EA035866B1 - Применение производных 2,4-тиазолидиндиона для лечения расстройств центральной нервной системы и способ лечения с использованием таких производных - Google Patents
Применение производных 2,4-тиазолидиндиона для лечения расстройств центральной нервной системы и способ лечения с использованием таких производных Download PDFInfo
- Publication number
- EA035866B1 EA035866B1 EA201691997A EA201691997A EA035866B1 EA 035866 B1 EA035866 B1 EA 035866B1 EA 201691997 A EA201691997 A EA 201691997A EA 201691997 A EA201691997 A EA 201691997A EA 035866 B1 EA035866 B1 EA 035866B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- compound
- compounds
- mixture
- ethoxy
- thiazolidine
- Prior art date
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 36
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical class O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 title claims description 67
- 238000000034 method Methods 0.000 title claims description 48
- 208000015114 central nervous system disease Diseases 0.000 title claims description 36
- 150000001875 compounds Chemical class 0.000 claims abstract description 264
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 74
- 210000003169 central nervous system Anatomy 0.000 claims abstract description 28
- 239000000203 mixture Substances 0.000 claims description 118
- 150000003839 salts Chemical class 0.000 claims description 65
- 201000011452 Adrenoleukodystrophy Diseases 0.000 claims description 62
- 208000035475 disorder Diseases 0.000 claims description 37
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 34
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 34
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 33
- 201000006417 multiple sclerosis Diseases 0.000 claims description 30
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 29
- 239000003814 drug Substances 0.000 claims description 27
- 108010049137 Member 1 Subfamily D ATP Binding Cassette Transporter Proteins 0.000 claims description 26
- 208000012902 Nervous system disease Diseases 0.000 claims description 21
- 208000018737 Parkinson disease Diseases 0.000 claims description 20
- 208000024827 Alzheimer disease Diseases 0.000 claims description 19
- 206010003591 Ataxia Diseases 0.000 claims description 18
- 208000005264 motor neuron disease Diseases 0.000 claims description 15
- 208000002320 spinal muscular atrophy Diseases 0.000 claims description 15
- 208000023105 Huntington disease Diseases 0.000 claims description 13
- 208000032319 Primary lateral sclerosis Diseases 0.000 claims description 13
- 206010046298 Upper motor neurone lesion Diseases 0.000 claims description 13
- 230000003412 degenerative effect Effects 0.000 claims description 13
- 201000010901 lateral sclerosis Diseases 0.000 claims description 13
- 230000002265 prevention Effects 0.000 claims description 13
- 239000002552 dosage form Substances 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 201000002241 progressive bulbar palsy Diseases 0.000 claims description 7
- 201000000196 pseudobulbar palsy Diseases 0.000 claims description 7
- 239000000725 suspension Substances 0.000 claims description 7
- -1 pyridine-2- yl Chemical group 0.000 claims description 6
- 239000003826 tablet Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 239000006187 pill Substances 0.000 claims description 3
- 238000007918 intramuscular administration Methods 0.000 claims description 2
- 239000003614 peroxisome proliferator Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 238000007920 subcutaneous administration Methods 0.000 claims description 2
- 102000009030 Member 1 Subfamily D ATP Binding Cassette Transporter Human genes 0.000 claims 21
- 239000006186 oral dosage form Substances 0.000 claims 6
- 229940100688 oral solution Drugs 0.000 claims 2
- 239000000018 receptor agonist Substances 0.000 claims 1
- 229940044601 receptor agonist Drugs 0.000 claims 1
- OXVFDZYQLGRLCD-UHFFFAOYSA-N hydroxypioglitazone Chemical compound N1=CC(C(O)C)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 OXVFDZYQLGRLCD-UHFFFAOYSA-N 0.000 abstract description 26
- 210000000653 nervous system Anatomy 0.000 abstract description 14
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 67
- 201000010099 disease Diseases 0.000 description 36
- 229960005095 pioglitazone Drugs 0.000 description 35
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 210000004556 brain Anatomy 0.000 description 29
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- DBTIHDIIXPQOFR-JMHKOBKLSA-N mycinamicin IV Chemical compound O([C@@H]1[C@@H](C)/C=C/C(=O)O[C@@H]([C@H](/C=C/C=C/C(=O)[C@H](C)C[C@@H]1C)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@@H]1O[C@H](C)C[C@H](N(C)C)[C@H]1O DBTIHDIIXPQOFR-JMHKOBKLSA-N 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 208000010796 X-linked adrenoleukodystrophy Diseases 0.000 description 21
- 241000699670 Mus sp. Species 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 102000010909 Monoamine Oxidase Human genes 0.000 description 18
- 108010062431 Monoamine oxidase Proteins 0.000 description 18
- 230000000694 effects Effects 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- 210000002381 plasma Anatomy 0.000 description 17
- 102100024643 ATP-binding cassette sub-family D member 1 Human genes 0.000 description 16
- 230000004770 neurodegeneration Effects 0.000 description 16
- 208000015122 neurodegenerative disease Diseases 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 14
- 229940079593 drug Drugs 0.000 description 13
- 239000002207 metabolite Substances 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 12
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 12
- 229930195712 glutamate Natural products 0.000 description 12
- 210000000278 spinal cord Anatomy 0.000 description 12
- OXVFDZYQLGRLCD-SJKOYZFVSA-N leriglitazone Chemical compound N1=CC([C@H](O)C)=CC=C1CCOC(C=C1)=CC=C1C[C@@H]1C(=O)NC(=O)S1 OXVFDZYQLGRLCD-SJKOYZFVSA-N 0.000 description 11
- 208000003174 Brain Neoplasms Diseases 0.000 description 10
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 10
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 10
- 238000009826 distribution Methods 0.000 description 10
- 206010015037 epilepsy Diseases 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 230000002490 cerebral effect Effects 0.000 description 9
- 208000026106 cerebrovascular disease Diseases 0.000 description 9
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 9
- 210000002569 neuron Anatomy 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 230000003612 virological effect Effects 0.000 description 9
- 206010010904 Convulsion Diseases 0.000 description 8
- 208000033866 Rare inborn errors of metabolism Diseases 0.000 description 8
- 230000008499 blood brain barrier function Effects 0.000 description 8
- 210000001218 blood-brain barrier Anatomy 0.000 description 8
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- 208000012268 mitochondrial disease Diseases 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- NPAXFQZLUHJHMA-UHFFFAOYSA-N 5-[[4-[2-[5-[1-(methoxymethoxy)ethyl]pyridin-2-yl]ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound N1=CC(C(C)OCOC)=CC=C1CCOC(C=C1)=CC=C1C=C1C(=O)NC(=O)S1 NPAXFQZLUHJHMA-UHFFFAOYSA-N 0.000 description 7
- MYLBTCQBKAKUTJ-UHFFFAOYSA-N 7-methyl-6,8-bis(methylsulfanyl)pyrrolo[1,2-a]pyrazine Chemical compound C1=CN=CC2=C(SC)C(C)=C(SC)N21 MYLBTCQBKAKUTJ-UHFFFAOYSA-N 0.000 description 7
- 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 7
- 208000018126 Adrenomyeloneuropathy Diseases 0.000 description 7
- 108010016731 PPAR gamma Proteins 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000004296 chiral HPLC Methods 0.000 description 7
- 235000014113 dietary fatty acids Nutrition 0.000 description 7
- 201000002491 encephalomyelitis Diseases 0.000 description 7
- 229930195729 fatty acid Natural products 0.000 description 7
- 239000000194 fatty acid Substances 0.000 description 7
- 150000004665 fatty acids Chemical class 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 230000002068 genetic effect Effects 0.000 description 7
- 208000036546 leukodystrophy Diseases 0.000 description 7
- 201000008152 organic acidemia Diseases 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 6
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 210000002161 motor neuron Anatomy 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 230000009885 systemic effect Effects 0.000 description 6
- 208000016192 Demyelinating disease Diseases 0.000 description 5
- 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 5
- 241000700159 Rattus Species 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 208000006011 Stroke Diseases 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 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 5
- 238000012512 characterization method Methods 0.000 description 5
- 210000003618 cortical neuron Anatomy 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- JGUQDUKBUKFFRO-CIIODKQPSA-N dimethylglyoxime Chemical compound O/N=C(/C)\C(\C)=N\O JGUQDUKBUKFFRO-CIIODKQPSA-N 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 230000036470 plasma concentration Effects 0.000 description 5
- 230000001681 protective effect Effects 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- AOHSDRCYABCFTI-UHFFFAOYSA-N 5-[1-(methoxymethoxy)ethyl]-2-methylpyridine Chemical compound COCOC(C)C1=CC=C(C)N=C1 AOHSDRCYABCFTI-UHFFFAOYSA-N 0.000 description 4
- 230000035502 ADME Effects 0.000 description 4
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 4
- 206010012305 Demyelination Diseases 0.000 description 4
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 201000009906 Meningitis Diseases 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 208000032109 Transient ischaemic attack Diseases 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 229910052805 deuterium Inorganic materials 0.000 description 4
- 230000006806 disease prevention Effects 0.000 description 4
- 206010014599 encephalitis Diseases 0.000 description 4
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 4
- 210000002950 fibroblast Anatomy 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 230000003959 neuroinflammation Effects 0.000 description 4
- 230000035515 penetration Effects 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 201000010875 transient cerebral ischemia Diseases 0.000 description 4
- DCYLRSYWXFRFOX-UHFFFAOYSA-N 2-[5-[1-(methoxymethoxy)ethyl]pyridin-2-yl]ethanol Chemical compound COCOC(C)C1=CC=C(CCO)N=C1 DCYLRSYWXFRFOX-UHFFFAOYSA-N 0.000 description 3
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 3
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 3
- 208000001089 Multiple system atrophy Diseases 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 206010029350 Neurotoxicity Diseases 0.000 description 3
- 229940080774 Peroxisome proliferator-activated receptor gamma agonist Drugs 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 208000030886 Traumatic Brain injury Diseases 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 3
- 208000028867 ischemia Diseases 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000003141 lower extremity Anatomy 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000012429 reaction media Substances 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- OXVFDZYQLGRLCD-SJCJKPOMSA-N (5s)-5-[[4-[2-[5-[(1s)-1-hydroxyethyl]pyridin-2-yl]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound N1=CC([C@@H](O)C)=CC=C1CCOC(C=C1)=CC=C1C[C@H]1C(=O)NC(=O)S1 OXVFDZYQLGRLCD-SJCJKPOMSA-N 0.000 description 2
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 2
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
- IDCLTMRSSAXUNY-UHFFFAOYSA-N 5-hydroxylansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC(O)=CC=C2N1 IDCLTMRSSAXUNY-UHFFFAOYSA-N 0.000 description 2
- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 description 2
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 2
- 206010003694 Atrophy Diseases 0.000 description 2
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 2
- 108010065524 CD52 Antigen Proteins 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 2
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 2
- 206010013710 Drug interaction Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 208000024412 Friedreich ataxia Diseases 0.000 description 2
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 2
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 2
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 2
- 206010022998 Irritability Diseases 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 2
- 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 2
- 108020005196 Mitochondrial DNA Proteins 0.000 description 2
- 208000026072 Motor neurone disease Diseases 0.000 description 2
- 102000002233 Myelin-Oligodendrocyte Glycoprotein Human genes 0.000 description 2
- 108010000123 Myelin-Oligodendrocyte Glycoprotein Proteins 0.000 description 2
- 108091093105 Nuclear DNA Proteins 0.000 description 2
- 206010033799 Paralysis Diseases 0.000 description 2
- 108010081690 Pertussis Toxin Proteins 0.000 description 2
- 241000233805 Phoenix Species 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 208000010366 Postpoliomyelitis syndrome Diseases 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 230000037444 atrophy Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 231100000153 central nervous system (CNS) toxicity Toxicity 0.000 description 2
- 210000003710 cerebral cortex Anatomy 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 230000006020 chronic inflammation Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 238000002716 delivery method Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 210000002257 embryonic structure Anatomy 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 238000005462 in vivo assay Methods 0.000 description 2
- 238000000622 liquid--liquid extraction Methods 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 210000002418 meninge Anatomy 0.000 description 2
- 230000037353 metabolic pathway Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 210000000274 microglia Anatomy 0.000 description 2
- 238000002552 multiple reaction monitoring Methods 0.000 description 2
- 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 2
- 210000004498 neuroglial cell Anatomy 0.000 description 2
- 230000016273 neuron death Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 210000002250 primary motor neuron Anatomy 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000011002 quantification 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
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- 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 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000009529 traumatic brain injury Effects 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 description 1
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- OXVFDZYQLGRLCD-YVEFUNNKSA-N (5r)-5-[[4-[2-[5-[(1s)-1-hydroxyethyl]pyridin-2-yl]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound N1=CC([C@@H](O)C)=CC=C1CCOC(C=C1)=CC=C1C[C@@H]1C(=O)NC(=O)S1 OXVFDZYQLGRLCD-YVEFUNNKSA-N 0.000 description 1
- OXVFDZYQLGRLCD-PXAZEXFGSA-N (5s)-5-[[4-[2-[5-[(1r)-1-hydroxyethyl]pyridin-2-yl]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound N1=CC([C@H](O)C)=CC=C1CCOC(C=C1)=CC=C1C[C@H]1C(=O)NC(=O)S1 OXVFDZYQLGRLCD-PXAZEXFGSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- LYMOQGXOROSRPJ-UHFFFAOYSA-N 1-(6-methylpyridin-3-yl)ethanol Chemical compound CC(O)C1=CC=C(C)N=C1 LYMOQGXOROSRPJ-UHFFFAOYSA-N 0.000 description 1
- PVRYOKQFLBSILA-UHFFFAOYSA-N 1-(6-methylpyridin-3-yl)ethanone Chemical compound CC(=O)C1=CC=C(C)N=C1 PVRYOKQFLBSILA-UHFFFAOYSA-N 0.000 description 1
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 1
- OBQPKGCVMCIETH-UHFFFAOYSA-N 1-chloro-1-(1-chloroethoxy)ethane Chemical group CC(Cl)OC(C)Cl OBQPKGCVMCIETH-UHFFFAOYSA-N 0.000 description 1
- 150000001473 2,4-thiazolidinediones Chemical class 0.000 description 1
- MGYSTOQOSMRLQF-JZUJSFITSA-N 2-hydroxy-1-[(3s,9r,10s,13s,14r,17s)-3-hydroxy-10,13-dimethyl-2,3,4,9,11,12,14,15,16,17-decahydro-1h-cyclopenta[a]phenanthren-17-yl]ethanone Chemical compound C1[C@@H](O)CC[C@@]2(C)[C@@H]3CC[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4C3=CC=C21 MGYSTOQOSMRLQF-JZUJSFITSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 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
- PPCLBBXZDXYYQR-UHFFFAOYSA-N 4-[2-[5-[1-(methoxymethoxy)ethyl]pyridin-2-yl]ethoxy]benzaldehyde Chemical compound N1=CC(C(C)OCOC)=CC=C1CCOC1=CC=C(C=O)C=C1 PPCLBBXZDXYYQR-UHFFFAOYSA-N 0.000 description 1
- JMLKLMFMQRAJNI-UHFFFAOYSA-N 5-[[4-[2-(5-acetylpyridin-2-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound N1=CC(C(=O)C)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 JMLKLMFMQRAJNI-UHFFFAOYSA-N 0.000 description 1
- UDDCGCGNWXOFEI-UHFFFAOYSA-N 5-[[4-[2-[5-[1-(methoxymethoxy)ethyl]pyridin-2-yl]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound N1=CC(C(C)OCOC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 UDDCGCGNWXOFEI-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 231100000582 ATP assay Toxicity 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- 102100028116 Amine oxidase [flavin-containing] B Human genes 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- 235000011437 Amygdalus communis Nutrition 0.000 description 1
- ICRHGPYYXMWHIE-LPEHRKFASA-N Arg-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O ICRHGPYYXMWHIE-LPEHRKFASA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- VKYXHVFPMYEGSY-UHFFFAOYSA-N CS(=O)(=O)OCCC1=NC=C(C=C1)C(C)OCOC Chemical compound CS(=O)(=O)OCCC1=NC=C(C=C1)C(C)OCOC VKYXHVFPMYEGSY-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000006378 Catechol O-methyltransferase Human genes 0.000 description 1
- 108020002739 Catechol O-methyltransferase Proteins 0.000 description 1
- 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 description 1
- 201000006082 Chickenpox Diseases 0.000 description 1
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 102000003849 Cytochrome P450 Human genes 0.000 description 1
- 238000001061 Dunnett's test Methods 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 229940122459 Glutamate antagonist Drugs 0.000 description 1
- IROABALAWGJQGM-OALUTQOASA-N Gly-Trp-Tyr Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)O)NC(=O)CN IROABALAWGJQGM-OALUTQOASA-N 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 208000028782 Hereditary disease Diseases 0.000 description 1
- MMFKFJORZBJVNF-UWVGGRQHSA-N His-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CN=CN1 MMFKFJORZBJVNF-UWVGGRQHSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000768078 Homo sapiens Amine oxidase [flavin-containing] B Proteins 0.000 description 1
- 101001093899 Homo sapiens Retinoic acid receptor RXR-alpha Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010062767 Hypophysitis 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
- 108010032774 Interleukin-2 Receptor alpha Subunit Proteins 0.000 description 1
- 102000007351 Interleukin-2 Receptor alpha Subunit Human genes 0.000 description 1
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 102000010904 Mediator Complex Subunit 1 Human genes 0.000 description 1
- 108010062495 Mediator Complex Subunit 1 Proteins 0.000 description 1
- 208000024556 Mendelian disease Diseases 0.000 description 1
- ADHNYKZHPOEULM-BQBZGAKWSA-N Met-Glu Chemical compound CSCC[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O ADHNYKZHPOEULM-BQBZGAKWSA-N 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 108090000192 Methionyl aminopeptidases Proteins 0.000 description 1
- 102100021118 Microtubule-associated protein 2 Human genes 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 208000005647 Mumps Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 208000003926 Myelitis Diseases 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 102000000536 PPAR gamma Human genes 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 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 1
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
- 102100038831 Peroxisome proliferator-activated receptor alpha Human genes 0.000 description 1
- WEDZFLRYSIDIRX-IHRRRGAJSA-N Phe-Ser-Arg Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=CC=C1 WEDZFLRYSIDIRX-IHRRRGAJSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 206010037742 Rabies Diseases 0.000 description 1
- 208000035977 Rare disease Diseases 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102100035178 Retinoic acid receptor RXR-alpha Human genes 0.000 description 1
- 241000223253 Rhodotorula glutinis Species 0.000 description 1
- 241000223254 Rhodotorula mucilaginosa Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 229940123464 Thiazolidinedione Drugs 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- AKFLVKKWVZMFOT-IHRRRGAJSA-N Tyr-Arg-Asn Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O AKFLVKKWVZMFOT-IHRRRGAJSA-N 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 206010046980 Varicella Diseases 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 210000001766 X chromosome Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000008484 agonism Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 235000020224 almond Nutrition 0.000 description 1
- 238000003016 alphascreen Methods 0.000 description 1
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 1
- 229960003805 amantadine Drugs 0.000 description 1
- 239000003194 amino acid receptor blocking agent Substances 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940035678 anti-parkinson drug Drugs 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 229940082992 antihypertensives mao inhibitors Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 230000007844 axonal damage Effects 0.000 description 1
- 230000003376 axonal effect Effects 0.000 description 1
- 230000007845 axonopathy Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 238000004638 bioanalytical method Methods 0.000 description 1
- 239000011942 biocatalyst Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000000476 body water Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 description 1
- 235000005487 catechin Nutrition 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229940061627 chloromethyl methyl ether Drugs 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229950001002 cianidanol Drugs 0.000 description 1
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 229950002858 clorgiline Drugs 0.000 description 1
- BTFHLQRNAMSNLC-UHFFFAOYSA-N clorgyline Chemical compound C#CCN(C)CCCOC1=CC=C(Cl)C=C1Cl BTFHLQRNAMSNLC-UHFFFAOYSA-N 0.000 description 1
- 230000003081 coactivator Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000003271 compound fluorescence assay Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 210000003792 cranial nerve Anatomy 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 229960001577 dantron Drugs 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 description 1
- 229960004419 dimethyl fumarate Drugs 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000002641 enzyme replacement therapy Methods 0.000 description 1
- 238000006345 epimerization reaction Methods 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 230000003492 excitotoxic effect Effects 0.000 description 1
- 231100000063 excitotoxicity Toxicity 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 108010015792 glycyllysine Proteins 0.000 description 1
- 231100000226 haematotoxicity Toxicity 0.000 description 1
- 238000011134 hematopoietic stem cell transplantation Methods 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 108010025306 histidylleucine Proteins 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 208000016245 inborn errors of metabolism Diseases 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- GKWPCEFFIHSJOE-UHFFFAOYSA-N laquinimod Chemical compound OC=1C2=C(Cl)C=CC=C2N(C)C(=O)C=1C(=O)N(CC)C1=CC=CC=C1 GKWPCEFFIHSJOE-UHFFFAOYSA-N 0.000 description 1
- 229960004577 laquinimod Drugs 0.000 description 1
- 229960004502 levodopa Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
- 229960004640 memantine Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- LLCOIQRNSJBFSN-UHFFFAOYSA-N methane;sulfurochloridic acid Chemical compound C.OS(Cl)(=O)=O LLCOIQRNSJBFSN-UHFFFAOYSA-N 0.000 description 1
- 108010056582 methionylglutamic acid Proteins 0.000 description 1
- VYPPZXZHYDSBSJ-UHFFFAOYSA-N methyl 6-methylpyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(C)N=C1 VYPPZXZHYDSBSJ-UHFFFAOYSA-N 0.000 description 1
- 230000006724 microglial activation Effects 0.000 description 1
- 230000003228 microsomal effect Effects 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000004898 mitochondrial function Effects 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 208000010805 mumps infectious disease Diseases 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 229960005027 natalizumab Drugs 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 230000002314 neuroinflammatory effect Effects 0.000 description 1
- 230000009251 neurologic dysfunction Effects 0.000 description 1
- 208000015015 neurological dysfunction Diseases 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 239000003900 neurotrophic factor Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000008203 oral pharmaceutical composition Substances 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000007833 oxidative deamination reaction Methods 0.000 description 1
- 230000009745 pathological pathway Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 210000004560 pineal gland Anatomy 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 210000002243 primary neuron Anatomy 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 201000008752 progressive muscular atrophy Diseases 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000006920 protein precipitation Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 231100000057 systemic toxicity Toxicity 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Dispersion Chemistry (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Oncology (AREA)
- Psychiatry (AREA)
- Communicable Diseases (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Virology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14382130 | 2014-04-02 | ||
| PCT/EP2015/057224 WO2015150476A1 (en) | 2014-04-02 | 2015-04-01 | 2,4-thiazolidinedione derivatives in the treatment of central nervous system disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201691997A1 EA201691997A1 (ru) | 2017-02-28 |
| EA035866B1 true EA035866B1 (ru) | 2020-08-21 |
Family
ID=50513194
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201691997A EA035866B1 (ru) | 2014-04-02 | 2015-04-01 | Применение производных 2,4-тиазолидиндиона для лечения расстройств центральной нервной системы и способ лечения с использованием таких производных |
| EA202091120A EA202091120A3 (ru) | 2014-04-02 | 2015-04-01 | Производные 2,4-тиазолинидона в лечении расстройств центральной нервной системы |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA202091120A EA202091120A3 (ru) | 2014-04-02 | 2015-04-01 | Производные 2,4-тиазолинидона в лечении расстройств центральной нервной системы |
Country Status (24)
| Country | Link |
|---|---|
| US (3) | US9782395B2 (enExample) |
| EP (2) | EP3388064B1 (enExample) |
| JP (2) | JP6745726B2 (enExample) |
| KR (1) | KR102418167B1 (enExample) |
| CN (1) | CN106470991B (enExample) |
| AU (1) | AU2015239112C1 (enExample) |
| CA (1) | CA2943373C (enExample) |
| CL (1) | CL2016002508A1 (enExample) |
| CY (2) | CY1120454T1 (enExample) |
| DK (2) | DK3388064T3 (enExample) |
| EA (2) | EA035866B1 (enExample) |
| ES (2) | ES2872335T3 (enExample) |
| HR (2) | HRP20180983T1 (enExample) |
| HU (2) | HUE055351T2 (enExample) |
| IL (1) | IL248037B (enExample) |
| LT (2) | LT3388064T (enExample) |
| MX (1) | MX373234B (enExample) |
| NZ (1) | NZ725492A (enExample) |
| PL (2) | PL3388064T3 (enExample) |
| PT (2) | PT3388064T (enExample) |
| SG (1) | SG11201608218QA (enExample) |
| SI (2) | SI3125888T1 (enExample) |
| WO (1) | WO2015150476A1 (enExample) |
| ZA (1) | ZA201607286B (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8722710B2 (en) | 2007-09-26 | 2014-05-13 | Deuterx, Llc | Deuterium-enriched pioglitazone |
| US20130158077A1 (en) | 2011-12-19 | 2013-06-20 | Ares Trading S.A. | Pharmaceutical compositions |
| CA2941562C (en) | 2013-03-14 | 2021-09-21 | Deuterx, Llc | Deuterium-enriched 2,4-thiazolidinediones and methods of treatment |
| WO2015109037A1 (en) | 2014-01-15 | 2015-07-23 | Deuterx, Llc | Methods of treating neurological, metabolic, and other disorders using enantiopure deuterium-enriched pioglitazone |
| LT3388064T (lt) * | 2014-04-02 | 2021-05-25 | Minoryx Therapeutics S.L. | 2,4-tiazolidindiono dariniai centrinės nervų sistemos sutrikimų gydyme |
| US11938122B2 (en) * | 2016-12-01 | 2024-03-26 | Minoryx Therapeutics S.L. | 5-[[4-[2-[5-(1-hydroxyethyl)pyridin-2-yl]ethoxy]phenyl]methyl]-1,3- thiazolidine-2,4-dione for treating nonalcoholic fatty liver disease |
| PT3559010T (pt) | 2016-12-23 | 2022-09-01 | Minoryx Therapeutics S L | Processo para preparar 5-[[4-[2-[5-(1-hidroxietil)-2-piridinil]etoxi]fenil]metil]-2,4-tiazolidinadiona e seus sais |
| MX2020013181A (es) * | 2018-06-06 | 2021-02-26 | Minoryx Therapeutics S L | Metodo para administrar una cantidad terapeuticamente efectiva de 5-[[4-[2-[5-(1-hidroxietil)piridin-2-il]etoxi]fenil]metil]-1,3-th iazolidin-2,4-diona. |
| HRP20250591T1 (hr) * | 2018-06-06 | 2025-07-04 | Minoryx Therapeutics S.L. | 5‑[[4‑[2‑[5‑(1‑hidroksietil)piridin‑2‑il]etoksi]fenil]metil]‑1,3‑tiazolidin‑2,4‑dion i njegove soli, namijenjen upotrebi u liječenju mitohondrijskih bolesti |
| WO2019234690A1 (en) * | 2018-06-06 | 2019-12-12 | Minoryx Therapeutics S.L. | Use of 5-[[4-[2-[5-acetylpyridin-2-yl]ethoxy]benzyl]-1,3-thiazolidine-2,4-dione and its salts |
| MX2022013021A (es) | 2020-04-30 | 2023-01-16 | Minoryx Therapeutics S L | Leriglitazona para tratar inflamacion pulmonar y enfermedad pulmonar intersticial. |
| US11767317B1 (en) | 2020-06-30 | 2023-09-26 | Poxel Sa | Methods of synthesizing enantiopure deuterium-enriched pioglitazone |
| US11319313B2 (en) | 2020-06-30 | 2022-05-03 | Poxel Sa | Crystalline forms of deuterium-enriched pioglitazone |
| EP4642456A1 (en) | 2022-12-28 | 2025-11-05 | Minoryx Therapeutics S.L. | Optimized dosing of leriglitazone |
| AU2024268104A1 (en) | 2023-05-09 | 2025-11-27 | Minoryx Therapeutics S.L. | Polymorphic forms and formulations of leriglitazone |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992018501A1 (en) * | 1991-04-11 | 1992-10-29 | The Upjohn Company | Thiazolidinedione derivatives, production and use thereof |
| WO2013040419A1 (en) * | 2011-09-14 | 2013-03-21 | The Trustees Of Columbia University In The City Of New York | Compositions and methods for treating hyperprolinemia-associated mental disorders |
| US20130274295A1 (en) * | 2012-03-23 | 2013-10-17 | Fundacio Institut D'investigacio Biomedica De Bellvitge (Idibell) | Pioglitazone for use in the treatment of adrenoleukodystrophy |
| WO2014152843A1 (en) * | 2013-03-14 | 2014-09-25 | Deuterx, Llc | Deuterium-enriched 2,4-thiazolidinediones and methods of treatment |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5441971A (en) | 1991-04-11 | 1995-08-15 | The Upjohn Company | Thiazolidinedione derivatives, production and use thereof |
| WO1993022445A1 (en) * | 1992-05-05 | 1993-11-11 | The Upjohn Company | A process for producing pioglitazone metabolite |
| US5952509A (en) | 1996-06-27 | 1999-09-14 | Takeda Chemical Industries, Ltd. | Production of benzaldehyde compounds |
| US6191154B1 (en) | 1998-11-27 | 2001-02-20 | Case Western Reserve University | Compositions and methods for the treatment of Alzheimer's disease, central nervous system injury, and inflammatory diseases |
| US6294192B1 (en) | 1999-02-26 | 2001-09-25 | Lipocine, Inc. | Triglyceride-free compositions and methods for improved delivery of hydrophobic therapeutic agents |
| US6720001B2 (en) | 1999-10-18 | 2004-04-13 | Lipocine, Inc. | Emulsion compositions for polyfunctional active ingredients |
| ATE319449T1 (de) | 2001-12-21 | 2006-03-15 | Smithkline Beecham Corp | Dosierschema für ppar-gamma-aktivatoren |
| US8993773B2 (en) | 2002-07-16 | 2015-03-31 | Cadila Healthcare Limited | Process to prepare pioglitazone via several novel intermediates |
| AU2003254146A1 (en) * | 2003-07-24 | 2005-03-07 | Case Western Reserve University | Methods for the treatment of parkinson's disease |
| ES2654908T3 (es) * | 2006-03-16 | 2018-02-15 | Metabolic Solutions Development Company Llc | Análogos de tiazolidindiona para el tratamiento de enfermedades mediadas por una inflamación metabólica |
| US8722710B2 (en) | 2007-09-26 | 2014-05-13 | Deuterx, Llc | Deuterium-enriched pioglitazone |
| EP3202401B1 (en) * | 2009-12-15 | 2019-10-23 | Cirius Therapeutics, Inc. | Ppar-sparing thiazolidinediones and combinations for the treatment of neurodegenerative diseases |
| US8895536B2 (en) | 2010-10-29 | 2014-11-25 | Infirst Healthcare Ltd. | Compositions and methods for treating chronic inflammation and inflammatory diseases |
| US20140178456A1 (en) | 2012-08-30 | 2014-06-26 | Udaya Sankar Devanaboyina | Methods and compositions for treating type 2 diabetes and related conditions |
| WO2015109037A1 (en) | 2014-01-15 | 2015-07-23 | Deuterx, Llc | Methods of treating neurological, metabolic, and other disorders using enantiopure deuterium-enriched pioglitazone |
| LT3388064T (lt) * | 2014-04-02 | 2021-05-25 | Minoryx Therapeutics S.L. | 2,4-tiazolidindiono dariniai centrinės nervų sistemos sutrikimų gydyme |
-
2015
- 2015-04-01 LT LTEP18173541.6T patent/LT3388064T/lt unknown
- 2015-04-01 LT LTEP15713499.0T patent/LT3125888T/lt unknown
- 2015-04-01 ES ES18173541T patent/ES2872335T3/es active Active
- 2015-04-01 KR KR1020167030649A patent/KR102418167B1/ko active Active
- 2015-04-01 NZ NZ725492A patent/NZ725492A/en unknown
- 2015-04-01 EP EP18173541.6A patent/EP3388064B1/en active Active
- 2015-04-01 HU HUE18173541A patent/HUE055351T2/hu unknown
- 2015-04-01 JP JP2016560727A patent/JP6745726B2/ja active Active
- 2015-04-01 EA EA201691997A patent/EA035866B1/ru unknown
- 2015-04-01 DK DK18173541.6T patent/DK3388064T3/da active
- 2015-04-01 EP EP15713499.0A patent/EP3125888B1/en active Active
- 2015-04-01 SI SI201530325T patent/SI3125888T1/en unknown
- 2015-04-01 SG SG11201608218QA patent/SG11201608218QA/en unknown
- 2015-04-01 CA CA2943373A patent/CA2943373C/en active Active
- 2015-04-01 SI SI201531591T patent/SI3388064T1/sl unknown
- 2015-04-01 DK DK15713499.0T patent/DK3125888T3/en active
- 2015-04-01 AU AU2015239112A patent/AU2015239112C1/en active Active
- 2015-04-01 HR HRP20180983TT patent/HRP20180983T1/hr unknown
- 2015-04-01 PT PT181735416T patent/PT3388064T/pt unknown
- 2015-04-01 PT PT157134990T patent/PT3125888T/pt unknown
- 2015-04-01 CN CN201580018404.6A patent/CN106470991B/zh active Active
- 2015-04-01 PL PL18173541T patent/PL3388064T3/pl unknown
- 2015-04-01 HU HUE15713499A patent/HUE039555T2/hu unknown
- 2015-04-01 ES ES15713499.0T patent/ES2678046T3/es active Active
- 2015-04-01 MX MX2016012687A patent/MX373234B/es active IP Right Grant
- 2015-04-01 WO PCT/EP2015/057224 patent/WO2015150476A1/en not_active Ceased
- 2015-04-01 PL PL15713499T patent/PL3125888T3/pl unknown
- 2015-04-01 EA EA202091120A patent/EA202091120A3/ru unknown
-
2016
- 2016-05-05 US US15/147,484 patent/US9782395B2/en active Active
- 2016-09-26 IL IL248037A patent/IL248037B/en active IP Right Grant
- 2016-10-03 CL CL2016002508A patent/CL2016002508A1/es unknown
- 2016-10-21 ZA ZA2016/07286A patent/ZA201607286B/en unknown
-
2017
- 2017-10-05 US US15/725,950 patent/US10179126B2/en active Active
-
2018
- 2018-07-23 CY CY20181100765T patent/CY1120454T1/el unknown
- 2018-12-13 US US16/218,829 patent/US20190255032A1/en not_active Abandoned
-
2020
- 2020-05-07 JP JP2020081949A patent/JP2020117539A/ja active Pending
-
2021
- 2021-03-30 HR HRP20210518TT patent/HRP20210518T1/hr unknown
- 2021-04-27 CY CY20211100363T patent/CY1124088T1/el unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992018501A1 (en) * | 1991-04-11 | 1992-10-29 | The Upjohn Company | Thiazolidinedione derivatives, production and use thereof |
| WO2013040419A1 (en) * | 2011-09-14 | 2013-03-21 | The Trustees Of Columbia University In The City Of New York | Compositions and methods for treating hyperprolinemia-associated mental disorders |
| US20130274295A1 (en) * | 2012-03-23 | 2013-10-17 | Fundacio Institut D'investigacio Biomedica De Bellvitge (Idibell) | Pioglitazone for use in the treatment of adrenoleukodystrophy |
| WO2014152843A1 (en) * | 2013-03-14 | 2014-09-25 | Deuterx, Llc | Deuterium-enriched 2,4-thiazolidinediones and methods of treatment |
Non-Patent Citations (4)
| Title |
|---|
| SOHDA T, IKEDA H, MEGURO K: "STUDIES ON ANTIDIABETIC AGENTS. XII. SYNTHESIS AND ACTIVITY OF THE METABOLITES OF (PLUS OR MINUS)-5-�P-�2-(5-ETHYL-2-PYRIDYL)ETHOXY�BENZYL�-2,4-THIAZOLIDINEDIONE (PIOGLITAZONE)", CHEMICAL AND PHARMACEUTICAL BULLETIN, PHARMACEUTICAL SOCIETY OF JAPAN, JP, vol. 43, no. 12, 1 December 1995 (1995-12-01), JP, pages 2168 - 2172, XP008057606, ISSN: 0009-2363 * |
| ST�PHANE FOURCADE, JONE L�PEZ-ERAUSKIN, MONTSERRAT RUIZ, ISIDRE FERRER, AURORA PUJOL: "Mitochondrial dysfunction and oxidative damage cooperatively fuel axonal degeneration in X-linked adrenoleukodystrophy", BIOCHIMIE, ELSEVIER MASSON SAS, vol. 98, 1 March 2014 (2014-03-01), pages 143 - 149, XP055118520, ISSN: 03009084, DOI: 10.1016/j.biochi.2013.09.012 * |
| SUNDARARAJAN, S. ; JIANG, Q. ; HENEKA, M. ; LANDRETH, G.: "PPAR@c as a therapeutic target in central nervous system diseases", NEUROCHEMISTRY INTERNATIONAL, ELSEVIER, AMSTERDAM, NL, vol. 49, no. 2, 1 July 2006 (2006-07-01), AMSTERDAM, NL, pages 136 - 144, XP027957978, ISSN: 0197-0186 * |
| TOSHIMASA ITOH ET AL.: "Peroxisome proliferator activated receptor Î and oxidized docosahexaenoic acids as new class of ligand", NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY, SPRINGER, BERLIN, DE, vol. 377, no. 4-6, 8 January 2008 (2008-01-08), pages 541-547, XP019620914, ISSN: 1432-1912, page 542 * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EA035866B1 (ru) | Применение производных 2,4-тиазолидиндиона для лечения расстройств центральной нервной системы и способ лечения с использованием таких производных | |
| US20110230497A1 (en) | Biologically active amides | |
| US11534434B2 (en) | Xanomeline derivatives and methods for treating neurological disorders | |
| JP7510170B2 (ja) | ５－［［４－［２－［５－アセチルピリジン－２－イル］エトキシ］ベンジル］－１，３－チアゾリジン－２，４－ジオンおよびその塩の使用 | |
| WO2015088625A2 (en) | Compounds and methods of promoting myelination | |
| US20170119795A1 (en) | Fused triterpene compounds and uses thereof | |
| WO2019189781A1 (ja) | 神経細胞内カルシウム濃度上昇抑制剤 | |
| HK1261676A1 (en) | 2,4-thiazolidinedione derivatives in the treatment of central nervous system disorders | |
| HK1261676B (en) | 2,4-thiazolidinedione derivatives in the treatment of central nervous system disorders | |
| EA042526B1 (ru) | Производные 2,4-тиазолидиндиона в лечении расстройств центральной нервной системы | |
| HK1233953B (en) | 2,4-thiazolidinedione derivatives in the treatment of central nervous system disorders | |
| HK1233953A1 (en) | 2,4-thiazolidinedione derivatives in the treatment of central nervous system disorders | |
| HK1233640A1 (en) | 2,4-thiazolidinedione derivatives in the treatment of central nervous system disorders | |
| HK1233640B (zh) | 在中枢神经系统障碍治疗中的2，4-噻唑烷二酮衍生物 | |
| BR112016022974B1 (pt) | Uso de um composto ou mistura dos compostos derivados de 2,4-tiazolidinadiona no tratamento de distúrbios do sistema nervoso central | |
| EP4570798A1 (en) | Aromatic heterocyclic cyclohexyl aminoalkyl piperidine derivative, preparation method and use thereof | |
| JP7382944B2 (ja) | 神経変性疾患を予防・治療するための新規な化合物及びその応用 | |
| US20230257350A1 (en) | Compounds and methods of promoting oligodendrocyte precursor differentiation | |
| EP3543231A1 (en) | Compounds for treating cns- and neurodegenerative diseases | |
| EA047194B1 (ru) | Применение 5-[4-[2-[5-ацетилпиридин-2-ил]этокси]бензил]-1,3-тиазолидин-2,4-диона и его солей |