound C1=CC(NC(=O)C)=CC=C1C(=O)NCCN1CC(CN(CC(O)COC=2C=CC(=CC=2)C#N)C2)CC2C1 LIJRFBYDYPFCCV-UHFFFAOYSA-N 0.000 description 1
• IOCDUQAXXCSILV-UHFFFAOYSA-N 4-amino-n-[2-[3-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethyl]benzamide Chemical compound C1=CC(N)=CC=C1C(=O)NCCN1CC(CN(CC(O)COC=2C=CC(=CC=2)C#N)C2)CC2C1 IOCDUQAXXCSILV-UHFFFAOYSA-N 0.000 description 1
• DMAYBPBPEUFIHJ-UHFFFAOYSA-N 4-bromobut-1-ene Chemical compound BrCCC=C DMAYBPBPEUFIHJ-UHFFFAOYSA-N 0.000 description 1
• NMPUCSARJMTEKZ-UHFFFAOYSA-N 4-cyano-n-[2-[3-[2-[(4-cyanobenzoyl)amino]ethyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethyl]benzamide Chemical compound C=1C=C(C#N)C=CC=1C(=O)NCCN(C1)CC(C2)CC1CN2CCNC(=O)C1=CC=C(C#N)C=C1 NMPUCSARJMTEKZ-UHFFFAOYSA-N 0.000 description 1
• LTYDCNYOOCJGJL-UHFFFAOYSA-N 4-cyano-n-[3-[3-(2-cyanopropyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propyl]benzamide Chemical compound C1N(CC(C)C#N)CC(C2)CC1CN2CCCNC(=O)C1=CC=C(C#N)C=C1 LTYDCNYOOCJGJL-UHFFFAOYSA-N 0.000 description 1
• OZWLPUSEMMCGHH-UHFFFAOYSA-N 4-cyano-n-[3-[3-(3,3-dimethyl-2-oxobutyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propyl]benzamide Chemical compound C1N(CC(=O)C(C)(C)C)CC(C2)CC1CN2CCCNC(=O)C1=CC=C(C#N)C=C1 OZWLPUSEMMCGHH-UHFFFAOYSA-N 0.000 description 1
• XBJBETHENOWHAK-UHFFFAOYSA-N 4-cyano-n-[3-[3-(3-ethylsulfonylpropyl)-3,7-diazabicyclo[3.3.1]nonan-7-yl]propyl]benzamide Chemical compound C1N(CCCS(=O)(=O)CC)CC(C2)CC1CN2CCCNC(=O)C1=CC=C(C#N)C=C1 XBJBETHENOWHAK-UHFFFAOYSA-N 0.000 description 1
• QFYPVWZTCUYFRA-UHFFFAOYSA-N 4-cyano-n-[3-[3-[2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-oxoethyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]propyl]benzamide Chemical compound C=1C=C2OCCOC2=CC=1C(=O)CN(C1)CC(C2)CC1CN2CCCNC(=O)C1=CC=C(C#N)C=C1 QFYPVWZTCUYFRA-UHFFFAOYSA-N 0.000 description 1
• OVBDMFIGFXGOSQ-UHFFFAOYSA-N 4-cyano-n-[3-[3-[2-(2-methoxyethoxy)ethyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]propyl]benzamide Chemical compound C1N(CCOCCOC)CC(C2)CC1CN2CCCNC(=O)C1=CC=C(C#N)C=C1 OVBDMFIGFXGOSQ-UHFFFAOYSA-N 0.000 description 1
• WQFQMUSGLTYFSL-UHFFFAOYSA-N 4-cyano-n-[3-[3-[2-(3,4-dimethoxyphenyl)ethyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]propyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1CCN1CC(CN(CCCNC(=O)C=2C=CC(=CC=2)C#N)C2)CC2C1 WQFQMUSGLTYFSL-UHFFFAOYSA-N 0.000 description 1
• GTCNNMPVAILAJW-UHFFFAOYSA-N 4-cyano-n-[3-[7-(4-oxoheptyl)-3,7-diazabicyclo[3.3.1]nonan-3-yl]propyl]benzamide Chemical compound C1N(CCCC(=O)CCC)CC(C2)CC1CN2CCCNC(=O)C1=CC=C(C#N)C=C1 GTCNNMPVAILAJW-UHFFFAOYSA-N 0.000 description 1
• CVNOWLNNPYYEOH-UHFFFAOYSA-N 4-cyanophenol Chemical compound OC1=CC=C(C#N)C=C1 CVNOWLNNPYYEOH-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
• CDZMKWXWMRMISX-ABHNRTSZSA-N 7-[(2s)-3-(4-cyanophenoxy)-2-hydroxypropyl]-n-ethyl-3,7-diazabicyclo[3.3.1]nonane-3-carbothioamide Chemical compound C([C@@H](O)CN1CC2CC(C1)CN(C2)C(=S)NCC)OC1=CC=C(C#N)C=C1 CDZMKWXWMRMISX-ABHNRTSZSA-N 0.000 description 1
• VSJOQKLJOKELOR-UHFFFAOYSA-N 7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonane-3-carbonitrile Chemical compound C1C(CN(C2)C#N)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 VSJOQKLJOKELOR-UHFFFAOYSA-N 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
• 125000005330 8 membered heterocyclic group Chemical group 0.000 description 1
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
• 239000005695 Ammonium acetate Substances 0.000 description 1
• 229910015900 BF3 Inorganic materials 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• LSCPBCLIVVVNJM-KNMGBQSGSA-N COc1ccc(C[C@H](NC(=O)OC(C)(C)C)C(=O)N2CC3CC(CN(C[C@H](O)COc4ccc(cc4)C#N)C3)C2)cc1 Chemical compound COc1ccc(C[C@H](NC(=O)OC(C)(C)C)C(=O)N2CC3CC(CN(C[C@H](O)COc4ccc(cc4)C#N)C3)C2)cc1 LSCPBCLIVVVNJM-KNMGBQSGSA-N 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 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
• XIWZLSFPKZDWMZ-UHFFFAOYSA-N F[S](F)F.CCNCC Chemical compound F[S](F)F.CCNCC XIWZLSFPKZDWMZ-UHFFFAOYSA-N 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• 241000282412 Homo Species 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
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 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
• KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 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
• 241000700159 Rattus Species 0.000 description 1
• XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• 206010042600 Supraventricular arrhythmias Diseases 0.000 description 1
• 208000001871 Tachycardia Diseases 0.000 description 1
• 208000018452 Torsade de pointes Diseases 0.000 description 1
• 208000002363 Torsades de Pointes 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
• 238000006959 Williamson synthesis reaction Methods 0.000 description 1
• 238000006044 Wolff rearrangement reaction Methods 0.000 description 1
• PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical class [Zn+2] PTFCDOFLOPIGGS-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
• 239000003377 acid catalyst Substances 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 239000008186 active pharmaceutical agent Substances 0.000 description 1
• 125000002015 acyclic group Chemical group 0.000 description 1
• 125000004442 acylamino group Chemical group 0.000 description 1
• 150000004703 alkoxides Chemical class 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
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 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
• 235000019257 ammonium acetate Nutrition 0.000 description 1
• 229940043376 ammonium acetate Drugs 0.000 description 1
• 239000000908 ammonium hydroxide Substances 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
• 230000008901 benefit 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
• 150000003939 benzylamines Chemical class 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 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
• 230000036772 blood pressure Effects 0.000 description 1
• 238000009530 blood pressure measurement Methods 0.000 description 1
• 238000010241 blood sampling Methods 0.000 description 1
• 238000009835 boiling 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
• 230000036471 bradycardia Effects 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• WEDIIKBPDQQQJU-UHFFFAOYSA-N butane-1-sulfonyl chloride Chemical compound CCCCS(Cl)(=O)=O WEDIIKBPDQQQJU-UHFFFAOYSA-N 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 230000011128 cardiac conduction Effects 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000006285 cell suspension Substances 0.000 description 1
• 210000001773 cervical plexus Anatomy 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
• 125000005390 cinnolyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• 229940082627 class iii antiarrhythmics Drugs 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 238000004590 computer program Methods 0.000 description 1
• ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
• 125000000753 cycloalkyl group Chemical group 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
• 229960003957 dexamethasone Drugs 0.000 description 1
• 230000035487 diastolic blood pressure Effects 0.000 description 1
• 230000003205 diastolic effect Effects 0.000 description 1
• VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
• 125000000532 dioxanyl group Chemical group 0.000 description 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
• 208000035475 disorder Diseases 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
• 238000009509 drug development Methods 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
• 108010075324 emt protein-tyrosine kinase Proteins 0.000 description 1
• 238000006345 epimerization reaction Methods 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
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
• 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 239000012894 fetal calf serum Substances 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 238000005755 formation reaction Methods 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
• 230000000004 hemodynamic effect Effects 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
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
• 229910000041 hydrogen chloride Inorganic materials 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
• 230000001939 inductive effect Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000013067 intermediate product Substances 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 239000007928 intraperitoneal injection Substances 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 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
• 210000005246 left atrium Anatomy 0.000 description 1
• 210000005240 left ventricle Anatomy 0.000 description 1
• 239000011968 lewis acid catalyst Substances 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 230000010534 mechanism of action Effects 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 230000028161 membrane depolarization Effects 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
• 229940087646 methanolamine Drugs 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
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 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
• 208000031225 myocardial ischemia Diseases 0.000 description 1
• 210000004165 myocardium Anatomy 0.000 description 1
• PQDCSCHJYFYCGY-UHFFFAOYSA-N n'-cyano-7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-n-methyl-n-propan-2-yl-3,7-diazabicyclo[3.3.1]nonane-3-carboximidamide Chemical compound C1N(C(=NC#N)N(C)C(C)C)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 PQDCSCHJYFYCGY-UHFFFAOYSA-N 0.000 description 1
• OTAWSFIAOAJZDE-UHFFFAOYSA-N n-[2-[3-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethyl]-4-(methanesulfonamido)benzamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C(=O)NCCN1CC(CN(CC(O)COC=2C=CC(=CC=2)C#N)C2)CC2C1 OTAWSFIAOAJZDE-UHFFFAOYSA-N 0.000 description 1
• GJJNIEAYDFRHRV-UHFFFAOYSA-N n-[2-[3-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethyl]-4-nitrobenzamide Chemical compound C1C(CN(CCNC(=O)C=2C=CC(=CC=2)[N+]([O-])=O)C2)CC2CN1CC(O)COC1=CC=C(C#N)C=C1 GJJNIEAYDFRHRV-UHFFFAOYSA-N 0.000 description 1
• UMQUFJULMQHMTL-UHFFFAOYSA-N n-[2-[7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-2-oxoethyl]acetamide Chemical compound C1N(C(=O)CNC(=O)C)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 UMQUFJULMQHMTL-UHFFFAOYSA-N 0.000 description 1
• KFAWWPIHKRFIMH-UHFFFAOYSA-N n-[3-[3-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]propyl]-n-(3,4-dimethoxyphenyl)-4-nitrobenzamide Chemical compound C1=C(OC)C(OC)=CC=C1N(C(=O)C=1C=CC(=CC=1)[N+]([O-])=O)CCCN1CC(CN(CC(O)COC=2C=CC(=CC=2)C#N)C2)CC2C1 KFAWWPIHKRFIMH-UHFFFAOYSA-N 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• 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 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [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
• 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
• 210000003516 pericardium Anatomy 0.000 description 1
• 239000012071 phase Substances 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
• 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
• 239000000843 powder Substances 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 230000001536 pro-arrhythmogenic effect Effects 0.000 description 1
• XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 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
• 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
• 230000006340 racemization Effects 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 238000007363 ring formation reaction Methods 0.000 description 1
• 239000000523 sample Substances 0.000 description 1
• 238000005070 sampling Methods 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 238000007423 screening assay Methods 0.000 description 1
• 229910052710 silicon Inorganic materials 0.000 description 1
• 239000010703 silicon Substances 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
• 239000007790 solid phase Substances 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
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 239000000725 suspension Substances 0.000 description 1
• 230000035488 systolic blood pressure Effects 0.000 description 1
• 230000006794 tachycardia Effects 0.000 description 1
• 239000008399 tap water Substances 0.000 description 1
• 235000020679 tap water Nutrition 0.000 description 1
• 229960002926 tedisamil Drugs 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
• ICNWQSARBNRXSN-UHFFFAOYSA-N tert-butyl 3-[[7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonane-3-carbothioyl]amino]propanoate Chemical compound C1N(C(=S)NCCC(=O)OC(C)(C)C)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 ICNWQSARBNRXSN-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
• OMJXIMJLBUMUJI-UHFFFAOYSA-N tert-butyl n-[1-(3-butylsulfonyl-3,7-diazabicyclo[3.3.1]nonan-7-yl)-4-(4-cyanophenoxy)butan-2-yl]carbamate Chemical compound C1N(S(=O)(=O)CCCC)CC(C2)CC1CN2CC(NC(=O)OC(C)(C)C)CCOC1=CC=C(C#N)C=C1 OMJXIMJLBUMUJI-UHFFFAOYSA-N 0.000 description 1
• YWBADHLGYONUAC-UHFFFAOYSA-N tert-butyl n-[2-[3-[2-amino-3-(4-cyanophenoxy)propyl]-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethyl]carbamate Chemical compound C1N(CCNC(=O)OC(C)(C)C)CC(C2)CC1CN2CC(N)COC1=CC=C(C#N)C=C1 YWBADHLGYONUAC-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
• XIHYHBDKJKJBBZ-UHFFFAOYSA-N tert-butyl n-[2-[7-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl]-2-oxoethyl]carbamate Chemical compound C1N(C(=O)CNC(=O)OC(C)(C)C)CC(C2)CC1CN2CC(O)COC1=CC=C(C#N)C=C1 XIHYHBDKJKJBBZ-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
• ISTGQSQWSKCNFJ-UHFFFAOYSA-N tert-butyl n-ethylcarbamate Chemical compound CCNC(=O)OC(C)(C)C ISTGQSQWSKCNFJ-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
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000005490 tosylate group Chemical group 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 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
• 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
• 238000005303 weighing Methods 0.000 description 1
• 229940102001 zinc bromide Drugs 0.000 description 1