NO327635B1 - Substituerte piperazinforbindelser, anvendelse derav og farmasoytisk preparat omfattende slike - Google Patents

Info

Publication number

NO327635B1

NO327635B1 NO20040234A NO20040234A NO327635B1 NO 327635 B1 NO327635 B1 NO 327635B1 NO 20040234 A NO20040234 A NO 20040234A NO 20040234 A NO20040234 A NO 20040234A NO 327635 B1 NO327635 B1 NO 327635B1

Authority

NO

Norway

Prior art keywords

formula

compound according

compound

phenyl

alkyl

Prior art date

2001-07-19

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• 150000004885 piperazines Chemical class 0.000 title description 5
• 239000008194 pharmaceutical composition Substances 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 248
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
• 201000010099 disease Diseases 0.000 claims abstract description 15
• 206010002383 Angina Pectoris Diseases 0.000 claims abstract description 12
• 241000124008 Mammalia Species 0.000 claims abstract description 9
• 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 7
• 206010022562 Intermittent claudication Diseases 0.000 claims abstract description 6
• 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 6
• 208000021156 intermittent vascular claudication Diseases 0.000 claims abstract description 6
• 208000010125 myocardial infarction Diseases 0.000 claims abstract description 6
• 206010003130 Arrhythmia supraventricular Diseases 0.000 claims abstract description 5
• 206010007559 Cardiac failure congestive Diseases 0.000 claims abstract description 5
• 208000007718 Stable Angina Diseases 0.000 claims abstract description 5
• 206010047281 Ventricular arrhythmia Diseases 0.000 claims abstract description 5
• -1 C3-C7-cycloalkyl Chemical group 0.000 claims description 111
• 238000002360 preparation method Methods 0.000 claims description 55
• 125000001424 substituent group Chemical group 0.000 claims description 54
• 229910052736 halogen Inorganic materials 0.000 claims description 32
• 150000002367 halogens Chemical class 0.000 claims description 32
• 230000003647 oxidation Effects 0.000 claims description 32
• 238000007254 oxidation reaction Methods 0.000 claims description 32
• 239000001257 hydrogen Substances 0.000 claims description 31
• 229910052739 hydrogen Inorganic materials 0.000 claims description 31
• 229910052760 oxygen Inorganic materials 0.000 claims description 31
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 30
• 239000001301 oxygen Substances 0.000 claims description 30
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 26
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
• 125000004432 carbon atom Chemical group C* 0.000 claims description 19
• 235000014113 dietary fatty acids Nutrition 0.000 claims description 17
• 239000000194 fatty acid Substances 0.000 claims description 17
• 229930195729 fatty acid Natural products 0.000 claims description 17
• 150000004665 fatty acids Chemical class 0.000 claims description 17
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
• 125000002947 alkylene group Chemical group 0.000 claims description 13
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
• 239000003112 inhibitor Substances 0.000 claims description 12
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 10
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 9
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 8
• BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 claims description 7
• 239000003814 drug Substances 0.000 claims description 7
• 210000001519 tissue Anatomy 0.000 claims description 7
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
• 229910052717 sulfur Chemical group 0.000 claims description 6
• 239000011593 sulfur Chemical group 0.000 claims description 6
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
• 125000002971 oxazolyl group Chemical group 0.000 claims description 5
• 229940079593 drug Drugs 0.000 claims description 4
• 208000014674 injury Diseases 0.000 claims description 4
• 125000001624 naphthyl group Chemical group 0.000 claims description 4
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 3
• 239000004305 biphenyl Substances 0.000 claims description 3
• 235000010290 biphenyl Nutrition 0.000 claims description 3
• 230000006378 damage Effects 0.000 claims description 3
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 3
• 210000000056 organ Anatomy 0.000 claims description 3
• 230000035939 shock Effects 0.000 claims description 3
• 210000002027 skeletal muscle Anatomy 0.000 claims description 3
• 230000008733 trauma Effects 0.000 claims description 3
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
• 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 claims description 2
• FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 claims description 2
• 229910006074 SO2NH2 Inorganic materials 0.000 claims description 2
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
• 125000004193 piperazinyl group Chemical group 0.000 claims 2
• WYDWTECDFUFLJT-UHFFFAOYSA-N 1-[4-[[5-(4-chlorophenyl)-1,2-oxazol-3-yl]methyl]piperazin-1-yl]-3-[(2-methyl-1,3-benzothiazol-5-yl)oxy]propan-2-ol Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC(O)CN(CC1)CCN1CC(=NO1)C=C1C1=CC=C(Cl)C=C1 WYDWTECDFUFLJT-UHFFFAOYSA-N 0.000 claims 1
• 150000002431 hydrogen Chemical class 0.000 claims 1
• 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 claims 1
• 125000000623 heterocyclic group Chemical group 0.000 abstract description 21
• 230000001746 atrial effect Effects 0.000 abstract description 7
• 206010002388 Angina unstable Diseases 0.000 abstract description 2
• 208000007814 Unstable Angina Diseases 0.000 abstract description 2
• 201000004332 intermediate coronary syndrome Diseases 0.000 abstract description 2
• 230000036470 plasma concentration Effects 0.000 abstract 1
• 125000000217 alkyl group Chemical group 0.000 description 58
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
• 239000000203 mixture Substances 0.000 description 55
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 53
• 238000006243 chemical reaction Methods 0.000 description 51
• 239000000243 solution Substances 0.000 description 51
• 125000001072 heteroaryl group Chemical group 0.000 description 45
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
• 125000003118 aryl group Chemical group 0.000 description 43
• 239000002904 solvent Substances 0.000 description 41
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
• 238000000034 method Methods 0.000 description 34
• 230000002829 reductive effect Effects 0.000 description 32
• 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 28
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 28
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• 125000003545 alkoxy group Chemical group 0.000 description 27
• 239000008103 glucose Substances 0.000 description 26
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
• 229910001868 water Inorganic materials 0.000 description 26
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 25
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
• 125000004181 carboxyalkyl group Chemical group 0.000 description 24
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 24
• 239000000047 product Substances 0.000 description 23
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
• 125000003342 alkenyl group Chemical group 0.000 description 20
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 20
• 239000012442 inert solvent Substances 0.000 description 19
• 125000000753 cycloalkyl group Chemical group 0.000 description 18
• 239000003826 tablet Substances 0.000 description 18
• 239000004480 active ingredient Substances 0.000 description 17
• 125000000304 alkynyl group Chemical group 0.000 description 17
• 125000000392 cycloalkenyl group Chemical group 0.000 description 16
• 230000010412 perfusion Effects 0.000 description 15
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 14
• 150000003839 salts Chemical class 0.000 description 14
• 239000000706 filtrate Substances 0.000 description 13
• 210000002216 heart Anatomy 0.000 description 13
• 239000003921 oil Substances 0.000 description 13
• 235000019198 oils Nutrition 0.000 description 13
• 239000000843 powder Substances 0.000 description 13
• 150000001412 amines Chemical class 0.000 description 12
• 238000004587 chromatography analysis Methods 0.000 description 12
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
• 125000004414 alkyl thio group Chemical group 0.000 description 11
• 229910052757 nitrogen Inorganic materials 0.000 description 11
• 229930194542 Keto Natural products 0.000 description 10
• 125000002252 acyl group Chemical group 0.000 description 10
• 125000004442 acylamino group Chemical group 0.000 description 10
• 125000004423 acyloxy group Chemical group 0.000 description 10
• 125000005110 aryl thio group Chemical group 0.000 description 10
• 125000004104 aryloxy group Chemical group 0.000 description 10
• 239000002585 base Substances 0.000 description 10
• 239000003795 chemical substances by application Substances 0.000 description 10
• 125000005553 heteroaryloxy group Chemical group 0.000 description 10
• 125000000468 ketone group Chemical group 0.000 description 10
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 10
• 150000003573 thiols Chemical class 0.000 description 10
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 9
• 125000000033 alkoxyamino group Chemical group 0.000 description 9
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 9
• 125000006598 aminocarbonylamino group Chemical group 0.000 description 9
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 9
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 9
• 230000000747 cardiac effect Effects 0.000 description 9
• 230000034659 glycolysis Effects 0.000 description 9
• 125000005368 heteroarylthio group Chemical group 0.000 description 9
• 125000004470 heterocyclooxy group Chemical group 0.000 description 9
• 125000004468 heterocyclylthio group Chemical group 0.000 description 9
• 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 9
• 239000004615 ingredient Substances 0.000 description 9
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 9
• 238000012360 testing method Methods 0.000 description 9
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 8
• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
• 125000000547 substituted alkyl group Chemical group 0.000 description 8
• CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 8
• HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 7
• 230000000694 effects Effects 0.000 description 7
• 238000009472 formulation Methods 0.000 description 7
• 239000011541 reaction mixture Substances 0.000 description 7
• 239000007787 solid Substances 0.000 description 7
• YBJJKPOQWUEERM-UHFFFAOYSA-N 1-[(2-methyl-1,3-benzothiazol-5-yl)oxy]-3-piperazin-1-ylpropan-2-ol Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC(O)CN1CCNCC1 YBJJKPOQWUEERM-UHFFFAOYSA-N 0.000 description 6
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
• 238000004458 analytical method Methods 0.000 description 6
• 125000004429 atom Chemical group 0.000 description 6
• 235000013405 beer Nutrition 0.000 description 6
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• 238000005259 measurement Methods 0.000 description 6
• 150000007530 organic bases Chemical class 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 238000010992 reflux Methods 0.000 description 6
• 239000007858 starting material Substances 0.000 description 6
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
• 239000002775 capsule Substances 0.000 description 5
• 239000007789 gas Substances 0.000 description 5
• 150000002430 hydrocarbons Chemical group 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 230000036316 preload Effects 0.000 description 5
• 125000003107 substituted aryl group Chemical group 0.000 description 5
• 239000000725 suspension Substances 0.000 description 5
• TWENMNQDGGICPL-UHFFFAOYSA-N tert-butyl 4-[2-hydroxy-3-[(2-methyl-1,3-benzothiazol-5-yl)oxy]propyl]piperazine-1-carboxylate Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC(O)CN1CCN(C(=O)OC(C)(C)C)CC1 TWENMNQDGGICPL-UHFFFAOYSA-N 0.000 description 5
• LAKVUPMDDFICNR-UHFFFAOYSA-N 2-methyl-1,3-benzothiazol-5-ol Chemical compound OC1=CC=C2SC(C)=NC2=C1 LAKVUPMDDFICNR-UHFFFAOYSA-N 0.000 description 4
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
• XKLMZUWKNUAPSZ-UHFFFAOYSA-N N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide Chemical compound COC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC=2C(=CC=CC=2C)C)CC1 XKLMZUWKNUAPSZ-UHFFFAOYSA-N 0.000 description 4
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• 235000019270 ammonium chloride Nutrition 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 239000012267 brine Substances 0.000 description 4
• 238000004440 column chromatography Methods 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 230000002107 myocardial effect Effects 0.000 description 4
• 230000036284 oxygen consumption Effects 0.000 description 4
• 239000012071 phase Substances 0.000 description 4
• 239000006187 pill Substances 0.000 description 4
• 238000012746 preparative thin layer chromatography Methods 0.000 description 4
• 229930195734 saturated hydrocarbon Natural products 0.000 description 4
• 239000000741 silica gel Substances 0.000 description 4
• 229910002027 silica gel Inorganic materials 0.000 description 4
• 229910052938 sodium sulfate Inorganic materials 0.000 description 4
• 235000011152 sodium sulphate Nutrition 0.000 description 4
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
• 238000003756 stirring Methods 0.000 description 4
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• 230000001225 therapeutic effect Effects 0.000 description 4
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
• XCARGDPHZYJCMU-UHFFFAOYSA-N 2-chloro-n'-hydroxyethanimidamide Chemical compound ClCC(N)=NO XCARGDPHZYJCMU-UHFFFAOYSA-N 0.000 description 3
• YSPRCDGVFRVBED-UHFFFAOYSA-N 2-methyl-5-(oxiran-2-ylmethoxy)-1,3-benzothiazole Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC1CO1 YSPRCDGVFRVBED-UHFFFAOYSA-N 0.000 description 3
• ZLQQUIHBQATFOP-UHFFFAOYSA-N 3-(4-tert-butylphenyl)-5-(chloromethyl)-1,2,4-oxadiazole Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=NOC(CCl)=N1 ZLQQUIHBQATFOP-UHFFFAOYSA-N 0.000 description 3
• 230000002407 ATP formation Effects 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• 125000003710 aryl alkyl group Chemical group 0.000 description 3
• XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
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