NZ587157A - Benzodiazepine compound and pharmaceutical composition - Google Patents

Info

Publication number

NZ587157A

NZ587157A NZ587157A NZ58715709A NZ587157A NZ 587157 A NZ587157 A NZ 587157A NZ 587157 A NZ587157 A NZ 587157A NZ 58715709 A NZ58715709 A NZ 58715709A NZ 587157 A NZ587157 A NZ 587157A

Authority

NZ

New Zealand

Prior art keywords

ethyl

pyridin

optionally substituted

oxo

diazepine

Prior art date

2008-02-22

Links

• Espacenet
• Global Dossier
• Discuss

• -1 Benzodiazepine compound Chemical class 0.000 title claims abstract description 306
• 229940049706 benzodiazepine Drugs 0.000 title claims abstract description 29
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 18
• 150000001875 compounds Chemical class 0.000 claims abstract description 610
• 125000001424 substituent group Chemical group 0.000 claims abstract description 51
• 150000003839 salts Chemical class 0.000 claims abstract description 30
• 206010003119 arrhythmia Diseases 0.000 claims abstract description 15
• 230000006793 arrhythmia Effects 0.000 claims abstract description 13
• 238000004519 manufacturing process Methods 0.000 claims abstract description 6
• CMPJAGCXBOHFAF-UHFFFAOYSA-N n-[3-[(1-ethyl-3,3,5-trimethyl-2,4-dioxo-1,5-benzodiazepin-7-yl)oxy]propyl]-n-[2-(1-oxoisoquinolin-2-yl)ethyl]benzenesulfonamide Chemical compound C1=C2N(C)C(=O)C(C)(C)C(=O)N(CC)C2=CC=C1OCCCN(CCN1C(C2=CC=CC=C2C=C1)=O)S(=O)(=O)C1=CC=CC=C1 CMPJAGCXBOHFAF-UHFFFAOYSA-N 0.000 claims abstract 2
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 115
• 125000000217 alkyl group Chemical group 0.000 claims description 109
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 98
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 91
• 150000002367 halogens Chemical class 0.000 claims description 61
• 229910052736 halogen Inorganic materials 0.000 claims description 53
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 53
• 125000004043 oxo group Chemical group O=* 0.000 claims description 38
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
• 125000002947 alkylene group Chemical group 0.000 claims description 24
• 125000003545 alkoxy group Chemical group 0.000 claims description 21
• 239000001257 hydrogen Substances 0.000 claims description 21
• 229910052739 hydrogen Inorganic materials 0.000 claims description 21
• 125000001544 thienyl group Chemical group 0.000 claims description 17
• 125000002541 furyl group Chemical group 0.000 claims description 16
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
• 125000004076 pyridyl group Chemical group 0.000 claims description 16
• LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 12
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
• 125000002971 oxazolyl group Chemical group 0.000 claims description 10
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
• 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 8
• 125000005956 isoquinolyl group Chemical group 0.000 claims description 8
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
• 125000000335 thiazolyl group Chemical group 0.000 claims description 8
• 125000001425 triazolyl group Chemical group 0.000 claims description 8
• 125000001589 carboacyl group Chemical group 0.000 claims description 7
• 125000002883 imidazolyl group Chemical group 0.000 claims description 7
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
• 125000005493 quinolyl group Chemical group 0.000 claims description 7
• 125000005877 1,4-benzodioxanyl group Chemical group 0.000 claims description 6
• 125000004450 alkenylene group Chemical group 0.000 claims description 6
• 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 6
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 6
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 6
• 125000005946 imidazo[1,2-a]pyridyl group Chemical group 0.000 claims description 6
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 6
• 125000001041 indolyl group Chemical group 0.000 claims description 6
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 6
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 6
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 6
• TZOYXRMEFDYWDQ-UHFFFAOYSA-N 3,4-dihydro-1h-quinolin-2-one Chemical compound C1=CC=C2NC(=O)CCC2=C1 TZOYXRMEFDYWDQ-UHFFFAOYSA-N 0.000 claims description 5
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
• 125000005530 alkylenedioxy group Chemical group 0.000 claims description 5
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 5
• 125000002757 morpholinyl group Chemical group 0.000 claims description 5
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 125000001624 naphthyl group Chemical group 0.000 claims description 4
• ILVVNQGRTQBKCL-UHFFFAOYSA-N 1,3,5-trimethyl-1,5-benzodiazepine-2,4-dione Chemical compound CN1C(=O)C(C)C(=O)N(C)C2=CC=CC=C21 ILVVNQGRTQBKCL-UHFFFAOYSA-N 0.000 claims description 3
• KJMBLIYINJNYGO-UHFFFAOYSA-N n-methyl-n-[2-[pyridin-4-ylmethyl-[3-[(1,3,3,5-tetramethyl-2,4-dioxo-1,5-benzodiazepin-7-yl)oxy]propyl]amino]ethyl]benzamide;dihydrochloride Chemical compound Cl.Cl.C=1C=CC=CC=1C(=O)N(C)CCN(CCCOC=1C=C2N(C)C(=O)C(C)(C)C(=O)N(C)C2=CC=1)CC1=CC=NC=C1 KJMBLIYINJNYGO-UHFFFAOYSA-N 0.000 claims description 3
• 125000004193 piperazinyl group Chemical group 0.000 claims description 3
• MGRLWDRGBXQTMU-UHFFFAOYSA-N 4-[[3-[(1-ethyl-3,3,5-trimethyl-2,4-dioxo-1,5-benzodiazepin-7-yl)oxy]propyl-[2-(1-oxoisoquinolin-2-yl)ethyl]amino]methyl]benzonitrile Chemical compound C1=C2N(C)C(=O)C(C)(C)C(=O)N(CC)C2=CC=C1OCCCN(CCN1C(C2=CC=CC=C2C=C1)=O)CC1=CC=C(C#N)C=C1 MGRLWDRGBXQTMU-UHFFFAOYSA-N 0.000 claims description 2
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 2
• 125000003282 alkyl amino group Chemical group 0.000 claims description 2
• 125000004414 alkyl thio group Chemical group 0.000 claims description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
• 125000005936 piperidyl group Chemical group 0.000 claims description 2
• BCTRLWGBBPOMCO-UHFFFAOYSA-N 1,3,3,5-tetramethyl-7-[3-[2-pyridin-3-ylethyl(pyridin-4-ylmethyl)amino]propoxy]-1,5-benzodiazepine-2,4-dione Chemical compound C1=C2N(C)C(=O)C(C)(C)C(=O)N(C)C2=CC=C1OCCCN(CC=1C=CN=CC=1)CCC1=CC=CN=C1 BCTRLWGBBPOMCO-UHFFFAOYSA-N 0.000 claims 1
• UNFHOAZOCIELCW-UHFFFAOYSA-N 1,5-dihydro-1,5-benzodiazepine-2,4-dione Chemical compound N1C(=O)CC(=O)NC2=CC=CC=C21 UNFHOAZOCIELCW-UHFFFAOYSA-N 0.000 claims 1
• CBJBDCXJQSNMSZ-UHFFFAOYSA-N 1-ethyl-3,3,5-trimethyl-7-[3-[(2-methylpyridin-3-yl)methyl-[2-(4-oxothieno[3,2-c]pyridin-5-yl)ethyl]amino]propoxy]-1,5-benzodiazepine-2,4-dione Chemical compound C1=C2N(C)C(=O)C(C)(C)C(=O)N(CC)C2=CC=C1OCCCN(CCN1C(C=2C=CSC=2C=C1)=O)CC1=CC=CN=C1C CBJBDCXJQSNMSZ-UHFFFAOYSA-N 0.000 claims 1
• OXMXIXOKIIPOHL-UHFFFAOYSA-N 3-[[3-[(1-ethyl-3,3,5-trimethyl-2,4-dioxo-1,5-benzodiazepin-7-yl)oxy]propyl-(2-pyridin-3-ylethyl)amino]methyl]benzonitrile Chemical compound C1=C2N(C)C(=O)C(C)(C)C(=O)N(CC)C2=CC=C1OCCCN(CC=1C=C(C=CC=1)C#N)CCC1=CC=CN=C1 OXMXIXOKIIPOHL-UHFFFAOYSA-N 0.000 claims 1
• UVMFWOKHXJEFRH-UHFFFAOYSA-N 4-[[3-[(1-ethyl-3,3,5-trimethyl-2,4-dioxo-1,5-benzodiazepin-7-yl)oxy]propyl-[2-(7-oxofuro[2,3-c]pyridin-6-yl)ethyl]amino]methyl]benzonitrile Chemical compound C1=C2N(C)C(=O)C(C)(C)C(=O)N(CC)C2=CC=C1OCCCN(CCN1C(C=2OC=CC=2C=C1)=O)CC1=CC=C(C#N)C=C1 UVMFWOKHXJEFRH-UHFFFAOYSA-N 0.000 claims 1
• 241001024304 Mino Species 0.000 claims 1
• OWCDMRFUFMERMZ-UHFFFAOYSA-N benzenesulfonamide;hydrochloride Chemical compound Cl.NS(=O)(=O)C1=CC=CC=C1 OWCDMRFUFMERMZ-UHFFFAOYSA-N 0.000 claims 1
• 150000001557 benzodiazepines Chemical class 0.000 abstract description 3
• BEYMVCMQFKLZRH-UHFFFAOYSA-N 1-ethyl-3,3,5-trimethyl-7-[3-[2-pyridin-3-ylethyl(pyridin-4-ylmethyl)amino]propoxy]-1,5-benzodiazepine-2,4-dione;trihydrochloride Chemical compound Cl.Cl.Cl.C1=C2N(C)C(=O)C(C)(C)C(=O)N(CC)C2=CC=C1OCCCN(CC=1C=CN=CC=1)CCC1=CC=CN=C1 BEYMVCMQFKLZRH-UHFFFAOYSA-N 0.000 abstract 1
• SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 abstract 1
• 230000015572 biosynthetic process Effects 0.000 description 391
• 238000003786 synthesis reaction Methods 0.000 description 389
• 238000000034 method Methods 0.000 description 387
• 239000007858 starting material Substances 0.000 description 350
• 238000005481 NMR spectroscopy Methods 0.000 description 234
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 222
• 238000006243 chemical reaction Methods 0.000 description 191
• 238000005160 1H NMR spectroscopy Methods 0.000 description 122
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 120
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 120
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 117
• 101150041968 CDC13 gene Proteins 0.000 description 95
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 95
• 239000000843 powder Substances 0.000 description 87
• 239000000243 solution Substances 0.000 description 87
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 75
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 69
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
• 239000002904 solvent Substances 0.000 description 55
• 238000002844 melting Methods 0.000 description 54
• 230000008018 melting Effects 0.000 description 54
• 239000011541 reaction mixture Substances 0.000 description 53
• 239000002253 acid Substances 0.000 description 51
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
• 239000000203 mixture Substances 0.000 description 41
• 239000012044 organic layer Substances 0.000 description 38
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
• 239000012264 purified product Substances 0.000 description 36
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
• 238000000605 extraction Methods 0.000 description 33
• 238000010898 silica gel chromatography Methods 0.000 description 33
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 29
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
• 150000001412 amines Chemical class 0.000 description 28
• 239000007787 solid Substances 0.000 description 28
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• 238000012360 testing method Methods 0.000 description 27
• 108091006146 Channels Proteins 0.000 description 26
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
• 150000007514 bases Chemical class 0.000 description 24
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
• 210000004027 cell Anatomy 0.000 description 22
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 22
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 21
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 21
• 239000003921 oil Substances 0.000 description 21
• 235000019198 oils Nutrition 0.000 description 21
• 239000003638 chemical reducing agent Substances 0.000 description 20
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 18
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• 150000007513 acids Chemical class 0.000 description 18
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 18
• 239000007864 aqueous solution Substances 0.000 description 17
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 14
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
• 229960004132 diethyl ether Drugs 0.000 description 14
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 14
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 14
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 13
• 102100033063 G protein-activated inward rectifier potassium channel 1 Human genes 0.000 description 13
• 101000944266 Homo sapiens G protein-activated inward rectifier potassium channel 1 Proteins 0.000 description 13
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 13
• 150000001298 alcohols Chemical class 0.000 description 13
• 125000001931 aliphatic group Chemical group 0.000 description 13
• 239000003795 chemical substances by application Substances 0.000 description 13
• 150000002170 ethers Chemical class 0.000 description 13
• 229940052303 ethers for general anesthesia Drugs 0.000 description 13
• 150000002148 esters Chemical class 0.000 description 12
• 125000000623 heterocyclic group Chemical group 0.000 description 12
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 11
• 239000003814 drug Substances 0.000 description 11
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 11
• 235000019253 formic acid Nutrition 0.000 description 11
• 229910052757 nitrogen Inorganic materials 0.000 description 11
• 229910000027 potassium carbonate Inorganic materials 0.000 description 11
• 235000011181 potassium carbonates Nutrition 0.000 description 11
• 229910052938 sodium sulfate Inorganic materials 0.000 description 11
• 235000011152 sodium sulphate Nutrition 0.000 description 11
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
• 150000008065 acid anhydrides Chemical class 0.000 description 10
• 239000002299 complementary DNA Substances 0.000 description 10
• 235000011167 hydrochloric acid Nutrition 0.000 description 10
• 102100021237 G protein-activated inward rectifier potassium channel 4 Human genes 0.000 description 9
• 101000614712 Homo sapiens G protein-activated inward rectifier potassium channel 4 Proteins 0.000 description 9
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
• 150000001408 amides Chemical class 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• 125000004433 nitrogen atom Chemical group N* 0.000 description 9
• 239000000825 pharmaceutical preparation Substances 0.000 description 9
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
• 230000008569 process Effects 0.000 description 9
• 238000010992 reflux Methods 0.000 description 9
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 8
• 101100019741 Homo sapiens KCNJ3 gene Proteins 0.000 description 8
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 8
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 8
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
• 125000005605 benzo group Chemical group 0.000 description 8
• 239000012230 colorless oil Substances 0.000 description 8
• 230000002999 depolarising effect Effects 0.000 description 8
• 150000008282 halocarbons Chemical class 0.000 description 8
• MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 8
• 125000002911 monocyclic heterocycle group Chemical group 0.000 description 8
• 235000017557 sodium bicarbonate Nutrition 0.000 description 8
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
• 230000000638 stimulation Effects 0.000 description 8
• 238000003756 stirring Methods 0.000 description 8
• CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 8
• 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 8
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 7
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 7
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 7
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
• 229920002472 Starch Polymers 0.000 description 7
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 7
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