CA2935944A1 - Substituted benzoxazine and related compounds - Google Patents
Substituted benzoxazine and related compounds Download PDFInfo
- Publication number
- CA2935944A1 CA2935944A1 CA2935944A CA2935944A CA2935944A1 CA 2935944 A1 CA2935944 A1 CA 2935944A1 CA 2935944 A CA2935944 A CA 2935944A CA 2935944 A CA2935944 A CA 2935944A CA 2935944 A1 CA2935944 A1 CA 2935944A1
- Authority
- CA
- Canada
- Prior art keywords
- substituted
- cycloalkyl
- amino
- group
- alkyl
- Prior art date
- 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.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 317
- 150000005130 benzoxazines Chemical class 0.000 title description 6
- 238000000034 method Methods 0.000 claims abstract description 89
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- -1 amino, substituted amino, aminosulfinyl Chemical group 0.000 claims description 407
- 125000001072 heteroaryl group Chemical group 0.000 claims description 204
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 174
- 125000003118 aryl group Chemical group 0.000 claims description 108
- 125000000217 alkyl group Chemical group 0.000 claims description 104
- 125000003107 substituted aryl group Chemical group 0.000 claims description 99
- 229910052739 hydrogen Inorganic materials 0.000 claims description 98
- 229910052799 carbon Inorganic materials 0.000 claims description 96
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 95
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 95
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 90
- 239000001257 hydrogen Substances 0.000 claims description 88
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 87
- 125000000304 alkynyl group Chemical group 0.000 claims description 85
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 85
- 125000003342 alkenyl group Chemical group 0.000 claims description 84
- 108090000623 proteins and genes Proteins 0.000 claims description 84
- 125000003545 alkoxy group Chemical group 0.000 claims description 82
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 81
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 81
- 102000004169 proteins and genes Human genes 0.000 claims description 79
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 74
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 69
- 150000002431 hydrogen Chemical group 0.000 claims description 65
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 60
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 60
- 125000002252 acyl group Chemical group 0.000 claims description 58
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 58
- 125000004442 acylamino group Chemical group 0.000 claims description 53
- 125000004423 acyloxy group Chemical group 0.000 claims description 53
- 125000004682 aminothiocarbonyl group Chemical group NC(=S)* 0.000 claims description 53
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 53
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 53
- 229910052736 halogen Inorganic materials 0.000 claims description 52
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 50
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 49
- 150000002367 halogens Chemical group 0.000 claims description 49
- 125000001091 aminosulfinyl group Chemical group [H]N([H])S(*)=O 0.000 claims description 47
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 47
- 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 claims description 43
- 201000010099 disease Diseases 0.000 claims description 34
- 229910052757 nitrogen Inorganic materials 0.000 claims description 29
- 210000002569 neuron Anatomy 0.000 claims description 27
- 229910052760 oxygen Inorganic materials 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 238000009825 accumulation Methods 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 208000023105 Huntington disease Diseases 0.000 claims description 16
- 230000007356 neuronal autophagy Effects 0.000 claims description 15
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 14
- 210000004027 cell Anatomy 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 125000001188 haloalkyl group Chemical group 0.000 claims description 11
- 230000001404 mediated effect Effects 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 230000001939 inductive effect Effects 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 210000000274 microglia Anatomy 0.000 claims description 5
- 210000002540 macrophage Anatomy 0.000 claims description 4
- 210000001130 astrocyte Anatomy 0.000 claims description 3
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 3
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims 20
- 101100495911 Arabidopsis thaliana CHR10 gene Proteins 0.000 claims 3
- OCJFARHMGPSLOB-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzoxazin-4-yl)-2-(4-methylpiperazin-1-yl)ethanone Chemical compound O1C2=C(N(CC1)C(CN1CCN(CC1)C)=O)C=CC=C2 OCJFARHMGPSLOB-UHFFFAOYSA-N 0.000 claims 1
- GAQJGYRKYAEBOH-UHFFFAOYSA-N 1-(6-methyl-2,3-dihydro-1,4-benzoxazin-4-yl)-2-(1-methylpiperidin-4-yl)ethanone Chemical compound CC1=CC2=C(OCCN2C(CC2CCN(CC2)C)=O)C=C1 GAQJGYRKYAEBOH-UHFFFAOYSA-N 0.000 claims 1
- PWIHPHVXDPLHFA-UHFFFAOYSA-N 1-(6-methyl-2,3-dihydro-1,4-benzoxazin-4-yl)-2-(4-methylpiperazin-1-yl)ethanone Chemical compound CC1=CC2=C(OCCN2C(CN2CCN(CC2)C)=O)C=C1 PWIHPHVXDPLHFA-UHFFFAOYSA-N 0.000 claims 1
- UDVOITWXDYRCKU-UHFFFAOYSA-N 1-(6-methyl-2,3-dihydro-1,4-benzoxazin-4-yl)-2-(4-phenylpiperazin-1-yl)ethanone Chemical compound CC1=CC2=C(OCCN2C(CN2CCN(CC2)C2=CC=CC=C2)=O)C=C1 UDVOITWXDYRCKU-UHFFFAOYSA-N 0.000 claims 1
- SRHOPNLKQKJWGE-UHFFFAOYSA-N 1-(6-methyl-2,3-dihydro-1,4-benzoxazin-4-yl)-2-morpholin-4-ylethanone Chemical compound CC1=CC2=C(OCCN2C(CN2CCOCC2)=O)C=C1 SRHOPNLKQKJWGE-UHFFFAOYSA-N 0.000 claims 1
- KGVHKLONKNTRGM-UHFFFAOYSA-N 1-(6-methyl-2,3-dihydro-1,4-benzoxazin-4-yl)-2-piperazin-1-ylethanone Chemical compound CC1=CC2=C(OCCN2C(CN2CCNCC2)=O)C=C1 KGVHKLONKNTRGM-UHFFFAOYSA-N 0.000 claims 1
- PHGAUFDUNAZJDS-UHFFFAOYSA-N 1-(6-methyl-2,3-dihydro-1,4-benzoxazin-4-yl)-3-(4-methylpiperazin-1-yl)propan-1-one Chemical compound CC1=CC2=C(OCCN2C(CCN2CCN(CC2)C)=O)C=C1 PHGAUFDUNAZJDS-UHFFFAOYSA-N 0.000 claims 1
- RVZOUOLVWDZPGJ-UHFFFAOYSA-N 2-(4-acetylpiperazin-1-yl)-1-(6-methyl-2,3-dihydro-1,4-benzoxazin-4-yl)ethanone Chemical compound C(C)(=O)N1CCN(CC1)CC(=O)N1C2=C(OCC1)C=CC(=C2)C RVZOUOLVWDZPGJ-UHFFFAOYSA-N 0.000 claims 1
- IDZUBCSBBQHFMA-UHFFFAOYSA-N 2-(6-methyl-2,3-dihydro-1,4-benzoxazin-4-yl)-1-(4-methylpiperazin-1-yl)ethanone Chemical compound CC1=CC2=C(OCCN2CC(=O)N2CCN(CC2)C)C=C1 IDZUBCSBBQHFMA-UHFFFAOYSA-N 0.000 claims 1
- AIMRJUQIXXNWDB-UHFFFAOYSA-N 2-chloro-10-[3-(4-methyl-1,4-dioxidopiperazine-1,4-diium-1-yl)propyl]phenothiazine 5-oxide Chemical compound C1C[N+](C)([O-])CC[N+]1([O-])CCCN1C2=CC(Cl)=CC=C2S(=O)C2=CC=CC=C21 AIMRJUQIXXNWDB-UHFFFAOYSA-N 0.000 claims 1
- PCHXNFMZHDHKCX-UHFFFAOYSA-N 2-chloro-10-[3-(4-methylpiperazin-1-yl)propyl]phenothiazine 5,5-dioxide Chemical compound ClC1=CC=2N(C3=CC=CC=C3S(C=2C=C1)(=O)=O)CCCN1CCN(CC1)C PCHXNFMZHDHKCX-UHFFFAOYSA-N 0.000 claims 1
- ZQLDDWQJGXKFCY-UHFFFAOYSA-N 3-(6-methyl-2,3-dihydro-1,4-benzoxazin-4-yl)-1-(4-methylpiperazin-1-yl)propan-1-one Chemical compound CC1=CC2=C(OCCN2CCC(=O)N2CCN(CC2)C)C=C1 ZQLDDWQJGXKFCY-UHFFFAOYSA-N 0.000 claims 1
- FQWHQYPWWBSDIL-UHFFFAOYSA-N 6-methyl-4-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1,4-benzoxazin-3-one Chemical compound C1CN(C)CCN1C(=O)CN1C2=CC(C)=CC=C2OCC1=O FQWHQYPWWBSDIL-UHFFFAOYSA-N 0.000 claims 1
- XCIQKIYJULNCJX-UHFFFAOYSA-N 6-methyl-4-[2-(4-methylpiperazin-1-yl)ethyl]-1,4-benzoxazin-3-one Chemical compound CC1=CC2=C(OCC(N2CCN2CCN(CC2)C)=O)C=C1 XCIQKIYJULNCJX-UHFFFAOYSA-N 0.000 claims 1
- ZBYCDFKRVRLSEI-UHFFFAOYSA-N 6-methyl-4-[2-(4-methylpiperazin-1-yl)ethyl]-2,3-dihydro-1,4-benzoxazine Chemical compound CN1CCN(CCN2CCOC3=C2C=C(C)C=C3)CC1 ZBYCDFKRVRLSEI-UHFFFAOYSA-N 0.000 claims 1
- MBWIXAFTDFPOFZ-UHFFFAOYSA-N 6-methyl-4-[3-(4-methylpiperazin-1-yl)-3-oxopropyl]-1,4-benzoxazin-3-one Chemical compound C1CN(C)CCN1C(=O)CCN1C2=CC(C)=CC=C2OCC1=O MBWIXAFTDFPOFZ-UHFFFAOYSA-N 0.000 claims 1
- LZZLDWUMRSHBKV-UHFFFAOYSA-N 6-methyl-4-[3-(4-methylpiperazin-1-yl)propyl]-1,4-benzoxazin-3-one Chemical compound CC1=CC2=C(OCC(N2CCCN2CCN(CC2)C)=O)C=C1 LZZLDWUMRSHBKV-UHFFFAOYSA-N 0.000 claims 1
- PQDHXHJXAQGFRE-UHFFFAOYSA-N 6-methyl-4-[3-(4-methylpiperazin-1-yl)propyl]-2,3-dihydro-1,4-benzoxazine Chemical compound CN1CCN(CCCN2CCOC3=C2C=C(C)C=C3)CC1 PQDHXHJXAQGFRE-UHFFFAOYSA-N 0.000 claims 1
- NDGVSTADYFEGTM-UHFFFAOYSA-N N-[2-[4-[2-(6-methyl-2,3-dihydro-1,4-benzoxazin-4-yl)acetyl]piperazin-1-yl]ethyl]methanesulfonamide Chemical compound CC1=CC2=C(OCCN2CC(=O)N2CCN(CCNS(C)(=O)=O)CC2)C=C1 NDGVSTADYFEGTM-UHFFFAOYSA-N 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 61
- 125000000623 heterocyclic group Chemical group 0.000 description 111
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 87
- 238000002360 preparation method Methods 0.000 description 61
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 48
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 46
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 36
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 35
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 35
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 29
- 239000011541 reaction mixture Substances 0.000 description 28
- 239000000243 solution Substances 0.000 description 26
- 125000001424 substituent group Chemical group 0.000 description 25
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- VKWQSTIJYWQSAL-UHFFFAOYSA-N 6-methyl-3,4-dihydro-2h-1,4-benzoxazine Chemical compound O1CCNC2=CC(C)=CC=C21 VKWQSTIJYWQSAL-UHFFFAOYSA-N 0.000 description 19
- 108020001305 NR1 subfamily Proteins 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 238000009472 formulation Methods 0.000 description 18
- 239000000047 product Substances 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- 208000035475 disorder Diseases 0.000 description 16
- 239000012267 brine Substances 0.000 description 15
- 125000005843 halogen group Chemical group 0.000 description 15
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 15
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 15
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 125000004414 alkyl thio group Chemical group 0.000 description 12
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 12
- 125000005110 aryl thio group Chemical group 0.000 description 12
- 125000004104 aryloxy group Chemical group 0.000 description 12
- 125000005366 cycloalkylthio group Chemical group 0.000 description 12
- 125000005553 heteroaryloxy group Chemical group 0.000 description 12
- 125000005368 heteroarylthio group Chemical group 0.000 description 12
- 125000005844 heterocyclyloxy group Chemical group 0.000 description 12
- 125000004468 heterocyclylthio group Chemical group 0.000 description 12
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 12
- 239000007858 starting material Substances 0.000 description 11
- 125000004429 atom Chemical group 0.000 description 10
- 230000004900 autophagic degradation Effects 0.000 description 10
- 230000006378 damage Effects 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 239000004615 ingredient Substances 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 210000003169 central nervous system Anatomy 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 208000016604 Lyme disease Diseases 0.000 description 8
- 230000001413 cellular effect Effects 0.000 description 8
- 230000002490 cerebral effect Effects 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 8
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 8
- 208000015122 neurodegenerative disease Diseases 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 150000003573 thiols Chemical class 0.000 description 8
- 230000003612 virological effect Effects 0.000 description 8
- 201000011240 Frontotemporal dementia Diseases 0.000 description 7
- 229910004727 OSO3H Inorganic materials 0.000 description 7
- 208000018737 Parkinson disease Diseases 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- WHKWMTXTYKVFLK-UHFFFAOYSA-N 1-propan-2-ylpiperazine Chemical compound CC(C)N1CCNCC1 WHKWMTXTYKVFLK-UHFFFAOYSA-N 0.000 description 6
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 6
- 208000024827 Alzheimer disease Diseases 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 description 6
- 230000001580 bacterial effect Effects 0.000 description 6
- 125000000000 cycloalkoxy group Chemical group 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 229920000155 polyglutamine Polymers 0.000 description 6
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 125000005338 substituted cycloalkoxy group Chemical group 0.000 description 6
- 125000003441 thioacyl group Chemical group 0.000 description 6
- CMLFRMDBDNHMRA-UHFFFAOYSA-N 2h-1,2-benzoxazine Chemical class C1=CC=C2C=CNOC2=C1 CMLFRMDBDNHMRA-UHFFFAOYSA-N 0.000 description 5
- JSBZPNRRLJLZBE-UHFFFAOYSA-N 6-methyl-4h-1,4-benzoxazin-3-one Chemical compound O1CC(=O)NC2=CC(C)=CC=C21 JSBZPNRRLJLZBE-UHFFFAOYSA-N 0.000 description 5
- 201000006474 Brain Ischemia Diseases 0.000 description 5
- 206010008120 Cerebral ischaemia Diseases 0.000 description 5
- 239000007821 HATU Substances 0.000 description 5
- 206010021143 Hypoxia Diseases 0.000 description 5
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 208000005314 Multi-Infarct Dementia Diseases 0.000 description 5
- 239000007832 Na2SO4 Substances 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 5
- 208000006011 Stroke Diseases 0.000 description 5
- 201000004810 Vascular dementia Diseases 0.000 description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 206010008118 cerebral infarction Diseases 0.000 description 5
- 125000001309 chloro group Chemical group Cl* 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
- 230000007954 hypoxia Effects 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 208000014674 injury Diseases 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 description 5
- 230000000269 nucleophilic effect Effects 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 210000000278 spinal cord Anatomy 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000009885 systemic effect Effects 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 231100000331 toxic Toxicity 0.000 description 5
- 230000002588 toxic effect Effects 0.000 description 5
- 230000008733 trauma Effects 0.000 description 5
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 5
- LTWFBZQFHPDLNU-UHFFFAOYSA-N 2,3-dihydro-1h-pyrido[2,3-b][1,4]oxazine Chemical compound C1=CC=C2NCCOC2=N1 LTWFBZQFHPDLNU-UHFFFAOYSA-N 0.000 description 4
- AMSFZNPHLRKOIB-UHFFFAOYSA-N 2,3-dihydro-1h-pyrido[3,4-b][1,4]oxazine Chemical compound N1=CC=C2NCCOC2=C1 AMSFZNPHLRKOIB-UHFFFAOYSA-N 0.000 description 4
- WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 4
- YBBLSBDJIKMXNQ-UHFFFAOYSA-N 3,4-dihydro-2h-1,4-benzothiazine Chemical compound C1=CC=C2NCCSC2=C1 YBBLSBDJIKMXNQ-UHFFFAOYSA-N 0.000 description 4
- QQVXDMFULJVZLA-UHFFFAOYSA-N 3,4-dihydro-2h-pyrido[3,2-b][1,4]oxazine Chemical compound C1=CN=C2NCCOC2=C1 QQVXDMFULJVZLA-UHFFFAOYSA-N 0.000 description 4
- HKSOYMJNDHHYEI-UHFFFAOYSA-N 3,4-dihydro-2h-pyrido[4,3-b][1,4]oxazine Chemical compound C1=NC=C2NCCOC2=C1 HKSOYMJNDHHYEI-UHFFFAOYSA-N 0.000 description 4
- 206010065040 AIDS dementia complex Diseases 0.000 description 4
- 208000019901 Anxiety disease Diseases 0.000 description 4
- 206010012335 Dependence Diseases 0.000 description 4
- 208000020401 Depressive disease Diseases 0.000 description 4
- 206010013754 Drug withdrawal syndrome Diseases 0.000 description 4
- 208000014094 Dystonic disease Diseases 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 206010027202 Meningitis bacterial Diseases 0.000 description 4
- 206010027260 Meningitis viral Diseases 0.000 description 4
- 208000001089 Multiple system atrophy Diseases 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- 208000000474 Poliomyelitis Diseases 0.000 description 4
- 229910006069 SO3H Inorganic materials 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 208000000323 Tourette Syndrome Diseases 0.000 description 4
- 208000016620 Tourette disease Diseases 0.000 description 4
- 230000036592 analgesia Effects 0.000 description 4
- 230000002886 autophagic effect Effects 0.000 description 4
- 201000009904 bacterial meningitis Diseases 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 208000010118 dystonia Diseases 0.000 description 4
- 206010015037 epilepsy Diseases 0.000 description 4
- 230000004634 feeding behavior Effects 0.000 description 4
- 208000007386 hepatic encephalopathy Diseases 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 208000000747 high pressure neurological syndrome Diseases 0.000 description 4
- 125000001183 hydrocarbyl group Chemical group 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 230000004807 localization Effects 0.000 description 4
- 206010025135 lupus erythematosus Diseases 0.000 description 4
- 201000004792 malaria Diseases 0.000 description 4
- 201000006417 multiple sclerosis Diseases 0.000 description 4
- 208000031237 olivopontocerebellar atrophy Diseases 0.000 description 4
- 230000003071 parasitic effect Effects 0.000 description 4
- 108010040003 polyglutamine Proteins 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 201000000980 schizophrenia Diseases 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- 201000010044 viral meningitis Diseases 0.000 description 4
- ZVAPWJGRRUHKGP-UHFFFAOYSA-N 1h-1,5-benzodiazepine Chemical compound N1C=CC=NC2=CC=CC=C12 ZVAPWJGRRUHKGP-UHFFFAOYSA-N 0.000 description 3
- YRLORWPBJZEGBX-UHFFFAOYSA-N 3,4-dihydro-2h-1,4-benzoxazine Chemical compound C1=CC=C2NCCOC2=C1 YRLORWPBJZEGBX-UHFFFAOYSA-N 0.000 description 3
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 150000001204 N-oxides Chemical class 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 208000029028 brain injury Diseases 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 3
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 239000000411 inducer Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000000386 microscopy Methods 0.000 description 3
- 201000000585 muscular atrophy Diseases 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 229940124531 pharmaceutical excipient Drugs 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
- 229920002554 vinyl polymer Polymers 0.000 description 3
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- BJIZNPTWGDICTC-UHFFFAOYSA-N 2-(1-methylpiperidin-4-yl)acetyl chloride Chemical compound CN1CCC(CC(Cl)=O)CC1 BJIZNPTWGDICTC-UHFFFAOYSA-N 0.000 description 2
- ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical compound C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 description 2
- GRISFWUABAJHHA-UHFFFAOYSA-N 4-(2-chloroethyl)-6-methyl-1,4-benzoxazin-3-one Chemical compound CC1=CC2=C(OCC(=O)N2CCCl)C=C1 GRISFWUABAJHHA-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-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
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 101100277337 Arabidopsis thaliana DDM1 gene Proteins 0.000 description 2
- 102000014461 Ataxins Human genes 0.000 description 2
- 108010078286 Ataxins Proteins 0.000 description 2
- 102000004321 Atrophin-1 Human genes 0.000 description 2
- 108090000806 Atrophin-1 Proteins 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 206010008025 Cerebellar ataxia Diseases 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- 201000008163 Dentatorubral pallidoluysian atrophy Diseases 0.000 description 2
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 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
- 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 2
- 241000282412 Homo Species 0.000 description 2
- 238000006736 Huisgen cycloaddition reaction Methods 0.000 description 2
- 102000016252 Huntingtin Human genes 0.000 description 2
- 108050004784 Huntingtin Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 208000033063 Progressive myoclonic epilepsy Diseases 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 241001061127 Thione Species 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000002253 acid Substances 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
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 201000004562 autosomal dominant cerebellar ataxia Diseases 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- 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 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 101150113676 chr1 gene Proteins 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 206010013663 drug dependence Diseases 0.000 description 2
- 229940088679 drug related substance Drugs 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- FVIZARNDLVOMSU-UHFFFAOYSA-N ginsenoside K Natural products C1CC(C2(CCC3C(C)(C)C(O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O FVIZARNDLVOMSU-UHFFFAOYSA-N 0.000 description 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 210000003712 lysosome Anatomy 0.000 description 2
- 230000001868 lysosomic effect Effects 0.000 description 2
- 230000004142 macroautophagy Effects 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 2
- KQEVIFKPZOGBMZ-UHFFFAOYSA-N methyl 3-bromopropanoate Chemical compound COC(=O)CCBr KQEVIFKPZOGBMZ-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 239000006199 nebulizer Substances 0.000 description 2
- 230000000626 neurodegenerative effect Effects 0.000 description 2
- 230000016273 neuron death Effects 0.000 description 2
- 230000006576 neuronal survival Effects 0.000 description 2
- 210000003463 organelle Anatomy 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 210000002243 primary neuron Anatomy 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 208000011117 substance-related disease Diseases 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 235000013311 vegetables Nutrition 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 description 1
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- BMEMBBFDTYHTLH-UHFFFAOYSA-N 1-(2-methoxyethyl)piperazine Chemical compound COCCN1CCNCC1 BMEMBBFDTYHTLH-UHFFFAOYSA-N 0.000 description 1
- XPDSXKIDJNKIQY-UHFFFAOYSA-N 1-cyclohexylpiperazine Chemical compound C1CCCCC1N1CCNCC1 XPDSXKIDJNKIQY-UHFFFAOYSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 1
- PKDPUENCROCRCH-UHFFFAOYSA-N 1-piperazin-1-ylethanone Chemical compound CC(=O)N1CCNCC1 PKDPUENCROCRCH-UHFFFAOYSA-N 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
- SAQAERNKMHATDZ-UHFFFAOYSA-N 2-bromo-1h-pyrrole Chemical class BrC1=CC=CN1 SAQAERNKMHATDZ-UHFFFAOYSA-N 0.000 description 1
- DPXJXQYTQBUEMC-UHFFFAOYSA-N 2-chloro-1-(2,3-dihydro-1,4-benzoxazin-4-yl)ethanone Chemical compound C1=CC=C2N(C(=O)CCl)CCOC2=C1 DPXJXQYTQBUEMC-UHFFFAOYSA-N 0.000 description 1
- IPMHFKFXPGKGKB-UHFFFAOYSA-N 2-chloro-1-(6-methyl-2,3-dihydro-1,4-benzoxazin-4-yl)ethanone Chemical compound O1CCN(C(=O)CCl)C2=CC(C)=CC=C21 IPMHFKFXPGKGKB-UHFFFAOYSA-N 0.000 description 1
- VLRSADZEDXVUPG-UHFFFAOYSA-N 2-naphthalen-1-ylpyridine Chemical compound N1=CC=CC=C1C1=CC=CC2=CC=CC=C12 VLRSADZEDXVUPG-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
- PVTXJGJDOHYFOX-UHFFFAOYSA-N 2h-1,4-benzoxazine Chemical compound C1=CC=C2N=CCOC2=C1 PVTXJGJDOHYFOX-UHFFFAOYSA-N 0.000 description 1
- IHBVNSPHKMCPST-UHFFFAOYSA-N 3-bromopropanoyl chloride Chemical compound ClC(=O)CCBr IHBVNSPHKMCPST-UHFFFAOYSA-N 0.000 description 1
- OEJAGPGZKJGHKL-UHFFFAOYSA-N 3-chloro-1-(4-methylpiperazin-1-yl)propan-1-one Chemical compound CN1CCN(C(=O)CCCl)CC1 OEJAGPGZKJGHKL-UHFFFAOYSA-N 0.000 description 1
- CBKDCOKSXCTDAA-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1-benzothiophene Chemical compound C1CCCC2=C1C=CS2 CBKDCOKSXCTDAA-UHFFFAOYSA-N 0.000 description 1
- YWKVYGFJHOLYRV-UHFFFAOYSA-N 4-piperazin-1-ylbutanenitrile Chemical compound N#CCCCN1CCNCC1 YWKVYGFJHOLYRV-UHFFFAOYSA-N 0.000 description 1
- GDRVFDDBLLKWRI-UHFFFAOYSA-N 4H-quinolizine Chemical compound C1=CC=CN2CC=CC=C21 GDRVFDDBLLKWRI-UHFFFAOYSA-N 0.000 description 1
- XISPDFMAOWZEQG-UHFFFAOYSA-N 4h-1,4-oxazin-3-one Chemical compound O=C1COC=CN1 XISPDFMAOWZEQG-UHFFFAOYSA-N 0.000 description 1
- 208000007848 Alcoholism Diseases 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
- 101100439662 Arabidopsis thaliana CHR5 gene Proteins 0.000 description 1
- 101100244083 Arabidopsis thaliana PKL gene Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 description 1
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PLDUPXSUYLZYBN-UHFFFAOYSA-N Fluphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 PLDUPXSUYLZYBN-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000005431 Molecular Chaperones Human genes 0.000 description 1
- 108010006519 Molecular Chaperones Proteins 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 206010057852 Nicotine dependence Diseases 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 101150110423 SNCA gene Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 229930006000 Sucrose Natural products 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
- 241000282887 Suidae Species 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 208000025569 Tobacco Use disease Diseases 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- VVGPECAOVDZTLZ-UHFFFAOYSA-N [N]NC(N)=N Chemical group [N]NC(N)=N VVGPECAOVDZTLZ-UHFFFAOYSA-N 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
- 239000011149 active material Substances 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 125000006598 aminocarbonylamino group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 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
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000004957 autophagosome Anatomy 0.000 description 1
- 230000008335 axon cargo transport Effects 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 229910052797 bismuth Inorganic materials 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000004720 cerebrum Anatomy 0.000 description 1
- 238000010568 chiral column chromatography Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- 230000010405 clearance mechanism Effects 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 229960002069 diamorphine Drugs 0.000 description 1
- MQYQOVYIJOLTNX-UHFFFAOYSA-N dichloromethane;n,n-dimethylformamide Chemical compound ClCCl.CN(C)C=O MQYQOVYIJOLTNX-UHFFFAOYSA-N 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
- IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical compound C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 229960002690 fluphenazine Drugs 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 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
- 238000009650 gentamicin protection assay Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
- 150000002309 glutamines Chemical class 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 235000021552 granulated sugar Nutrition 0.000 description 1
- 125000005252 haloacyl group Chemical group 0.000 description 1
- 125000005216 haloheteroaryl group Chemical group 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 239000002117 illicit drug Substances 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 1
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003434 inspiratory effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000012792 lyophilization process Methods 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- VBQRSKINXAGOTC-UHFFFAOYSA-N methyl 3-(6-methyl-3-oxo-1,4-benzoxazin-4-yl)propanoate Chemical compound COC(=O)CCN1C(=O)COC2=C1C=C(C)C=C2 VBQRSKINXAGOTC-UHFFFAOYSA-N 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 231100000324 minimal toxicity Toxicity 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- 230000020763 muscle atrophy Effects 0.000 description 1
- XPSRIHVLKNYNAR-UHFFFAOYSA-N n-(2-piperazin-1-ylethyl)acetamide Chemical compound CC(=O)NCCN1CCNCC1 XPSRIHVLKNYNAR-UHFFFAOYSA-N 0.000 description 1
- VEVPKZFGXDGXNV-UHFFFAOYSA-N n-(2-piperazin-1-ylethyl)methanesulfonamide Chemical compound CS(=O)(=O)NCCN1CCNCC1 VEVPKZFGXDGXNV-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003935 n-pentoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000004898 n-terminal fragment Anatomy 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000000701 neuroleptic effect Effects 0.000 description 1
- 230000006764 neuronal dysfunction Effects 0.000 description 1
- 230000003955 neuronal function Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 101150009274 nhr-1 gene Proteins 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- DSKIOWHQLUWFLG-SPIKMXEPSA-N prochlorperazine maleate Chemical class [H+].[H+].[H+].[H+].[O-]C(=O)\C=C/C([O-])=O.[O-]C(=O)\C=C/C([O-])=O.C1CN(C)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 DSKIOWHQLUWFLG-SPIKMXEPSA-N 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000009979 protective mechanism Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 102200036626 rs104893877 Human genes 0.000 description 1
- 102220024375 rs201069984 Human genes 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000000600 sorbitol Substances 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
- 238000001694 spray drying Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 230000006663 ubiquitin-proteasome pathway Effects 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
- C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
-
- 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
- A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/16—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/18—[b, e]-condensed with two six-membered rings
- C07D279/22—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom
- C07D279/24—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom
- C07D279/28—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom with other substituents attached to the ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Dispersion Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Indole Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461925619P | 2014-01-09 | 2014-01-09 | |
| US61/925,619 | 2014-01-09 | ||
| US201461927911P | 2014-01-15 | 2014-01-15 | |
| US61/927,911 | 2014-01-15 | ||
| PCT/US2015/010690 WO2015106025A1 (en) | 2014-01-09 | 2015-01-08 | Substituted benzoxazine and related compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2935944A1 true CA2935944A1 (en) | 2015-07-16 |
Family
ID=53524338
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2935944A Abandoned CA2935944A1 (en) | 2014-01-09 | 2015-01-08 | Substituted benzoxazine and related compounds |
Country Status (5)
| Country | Link |
|---|---|
| US (2) | US10087151B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP3091984B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP6510539B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2935944A1 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2015106025A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201106817D0 (en) | 2011-04-21 | 2011-06-01 | Astex Therapeutics Ltd | New compound |
| US9980973B2 (en) | 2012-10-19 | 2018-05-29 | Astex Therapeutics Limited | Bicyclic heterocycle compounds and their uses in therapy |
| GB201218850D0 (en) | 2012-10-19 | 2012-12-05 | Astex Therapeutics Ltd | Bicyclic heterocycle compounds and their uses in therapy |
| GB201218864D0 (en) | 2012-10-19 | 2012-12-05 | Astex Therapeutics Ltd | Bicyclic heterocycle compounds and their uses in therapy |
| GB201218862D0 (en) | 2012-10-19 | 2012-12-05 | Astex Therapeutics Ltd | Bicyclic heterocycle compounds and their uses in therapy |
| TWI649319B (zh) | 2013-12-20 | 2019-02-01 | 英商阿斯迪克治療公司 | 雙環雜環化合物及其治療用途 |
| WO2015106025A1 (en) * | 2014-01-09 | 2015-07-16 | The J. David Gladstone Institutes, A Testamentary Trust Established Under The Will Of J. David Gladstone | Substituted benzoxazine and related compounds |
| GB201504064D0 (en) | 2015-03-10 | 2015-04-22 | Accretion Biotechnology Ltd | Method and kits for preparing radionuclide complexes |
| JO3637B1 (ar) | 2015-04-28 | 2020-08-27 | Janssen Sciences Ireland Uc | مركبات بيرازولو- وترايازولو- بيريميدين مضادة للفيروسات rsv |
| TWI730980B (zh) | 2015-08-26 | 2021-06-21 | 比利時商健生藥品公司 | 使用作為ｐｒｍｔ５抑制劑之新穎經６-６雙環芳香環取代之核苷類似物 |
| BR112018006873A2 (pt) | 2015-10-05 | 2018-11-06 | The Trustees Of Columbia University In The City Of New York | ativadores do fluxo autofágico e fosfolipase d e depuração de agregados de proteína incluindo tau e tratamento de proteinopatias |
| US10898504B2 (en) | 2016-03-10 | 2021-01-26 | Janssen Pharmaceutica Nv | Substituted nucleoside analogues for use as PRMT5 inhibitors |
| GB201610956D0 (en) * | 2016-06-23 | 2016-08-10 | Takeda Pharmaceuticals Co | Novel compounds |
| JP7101171B2 (ja) | 2016-10-03 | 2022-07-14 | ヤンセン ファーマシューティカ エヌ．ベー． | Ｐｒｍｔ５阻害剤として使用するための新規な単環式および二環式環系置換カルバヌクレオシド類似体 |
| US11279970B2 (en) | 2017-02-27 | 2022-03-22 | Janssen Pharmaceutica Nv | Use of biomarkers in identifying cancer patients that will be responsive to treatment with a PRMT5 inhibitor |
| GB2568549A (en) * | 2017-11-21 | 2019-05-22 | Univ Leicester | New compounds and uses |
| TW201932470A (zh) | 2017-11-29 | 2019-08-16 | 愛爾蘭商健生科學愛爾蘭無限公司 | 具有抗ｒｓｖ活性之吡唑并嘧啶 |
| AU2018379456B2 (en) | 2017-12-08 | 2022-11-24 | Janssen Pharmaceutica Nv | Novel spirobicyclic analogues |
| US11491157B2 (en) | 2018-01-31 | 2022-11-08 | Janssen Sciences Ireland Unlimited Company Co Cork, IE | Cycloalkyl substituted pyrazolopyrimidines having activity against RSV |
| US11708369B2 (en) | 2018-04-23 | 2023-07-25 | Janssen Sciences Ireland Unlimited Company | Heteroaromatic compounds having activity against RSV |
| WO2020061101A1 (en) | 2018-09-18 | 2020-03-26 | Nikang Therapeutics, Inc. | Tri-substituted heteroaryl derivatives as src homology-2 phosphatase inhibitors |
| US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
| US11384083B2 (en) | 2019-02-15 | 2022-07-12 | Incyte Corporation | Substituted spiro[cyclopropane-1,5′-pyrrolo[2,3-d]pyrimidin]-6′(7′h)-ones as CDK2 inhibitors |
| WO2020180959A1 (en) | 2019-03-05 | 2020-09-10 | Incyte Corporation | Pyrazolyl pyrimidinylamine compounds as cdk2 inhibitors |
| WO2020205560A1 (en) | 2019-03-29 | 2020-10-08 | Incyte Corporation | Sulfonylamide compounds as cdk2 inhibitors |
| WO2020223558A1 (en) | 2019-05-01 | 2020-11-05 | Incyte Corporation | Tricyclic amine compounds as cdk2 inhibitors |
| WO2020223469A1 (en) | 2019-05-01 | 2020-11-05 | Incyte Corporation | N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-di hydro-1h-imidazo[4,5-h]quinazolin-8-amine derivatives and related compounds as cyclin-dependent kinase 2 (cdk2) inhibitors for treating cancer |
| TW202112375A (zh) | 2019-06-06 | 2021-04-01 | 比利時商健生藥品公司 | 使用ｐｒｍｔ５抑制劑治療癌症之方法 |
| PE20221010A1 (es) | 2019-08-14 | 2022-06-15 | Incyte Corp | Compuestos de imidazolil pirimidinilamina como inhibidores de cdk2 |
| WO2021072232A1 (en) | 2019-10-11 | 2021-04-15 | Incyte Corporation | Bicyclic amines as cdk2 inhibitors |
| US11981671B2 (en) | 2021-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
| US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB921315A (en) | 1958-03-31 | 1963-03-20 | Wellcome Found | The manufacture of 8-aminoalkylamino quinoline derivatives |
| CH501659A (de) * | 1966-08-11 | 1971-01-15 | Knoll Ag | Verfahren zur Herstellung von N-Aminoacyl-3,4-dihydro-(2H)-1,4-benzoxazinen |
| DE1595863C3 (de) | 1966-08-11 | 1978-03-02 | Knoll Ag, 6700 Ludwigshafen | 4-Piperidinoacetyl-3,4-dihydro-(2H)-l,4-benioxazin und Verfahren zu dessen Herstellung |
| GB1173942A (en) * | 1967-06-06 | 1969-12-10 | Bellon Labor Sa Roger | New 2,3-Dihydro-1,4-Benzoxazines |
| US4107288A (en) | 1974-09-18 | 1978-08-15 | Pharmaceutical Society Of Victoria | Injectable compositions, nanoparticles useful therein, and process of manufacturing same |
| DE3204153A1 (de) | 1982-02-06 | 1983-08-11 | Dr. Karl Thomae Gmbh, 7950 Biberach | Substituierte thienobenzodiazepinone, verfahren zu ihrer herstellung und sie enthaltende arzneimittel |
| US5145684A (en) | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
| US5652363A (en) | 1995-10-05 | 1997-07-29 | C.D. Searle & Co. | Pyrido-1,4-oxazinylalkyl-benzamide derivatives |
| US6084098A (en) * | 1999-02-26 | 2000-07-04 | Neurogen Corporation | Benzylpiperazinyl and piperidinyl ethanone derivatives: dopamine receptor subtype specific ligands |
| DE19934432A1 (de) * | 1999-07-22 | 2001-02-01 | Merck Patent Gmbh | Indolderivate |
| AU2002357791B9 (en) | 2001-12-05 | 2008-09-25 | The J. David Gladstone Institutes | Robotic microscopy systems |
| EP1506179B1 (en) * | 2002-05-13 | 2006-01-25 | F. Hoffmann-La Roche Ag | Benzoxazine derivatives as 5-ht6 modulators and uses thereof |
| US20050165011A1 (en) | 2002-05-15 | 2005-07-28 | Gellibert Francoise J. | Benzoxazine and benzoxazinone substituted triazoles |
| US7378415B2 (en) | 2004-09-30 | 2008-05-27 | Roche Palo Alto Llc | Benzoxazine and quinoxaline derivatives and uses thereof |
| US7790726B2 (en) * | 2005-08-16 | 2010-09-07 | Chemocentryx, Inc. | Monocyclic and bicyclic compounds and methods of use |
| US20080064871A1 (en) | 2006-05-26 | 2008-03-13 | Japan Tobacco Inc. | Production Method of Nitrogen-Containing Fused Ring Compounds |
| US9604926B2 (en) * | 2007-08-16 | 2017-03-28 | The University Of Mississippi | Highly selective sigma receptor radioligands |
| US8686008B2 (en) * | 2007-08-16 | 2014-04-01 | The University Of Mississippi | Highly selective sigma receptor ligands |
| CN101224207A (zh) | 2007-10-12 | 2008-07-23 | 中国科学院上海有机化学研究所 | 具有诱导自吞噬治疗错误折叠蛋白聚集所致疾病的药物及其筛选方法 |
| CA2709784A1 (en) | 2007-12-21 | 2009-07-09 | University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| CA2718709C (en) | 2008-03-31 | 2016-08-09 | C & C Research Laboratories | Heterocyclic derivatives |
| RS57045B1 (sr) | 2009-05-08 | 2018-05-31 | Astellas Pharma Inc | Jedinjenje diamino heterocikličnog karboksamida |
| JP2013509442A (ja) * | 2009-10-29 | 2013-03-14 | サートリス ファーマシューティカルズ， インコーポレイテッド | サーチュイン調節因子としての二環式ピリジンおよび類似体 |
| CN102918031A (zh) | 2010-05-28 | 2013-02-06 | 通用电气健康护理有限公司 | 放射标记的化合物及其方法 |
| WO2012020567A1 (en) * | 2010-08-09 | 2012-02-16 | Raqualia Pharma Inc. | Acyl piperazine derivatives as ttx-s blockers |
| AU2011343039B2 (en) * | 2010-12-14 | 2017-03-02 | Electrophoretics Limited | Casein kinase 1delta (CK1delta) inhibitors |
| MX352181B (es) | 2012-02-02 | 2017-11-13 | Idorsia Pharmaceuticals Ltd | Compuestos 4- (benzoimidazol-2-il) -tiazol y derivados aza relacionados. |
| WO2015106025A1 (en) * | 2014-01-09 | 2015-07-16 | The J. David Gladstone Institutes, A Testamentary Trust Established Under The Will Of J. David Gladstone | Substituted benzoxazine and related compounds |
-
2015
- 2015-01-08 WO PCT/US2015/010690 patent/WO2015106025A1/en not_active Ceased
- 2015-01-08 EP EP15735106.5A patent/EP3091984B1/en active Active
- 2015-01-08 US US15/110,082 patent/US10087151B2/en active Active
- 2015-01-08 JP JP2016545983A patent/JP6510539B2/ja not_active Expired - Fee Related
- 2015-01-08 CA CA2935944A patent/CA2935944A1/en not_active Abandoned
-
2018
- 2018-08-17 US US16/104,840 patent/US10611741B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US20190106394A1 (en) | 2019-04-11 |
| US10611741B2 (en) | 2020-04-07 |
| WO2015106025A1 (en) | 2015-07-16 |
| EP3091984A1 (en) | 2016-11-16 |
| US20160326123A1 (en) | 2016-11-10 |
| JP2017502073A (ja) | 2017-01-19 |
| EP3091984A4 (en) | 2017-06-21 |
| US10087151B2 (en) | 2018-10-02 |
| EP3091984B1 (en) | 2020-04-22 |
| JP6510539B2 (ja) | 2019-05-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10611741B2 (en) | Substituted benzoxazine and related compounds | |
| CN112312904A (zh) | 螺环化合物 | |
| KR101705727B1 (ko) | 아릴피페라진 유도체의 조성물, 합성, 및 사용 방법 | |
| CN112041307B (zh) | 作为选择性雌激素受体降解剂的取代的苯并噻吩类似物 | |
| EP3774736B1 (en) | Compounds as modulators of tlr2 signaling | |
| CN101627013A (zh) | 酰基胍衍生物 | |
| CN113336673A (zh) | 一种金刚烷胺类化合物及其制备方法和用途 | |
| WO2010012121A1 (zh) | 芳烷基哌啶（嗪）衍生物及其在治疗精神分裂症中的应用 | |
| CN101302214A (zh) | 芳烷基哌啶(嗪)衍生物及在治疗精神神经疾病中的应用 | |
| CN101384549B (zh) | 吡咯衍生物或其盐 | |
| CN114008040B (zh) | 用于调节fxr的化合物 | |
| CA3131805C (en) | Novel compounds for the treatment, alleviation or prevention of disorders associated with tau aggregates | |
| WO2019089478A1 (en) | Substituted phenyl sulfonyl phenyl triazole thiones and uses thereof | |
| CN105712952B (zh) | 2-取代氧基-5-甲砜基苯基哌嗪酰胺类似物及其制备方法和用途 | |
| WO2022074587A1 (en) | Mu-opioid receptor agonists and uses therefor | |
| CN112118891A (zh) | 作为流感病毒复制抑制剂的稠和多环吡啶酮化合物 | |
| CN101243046A (zh) | 酰基胍衍生物或其盐 | |
| AU2016205137A1 (en) | Furoquinolinediones as inhibitors of TDP2 | |
| CN105085436A (zh) | 磺酰胺类衍生物及其在药物上的应用 | |
| JP2024532558A (ja) | チエノ縮合環化合物及びその調製方法と使用 | |
| CN101759665A (zh) | 取代苯基哌嗪芳烷醇衍生物及其在制备镇痛药物中的应用 | |
| WO2025124571A1 (zh) | Nmda受体拮抗剂及其用途 | |
| KR20240115832A (ko) | 헌팅턴병을 치료하기 위한 htt 조절제 | |
| WO2024222860A1 (zh) | 一种吗啉杂环类化合物的盐及其制备方法和应用 | |
| HK40059280B (zh) | 可用作RORγ调节剂的苯胺类化合物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20210831 |
|
| FZDE | Discontinued |
Effective date: 20210831 |