SK286774B6 - Substituované N-fenyl-2-hydroxy-2-metyl-3,3,3- trifluórpropánamidové deriváty, spôsob ich prípravy a farmaceutický prostriedok, ktorý ich obsahuje - Google Patents

Info

Publication number

SK286774B6

SK286774B6 SK300-2002A SK3002002A SK286774B6 SK 286774 B6 SK286774 B6 SK 286774B6 SK 3002002 A SK3002002 A SK 3002002A SK 286774 B6 SK286774 B6 SK 286774B6

Authority

SK

Slovakia

Prior art keywords

optionally substituted

group

methyl

groups

alkyl

Prior art date

1999-09-04

Links

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• Global Dossier
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• 238000000034 method Methods 0.000 title claims abstract description 194
• 238000002360 preparation method Methods 0.000 title claims abstract description 12
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 5
• 230000008569 process Effects 0.000 title claims description 6
• JHSBXNFXGVSVQO-UHFFFAOYSA-N 3,3,3-trifluoro-2-hydroxy-2-methyl-n-phenylpropanamide Chemical class FC(F)(F)C(O)(C)C(=O)NC1=CC=CC=C1 JHSBXNFXGVSVQO-UHFFFAOYSA-N 0.000 title 1
• -1 chloro, bromo, methyl Chemical group 0.000 claims abstract description 302
• 150000001875 compounds Chemical class 0.000 claims abstract description 250
• 150000003839 salts Chemical class 0.000 claims abstract description 48
• 238000001727 in vivo Methods 0.000 claims abstract description 46
• 150000002148 esters Chemical class 0.000 claims abstract description 44
• 241001465754 Metazoa Species 0.000 claims abstract description 26
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 23
• 239000001257 hydrogen Substances 0.000 claims abstract description 22
• 241000282414 Homo sapiens Species 0.000 claims abstract description 18
• 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 15
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 12
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 12
• 238000004519 manufacturing process Methods 0.000 claims abstract description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 195
• 125000000217 alkyl group Chemical group 0.000 claims description 144
• 125000004432 carbon atom Chemical group C* 0.000 claims description 112
• 229910052799 carbon Inorganic materials 0.000 claims description 93
• 229910052757 nitrogen Inorganic materials 0.000 claims description 87
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 69
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 45
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 44
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 44
• 229910052736 halogen Inorganic materials 0.000 claims description 40
• 150000002367 halogens Chemical class 0.000 claims description 40
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 35
• 229910052731 fluorine Inorganic materials 0.000 claims description 30
• 125000001072 heteroaryl group Chemical group 0.000 claims description 30
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
• 229910052801 chlorine Inorganic materials 0.000 claims description 29
• 239000000460 chlorine Substances 0.000 claims description 25
• 125000000623 heterocyclic group Chemical group 0.000 claims description 24
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
• 125000005505 thiomorpholino group Chemical group 0.000 claims description 23
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 20
• 229910052717 sulfur Inorganic materials 0.000 claims description 20
• 238000011282 treatment Methods 0.000 claims description 20
• 239000002253 acid Substances 0.000 claims description 19
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
• 239000011737 fluorine Substances 0.000 claims description 17
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 16
• 206010012601 diabetes mellitus Diseases 0.000 claims description 16
• 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 15
• 125000005842 heteroatom Chemical group 0.000 claims description 15
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 14
• 125000003545 alkoxy group Chemical group 0.000 claims description 14
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 14
• 229910052794 bromium Inorganic materials 0.000 claims description 14
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
• 125000006239 protecting group Chemical group 0.000 claims description 14
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
• 239000003814 drug Substances 0.000 claims description 13
• 229910052760 oxygen Inorganic materials 0.000 claims description 13
• 239000001301 oxygen Substances 0.000 claims description 13
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
• 239000011593 sulfur Substances 0.000 claims description 11
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
• 208000018262 Peripheral vascular disease Diseases 0.000 claims description 10
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 10
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
• 208000031225 myocardial ischemia Diseases 0.000 claims description 10
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 9
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 8
• 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 7
• 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 6
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 6
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 5
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 4
• 230000001590 oxidative effect Effects 0.000 claims description 4
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 3
• DLTGWXUOKOEXOM-MRXNPFEDSA-N (2r)-n-(2-chloro-3-morpholin-4-yl-4-propan-2-ylsulfonylphenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide Chemical compound CC(C)S(=O)(=O)C1=CC=C(NC(=O)[C@@](C)(O)C(F)(F)F)C(Cl)=C1N1CCOCC1 DLTGWXUOKOEXOM-MRXNPFEDSA-N 0.000 claims description 2
• 125000006241 alcohol protecting group Chemical group 0.000 claims description 2
• 230000008878 coupling Effects 0.000 claims description 2
• 238000010168 coupling process Methods 0.000 claims description 2
• 238000005859 coupling reaction Methods 0.000 claims description 2
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
• 125000003884 phenylalkyl group Chemical group 0.000 claims description 2
• YVFKGEVOGBEGBA-OAHLLOKOSA-N (2r)-n-[2-chloro-4-ethylsulfonyl-3-(1-oxo-1,4-thiazinan-4-yl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide Chemical compound CCS(=O)(=O)C1=CC=C(NC(=O)[C@@](C)(O)C(F)(F)F)C(Cl)=C1N1CCS(=O)CC1 YVFKGEVOGBEGBA-OAHLLOKOSA-N 0.000 claims 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims 1
• 229910052782 aluminium Inorganic materials 0.000 claims 1
• 239000003085 diluting agent Substances 0.000 claims 1
• 125000006413 ring segment Chemical group 0.000 claims 1
• 230000000694 effects Effects 0.000 abstract description 47
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 333
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 169
• 239000000243 solution Substances 0.000 description 153
• 239000000203 mixture Substances 0.000 description 122
• 235000019439 ethyl acetate Nutrition 0.000 description 111
• 238000005481 NMR spectroscopy Methods 0.000 description 100
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 81
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 75
• 238000001704 evaporation Methods 0.000 description 64
• 230000008020 evaporation Effects 0.000 description 64
• 239000003039 volatile agent Substances 0.000 description 61
• 150000001721 carbon Chemical group 0.000 description 60
• 239000007787 solid Substances 0.000 description 59
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 54
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 51
• 239000007858 starting material Substances 0.000 description 50
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 46
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 44
• 239000011541 reaction mixture Substances 0.000 description 36
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 34
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
• 238000006243 chemical reaction Methods 0.000 description 31
• 239000000741 silica gel Substances 0.000 description 25
• 229910002027 silica gel Inorganic materials 0.000 description 25
• 238000010898 silica gel chromatography Methods 0.000 description 25
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• 238000004587 chromatography analysis Methods 0.000 description 23
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
• 239000000725 suspension Substances 0.000 description 18
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 17
• 229910052786 argon Inorganic materials 0.000 description 17
• CPIHPRQKNLHTQU-SECBINFHSA-N (2r)-n-(2-chloro-3-iodophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide Chemical compound FC(F)(F)[C@@](O)(C)C(=O)NC1=CC=CC(I)=C1Cl CPIHPRQKNLHTQU-SECBINFHSA-N 0.000 description 16
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 16
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
• 125000003277 amino group Chemical group 0.000 description 16
• 239000000284 extract Substances 0.000 description 16
• 125000004193 piperazinyl group Chemical group 0.000 description 16
• 125000004076 pyridyl group Chemical group 0.000 description 16
• 229920006395 saturated elastomer Polymers 0.000 description 16
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 15
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 15
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 14
• 125000005843 halogen group Chemical group 0.000 description 14
• 239000012044 organic layer Substances 0.000 description 14
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 14
• 238000003756 stirring Methods 0.000 description 14
• 239000006260 foam Substances 0.000 description 13
• 239000012074 organic phase Substances 0.000 description 13
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 12
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 12
• 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 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
• 239000008103 glucose Substances 0.000 description 12
• 238000007254 oxidation reaction Methods 0.000 description 12
• 239000000047 product Substances 0.000 description 12
• DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 12
• 239000005909 Kieselgur Substances 0.000 description 11
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical class [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 11
• 229960000583 acetic acid Drugs 0.000 description 11
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
• 230000003647 oxidation Effects 0.000 description 11
• RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 11
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 10
• 125000002252 acyl group Chemical group 0.000 description 10
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 10
• 201000010099 disease Diseases 0.000 description 10
• XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 10
• 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 10
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 10
• 239000002904 solvent Substances 0.000 description 10
• 125000004434 sulfur atom Chemical group 0.000 description 10
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 9
• 125000002393 azetidinyl group Chemical group 0.000 description 9
• 239000012362 glacial acetic acid Substances 0.000 description 9
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 9
• 239000003921 oil Substances 0.000 description 9
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
• UWKQJZCTQGMHKD-UHFFFAOYSA-N 2,6-di-tert-butylpyridine Chemical compound CC(C)(C)C1=CC=CC(C(C)(C)C)=N1 UWKQJZCTQGMHKD-UHFFFAOYSA-N 0.000 description 8
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 8
• ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 8
• ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 8
• 102000053067 Pyruvate Dehydrogenase Acetyl-Transferring Kinase Human genes 0.000 description 8
• 108700009582 Pyruvate Dehydrogenase Acetyl-Transferring Kinase Proteins 0.000 description 8
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 8
• 210000004027 cell Anatomy 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 8
• MZBSJLAGBUNNLH-UHFFFAOYSA-N 3,3,3-trifluoropropanamide Chemical compound NC(=O)CC(F)(F)F MZBSJLAGBUNNLH-UHFFFAOYSA-N 0.000 description 7
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
• LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 7
• 241000700159 Rattus Species 0.000 description 7
• 125000004644 alkyl sulfinyl group Chemical group 0.000 description 7
• 238000003556 assay Methods 0.000 description 7
• 125000004429 atom Chemical group 0.000 description 7
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
• 125000003226 pyrazolyl group Chemical group 0.000 description 7
• 125000001422 pyrrolinyl group Chemical group 0.000 description 7
• 125000000168 pyrrolyl group Chemical group 0.000 description 7
• 229940076788 pyruvate Drugs 0.000 description 7
• 210000001519 tissue Anatomy 0.000 description 7
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
• 150000001204 N-oxides Chemical class 0.000 description 6
• BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 6
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
• 239000012300 argon atmosphere Substances 0.000 description 6
• 239000002585 base Substances 0.000 description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 229910002092 carbon dioxide Inorganic materials 0.000 description 6
• 238000004440 column chromatography Methods 0.000 description 6
• JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 6
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 6
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