JP2013541502A5 - - Google Patents

Info

Publication number

JP2013541502A5

JP2013541502A5 JP2013523342A JP2013523342A JP2013541502A5 JP 2013541502 A5 JP2013541502 A5 JP 2013541502A5 JP 2013523342 A JP2013523342 A JP 2013523342A JP 2013523342 A JP2013523342 A JP 2013523342A JP 2013541502 A5 JP2013541502 A5 JP 2013541502A5

Authority

JP

Japan

Prior art keywords

alkyl

dione

independently

composition according

hydrogen

Prior art date

2011-08-04

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Granted

Links

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• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 73
• 239000000203 mixture Substances 0.000 claims description 44
• 229910052739 hydrogen Inorganic materials 0.000 claims description 31
• 239000001257 hydrogen Substances 0.000 claims description 31
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
• 150000001875 compounds Chemical class 0.000 claims description 23
• 150000003839 salts Chemical class 0.000 claims description 14
• 239000012453 solvate Substances 0.000 claims description 14
• 208000012268 mitochondrial disease Diseases 0.000 claims description 10
• 208000024412 Friedreich ataxia Diseases 0.000 claims description 8
• 208000011580 syndromic disease Diseases 0.000 claims description 8
• 150000004677 hydrates Chemical class 0.000 claims description 7
• 230000004065 mitochondrial dysfunction Effects 0.000 claims description 6
• FRASJONUBLZVQX-UHFFFAOYSA-N 1,4-naphthoquinone Chemical compound C1=CC=C2C(=O)C=CC(=O)C2=C1 FRASJONUBLZVQX-UHFFFAOYSA-N 0.000 claims description 5
• 206010058799 Mitochondrial encephalomyopathy Diseases 0.000 claims description 4
• 201000002169 Mitochondrial myopathy Diseases 0.000 claims description 4
• 208000036572 Myoclonic epilepsy Diseases 0.000 claims description 4
• 201000009028 early myoclonic encephalopathy Diseases 0.000 claims description 4
• 239000000835 fiber Substances 0.000 claims description 4
• 208000023692 inborn mitochondrial myopathy Diseases 0.000 claims description 4
• 150000002431 hydrogen Chemical class 0.000 claims description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
• 208000010444 Acidosis Diseases 0.000 claims description 2
• 208000031229 Cardiomyopathies Diseases 0.000 claims description 2
• 206010011878 Deafness Diseases 0.000 claims description 2
• 208000023105 Huntington disease Diseases 0.000 claims description 2
• 201000009623 Myopathy Diseases 0.000 claims description 2
• 208000018737 Parkinson disease Diseases 0.000 claims description 2
• 208000012202 Pervasive developmental disease Diseases 0.000 claims description 2
• 208000034189 Sclerosis Diseases 0.000 claims description 2
• 230000007950 acidosis Effects 0.000 claims description 2
• 208000026545 acidosis disease Diseases 0.000 claims description 2
• 208000029560 autism spectrum disease Diseases 0.000 claims description 2
• 230000010370 hearing loss Effects 0.000 claims description 2
• 231100000888 hearing loss Toxicity 0.000 claims description 2
• 208000016354 hearing loss disease Diseases 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 208000024891 symptom Diseases 0.000 claims description 2
• QDUAOKYKHMKPTA-UHFFFAOYSA-N 2-methyl-3-nonylnaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCCCCCCCC)=C(C)C(=O)C2=C1 QDUAOKYKHMKPTA-UHFFFAOYSA-N 0.000 claims 2
• -1 R 3c is Chemical group 0.000 claims 2
• LGFDNUSAWCHVJN-UHFFFAOYSA-N 2,3-dimethyl-1,4-naphthoquinone Chemical compound C1=CC=C2C(=O)C(C)=C(C)C(=O)C2=C1 LGFDNUSAWCHVJN-UHFFFAOYSA-N 0.000 claims 1
• ZYZWUEIPVNFQQC-UHFFFAOYSA-N 2-(3-hydroxy-3,7,11,15-tetramethylhexadecyl)-3-methylnaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCC(C)(O)CCCC(C)CCCC(C)CCCC(C)C)=C(C)C(=O)C2=C1 ZYZWUEIPVNFQQC-UHFFFAOYSA-N 0.000 claims 1
• PFCSRGNFXBREEI-UHFFFAOYSA-N 2-(3-hydroxy-3,7-dimethyloct-6-enyl)naphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCC(C)(O)CCC=C(C)C)=CC(=O)C2=C1 PFCSRGNFXBREEI-UHFFFAOYSA-N 0.000 claims 1
• BXRGMKVTCTWHRD-UHFFFAOYSA-N 2-butyl-3-methylnaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCCC)=C(C)C(=O)C2=C1 BXRGMKVTCTWHRD-UHFFFAOYSA-N 0.000 claims 1
• JZCYOZPRLAGWSS-UHFFFAOYSA-N 2-decyl-3-methylnaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCCCCCCCCC)=C(C)C(=O)C2=C1 JZCYOZPRLAGWSS-UHFFFAOYSA-N 0.000 claims 1
• DTGKPFYIFROSOP-UHFFFAOYSA-N 2-heptadecyl-3-methylnaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCCCCCCCCCCCCCCCC)=C(C)C(=O)C2=C1 DTGKPFYIFROSOP-UHFFFAOYSA-N 0.000 claims 1
• YAKBITAXCOOTRG-UHFFFAOYSA-N 2-heptyl-3-methylnaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCCCCCC)=C(C)C(=O)C2=C1 YAKBITAXCOOTRG-UHFFFAOYSA-N 0.000 claims 1
• DIIHNBLSXDGYNT-UHFFFAOYSA-N 2-hexyl-3-methylnaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCCCCC)=C(C)C(=O)C2=C1 DIIHNBLSXDGYNT-UHFFFAOYSA-N 0.000 claims 1
• FATIXBDICXNSAQ-UHFFFAOYSA-N 2-icosyl-3-methylnaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCCCCCCCCCCCCCCCCCCC)=C(C)C(=O)C2=C1 FATIXBDICXNSAQ-UHFFFAOYSA-N 0.000 claims 1
• MOYPRYFRIDZWHC-UHFFFAOYSA-N 2-methyl-3-(3,7,11-trimethyldodecyl)naphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCC(C)CCCC(C)CCCC(C)C)=C(C)C(=O)C2=C1 MOYPRYFRIDZWHC-UHFFFAOYSA-N 0.000 claims 1
• JCSUQQOAHQRPBF-UHFFFAOYSA-N 2-methyl-3-(3-methylbutyl)naphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCC(C)C)=C(C)C(=O)C2=C1 JCSUQQOAHQRPBF-UHFFFAOYSA-N 0.000 claims 1
• SUVLFHKXBHCAKS-UHFFFAOYSA-N 2-methyl-3-nonadecylnaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCCCCCCCCCCCCCCCCCC)=C(C)C(=O)C2=C1 SUVLFHKXBHCAKS-UHFFFAOYSA-N 0.000 claims 1
• ANJYWYTXJPIQLS-UHFFFAOYSA-N 2-methyl-3-octylnaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCCCCCCC)=C(C)C(=O)C2=C1 ANJYWYTXJPIQLS-UHFFFAOYSA-N 0.000 claims 1
• ONKIICPFVVQPJA-UHFFFAOYSA-N 2-methyl-3-pentadecylnaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCCCCCCCCCCCCCC)=C(C)C(=O)C2=C1 ONKIICPFVVQPJA-UHFFFAOYSA-N 0.000 claims 1
• XTMWDFCOWHNAPA-UHFFFAOYSA-N 2-methyl-3-pentylnaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCCCC)=C(C)C(=O)C2=C1 XTMWDFCOWHNAPA-UHFFFAOYSA-N 0.000 claims 1
• GIQISUKKXZTPJV-UHFFFAOYSA-N 2-methyl-3-propylnaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCC)=C(C)C(=O)C2=C1 GIQISUKKXZTPJV-UHFFFAOYSA-N 0.000 claims 1
• PUURYLDVOHSJSZ-UHFFFAOYSA-N 2-methyl-3-tetradecylnaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCCCCCCCCCCCCC)=C(C)C(=O)C2=C1 PUURYLDVOHSJSZ-UHFFFAOYSA-N 0.000 claims 1
• MVFUHAWRIKCIAB-UHFFFAOYSA-N 2-methyl-3-tridecylnaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(CCCCCCCCCCCCC)=C(C)C(=O)C2=C1 MVFUHAWRIKCIAB-UHFFFAOYSA-N 0.000 claims 1
• 229930192627 Naphthoquinone Natural products 0.000 claims 1
• 150000002791 naphthoquinones Chemical class 0.000 claims 1
• 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 6
• 235000017471 coenzyme Q10 Nutrition 0.000 description 6
• 102000018832 Cytochromes Human genes 0.000 description 4
• 108010052832 Cytochromes Proteins 0.000 description 4
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 4
• 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 3
• 210000004369 blood Anatomy 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 210000001175 cerebrospinal fluid Anatomy 0.000 description 3
• 239000012530 fluid Substances 0.000 description 3
• 230000002861 ventricular Effects 0.000 description 3
• 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 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
• DRBBFCLWYRJSJZ-UHFFFAOYSA-N N-phosphocreatine Chemical compound OC(=O)CN(C)C(=N)NP(O)(O)=O DRBBFCLWYRJSJZ-UHFFFAOYSA-N 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 2
• WDJHALXBUFZDSR-UHFFFAOYSA-M acetoacetate Chemical compound CC(=O)CC([O-])=O WDJHALXBUFZDSR-UHFFFAOYSA-M 0.000 description 2
• 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 2
• 210000002381 plasma Anatomy 0.000 description 2
• WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 1
• 0 C*C(C(c1cc(I)c(*=C)cc11)=N)=C(**(*)[I-])C1=Cl Chemical compound C*C(C(c1cc(I)c(*=C)cc11)=N)=C(**(*)[I-])C1=Cl 0.000 description 1
• 239000000090 biomarker Substances 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• 230000036284 oxygen consumption Effects 0.000 description 1
• 229950007002 phosphocreatine Drugs 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• 239000003642 reactive oxygen metabolite Substances 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1