JP2011503005A5

JP2011503005A5 -

Download PDF

Info

Publication number: JP2011503005A5
Authority: JP; Japan
Prior art keywords: hydroxy; methyl; trimethyl; dienyl; dioxocyclohexa
Prior art date: 2008-11-04
Legal status : Granted

Application number

JP2010532329A

Other languages

English (en)

Japanese (ja)

Other versions

JP5755881B2 (ja

JP2011503005A (ja

Filing date

2008-11-04

Publication date

2012-12-20

2008-11-04 Application filed filed Critical

2008-11-04 Priority claimed from PCT/US2008/082374 external-priority patent/WO2009061744A2/en

2011-01-27 Publication of JP2011503005A publication Critical patent/JP2011503005A/ja

2012-12-20 Publication of JP2011503005A5 publication Critical patent/JP2011503005A5/ja

2015-07-29 Application granted granted Critical

2015-07-29 Publication of JP5755881B2 publication Critical patent/JP5755881B2/ja

Status Active legal-status Critical Current

2028-11-04 Anticipated expiration legal-status Critical

Links

150000001875 compounds Chemical class 0.000 description 216
-1 6-amino-3-methyl-2,4-dioxo-1-phenyl-1,2,3,4-tetrahydropyrimidin-5-yl Chemical group 0.000 description 159
239000000090 biomarker Substances 0.000 description 134
239000000203 mixture Substances 0.000 description 108
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 98
150000003839 salts Chemical class 0.000 description 96
229910052739 hydrogen Inorganic materials 0.000 description 92
239000001257 hydrogen Substances 0.000 description 90
238000000034 method Methods 0.000 description 89
239000000651 prodrug Substances 0.000 description 65
229940002612 prodrug Drugs 0.000 description 65
201000010099 disease Diseases 0.000 description 62
239000000243 solution Substances 0.000 description 62
208000012268 mitochondrial disease Diseases 0.000 description 60
239000002207 metabolite Substances 0.000 description 58
239000012453 solvate Substances 0.000 description 57
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 56
210000004027 cell Anatomy 0.000 description 55
150000004677 hydrates Chemical class 0.000 description 54
125000003118 aryl group Chemical group 0.000 description 51
ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 48
235000017471 coenzyme Q10 Nutrition 0.000 description 47
229910052757 nitrogen Inorganic materials 0.000 description 41
RLNWRDKVJSXXPP-UHFFFAOYSA-N tert-butyl 2-[(2-bromoanilino)methyl]piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1CNC1=CC=CC=C1Br RLNWRDKVJSXXPP-UHFFFAOYSA-N 0.000 description 41
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 40
229910052760 oxygen Inorganic materials 0.000 description 37
208000024412 Friedreich ataxia Diseases 0.000 description 36
208000035475 disorder Diseases 0.000 description 35
239000007787 solid Substances 0.000 description 35
150000002431 hydrogen Chemical class 0.000 description 34
239000003921 oil Substances 0.000 description 34
235000019198 oils Nutrition 0.000 description 34
208000024891 symptom Diseases 0.000 description 34
125000000623 heterocyclic group Chemical group 0.000 description 33
230000003647 oxidation Effects 0.000 description 33
238000007254 oxidation reaction Methods 0.000 description 33
230000008878 coupling Effects 0.000 description 31
238000010168 coupling process Methods 0.000 description 31
238000005859 coupling reaction Methods 0.000 description 31
125000001072 heteroaryl group Chemical group 0.000 description 31
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 description 30
150000001408 amides Chemical class 0.000 description 30
230000002829 reductive effect Effects 0.000 description 28
201000000639 Leber hereditary optic neuropathy Diseases 0.000 description 27
125000004356 hydroxy functional group Chemical group O* 0.000 description 26
238000011282 treatment Methods 0.000 description 26
229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 25
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 24
102000018832 Cytochromes Human genes 0.000 description 24
108010052832 Cytochromes Proteins 0.000 description 24
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
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 23
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 23
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 23
125000004433 nitrogen atom Chemical group N* 0.000 description 23
239000001301 oxygen Substances 0.000 description 23
125000000217 alkyl group Chemical group 0.000 description 22
210000002950 fibroblast Anatomy 0.000 description 22
230000009467 reduction Effects 0.000 description 22
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 21
238000006243 chemical reaction Methods 0.000 description 21
239000011734 sodium Substances 0.000 description 21
208000018737 Parkinson disease Diseases 0.000 description 20
210000004369 blood Anatomy 0.000 description 19
239000008280 blood Substances 0.000 description 19
238000003818 flash chromatography Methods 0.000 description 19
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 16
LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 16
XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate 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](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 16
210000001175 cerebrospinal fluid Anatomy 0.000 description 16
229940076788 pyruvate Drugs 0.000 description 16
230000035806 respiratory chain Effects 0.000 description 16
238000006467 substitution reaction Methods 0.000 description 16
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
208000006011 Stroke Diseases 0.000 description 15
125000001246 bromo group Chemical group Br* 0.000 description 15
125000001309 chloro group Chemical group Cl* 0.000 description 15
239000003814 drug Substances 0.000 description 15
235000019439 ethyl acetate Nutrition 0.000 description 15
BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide 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](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 15
230000001629 suppression Effects 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
201000009623 Myopathy Diseases 0.000 description 14
DRBBFCLWYRJSJZ-UHFFFAOYSA-N N-phosphocreatine Chemical compound OC(=O)CN(C)C(=N)NP(O)(O)=O DRBBFCLWYRJSJZ-UHFFFAOYSA-N 0.000 description 14
125000003342 alkenyl group Chemical group 0.000 description 14
125000000304 alkynyl group Chemical group 0.000 description 14
239000002609 medium Substances 0.000 description 14
201000002169 Mitochondrial myopathy Diseases 0.000 description 13
208000023692 inborn mitochondrial myopathy Diseases 0.000 description 13
239000002904 solvent Substances 0.000 description 13
208000011580 syndromic disease Diseases 0.000 description 13
238000012360 testing method Methods 0.000 description 13
210000001519 tissue Anatomy 0.000 description 13
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
125000003545 alkoxy group Chemical group 0.000 description 12
DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 12
230000002708 enhancing effect Effects 0.000 description 12
230000004065 mitochondrial dysfunction Effects 0.000 description 12
210000002381 plasma Anatomy 0.000 description 12
239000000843 powder Substances 0.000 description 12
229920006395 saturated elastomer Polymers 0.000 description 12
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 11
230000000694 effects Effects 0.000 description 11
238000012216 screening Methods 0.000 description 11
238000002560 therapeutic procedure Methods 0.000 description 11
JJRHJDUELSYTPF-UHFFFAOYSA-N 2-hydroxy-n-(2-hydroxyethyl)-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CC1=C(C)C(=O)C(CCC(C)(O)C(=O)NCCO)=C(C)C1=O JJRHJDUELSYTPF-UHFFFAOYSA-N 0.000 description 10
HCAJQHYUCKICQH-VPENINKCSA-N 8-Oxo-7,8-dihydro-2'-deoxyguanosine Chemical compound C1=2NC(N)=NC(=O)C=2NC(=O)N1[C@H]1C[C@H](O)[C@@H](CO)O1 HCAJQHYUCKICQH-VPENINKCSA-N 0.000 description 10
208000014644 Brain disease Diseases 0.000 description 10
208000032274 Encephalopathy Diseases 0.000 description 10
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 10
208000021642 Muscular disease Diseases 0.000 description 10
230000009286 beneficial effect Effects 0.000 description 10
230000037396 body weight Effects 0.000 description 10
125000004432 carbon atom Chemical group C* 0.000 description 10
230000001684 chronic effect Effects 0.000 description 10
239000012530 fluid Substances 0.000 description 10
230000002438 mitochondrial effect Effects 0.000 description 10
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 10
230000002861 ventricular Effects 0.000 description 10
BAANPNDZFYBQIB-UHFFFAOYSA-N 2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CC1=C(C)C(=O)C(CCC(C)(O)C(N)=O)=C(C)C1=O BAANPNDZFYBQIB-UHFFFAOYSA-N 0.000 description 9
DCGQEWREDCYBSF-UHFFFAOYSA-N 2-hydroxy-n-[2-(2-hydroxyethoxy)ethyl]-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CC1=C(C)C(=O)C(CCC(C)(O)C(=O)NCCOCCO)=C(C)C1=O DCGQEWREDCYBSF-UHFFFAOYSA-N 0.000 description 9
206010003805 Autism Diseases 0.000 description 9
208000020706 Autistic disease Diseases 0.000 description 9
208000012202 Pervasive developmental disease Diseases 0.000 description 9
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
WDJHALXBUFZDSR-UHFFFAOYSA-M acetoacetate Chemical compound CC(=O)CC([O-])=O WDJHALXBUFZDSR-UHFFFAOYSA-M 0.000 description 9
206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 9
208000029560 autism spectrum disease Diseases 0.000 description 9
230000007812 deficiency Effects 0.000 description 9
239000000835 fiber Substances 0.000 description 9
125000005842 heteroatom Chemical group 0.000 description 9
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 9
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 9
230000000241 respiratory effect Effects 0.000 description 9
QIXDHVDGPXBRRD-UHFFFAOYSA-N 2,3,5-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound CC1=CC(=O)C(C)=C(C)C1=O QIXDHVDGPXBRRD-UHFFFAOYSA-N 0.000 description 8
NZTUDHWGKIMDSD-UHFFFAOYSA-N 2-[4-(4-benzylpiperazin-1-yl)-3-hydroxy-3-methyl-4-oxobutyl]-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)N2CCN(CC=3C=CC=CC=3)CC2)=C1C NZTUDHWGKIMDSD-UHFFFAOYSA-N 0.000 description 8
VLIAPFJRVHLZRF-UHFFFAOYSA-N 2-hydroxy-n-(2-hydroxypropyl)-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CC(O)CNC(=O)C(C)(O)CCC1=C(C)C(=O)C(C)=C(C)C1=O VLIAPFJRVHLZRF-UHFFFAOYSA-N 0.000 description 8
SIPLUPOCGVTMNA-UHFFFAOYSA-N 2-hydroxy-n-(3-hydroxypropyl)-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CC1=C(C)C(=O)C(CCC(C)(O)C(=O)NCCCO)=C(C)C1=O SIPLUPOCGVTMNA-UHFFFAOYSA-N 0.000 description 8
BRGNSBSIUIKKLP-UHFFFAOYSA-N 2-hydroxy-n-(5-hydroxypentyl)-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CC1=C(C)C(=O)C(CCC(C)(O)C(=O)NCCCCCO)=C(C)C1=O BRGNSBSIUIKKLP-UHFFFAOYSA-N 0.000 description 8
206010003591 Ataxia Diseases 0.000 description 8
ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 8
208000023105 Huntington disease Diseases 0.000 description 8
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
239000008346 aqueous phase Substances 0.000 description 8
125000004429 atom Chemical group 0.000 description 8
230000033228 biological regulation Effects 0.000 description 8
210000004556 brain Anatomy 0.000 description 8
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 8
229940079593 drug Drugs 0.000 description 8
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 8
208000006443 lactic acidosis Diseases 0.000 description 8
239000002502 liposome Substances 0.000 description 8
239000007788 liquid Substances 0.000 description 8
210000003470 mitochondria Anatomy 0.000 description 8
210000003205 muscle Anatomy 0.000 description 8
125000004430 oxygen atom Chemical group O* 0.000 description 8
239000000546 pharmaceutical excipient Substances 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
229910052717 sulfur Inorganic materials 0.000 description 8
125000004434 sulfur atom Chemical group 0.000 description 8
JJRHJDUELSYTPF-MRXNPFEDSA-N (2r)-2-hydroxy-n-(2-hydroxyethyl)-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CC1=C(C)C(=O)C(CC[C@@](C)(O)C(=O)NCCO)=C(C)C1=O JJRHJDUELSYTPF-MRXNPFEDSA-N 0.000 description 7
JJRHJDUELSYTPF-INIZCTEOSA-N (2s)-2-hydroxy-n-(2-hydroxyethyl)-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CC1=C(C)C(=O)C(CC[C@](C)(O)C(=O)NCCO)=C(C)C1=O JJRHJDUELSYTPF-INIZCTEOSA-N 0.000 description 7
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 7
YQWBZLQPLUEHID-UHFFFAOYSA-N 2-[3-hydroxy-3-methyl-4-(4-methylpiperazin-1-yl)-4-oxobutyl]-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound C1CN(C)CCN1C(=O)C(C)(O)CCC1=C(C)C(=O)C(C)=C(C)C1=O YQWBZLQPLUEHID-UHFFFAOYSA-N 0.000 description 7
WMKSYSBVGRPFNM-UHFFFAOYSA-N 2-[4-(4-acetylpiperazin-1-yl)-3-hydroxy-3-methyl-4-oxobutyl]-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound C1CN(C(=O)C)CCN1C(=O)C(C)(O)CCC1=C(C)C(=O)C(C)=C(C)C1=O WMKSYSBVGRPFNM-UHFFFAOYSA-N 0.000 description 7
WPNCZUXRTXNUOT-UHFFFAOYSA-N 2-hydroxy-2-methyl-n-(3-morpholin-4-ylpropyl)-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)NCCCN2CCOCC2)=C1C WPNCZUXRTXNUOT-UHFFFAOYSA-N 0.000 description 7
HNDAUTXEFVPLLV-UHFFFAOYSA-N 2-hydroxy-n-(1-hydroxypropan-2-yl)-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound OCC(C)NC(=O)C(C)(O)CCC1=C(C)C(=O)C(C)=C(C)C1=O HNDAUTXEFVPLLV-UHFFFAOYSA-N 0.000 description 7
DKBOCYFAYQVCDX-UHFFFAOYSA-N 2-hydroxy-n-(4-hydroxybutyl)-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CC1=C(C)C(=O)C(CCC(C)(O)C(=O)NCCCCO)=C(C)C1=O DKBOCYFAYQVCDX-UHFFFAOYSA-N 0.000 description 7
WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 7
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 7
206010010904 Convulsion Diseases 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
208000036572 Myoclonic epilepsy Diseases 0.000 description 7
125000005055 alkyl alkoxy group Chemical group 0.000 description 7
VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 7
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 7
208000026106 cerebrovascular disease Diseases 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
229910052736 halogen Chemical group 0.000 description 7
230000006872 improvement Effects 0.000 description 7
230000001965 increasing effect Effects 0.000 description 7
238000005259 measurement Methods 0.000 description 7
230000010627 oxidative phosphorylation Effects 0.000 description 7
125000004043 oxo group Chemical group O=* 0.000 description 7
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 7
229950007002 phosphocreatine Drugs 0.000 description 7
239000000047 product Substances 0.000 description 7
DHYJSHILHSHPHP-UHFFFAOYSA-N 2-(3-hydroxy-3-methyl-4-oxo-4-piperidin-1-ylbutyl)-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)N2CCCCC2)=C1C DHYJSHILHSHPHP-UHFFFAOYSA-N 0.000 description 6
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
WMKSYSBVGRPFNM-HXUWFJFHSA-N 2-[(3r)-4-(4-acetylpiperazin-1-yl)-3-hydroxy-3-methyl-4-oxobutyl]-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound C1CN(C(=O)C)CCN1C(=O)[C@](C)(O)CCC1=C(C)C(=O)C(C)=C(C)C1=O WMKSYSBVGRPFNM-HXUWFJFHSA-N 0.000 description 6
WMKSYSBVGRPFNM-FQEVSTJZSA-N 2-[(3s)-4-(4-acetylpiperazin-1-yl)-3-hydroxy-3-methyl-4-oxobutyl]-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound C1CN(C(=O)C)CCN1C(=O)[C@@](C)(O)CCC1=C(C)C(=O)C(C)=C(C)C1=O WMKSYSBVGRPFNM-FQEVSTJZSA-N 0.000 description 6
HHCFBRMRTMTSHY-UHFFFAOYSA-N 2-[3-hydroxy-4-(4-hydroxypiperidin-1-yl)-3-methyl-4-oxobutyl]-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)N2CCC(O)CC2)=C1C HHCFBRMRTMTSHY-UHFFFAOYSA-N 0.000 description 6
125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
PLNRBIZXDTUKSQ-UHFFFAOYSA-N 2-hydroxy-2-methyl-n-(3-methylbutyl)-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CC(C)CCNC(=O)C(C)(O)CCC1=C(C)C(=O)C(C)=C(C)C1=O PLNRBIZXDTUKSQ-UHFFFAOYSA-N 0.000 description 6
BUGSNVNVEDKWKS-UHFFFAOYSA-N 2-hydroxy-n,n-bis(2-hydroxyethyl)-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CC1=C(C)C(=O)C(CCC(C)(O)C(=O)N(CCO)CCO)=C(C)C1=O BUGSNVNVEDKWKS-UHFFFAOYSA-N 0.000 description 6
BXRSDZYHNKBTCJ-UHFFFAOYSA-N 2-hydroxy-n-(3-imidazol-1-ylpropyl)-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)NCCCN2C=NC=C2)=C1C BXRSDZYHNKBTCJ-UHFFFAOYSA-N 0.000 description 6
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 6
125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 description 6
125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 description 6
125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 6
125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
208000010444 Acidosis Diseases 0.000 description 6
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) 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-O 0.000 description 6
208000012902 Nervous system disease Diseases 0.000 description 6
206010033799 Paralysis Diseases 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 6
230000001154 acute effect Effects 0.000 description 6
230000008901 benefit Effects 0.000 description 6
239000001569 carbon dioxide Substances 0.000 description 6
229910002092 carbon dioxide Inorganic materials 0.000 description 6
238000004113 cell culture Methods 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
230000003247 decreasing effect Effects 0.000 description 6
230000004064 dysfunction Effects 0.000 description 6
201000009028 early myoclonic encephalopathy Diseases 0.000 description 6
230000002500 effect on skin Effects 0.000 description 6
238000009472 formulation Methods 0.000 description 6
239000012634 fragment Substances 0.000 description 6
239000008103 glucose Substances 0.000 description 6
RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 6
JGPMMRGNQUBGND-UHFFFAOYSA-N idebenone Chemical compound COC1=C(OC)C(=O)C(CCCCCCCCCCO)=C(C)C1=O JGPMMRGNQUBGND-UHFFFAOYSA-N 0.000 description 6
229960004135 idebenone Drugs 0.000 description 6
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
239000010410 layer Substances 0.000 description 6
230000002503 metabolic effect Effects 0.000 description 6
GNUWFWUNTMBWKG-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CN(C)CCNC(=O)C(C)(O)CCC1=C(C)C(=O)C(C)=C(C)C1=O GNUWFWUNTMBWKG-UHFFFAOYSA-N 0.000 description 6
OBNGFMRSGTXFDM-UHFFFAOYSA-N n-benzyl-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)NCC=2C=CC=CC=2)=C1C OBNGFMRSGTXFDM-UHFFFAOYSA-N 0.000 description 6
230000001575 pathological effect Effects 0.000 description 6
239000000523 sample Substances 0.000 description 6
238000005728 strengthening Methods 0.000 description 6
239000000725 suspension Substances 0.000 description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
230000001225 therapeutic effect Effects 0.000 description 6
230000035899 viability Effects 0.000 description 6
FRFMRBMRVXWHSC-UHFFFAOYSA-N 2-(3-hydroxy-3-methyl-4-oxo-4-piperazin-1-ylbutyl)-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)N2CCNCC2)=C1C FRFMRBMRVXWHSC-UHFFFAOYSA-N 0.000 description 5
HHCFBRMRTMTSHY-IBGZPJMESA-N 2-[(3s)-3-hydroxy-4-(4-hydroxypiperidin-1-yl)-3-methyl-4-oxobutyl]-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C(C)=C(C)C(=O)C(CC[C@](C)(O)C(=O)N2CCC(O)CC2)=C1C HHCFBRMRTMTSHY-IBGZPJMESA-N 0.000 description 5
CDVRPNAGCXXGTM-UHFFFAOYSA-N 2-hydroxy-2-methyl-n-(2-methylpropyl)-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CC(C)CNC(=O)C(C)(O)CCC1=C(C)C(=O)C(C)=C(C)C1=O CDVRPNAGCXXGTM-UHFFFAOYSA-N 0.000 description 5
OBDPZTIURVLZSL-UHFFFAOYSA-N 2-hydroxy-2-methyl-n-(2-phenylethyl)-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)NCCC=2C=CC=CC=2)=C1C OBDPZTIURVLZSL-UHFFFAOYSA-N 0.000 description 5
GOJQQMCDZIJTEP-UHFFFAOYSA-N 2-hydroxy-2-methyl-n-(2-pyridin-2-ylethyl)-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)NCCC=2N=CC=CC=2)=C1C GOJQQMCDZIJTEP-UHFFFAOYSA-N 0.000 description 5
QVQKBCCJCUVXPA-UHFFFAOYSA-N 2-hydroxy-2-methyl-n-[3-(2-oxopyrrolidin-1-yl)propyl]-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)NCCCN2C(CCC2)=O)=C1C QVQKBCCJCUVXPA-UHFFFAOYSA-N 0.000 description 5
ODQUVCGQJDOISS-UHFFFAOYSA-N 2-hydroxy-2-methyl-n-propyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CCCNC(=O)C(C)(O)CCC1=C(C)C(=O)C(C)=C(C)C1=O ODQUVCGQJDOISS-UHFFFAOYSA-N 0.000 description 5
FIFGTTTWBCKJMR-UHFFFAOYSA-N 2-hydroxy-n,n,2-trimethyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CN(C)C(=O)C(C)(O)CCC1=C(C)C(=O)C(C)=C(C)C1=O FIFGTTTWBCKJMR-UHFFFAOYSA-N 0.000 description 5
DGWQQRLFELGLHL-UHFFFAOYSA-N 2-hydroxy-n-methoxy-n,2-dimethyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CON(C)C(=O)C(C)(O)CCC1=C(C)C(=O)C(C)=C(C)C1=O DGWQQRLFELGLHL-UHFFFAOYSA-N 0.000 description 5
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 5
KVZLHPXEUGJPAH-UHFFFAOYSA-N 2-oxidanylpropanoic acid Chemical compound CC(O)C(O)=O.CC(O)C(O)=O KVZLHPXEUGJPAH-UHFFFAOYSA-N 0.000 description 5
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 5
BVYZEFLWUAIZRH-UHFFFAOYSA-N 6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound O1C(C)(C(N)=O)CCC2=C1C(C)=C(C)C(O)=C2C BVYZEFLWUAIZRH-UHFFFAOYSA-N 0.000 description 5
208000024827 Alzheimer disease Diseases 0.000 description 5
208000031229 Cardiomyopathies Diseases 0.000 description 5
208000010354 Coenzyme Q10 deficiency Diseases 0.000 description 5
108010016626 Dipeptides Proteins 0.000 description 5
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
208000025966 Neurological disease Diseases 0.000 description 5
208000006289 Rett Syndrome Diseases 0.000 description 5
208000036353 Rett disease Diseases 0.000 description 5
230000007950 acidosis Effects 0.000 description 5
208000026545 acidosis disease Diseases 0.000 description 5
239000003963 antioxidant agent Chemical class 0.000 description 5
235000006708 antioxidants Nutrition 0.000 description 5
238000003556 assay Methods 0.000 description 5
229940110767 coenzyme Q10 Drugs 0.000 description 5
239000003937 drug carrier Substances 0.000 description 5
239000000839 emulsion Substances 0.000 description 5
238000002474 experimental method Methods 0.000 description 5
125000001475 halogen functional group Chemical group 0.000 description 5
150000002367 halogens Chemical group 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 5
239000003550 marker Substances 0.000 description 5
GRZJNXJCZCOAGZ-UHFFFAOYSA-N n-(cyclopropylmethyl)-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)NCC2CC2)=C1C GRZJNXJCZCOAGZ-UHFFFAOYSA-N 0.000 description 5
ACDTVRFBXMLONS-UHFFFAOYSA-N n-cyclopropyl-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)NC2CC2)=C1C ACDTVRFBXMLONS-UHFFFAOYSA-N 0.000 description 5
GRWGZUJTRCTLET-UHFFFAOYSA-N n-ethyl-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CCNC(=O)C(C)(O)CCC1=C(C)C(=O)C(C)=C(C)C1=O GRWGZUJTRCTLET-UHFFFAOYSA-N 0.000 description 5
QTVMUPVNMLNUDT-UHFFFAOYSA-N n-ethyl-2-hydroxy-n,2-dimethyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CCN(C)C(=O)C(C)(O)CCC1=C(C)C(=O)C(C)=C(C)C1=O QTVMUPVNMLNUDT-UHFFFAOYSA-N 0.000 description 5
229950006238 nadide Drugs 0.000 description 5
210000000056 organ Anatomy 0.000 description 5
239000012044 organic layer Substances 0.000 description 5
230000036284 oxygen consumption Effects 0.000 description 5
208000021090 palsy Diseases 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
230000008569 process Effects 0.000 description 5
238000003756 stirring Methods 0.000 description 5
125000001424 substituent group Chemical group 0.000 description 5
229940124597 therapeutic agent Drugs 0.000 description 5
230000004102 tricarboxylic acid cycle Effects 0.000 description 5
239000003981 vehicle Substances 0.000 description 5
XXFLYELFTZOCRJ-UHFFFAOYSA-N (2-carbonochloridoyl-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-yl) acetate Chemical compound O1C(C)(C(Cl)=O)CCC2=C(C)C(OC(=O)C)=C(C)C(C)=C21 XXFLYELFTZOCRJ-UHFFFAOYSA-N 0.000 description 4
RUSBHGNKLCOSHQ-UHFFFAOYSA-N 2-[4-(4,4-difluoropiperidin-1-yl)-3-hydroxy-3-methyl-4-oxobutyl]-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)N2CCC(F)(F)CC2)=C1C RUSBHGNKLCOSHQ-UHFFFAOYSA-N 0.000 description 4
ZVUWULZKPPTQIJ-UHFFFAOYSA-N 2-[4-(4-benzoylpiperazin-1-yl)-3-hydroxy-3-methyl-4-oxobutyl]-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)N2CCN(CC2)C(=O)C=2C=CC=CC=2)=C1C ZVUWULZKPPTQIJ-UHFFFAOYSA-N 0.000 description 4
IBQDEFFOOZANGJ-UHFFFAOYSA-N 2-[4-(azepan-1-yl)-3-hydroxy-3-methyl-4-oxobutyl]-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)N2CCCCCC2)=C1C IBQDEFFOOZANGJ-UHFFFAOYSA-N 0.000 description 4
WPGQBIUQNUJYCQ-UHFFFAOYSA-N 2-hydroxy-2-methyl-n-(pyridin-2-ylmethyl)-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)NCC=2N=CC=CC=2)=C1C WPGQBIUQNUJYCQ-UHFFFAOYSA-N 0.000 description 4
LDKUKIDKPWSTMD-UHFFFAOYSA-N 2-hydroxy-n-(6-hydroxyhexyl)-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound CC1=C(C)C(=O)C(CCC(C)(O)C(=O)NCCCCCCO)=C(C)C1=O LDKUKIDKPWSTMD-UHFFFAOYSA-N 0.000 description 4
208000036640 Asperger disease Diseases 0.000 description 4
201000006062 Asperger syndrome Diseases 0.000 description 4
201000004569 Blindness Diseases 0.000 description 4
108091003079 Bovine Serum Albumin Proteins 0.000 description 4
102000009024 Epidermal Growth Factor Human genes 0.000 description 4
108090000379 Fibroblast growth factor 2 Proteins 0.000 description 4
208000026350 Inborn Genetic disease Diseases 0.000 description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
208000019022 Mood disease Diseases 0.000 description 4
RHSWDAWJROMVBG-UHFFFAOYSA-N N-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide Chemical compound C(CCC)(=O)NC1=C(C(C(=C(C1=O)C)C)=O)C RHSWDAWJROMVBG-UHFFFAOYSA-N 0.000 description 4
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
230000002411 adverse Effects 0.000 description 4
229940024606 amino acid Drugs 0.000 description 4
150000001413 amino acids Chemical class 0.000 description 4
125000005418 aryl aryl group Chemical group 0.000 description 4
BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 4
230000000747 cardiac effect Effects 0.000 description 4
230000007423 decrease Effects 0.000 description 4
230000002950 deficient Effects 0.000 description 4
238000011161 development Methods 0.000 description 4
230000018109 developmental process Effects 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
206010015037 epilepsy Diseases 0.000 description 4
206010016256 fatigue Diseases 0.000 description 4
239000012894 fetal calf serum Substances 0.000 description 4
239000006260 foam Substances 0.000 description 4
230000006870 function Effects 0.000 description 4
125000005843 halogen group Chemical group 0.000 description 4
230000036541 health Effects 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
239000004310 lactic acid Substances 0.000 description 4
235000014655 lactic acid Nutrition 0.000 description 4
208000002780 macular degeneration Diseases 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
238000004519 manufacturing process Methods 0.000 description 4
230000008811 mitochondrial respiratory chain Effects 0.000 description 4
208000005264 motor neuron disease Diseases 0.000 description 4
XZPHOPZWQOTSKF-UHFFFAOYSA-N n-hexyl-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound OC1=C(C)C(C)=C2OC(C(=O)NCCCCCC)(C)CCC2=C1C XZPHOPZWQOTSKF-UHFFFAOYSA-N 0.000 description 4
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
230000004770 neurodegeneration Effects 0.000 description 4
208000015122 neurodegenerative disease Diseases 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
230000036542 oxidative stress Effects 0.000 description 4
230000036961 partial effect Effects 0.000 description 4
239000008194 pharmaceutical composition Substances 0.000 description 4
239000002953 phosphate buffered saline Substances 0.000 description 4
239000006187 pill Substances 0.000 description 4
230000000750 progressive effect Effects 0.000 description 4
NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 description 4
230000002787 reinforcement Effects 0.000 description 4
238000011160 research Methods 0.000 description 4
201000000980 schizophrenia Diseases 0.000 description 4
241000894007 species Species 0.000 description 4
239000011550 stock solution Substances 0.000 description 4
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 4
239000011593 sulfur Substances 0.000 description 4
239000006188 syrup Substances 0.000 description 4
235000020357 syrup Nutrition 0.000 description 4
239000003826 tablet Substances 0.000 description 4
HCONDLUVGKRTMM-UHFFFAOYSA-N 2-[3-hydroxy-3-methyl-4-oxo-4-(4-propan-2-ylpiperazin-1-yl)butyl]-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound C1CN(C(C)C)CCN1C(=O)C(C)(O)CCC1=C(C)C(=O)C(C)=C(C)C1=O HCONDLUVGKRTMM-UHFFFAOYSA-N 0.000 description 3
VDQYQSWPEIJUKH-UHFFFAOYSA-N 2-[4-(4-fluoropiperidin-1-yl)-3-hydroxy-3-methyl-4-oxobutyl]-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)N2CCC(F)CC2)=C1C VDQYQSWPEIJUKH-UHFFFAOYSA-N 0.000 description 3
BKBPONGAFGJAEQ-UHFFFAOYSA-N 2-[4-[4-(cyclopropanecarbonyl)piperazin-1-yl]-3-hydroxy-3-methyl-4-oxobutyl]-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C(C)=C(C)C(=O)C(CCC(C)(O)C(=O)N2CCN(CC2)C(=O)C2CC2)=C1C BKBPONGAFGJAEQ-UHFFFAOYSA-N 0.000 description 3
HWKRAUXFMLQKLS-UHFFFAOYSA-N 2-oxidanylidenepropanoic acid Chemical compound CC(=O)C(O)=O.CC(=O)C(O)=O HWKRAUXFMLQKLS-UHFFFAOYSA-N 0.000 description 3
AFYJYAWBTFNDAN-UHFFFAOYSA-N 3,4-dihydro-2h-chromene-2-carboxamide Chemical compound C1=CC=C2OC(C(=O)N)CCC2=C1 AFYJYAWBTFNDAN-UHFFFAOYSA-N 0.000 description 3
VMEGFMNVSYVVOM-UHFFFAOYSA-N 6-decylubiquinone Chemical compound CCCCCCCCCCC1=C(C)C(=O)C(OC)=C(OC)C1=O VMEGFMNVSYVVOM-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
208000020925 Bipolar disease Diseases 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
206010012289 Dementia Diseases 0.000 description 3
208000000059 Dyspnea Diseases 0.000 description 3
206010013975 Dyspnoeas Diseases 0.000 description 3
102000015782 Electron Transport Complex III Human genes 0.000 description 3
108010024882 Electron Transport Complex III Proteins 0.000 description 3
208000028782 Hereditary disease Diseases 0.000 description 3
206010021118 Hypotonia Diseases 0.000 description 3
102000004877 Insulin Human genes 0.000 description 3
108090001061 Insulin Proteins 0.000 description 3
208000024556 Mendelian disease Diseases 0.000 description 3
208000026072 Motor neurone disease Diseases 0.000 description 3
208000007379 Muscle Hypotonia Diseases 0.000 description 3
238000004497 NIR spectroscopy Methods 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
206010034010 Parkinsonism Diseases 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
208000004756 Respiratory Insufficiency Diseases 0.000 description 3
208000007014 Retinitis pigmentosa Diseases 0.000 description 3
GLEVLJDDWXEYCO-UHFFFAOYSA-N Trolox Chemical compound O1C(C)(C(O)=O)CCC2=C1C(C)=C(C)C(O)=C2C GLEVLJDDWXEYCO-UHFFFAOYSA-N 0.000 description 3
230000002159 abnormal effect Effects 0.000 description 3
239000002253 acid Substances 0.000 description 3
230000009471 action Effects 0.000 description 3
239000013543 active substance Substances 0.000 description 3
239000002671 adjuvant Substances 0.000 description 3
230000004103 aerobic respiration Effects 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
239000002585 base Substances 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000002775 capsule Substances 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
239000000969 carrier Substances 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
208000024825 childhood disintegrative disease Diseases 0.000 description 3
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 3
230000006735 deficit Effects 0.000 description 3
206010012601 diabetes mellitus Diseases 0.000 description 3
230000002255 enzymatic effect Effects 0.000 description 3
230000029142 excretion Effects 0.000 description 3
239000007789 gas Substances 0.000 description 3
208000016361 genetic disease Diseases 0.000 description 3
229960003180 glutathione Drugs 0.000 description 3
230000034659 glycolysis Effects 0.000 description 3
239000003701 inert diluent Substances 0.000 description 3
229940125396 insulin Drugs 0.000 description 3
230000000670 limiting effect Effects 0.000 description 3
150000002632 lipids Chemical class 0.000 description 3
239000000463 material Substances 0.000 description 3
239000011159 matrix material Substances 0.000 description 3
230000004060 metabolic process Effects 0.000 description 3
125000006431 methyl cyclopropyl group Chemical group 0.000 description 3
GVZFUVXPTPGOQT-UHFFFAOYSA-M mitoq Chemical compound CS([O-])(=O)=O.O=C1C(OC)=C(OC)C(=O)C(CCCCCCCCCC[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C GVZFUVXPTPGOQT-UHFFFAOYSA-M 0.000 description 3
230000035772 mutation Effects 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
230000037081 physical activity Effects 0.000 description 3
230000002035 prolonged effect Effects 0.000 description 3
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 3
102000004169 proteins and genes Human genes 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
229940107700 pyruvic acid Drugs 0.000 description 3
239000003642 reactive oxygen metabolite Substances 0.000 description 3
201000004193 respiratory failure Diseases 0.000 description 3
230000029058 respiratory gaseous exchange Effects 0.000 description 3
230000004044 response Effects 0.000 description 3
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
210000002027 skeletal muscle Anatomy 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000000375 suspending agent Substances 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
229940035936 ubiquinone Drugs 0.000 description 3
239000011782 vitamin Chemical class 0.000 description 3
229940088594 vitamin Drugs 0.000 description 3
235000013343 vitamin Nutrition 0.000 description 3
229930003231 vitamin Chemical class 0.000 description 3
GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 3
BFATWCQXCJEFFQ-MRXNPFEDSA-N (2r)-6-hydroxy-n-(2-hydroxyethyl)-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound O1[C@@](C)(C(=O)NCCO)CCC2=C1C(C)=C(C)C(O)=C2C BFATWCQXCJEFFQ-MRXNPFEDSA-N 0.000 description 2
BFATWCQXCJEFFQ-INIZCTEOSA-N (2s)-6-hydroxy-n-(2-hydroxyethyl)-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound O1[C@](C)(C(=O)NCCO)CCC2=C1C(C)=C(C)C(O)=C2C BFATWCQXCJEFFQ-INIZCTEOSA-N 0.000 description 2
BCZRYYKBKGKTEC-UHFFFAOYSA-N (4-hydroxypiperidin-1-yl)-(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)methanone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)C(=O)N1CCC(O)CC1 BCZRYYKBKGKTEC-UHFFFAOYSA-N 0.000 description 2
WZGUDVFZOQAMJR-UHFFFAOYSA-N (6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1(C)OC2=C(C)C(C)=C(O)C(C)=C2CC1 WZGUDVFZOQAMJR-UHFFFAOYSA-N 0.000 description 2
RNHVYXAGIRNPGG-UHFFFAOYSA-N (6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)-piperidin-1-ylmethanone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)C(=O)N1CCCCC1 RNHVYXAGIRNPGG-UHFFFAOYSA-N 0.000 description 2
GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 2
HHCFBRMRTMTSHY-LJQANCHMSA-N 2-[(3r)-3-hydroxy-4-(4-hydroxypiperidin-1-yl)-3-methyl-4-oxobutyl]-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C(C)=C(C)C(=O)C(CC[C@@](C)(O)C(=O)N2CCC(O)CC2)=C1C HHCFBRMRTMTSHY-LJQANCHMSA-N 0.000 description 2
ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 2
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 2
KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 2
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
CUHJERIEOYEEOS-UHFFFAOYSA-N 6-acetyloxy-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxylic acid Chemical compound O1C(C)(C(O)=O)CCC2=C(C)C(OC(=O)C)=C(C)C(C)=C21 CUHJERIEOYEEOS-UHFFFAOYSA-N 0.000 description 2
KVEJPSUTFLSUTO-UHFFFAOYSA-N 6-hydroxy-2,5,7,8-tetramethyl-n-(2-methylpropyl)-3,4-dihydrochromene-2-carboxamide Chemical compound OC1=C(C)C(C)=C2OC(C(=O)NCC(C)C)(C)CCC2=C1C KVEJPSUTFLSUTO-UHFFFAOYSA-N 0.000 description 2
ZDNGYFKANRDTCD-UHFFFAOYSA-N 6-hydroxy-2,5,7,8-tetramethyl-n-(2-pyridin-2-ylethyl)-3,4-dihydrochromene-2-carboxamide Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)C(=O)NCCC1=CC=CC=N1 ZDNGYFKANRDTCD-UHFFFAOYSA-N 0.000 description 2
FAHJTPQBGQWIEC-UHFFFAOYSA-N 6-hydroxy-2,5,7,8-tetramethyl-n-(3-methylbutyl)-3,4-dihydrochromene-2-carboxamide Chemical compound OC1=C(C)C(C)=C2OC(C(=O)NCCC(C)C)(C)CCC2=C1C FAHJTPQBGQWIEC-UHFFFAOYSA-N 0.000 description 2
XVFQBRPTYPJBPP-UHFFFAOYSA-N 6-hydroxy-2,5,7,8-tetramethyl-n-(3-morpholin-4-ylpropyl)-3,4-dihydrochromene-2-carboxamide Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)C(=O)NCCCN1CCOCC1 XVFQBRPTYPJBPP-UHFFFAOYSA-N 0.000 description 2
FKQRJRBJQOHHRN-UHFFFAOYSA-N 6-hydroxy-2,5,7,8-tetramethyl-n-(pyridin-2-ylmethyl)-3,4-dihydrochromene-2-carboxamide Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)C(=O)NCC1=CC=CC=N1 FKQRJRBJQOHHRN-UHFFFAOYSA-N 0.000 description 2
MIYGPTPFHANOGL-UHFFFAOYSA-N 6-hydroxy-2,5,7,8-tetramethyl-n-propyl-3,4-dihydrochromene-2-carboxamide Chemical compound OC1=C(C)C(C)=C2OC(C(=O)NCCC)(C)CCC2=C1C MIYGPTPFHANOGL-UHFFFAOYSA-N 0.000 description 2
HYDIPFCEUJQXIH-UHFFFAOYSA-N 6-hydroxy-n,n,2,5,7,8-hexamethyl-3,4-dihydrochromene-2-carboxamide Chemical compound OC1=C(C)C(C)=C2OC(C(=O)N(C)C)(C)CCC2=C1C HYDIPFCEUJQXIH-UHFFFAOYSA-N 0.000 description 2
DHGQCPPGGBDFEH-UHFFFAOYSA-N 6-hydroxy-n,n-bis(2-hydroxyethyl)-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound O1C(C)(C(=O)N(CCO)CCO)CCC2=C1C(C)=C(C)C(O)=C2C DHGQCPPGGBDFEH-UHFFFAOYSA-N 0.000 description 2
AYJMGUNMVOVXSE-UHFFFAOYSA-N 6-hydroxy-n-(1-hydroxypropan-2-yl)-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound OC1=C(C)C(C)=C2OC(C(=O)NC(CO)C)(C)CCC2=C1C AYJMGUNMVOVXSE-UHFFFAOYSA-N 0.000 description 2
BFATWCQXCJEFFQ-UHFFFAOYSA-N 6-hydroxy-n-(2-hydroxyethyl)-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound O1C(C)(C(=O)NCCO)CCC2=C1C(C)=C(C)C(O)=C2C BFATWCQXCJEFFQ-UHFFFAOYSA-N 0.000 description 2
BYVXPZSZIRKAHU-UHFFFAOYSA-N 6-hydroxy-n-(2-hydroxypropyl)-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound OC1=C(C)C(C)=C2OC(C(=O)NCC(O)C)(C)CCC2=C1C BYVXPZSZIRKAHU-UHFFFAOYSA-N 0.000 description 2
SBZCZZFEMPCUME-UHFFFAOYSA-N 6-hydroxy-n-(2-methoxyethyl)-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound OC1=C(C)C(C)=C2OC(C(=O)NCCOC)(C)CCC2=C1C SBZCZZFEMPCUME-UHFFFAOYSA-N 0.000 description 2
MXHJBGQRROTDIH-UHFFFAOYSA-N 6-hydroxy-n-(3-hydroxypropyl)-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound O1C(C)(C(=O)NCCCO)CCC2=C1C(C)=C(C)C(O)=C2C MXHJBGQRROTDIH-UHFFFAOYSA-N 0.000 description 2
FBTPJYNQGXQBNG-UHFFFAOYSA-N 6-hydroxy-n-(4-hydroxybutyl)-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound O1C(C)(C(=O)NCCCCO)CCC2=C1C(C)=C(C)C(O)=C2C FBTPJYNQGXQBNG-UHFFFAOYSA-N 0.000 description 2
YWIFRCMFIXKSGO-UHFFFAOYSA-N 6-hydroxy-n-(5-hydroxypentyl)-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound O1C(C)(C(=O)NCCCCCO)CCC2=C1C(C)=C(C)C(O)=C2C YWIFRCMFIXKSGO-UHFFFAOYSA-N 0.000 description 2
WXRMHPJCWLRFPQ-UHFFFAOYSA-N 6-hydroxy-n-(6-hydroxyhexyl)-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound O1C(C)(C(=O)NCCCCCCO)CCC2=C1C(C)=C(C)C(O)=C2C WXRMHPJCWLRFPQ-UHFFFAOYSA-N 0.000 description 2
MMXLJTHMIWILOX-UHFFFAOYSA-N 6-hydroxy-n-[2-(2-hydroxyethoxy)ethyl]-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound O1C(C)(C(=O)NCCOCCO)CCC2=C1C(C)=C(C)C(O)=C2C MMXLJTHMIWILOX-UHFFFAOYSA-N 0.000 description 2
SRZKZESSIMXMIH-UHFFFAOYSA-N 6-hydroxy-n-[2-(4-hydroxyphenyl)ethyl]-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)C(=O)NCCC1=CC=C(O)C=C1 SRZKZESSIMXMIH-UHFFFAOYSA-N 0.000 description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 2
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical group [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
206010008874 Chronic Fatigue Syndrome Diseases 0.000 description 2
206010010356 Congenital anomaly Diseases 0.000 description 2
208000002155 Cytochrome-c Oxidase Deficiency Diseases 0.000 description 2
ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 2
206010012559 Developmental delay Diseases 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
208000014094 Dystonic disease Diseases 0.000 description 2
206010014561 Emphysema Diseases 0.000 description 2
101800003838 Epidermal growth factor Proteins 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
YPZRHBJKEMOYQH-UYBVJOGSSA-N FADH2 Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1COP(O)(=O)OP(O)(=O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C(NC(=O)NC2=O)=C2NC2=C1C=C(C)C(C)=C2 YPZRHBJKEMOYQH-UYBVJOGSSA-N 0.000 description 2
102000003974 Fibroblast growth factor 2 Human genes 0.000 description 2
102100024785 Fibroblast growth factor 2 Human genes 0.000 description 2
102000003869 Frataxin Human genes 0.000 description 2
108090000217 Frataxin Proteins 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
206010053759 Growth retardation Diseases 0.000 description 2
241000282412 Homo Species 0.000 description 2
101001109052 Homo sapiens NADH-ubiquinone oxidoreductase chain 4 Proteins 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
208000006136 Leigh Disease Diseases 0.000 description 2
208000017507 Leigh syndrome Diseases 0.000 description 2
208000019693 Lung disease Diseases 0.000 description 2
206010058467 Lung neoplasm malignant Diseases 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
206010058799 Mitochondrial encephalomyopathy Diseases 0.000 description 2
102000036675 Myoglobin Human genes 0.000 description 2
108010062374 Myoglobin Proteins 0.000 description 2
102100021506 NADH-ubiquinone oxidoreductase chain 4 Human genes 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
229930182555 Penicillin Natural products 0.000 description 2
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 2
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
208000020221 Short stature Diseases 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
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
230000005856 abnormality Effects 0.000 description 2
235000011054 acetic acid Nutrition 0.000 description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
239000000654 additive Substances 0.000 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 description 2
230000032683 aging Effects 0.000 description 2
238000003915 air pollution Methods 0.000 description 2
230000004099 anaerobic respiration Effects 0.000 description 2
230000003078 antioxidant effect Effects 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
125000003725 azepanyl group Chemical group 0.000 description 2
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 2
150000007514 bases Chemical class 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
238000011325 biochemical measurement Methods 0.000 description 2
230000003851 biochemical process Effects 0.000 description 2
229960000074 biopharmaceutical Drugs 0.000 description 2
210000001124 body fluid Anatomy 0.000 description 2
239000010839 body fluid Substances 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
201000011510 cancer Diseases 0.000 description 2
229910002091 carbon monoxide Inorganic materials 0.000 description 2
150000003857 carboxamides Chemical class 0.000 description 2
239000006143 cell culture medium Substances 0.000 description 2
230000030833 cell death Effects 0.000 description 2
230000001413 cellular effect Effects 0.000 description 2
210000003169 central nervous system Anatomy 0.000 description 2
230000002490 cerebral effect Effects 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
230000004087 circulation Effects 0.000 description 2
230000001054 cortical effect Effects 0.000 description 2
ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 2
230000007547 defect Effects 0.000 description 2
238000013461 design Methods 0.000 description 2
238000001514 detection method Methods 0.000 description 2
230000001627 detrimental effect Effects 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
238000012377 drug delivery Methods 0.000 description 2
208000010118 dystonia Diseases 0.000 description 2
239000003995 emulsifying agent Substances 0.000 description 2
229940116977 epidermal growth factor Drugs 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
230000005284 excitation Effects 0.000 description 2
230000003492 excitotoxic effect Effects 0.000 description 2
231100000063 excitotoxicity Toxicity 0.000 description 2
238000000605 extraction Methods 0.000 description 2
WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Natural products O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
125000002541 furyl group Chemical group 0.000 description 2
239000011521 glass Substances 0.000 description 2
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
239000008187 granular material Substances 0.000 description 2
230000012010 growth Effects 0.000 description 2
208000037824 growth disorder Diseases 0.000 description 2
231100000001 growth retardation Toxicity 0.000 description 2
125000000687 hydroquinonyl group Chemical group C1(O)=C(C=C(O)C=C1)* 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
125000002883 imidazolyl group Chemical group 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
239000007924 injection Substances 0.000 description 2
238000002347 injection Methods 0.000 description 2
208000014674 injury Diseases 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
208000028867 ischemia Diseases 0.000 description 2
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
229940011051 isopropyl acetate Drugs 0.000 description 2
208000037805 labour Diseases 0.000 description 2
230000003902 lesion Effects 0.000 description 2
230000033001 locomotion Effects 0.000 description 2
210000004072 lung Anatomy 0.000 description 2
201000005202 lung cancer Diseases 0.000 description 2
208000020816 lung neoplasm Diseases 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
210000001700 mitochondrial membrane Anatomy 0.000 description 2
239000003068 molecular probe Substances 0.000 description 2
125000002757 morpholinyl group Chemical group 0.000 description 2
208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 description 2
DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 2
OOQRZEHMOGEIMJ-UHFFFAOYSA-N n-(cyclopropylmethyl)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)C(=O)NCC1CC1 OOQRZEHMOGEIMJ-UHFFFAOYSA-N 0.000 description 2
SFIIZOBFOCEAII-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound OC1=C(C)C(C)=C2OC(C(=O)NCCN(C)C)(C)CCC2=C1C SFIIZOBFOCEAII-UHFFFAOYSA-N 0.000 description 2
YHDLWWYVEKBXTD-UHFFFAOYSA-N n-benzyl-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)C(=O)NCC1=CC=CC=C1 YHDLWWYVEKBXTD-UHFFFAOYSA-N 0.000 description 2
HZKPFWBHBGIULH-UHFFFAOYSA-N n-ethyl-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound OC1=C(C)C(C)=C2OC(C(=O)NCC)(C)CCC2=C1C HZKPFWBHBGIULH-UHFFFAOYSA-N 0.000 description 2
NHBIOXLONQGSBU-UHFFFAOYSA-N n-ethyl-6-hydroxy-n,2,5,7,8-pentamethyl-3,4-dihydrochromene-2-carboxamide Chemical compound OC1=C(C)C(C)=C2OC(C(=O)N(C)CC)(C)CCC2=C1C NHBIOXLONQGSBU-UHFFFAOYSA-N 0.000 description 2
230000003961 neuronal insult Effects 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
239000000346 nonvolatile oil Substances 0.000 description 2
108010007425 oligomycin sensitivity conferring protein Proteins 0.000 description 2
239000010502 orange oil Substances 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
210000000496 pancreas Anatomy 0.000 description 2
229940049954 penicillin Drugs 0.000 description 2
238000003359 percent control normalization Methods 0.000 description 2
230000002093 peripheral effect Effects 0.000 description 2
239000012071 phase Substances 0.000 description 2
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
150000003904 phospholipids Chemical class 0.000 description 2
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
125000004193 piperazinyl group Chemical group 0.000 description 2
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
125000003386 piperidinyl group Chemical group 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
239000002243 precursor Substances 0.000 description 2
230000002028 premature Effects 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
238000012545 processing Methods 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
208000005069 pulmonary fibrosis Diseases 0.000 description 2
238000000746 purification Methods 0.000 description 2
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 2
125000004076 pyridyl group Chemical group 0.000 description 2
125000000714 pyrimidinyl group Chemical group 0.000 description 2
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
125000000719 pyrrolidinyl group Chemical group 0.000 description 2
125000004151 quinonyl group Chemical group 0.000 description 2
239000000376 reactant Substances 0.000 description 2
230000027756 respiratory electron transport chain Effects 0.000 description 2
230000000284 resting effect Effects 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
238000013207 serial dilution Methods 0.000 description 2
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
239000007909 solid dosage form Substances 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
239000007858 starting material Substances 0.000 description 2
230000001954 sterilising effect Effects 0.000 description 2
238000004659 sterilization and disinfection Methods 0.000 description 2
229960005322 streptomycin Drugs 0.000 description 2
238000001356 surgical procedure Methods 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
125000005958 tetrahydrothienyl group Chemical group 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
229940042585 tocopherol acetate Drugs 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
230000008733 trauma Effects 0.000 description 2
201000008827 tuberculosis Diseases 0.000 description 2
DZGWFCGJZKJUFP-UHFFFAOYSA-N tyramine Chemical compound NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 2
VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 2
239000000080 wetting agent Substances 0.000 description 2
235000004835 α-tocopherol Nutrition 0.000 description 2
239000002076 α-tocopherol Substances 0.000 description 2
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
WEJRCMABQSYFIT-UHFFFAOYSA-N (4-benzylpiperazin-1-yl)-(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)methanone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)C(=O)N(CC1)CCN1CC1=CC=CC=C1 WEJRCMABQSYFIT-UHFFFAOYSA-N 0.000 description 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
0 *C(C(C(*)=C1*)=O)=CC1=O Chemical compound *C(C(C(*)=C1*)=O)=CC1=O 0.000 description 1
WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical group C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical group C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
HXKKHQJGJAFBHI-UHFFFAOYSA-N 1-aminopropan-2-ol Chemical compound CC(O)CN HXKKHQJGJAFBHI-UHFFFAOYSA-N 0.000 description 1
IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 1
PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N 1-propanol Substances CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical group C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
DDZGQYREBDXECY-UHFFFAOYSA-N 1h-pyrazolo[3,4-b]pyrazine Chemical compound C1=CN=C2C=NNC2=N1 DDZGQYREBDXECY-UHFFFAOYSA-N 0.000 description 1
AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical compound C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 description 1
GIAFURWZWWWBQT-UHFFFAOYSA-N 2-(2-aminoethoxy)ethanol Chemical compound NCCOCCO GIAFURWZWWWBQT-UHFFFAOYSA-N 0.000 description 1
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 1
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical group C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
WHBMMWSBFZVSSR-UHFFFAOYSA-M 3-hydroxybutyrate Chemical compound CC(O)CC([O-])=O WHBMMWSBFZVSSR-UHFFFAOYSA-M 0.000 description 1
KDHWOCLBMVSZPG-UHFFFAOYSA-N 3-imidazol-1-ylpropan-1-amine Chemical compound NCCCN1C=CN=C1 KDHWOCLBMVSZPG-UHFFFAOYSA-N 0.000 description 1
UIKUBYKUYUSRSM-UHFFFAOYSA-N 3-morpholinopropylamine Chemical compound NCCCN1CCOCC1 UIKUBYKUYUSRSM-UHFFFAOYSA-N 0.000 description 1
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 1
BLFRQYKZFKYQLO-UHFFFAOYSA-N 4-aminobutan-1-ol Chemical compound NCCCCO BLFRQYKZFKYQLO-UHFFFAOYSA-N 0.000 description 1
GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 1
LQGKDMHENBFVRC-UHFFFAOYSA-N 5-aminopentan-1-ol Chemical compound NCCCCCO LQGKDMHENBFVRC-UHFFFAOYSA-N 0.000 description 1
SUTWPJHCRAITLU-UHFFFAOYSA-N 6-aminohexan-1-ol Chemical compound NCCCCCCO SUTWPJHCRAITLU-UHFFFAOYSA-N 0.000 description 1
RLXCERRJVUPLCH-UHFFFAOYSA-N 6-hydroxy-2,5,7,8-tetramethyl-n-(oxolan-2-ylmethyl)-3,4-dihydrochromene-2-carboxamide Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)C(=O)NCC1CCCO1 RLXCERRJVUPLCH-UHFFFAOYSA-N 0.000 description 1
AKMFFCTZUUVDND-UHFFFAOYSA-N 6-hydroxy-2,5,7,8-tetramethyl-n-[3-(2-oxopyrrolidin-1-yl)propyl]-3,4-dihydrochromene-2-carboxamide Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)C(=O)NCCCN1CCCC1=O AKMFFCTZUUVDND-UHFFFAOYSA-N 0.000 description 1
HOFLDQRKBZIPRU-UHFFFAOYSA-N 6-hydroxy-n-methoxy-n,2,5,7,8-pentamethyl-3,4-dihydrochromene-2-carboxamide Chemical compound OC1=C(C)C(C)=C2OC(C(=O)N(C)OC)(C)CCC2=C1C HOFLDQRKBZIPRU-UHFFFAOYSA-N 0.000 description 1
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
101150015935 ATP2 gene Proteins 0.000 description 1
208000013824 Acidemia Diseases 0.000 description 1
206010069754 Acquired gene mutation Diseases 0.000 description 1
ORILYTVJVMAKLC-UHFFFAOYSA-N Adamantane Natural products C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
241001550224 Apha Species 0.000 description 1
206010003694 Atrophy Diseases 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
239000002126 C01EB10 - Adenosine Substances 0.000 description 1
OCNRUSMCVYCODX-UHFFFAOYSA-N C1(CC1)NC(=O)C1(OC=2C(=CC(C(C2CC1)C)(C)O)C)C Chemical compound C1(CC1)NC(=O)C1(OC=2C(=CC(C(C2CC1)C)(C)O)C)C OCNRUSMCVYCODX-UHFFFAOYSA-N 0.000 description 1
101100007300 Caenorhabditis elegans coq-2 gene Proteins 0.000 description 1
208000002177 Cataract Diseases 0.000 description 1
206010008025 Cerebellar ataxia Diseases 0.000 description 1
206010050389 Cerebral ataxia Diseases 0.000 description 1
201000000915 Chronic Progressive External Ophthalmoplegia Diseases 0.000 description 1
WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
206010010071 Coma Diseases 0.000 description 1
208000002330 Congenital Heart Defects Diseases 0.000 description 1
208000027205 Congenital disease Diseases 0.000 description 1
208000029767 Congenital, Hereditary, and Neonatal Diseases and Abnormalities Diseases 0.000 description 1
229920000858 Cyclodextrin Polymers 0.000 description 1
230000005778 DNA damage Effects 0.000 description 1
231100000277 DNA damage Toxicity 0.000 description 1
206010011891 Deafness neurosensory Diseases 0.000 description 1
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
241000792859 Enema Species 0.000 description 1
MBMLMWLHJBBADN-UHFFFAOYSA-N Ferrous sulfide Chemical class [Fe]=S MBMLMWLHJBBADN-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
108010024636 Glutathione Proteins 0.000 description 1
102000006587 Glutathione peroxidase Human genes 0.000 description 1
108700016172 Glutathione peroxidases Proteins 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
208000000038 Hypoparathyroidism Diseases 0.000 description 1
206010021143 Hypoxia Diseases 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical group C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
208000032382 Ischaemic stroke Diseases 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
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 1
201000003533 Leber congenital amaurosis Diseases 0.000 description 1
206010024264 Lethargy Diseases 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
208000036626 Mental retardation Diseases 0.000 description 1
206010027476 Metastases Diseases 0.000 description 1
108020005196 Mitochondrial DNA Proteins 0.000 description 1
108010085220 Multiprotein Complexes Proteins 0.000 description 1
102000007474 Multiprotein Complexes Human genes 0.000 description 1
101001135571 Mus musculus Tyrosine-protein phosphatase non-receptor type 2 Proteins 0.000 description 1
208000010428 Muscle Weakness Diseases 0.000 description 1
206010049565 Muscle fatigue Diseases 0.000 description 1
206010028372 Muscular weakness Diseases 0.000 description 1
206010052904 Musculoskeletal stiffness Diseases 0.000 description 1
208000002033 Myoclonus Diseases 0.000 description 1
206010028629 Myoglobinuria Diseases 0.000 description 1
HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
102000006746 NADH Dehydrogenase Human genes 0.000 description 1
108010086428 NADH Dehydrogenase Proteins 0.000 description 1
206010061309 Neoplasm progression Diseases 0.000 description 1
206010029164 Nephrotic syndrome Diseases 0.000 description 1
206010060860 Neurological symptom Diseases 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
239000005642 Oleic acid Substances 0.000 description 1
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
102000004316 Oxidoreductases Human genes 0.000 description 1
108090000854 Oxidoreductases Proteins 0.000 description 1
208000027089 Parkinsonian disease Diseases 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
239000004952 Polyamide Substances 0.000 description 1
229920002732 Polyanhydride Polymers 0.000 description 1
229920001710 Polyorthoester Polymers 0.000 description 1
208000036757 Postencephalitic parkinsonism Diseases 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
206010036790 Productive cough Diseases 0.000 description 1
WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 1
239000004365 Protease Substances 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
208000001647 Renal Insufficiency Diseases 0.000 description 1
208000032400 Retinal pigmentation Diseases 0.000 description 1
241000219061 Rheum Species 0.000 description 1
AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
240000004808 Saccharomyces cerevisiae Species 0.000 description 1
235000019485 Safflower oil Nutrition 0.000 description 1
BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
208000009966 Sensorineural Hearing Loss Diseases 0.000 description 1
208000032023 Signs and Symptoms Diseases 0.000 description 1
208000009415 Spinocerebellar Ataxias Diseases 0.000 description 1
208000010112 Spinocerebellar Degenerations Diseases 0.000 description 1
102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
206010044565 Tremor Diseases 0.000 description 1
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
241000251539 Vertebrata <Metazoa> Species 0.000 description 1
229930003427 Vitamin E Chemical class 0.000 description 1
206010047700 Vomiting Diseases 0.000 description 1
HGBRUSZDRNEVPA-UHFFFAOYSA-N [2-(hexylcarbamoyl)-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-yl] acetate Chemical compound CC(=O)OC1=C(C)C(C)=C2OC(C(=O)NCCCCCC)(C)CCC2=C1C HGBRUSZDRNEVPA-UHFFFAOYSA-N 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
229960005305 adenosine Drugs 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
238000013019 agitation Methods 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
229940087168 alpha tocopherol Drugs 0.000 description 1
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
238000010171 animal model Methods 0.000 description 1
125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
229940009098 aspartate Drugs 0.000 description 1
101150026213 atpB gene Proteins 0.000 description 1
230000037444 atrophy Effects 0.000 description 1
ZYKAJNJDLRLYLG-JIZZDEOASA-O azanium;(2s)-2-amino-3-hydroxypropanoic acid;nitrate Chemical compound [NH4+].[O-][N+]([O-])=O.OC[C@H](N)C(O)=O ZYKAJNJDLRLYLG-JIZZDEOASA-O 0.000 description 1
RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical group CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
239000012964 benzotriazole Substances 0.000 description 1
UUQMNUMQCIQDMZ-UHFFFAOYSA-N betahistine Chemical compound CNCCC1=CC=CC=N1 UUQMNUMQCIQDMZ-UHFFFAOYSA-N 0.000 description 1
230000002146 bilateral effect Effects 0.000 description 1
238000010256 biochemical assay Methods 0.000 description 1
230000008238 biochemical pathway Effects 0.000 description 1
238000005842 biochemical reaction Methods 0.000 description 1
238000010876 biochemical test Methods 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000031018 biological processes and functions Effects 0.000 description 1
239000012472 biological sample Substances 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
230000036760 body temperature Effects 0.000 description 1
239000012267 brine Substances 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
239000001273 butane Substances 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
230000011128 cardiac conduction Effects 0.000 description 1
230000005779 cell damage Effects 0.000 description 1
208000037887 cell injury Diseases 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
235000010980 cellulose Nutrition 0.000 description 1
210000001638 cerebellum Anatomy 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
238000010568 chiral column chromatography Methods 0.000 description 1
235000013985 cinnamic acid Nutrition 0.000 description 1
229930016911 cinnamic acid Natural products 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
230000009194 climbing Effects 0.000 description 1
230000007012 clinical effect Effects 0.000 description 1
239000003240 coconut oil Substances 0.000 description 1
235000019864 coconut oil Nutrition 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
235000008504 concentrate Nutrition 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
239000000599 controlled substance Substances 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
229910000365 copper sulfate Inorganic materials 0.000 description 1
ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
239000006071 cream Substances 0.000 description 1
239000013058 crude material Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000012258 culturing Methods 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
229940097362 cyclodextrins Drugs 0.000 description 1
208000026615 cytochrome-c oxidase deficiency disease Diseases 0.000 description 1
231100000135 cytotoxicity Toxicity 0.000 description 1
230000003013 cytotoxicity Effects 0.000 description 1
230000006378 damage Effects 0.000 description 1
230000034994 death Effects 0.000 description 1
230000003412 degenerative effect Effects 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
230000037430 deletion Effects 0.000 description 1
238000012217 deletion Methods 0.000 description 1
238000006392 deoxygenation reaction Methods 0.000 description 1
229910052805 deuterium Inorganic materials 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
238000003745 diagnosis Methods 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
238000009792 diffusion process Methods 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 1
150000002016 disaccharides Chemical class 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000009510 drug design Methods 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
230000002124 endocrine Effects 0.000 description 1
239000007920 enema Substances 0.000 description 1
229940079360 enema for constipation Drugs 0.000 description 1
230000037149 energy metabolism Effects 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
239000003623 enhancer Substances 0.000 description 1
230000001037 epileptic effect Effects 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 1
210000003527 eukaryotic cell Anatomy 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
239000003925 fat Substances 0.000 description 1
235000019197 fats Nutrition 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
235000013305 food Nutrition 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Chemical class CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
238000007429 general method Methods 0.000 description 1
238000010448 genetic screening Methods 0.000 description 1
229930195712 glutamate Natural products 0.000 description 1
150000004676 glycans Chemical class 0.000 description 1
229960001269 glycine hydrochloride Drugs 0.000 description 1
230000003862 health status Effects 0.000 description 1
230000005831 heart abnormality Effects 0.000 description 1
208000019622 heart disease Diseases 0.000 description 1
230000004217 heart function Effects 0.000 description 1
201000003636 hereditary ataxia Diseases 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
239000000017 hydrogel Substances 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
238000003384 imaging method Methods 0.000 description 1
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical group C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical group CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical group C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
230000006698 induction Effects 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
229940102223 injectable solution Drugs 0.000 description 1
229940102213 injectable suspension Drugs 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
230000009191 jumping Effects 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
201000006370 kidney failure Diseases 0.000 description 1
229940001447 lactate Drugs 0.000 description 1
239000008101 lactose Substances 0.000 description 1
210000003140 lateral ventricle Anatomy 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
239000004973 liquid crystal related substance Substances 0.000 description 1
239000008297 liquid dosage form Substances 0.000 description 1
210000002311 liver mitochondria Anatomy 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
230000003211 malignant effect Effects 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
239000012528 membrane Substances 0.000 description 1
208000030159 metabolic disease Diseases 0.000 description 1
230000037323 metabolic rate Effects 0.000 description 1
235000020938 metabolic status Nutrition 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
229960001252 methamphetamine Drugs 0.000 description 1
VUZPPFZMUPKLLV-UHFFFAOYSA-N methane;hydrate Chemical compound C.O VUZPPFZMUPKLLV-UHFFFAOYSA-N 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
WZDDJYDVKVFLCX-UHFFFAOYSA-N methyl 2-[(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carbonyl)amino]acetate Chemical compound OC1=C(C)C(C)=C2OC(C(=O)NCC(=O)OC)(C)CCC2=C1C WZDDJYDVKVFLCX-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
239000003094 microcapsule Substances 0.000 description 1
239000011859 microparticle Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000003595 mist Substances 0.000 description 1
230000004898 mitochondrial function Effects 0.000 description 1
230000006705 mitochondrial oxidative phosphorylation Effects 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
239000003607 modifier Substances 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
150000002772 monosaccharides Chemical class 0.000 description 1
230000004973 motor coordination Effects 0.000 description 1
238000001964 muscle biopsy Methods 0.000 description 1
210000000663 muscle cell Anatomy 0.000 description 1
230000002151 myoclonic effect Effects 0.000 description 1
ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
208000009928 nephrosis Diseases 0.000 description 1
231100001027 nephrosis Toxicity 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
230000000626 neurodegenerative effect Effects 0.000 description 1
238000002610 neuroimaging Methods 0.000 description 1
230000000926 neurological effect Effects 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
235000015097 nutrients Nutrition 0.000 description 1
206010029864 nystagmus Diseases 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
230000002853 ongoing effect Effects 0.000 description 1
208000001749 optic atrophy Diseases 0.000 description 1
238000005457 optimization Methods 0.000 description 1
230000004768 organ dysfunction Effects 0.000 description 1
210000004789 organ system Anatomy 0.000 description 1
210000003463 organelle Anatomy 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
230000001151 other effect Effects 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
230000004783 oxidative metabolism Effects 0.000 description 1
KQOATKAFTRNONV-UHFFFAOYSA-N oxolan-2-amine Chemical compound NC1CCCO1 KQOATKAFTRNONV-UHFFFAOYSA-N 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000037361 pathway Effects 0.000 description 1
239000000863 peptide conjugate Substances 0.000 description 1
239000002304 perfume Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229960003531 phenolsulfonphthalein Drugs 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
150000008105 phosphatidylcholines Chemical class 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
230000035479 physiological effects, processes and functions Effects 0.000 description 1
150000004885 piperazines Chemical class 0.000 description 1
HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
229920002627 poly(phosphazenes) Polymers 0.000 description 1
229920002647 polyamide Polymers 0.000 description 1
229920000728 polyester Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229920001282 polysaccharide Polymers 0.000 description 1
239000005017 polysaccharide Substances 0.000 description 1
229920002635 polyurethane Polymers 0.000 description 1
239000004814 polyurethane Substances 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
238000002600 positron emission tomography Methods 0.000 description 1
208000000170 postencephalitic Parkinson disease Diseases 0.000 description 1
230000001144 postural effect Effects 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
230000002265 prevention Effects 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
210000000512 proximal kidney tubule Anatomy 0.000 description 1
210000002804 pyramidal tract Anatomy 0.000 description 1
USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical group C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical group C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
150000004728 pyruvic acid derivatives Chemical class 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical group N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical group C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000011514 reflex Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000008439 repair process Effects 0.000 description 1
230000003252 repetitive effect Effects 0.000 description 1
235000005713 safflower oil Nutrition 0.000 description 1
239000003813 safflower oil Substances 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
230000007017 scission Effects 0.000 description 1
239000011669 selenium Substances 0.000 description 1
229910052711 selenium Inorganic materials 0.000 description 1
231100000879 sensorineural hearing loss Toxicity 0.000 description 1
208000023573 sensorineural hearing loss disease Diseases 0.000 description 1
210000001044 sensory neuron Anatomy 0.000 description 1
230000007841 sensory neuronopathy Effects 0.000 description 1
229940076279 serotonin Drugs 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
230000001568 sexual effect Effects 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000002689 soil Substances 0.000 description 1
230000037439 somatic mutation Effects 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
239000007921 spray Substances 0.000 description 1
208000024794 sputum Diseases 0.000 description 1
210000003802 sputum Anatomy 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
230000035882 stress Effects 0.000 description 1
208000023516 stroke disease Diseases 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000005846 sugar alcohols Polymers 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
229920001059 synthetic polymer Polymers 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
229930192474 thiophene Chemical group 0.000 description 1
230000009092 tissue dysfunction Effects 0.000 description 1
229960000984 tocofersolan Drugs 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000032258 transport Effects 0.000 description 1
ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
210000005239 tubule Anatomy 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
230000005751 tumor progression Effects 0.000 description 1
229960003732 tyramine Drugs 0.000 description 1
229940040064 ubiquinol Drugs 0.000 description 1
QNTNKSLOFHEFPK-UPTCCGCDSA-N ubiquinol-10 Chemical compound COC1=C(O)C(C)=C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)C(O)=C1OC QNTNKSLOFHEFPK-UPTCCGCDSA-N 0.000 description 1
230000002485 urinary effect Effects 0.000 description 1
230000036325 urinary excretion Effects 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
239000004034 viscosity adjusting agent Substances 0.000 description 1
230000000007 visual effect Effects 0.000 description 1
235000019165 vitamin E Nutrition 0.000 description 1
239000011709 vitamin E Chemical class 0.000 description 1
229940046009 vitamin E Drugs 0.000 description 1
150000003722 vitamin derivatives Chemical class 0.000 description 1
235000019195 vitamin supplement Nutrition 0.000 description 1
230000002747 voluntary effect Effects 0.000 description 1
230000008673 vomiting Effects 0.000 description 1
230000003442 weekly effect Effects 0.000 description 1
210000004885 white matter Anatomy 0.000 description 1

JP2010532329A 2007-11-06 2008-11-04 ミトコンドリア病を治療するための４−（ｐ−キノリル）−２−ヒドロキシブタンアミド誘導体 Active JP5755881B2 (ja)