NZ530705A - Substituted piperazine compounds and their use as fatty acid oxidation inhibitors - Google Patents

Info

Publication number

NZ530705A

NZ530705A NZ530705A NZ53070502A NZ530705A NZ 530705 A NZ530705 A NZ 530705A NZ 530705 A NZ530705 A NZ 530705A NZ 53070502 A NZ53070502 A NZ 53070502A NZ 530705 A NZ530705 A NZ 530705A

Authority

NZ

New Zealand

Prior art keywords

compound

formula

yloxy

propan

methyl

Prior art date

2001-07-19

Links

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• 230000003647 oxidation Effects 0.000 title claims abstract description 35
• 238000007254 oxidation reaction Methods 0.000 title claims abstract description 35
• 235000014113 dietary fatty acids Nutrition 0.000 title claims abstract description 19
• 239000000194 fatty acid Substances 0.000 title claims abstract description 19
• 229930195729 fatty acid Natural products 0.000 title claims abstract description 19
• 150000004665 fatty acids Chemical class 0.000 title claims abstract description 19
• 239000003112 inhibitor Substances 0.000 title claims abstract description 15
• 150000004885 piperazines Chemical class 0.000 title description 6
• 150000001875 compounds Chemical class 0.000 claims abstract description 242
• 238000002360 preparation method Methods 0.000 claims abstract description 53
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 49
• 239000001257 hydrogen Substances 0.000 claims abstract description 38
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 38
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 32
• 239000001301 oxygen Substances 0.000 claims abstract description 32
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 32
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 22
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 20
• 201000010099 disease Diseases 0.000 claims abstract description 17
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
• 125000002947 alkylene group Chemical group 0.000 claims abstract description 15
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
• 241000124008 Mammalia Species 0.000 claims abstract description 9
• 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 9
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 7
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 7
• 239000011593 sulfur Chemical group 0.000 claims abstract description 7
• 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 6
• 206010047281 Ventricular arrhythmia Diseases 0.000 claims abstract description 5
• 230000006378 damage Effects 0.000 claims abstract description 5
• 206010007559 Cardiac failure congestive Diseases 0.000 claims abstract description 4
• 125000002950 monocyclic group Chemical group 0.000 claims abstract description 3
• 210000002027 skeletal muscle Anatomy 0.000 claims abstract 2
• -1 2-cyclohexylbenzo-1,3-thiazol-5-yl Chemical group 0.000 claims description 108
• 125000000217 alkyl group Chemical group 0.000 claims description 66
• 239000000203 mixture Substances 0.000 claims description 65
• 238000000034 method Methods 0.000 claims description 39
• 125000003545 alkoxy group Chemical group 0.000 claims description 30
• 229910052736 halogen Inorganic materials 0.000 claims description 29
• 150000002367 halogens Chemical class 0.000 claims description 29
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 19
• 206010002383 Angina Pectoris Diseases 0.000 claims description 10
• 230000034659 glycolysis Effects 0.000 claims description 10
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
• 125000004193 piperazinyl group Chemical group 0.000 claims description 10
• 230000000694 effects Effects 0.000 claims description 8
• 210000001519 tissue Anatomy 0.000 claims description 7
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 6
• 230000002107 myocardial effect Effects 0.000 claims description 6
• BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 claims description 5
• 206010022562 Intermittent claudication Diseases 0.000 claims description 5
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 5
• 208000021156 intermittent vascular claudication Diseases 0.000 claims description 5
• 208000010125 myocardial infarction Diseases 0.000 claims description 5
• 206010003130 Arrhythmia supraventricular Diseases 0.000 claims description 4
• 208000007718 Stable Angina Diseases 0.000 claims description 4
• 208000014674 injury Diseases 0.000 claims description 4
• 239000000463 material Substances 0.000 claims description 4
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
• 208000028867 ischemia Diseases 0.000 claims description 3
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 3
• 230000005226 mechanical processes and functions Effects 0.000 claims description 3
• 210000000056 organ Anatomy 0.000 claims description 3
• 230000035939 shock Effects 0.000 claims description 3
• 230000008733 trauma Effects 0.000 claims description 3
• FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 claims description 2
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
• 230000008569 process Effects 0.000 claims description 2
• 239000000758 substrate Substances 0.000 claims description 2
• 230000007306 turnover Effects 0.000 claims description 2
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
• 238000012986 modification Methods 0.000 claims 2
• 230000004048 modification Effects 0.000 claims 2
• 239000002126 C01EB10 - Adenosine Substances 0.000 claims 1
• 229960005305 adenosine Drugs 0.000 claims 1
• 230000035479 physiological effects, processes and functions Effects 0.000 claims 1
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims 1
• 125000000623 heterocyclic group Chemical group 0.000 abstract description 23
• 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 2
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
• 238000006243 chemical reaction Methods 0.000 description 57
• 125000001424 substituent group Chemical group 0.000 description 52
• 239000000243 solution Substances 0.000 description 50
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 46
• 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 39
• 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 27
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• 239000004480 active ingredient Substances 0.000 description 27
• 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 27
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 25
• 125000004181 carboxyalkyl group Chemical group 0.000 description 25
• 239000008103 glucose Substances 0.000 description 25
• 125000004093 cyano group Chemical group *C#N 0.000 description 24
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 24
• 239000000047 product Substances 0.000 description 23
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 21
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 21
• 125000003342 alkenyl group Chemical group 0.000 description 20
• 125000000753 cycloalkyl group Chemical group 0.000 description 20
• 239000012442 inert solvent Substances 0.000 description 19
• 239000004615 ingredient Substances 0.000 description 19
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
• 150000001412 amines Chemical class 0.000 description 18
• 125000000392 cycloalkenyl group Chemical group 0.000 description 18
• 125000000304 alkynyl group Chemical group 0.000 description 17
• 239000003826 tablet Substances 0.000 description 17
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 15
• 230000010412 perfusion Effects 0.000 description 15
• 239000002253 acid Substances 0.000 description 14
• 150000002431 hydrogen Chemical class 0.000 description 14
• 239000000706 filtrate Substances 0.000 description 13
• 239000003921 oil Substances 0.000 description 13
• 235000019198 oils Nutrition 0.000 description 13
• 150000003839 salts Chemical class 0.000 description 13
• 238000004587 chromatography analysis Methods 0.000 description 12
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
• 239000000843 powder Substances 0.000 description 12
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
• 125000004414 alkyl thio group Chemical group 0.000 description 11
• 229910052757 nitrogen Inorganic materials 0.000 description 11
• 125000000547 substituted alkyl group Chemical group 0.000 description 11
• 229930194542 Keto Natural products 0.000 description 10
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 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
• 125000000468 ketone group Chemical group 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
• 125000006598 aminocarbonylamino group Chemical group 0.000 description 9
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 9
• 230000000747 cardiac effect Effects 0.000 description 9
• 239000003795 chemical substances by application Substances 0.000 description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
• 125000005553 heteroaryloxy 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
• 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
• 238000003756 stirring Methods 0.000 description 9
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 9
• VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 description 8
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-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
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 8
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 8
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
• 238000009472 formulation Methods 0.000 description 7
• 125000005368 heteroarylthio group Chemical group 0.000 description 7
• 239000007787 solid Substances 0.000 description 7
• 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
• 229920002472 Starch Polymers 0.000 description 6
• 125000004429 atom Chemical group 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
• 235000019359 magnesium stearate Nutrition 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
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
• 238000010992 reflux Methods 0.000 description 6
• 235000019698 starch Nutrition 0.000 description 6
• LAKVUPMDDFICNR-UHFFFAOYSA-N 2-methyl-1,3-benzothiazol-5-ol Chemical compound OC1=CC=C2SC(C)=NC2=C1 LAKVUPMDDFICNR-UHFFFAOYSA-N 0.000 description 5
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 5
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
• 239000007864 aqueous solution Substances 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• 230000001746 atrial effect Effects 0.000 description 5
• 239000002775 capsule Substances 0.000 description 5
• 238000000605 extraction Methods 0.000 description 5
• 239000007789 gas Substances 0.000 description 5
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 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
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 5
• 239000008108 microcrystalline cellulose Substances 0.000 description 5
• 229940016286 microcrystalline cellulose Drugs 0.000 description 5
• 239000012071 phase Substances 0.000 description 5
• 230000036316 preload Effects 0.000 description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
• 239000008107 starch Substances 0.000 description 5
• 125000005017 substituted alkenyl group Chemical group 0.000 description 5
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 5
• 239000000725 suspension Substances 0.000 description 5
• IPCSVZSSVZVIGE-BFDQMJDGSA-N 5-tritiohexadecanoic acid Chemical compound C(CCCC(CCCCCCCCCCC)[3H])(=O)O IPCSVZSSVZVIGE-BFDQMJDGSA-N 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 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
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-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
• 239000012267 brine Substances 0.000 description 4
• 238000004440 column chromatography Methods 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 238000011067 equilibration Methods 0.000 description 4
• 150000002148 esters Chemical class 0.000 description 4
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
• 238000005259 measurement Methods 0.000 description 4
• 230000036284 oxygen consumption Effects 0.000 description 4
• 239000006187 pill Substances 0.000 description 4
• 239000002243 precursor Substances 0.000 description 4
• 238000012746 preparative thin layer chromatography Methods 0.000 description 4
• 238000010791 quenching Methods 0.000 description 4
• 239000011541 reaction mixture Substances 0.000 description 4
• 239000000523 sample Substances 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
• 208000024891 symptom Diseases 0.000 description 4
• 239000000454 talc Substances 0.000 description 4
• 229910052623 talc Inorganic materials 0.000 description 4
• 235000012222 talc Nutrition 0.000 description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
• CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 4
• DGQOCLATAPFASR-UHFFFAOYSA-N tetrahydroxy-1,4-benzoquinone Chemical compound OC1=C(O)C(=O)C(O)=C(O)C1=O DGQOCLATAPFASR-UHFFFAOYSA-N 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
• 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
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
• NAWDYIZEMPQZHO-UHFFFAOYSA-N ytterbium Chemical compound [Yb] NAWDYIZEMPQZHO-UHFFFAOYSA-N 0.000 description 4
• OFJBYLCQNJHFMI-UHFFFAOYSA-N 2,5-dihydro-1,2-oxazole Chemical class C1ONC=C1 OFJBYLCQNJHFMI-UHFFFAOYSA-N 0.000 description 3
• XCARGDPHZYJCMU-UHFFFAOYSA-N 2-chloro-n'-hydroxyethanimidamide Chemical compound ClCC(N)=NO XCARGDPHZYJCMU-UHFFFAOYSA-N 0.000 description 3
• 230000002407 ATP formation Effects 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-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
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 229930195725 Mannitol Natural products 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
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-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
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