ES2637288T3 - N-((1H-indol-3-il)-alquil)-4-bencil)benzamida y derivados de N-((1H-pirrolo[2,3-b]piridin-3-il)-alquil)-4-bencil)benzamida como inhibidores de la agregación de alfa-sinucleína para el tratamiento de trastornos neurodegenerativos - Google Patents
N-((1H-indol-3-il)-alquil)-4-bencil)benzamida y derivados de N-((1H-pirrolo[2,3-b]piridin-3-il)-alquil)-4-bencil)benzamida como inhibidores de la agregación de alfa-sinucleína para el tratamiento de trastornos neurodegenerativos Download PDFInfo
- Publication number
- ES2637288T3 ES2637288T3 ES11805450.1T ES11805450T ES2637288T3 ES 2637288 T3 ES2637288 T3 ES 2637288T3 ES 11805450 T ES11805450 T ES 11805450T ES 2637288 T3 ES2637288 T3 ES 2637288T3
- Authority
- ES
- Spain
- Prior art keywords
- benzamide
- mmol
- heterocycle
- ethyl
- chloro
- 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.)
- Active
Links
- -1 1H-indole-3-yl Chemical group 0.000 title claims abstract description 178
- 238000011282 treatment Methods 0.000 title claims description 8
- 208000015122 neurodegenerative disease Diseases 0.000 title claims 3
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 title description 20
- 102000003802 alpha-Synuclein Human genes 0.000 title description 14
- 108090000185 alpha-Synuclein Proteins 0.000 title description 14
- 230000002776 aggregation Effects 0.000 title description 8
- 238000004220 aggregation Methods 0.000 title description 8
- 239000003112 inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 92
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 44
- 239000001257 hydrogen Substances 0.000 claims abstract description 44
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 37
- 150000002367 halogens Chemical class 0.000 claims abstract description 35
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 30
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 29
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
- 125000004122 cyclic group Chemical group 0.000 claims description 10
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 150000004677 hydrates Chemical class 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 201000011240 Frontotemporal dementia Diseases 0.000 claims 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 1
- 208000011990 Corticobasal Degeneration Diseases 0.000 claims 1
- 206010067889 Dementia with Lewy bodies Diseases 0.000 claims 1
- 201000010374 Down Syndrome Diseases 0.000 claims 1
- 208000009829 Lewy Body Disease Diseases 0.000 claims 1
- 208000001089 Multiple system atrophy Diseases 0.000 claims 1
- 208000014060 Niemann-Pick disease Diseases 0.000 claims 1
- 206010033799 Paralysis Diseases 0.000 claims 1
- 208000027089 Parkinsonian disease Diseases 0.000 claims 1
- 206010034010 Parkinsonism Diseases 0.000 claims 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims 1
- 208000030886 Traumatic Brain injury Diseases 0.000 claims 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 1
- 210000000349 chromosome Anatomy 0.000 claims 1
- 125000004438 haloalkoxy group Chemical group 0.000 claims 1
- LKPAAZZXRWGIGQ-UHFFFAOYSA-N n-[2-(5-hydroxy-1h-indol-3-yl)ethyl]pyridine-3-carboxamide Chemical compound C12=CC(O)=CC=C2NC=C1CCNC(=O)C1=CC=CN=C1 LKPAAZZXRWGIGQ-UHFFFAOYSA-N 0.000 claims 1
- 208000033510 neuroaxonal dystrophy Diseases 0.000 claims 1
- 208000002593 pantothenate kinase-associated neurodegeneration Diseases 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 230000000750 progressive effect Effects 0.000 claims 1
- 125000004546 quinazolin-4-yl group Chemical group N1=CN=C(C2=CC=CC=C12)* 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 230000009529 traumatic brain injury Effects 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 abstract description 121
- 229910052760 oxygen Inorganic materials 0.000 abstract description 97
- 125000003342 alkenyl group Chemical group 0.000 abstract description 85
- 125000000304 alkynyl group Chemical group 0.000 abstract description 83
- 125000005842 heteroatom Chemical group 0.000 abstract description 82
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 71
- 125000000217 alkyl group Chemical group 0.000 abstract description 69
- 229910052799 carbon Inorganic materials 0.000 abstract description 59
- 125000003118 aryl group Chemical group 0.000 abstract description 58
- 125000006270 aryl alkenylene group Chemical group 0.000 abstract description 43
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 31
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 21
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 19
- 125000004429 atom Chemical group 0.000 abstract description 15
- 125000006588 heterocycloalkylene group Chemical group 0.000 abstract description 14
- 125000004419 alkynylene group Chemical group 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 192
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 129
- 238000002360 preparation method Methods 0.000 description 58
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 57
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 57
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 53
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 51
- 238000003818 flash chromatography Methods 0.000 description 50
- 238000000034 method Methods 0.000 description 50
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 48
- 239000003480 eluent Substances 0.000 description 46
- 239000000741 silica gel Substances 0.000 description 45
- 229910002027 silica gel Inorganic materials 0.000 description 45
- 239000007787 solid Substances 0.000 description 44
- 239000000203 mixture Substances 0.000 description 43
- 150000001721 carbon Chemical group 0.000 description 33
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- 229910000029 sodium carbonate Inorganic materials 0.000 description 25
- 150000002430 hydrocarbons Chemical group 0.000 description 22
- 239000000243 solution Substances 0.000 description 20
- 239000013067 intermediate product Substances 0.000 description 19
- 235000009518 sodium iodide Nutrition 0.000 description 19
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 18
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 18
- 239000007821 HATU Substances 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 17
- 229930195733 hydrocarbon Natural products 0.000 description 16
- 239000013058 crude material Substances 0.000 description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
- 239000012074 organic phase Substances 0.000 description 15
- 239000011734 sodium Substances 0.000 description 14
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 description 13
- 125000004076 pyridyl group Chemical group 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 125000006590 (C2-C6) alkenylene group Chemical group 0.000 description 12
- 125000006591 (C2-C6) alkynylene group Chemical group 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- 239000004215 Carbon black (E152) Substances 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 10
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
- 101150070547 MAPT gene Proteins 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 102100040243 Microtubule-associated protein tau Human genes 0.000 description 9
- 125000002947 alkylene group Chemical group 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 125000002541 furyl group Chemical group 0.000 description 9
- 125000001072 heteroaryl group Chemical group 0.000 description 9
- 125000002757 morpholinyl group Chemical group 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 125000001544 thienyl group Chemical group 0.000 description 9
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- 125000002883 imidazolyl group Chemical group 0.000 description 8
- 125000003226 pyrazolyl group Chemical group 0.000 description 8
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 8
- PBANXRNIXGEHPZ-UHFFFAOYSA-N 2-(5-chloro-1h-indol-3-yl)ethanamine;hydron;chloride Chemical compound Cl.C1=C(Cl)C=C2C(CCN)=CNC2=C1 PBANXRNIXGEHPZ-UHFFFAOYSA-N 0.000 description 7
- SJHWVLADKRXQQR-UHFFFAOYSA-N 4-[(3-fluorophenyl)methyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CC1=CC=CC(F)=C1 SJHWVLADKRXQQR-UHFFFAOYSA-N 0.000 description 7
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 7
- 125000001041 indolyl group Chemical group 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 7
- 125000005936 piperidyl group Chemical group 0.000 description 7
- 125000000168 pyrrolyl group Chemical group 0.000 description 7
- 125000000335 thiazolyl group Chemical group 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 6
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 6
- FIKAKWIAUPDISJ-UHFFFAOYSA-L paraquat dichloride Chemical compound [Cl-].[Cl-].C1=C[N+](C)=CC=C1C1=CC=[N+](C)C=C1 FIKAKWIAUPDISJ-UHFFFAOYSA-L 0.000 description 6
- 125000003373 pyrazinyl group Chemical group 0.000 description 6
- 125000002098 pyridazinyl group Chemical group 0.000 description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- 239000000377 silicon dioxide Substances 0.000 description 6
- 125000003831 tetrazolyl group Chemical group 0.000 description 6
- 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 6
- MYTGFBZJLDLWQG-UHFFFAOYSA-N 5-chloro-1h-indole Chemical compound ClC1=CC=C2NC=CC2=C1 MYTGFBZJLDLWQG-UHFFFAOYSA-N 0.000 description 5
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 5
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 5
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 5
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 5
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 5
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 5
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 4
- 125000004931 azocinyl group Chemical group N1=C(C=CC=CC=C1)* 0.000 description 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 4
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 4
- 125000004935 benzoxazolinyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 description 4
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 239000011737 fluorine Chemical group 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 125000003838 furazanyl group Chemical group 0.000 description 4
- 125000002632 imidazolidinyl group Chemical group 0.000 description 4
- 125000002636 imidazolinyl group Chemical group 0.000 description 4
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 4
- 125000004936 isatinoyl group Chemical group N1(C(=O)C(=O)C2=CC=CC=C12)C(=O)* 0.000 description 4
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 4
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 4
- 125000001786 isothiazolyl group Chemical group 0.000 description 4
- 125000000842 isoxazolyl group Chemical group 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 4
- 125000000160 oxazolidinyl group Chemical group 0.000 description 4
- 125000004095 oxindolyl group Chemical group N1(C(CC2=CC=CC=C12)=O)* 0.000 description 4
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 4
- 125000004193 piperazinyl group Chemical group 0.000 description 4
- 125000003386 piperidinyl group Chemical group 0.000 description 4
- 238000002953 preparative HPLC Methods 0.000 description 4
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 4
- 125000002755 pyrazolinyl group Chemical group 0.000 description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 description 4
- 125000001422 pyrrolinyl group Chemical group 0.000 description 4
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 4
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 4
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 4
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 4
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 4
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 125000004306 triazinyl group Chemical group 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- QWQBQRYFWNIDOC-UHFFFAOYSA-N (3,5-difluorophenyl)boronic acid Chemical compound OB(O)C1=CC(F)=CC(F)=C1 QWQBQRYFWNIDOC-UHFFFAOYSA-N 0.000 description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- 125000005955 1H-indazolyl group Chemical group 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical group [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 102000019355 Synuclein Human genes 0.000 description 3
- 108050006783 Synuclein Proteins 0.000 description 3
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 3
- 125000004450 alkenylene group Chemical group 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 150000005840 aryl radicals Chemical class 0.000 description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 125000004404 heteroalkyl group Chemical group 0.000 description 3
- 125000004474 heteroalkylene group Chemical group 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 125000004926 indolenyl group Chemical group 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 3
- PHWVFUURVAMANF-UHFFFAOYSA-N n-[(5-chloro-1h-indol-3-yl)methyl]-4-[(3-fluorophenyl)methyl]benzamide Chemical compound FC1=CC=CC(CC=2C=CC(=CC=2)C(=O)NCC=2C3=CC(Cl)=CC=C3NC=2)=C1 PHWVFUURVAMANF-UHFFFAOYSA-N 0.000 description 3
- HOHPLBPAUAONIC-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-(3-cyanoanilino)benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=1)=CC=CC=1NC1=CC=CC(C#N)=C1 HOHPLBPAUAONIC-UHFFFAOYSA-N 0.000 description 3
- UIUISBUPJSQSHL-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-(furan-2-ylmethyl)benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=1)=CC=CC=1CC1=CC=CO1 UIUISBUPJSQSHL-UHFFFAOYSA-N 0.000 description 3
- HKPLCQJMVFAYTF-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[(3-methoxyphenyl)methyl]benzamide Chemical compound COC1=CC=CC(CC=2C=C(C=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 HKPLCQJMVFAYTF-UHFFFAOYSA-N 0.000 description 3
- MUKZWNKZCWLNMI-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[(5-fluoropyridin-3-yl)methyl]benzamide Chemical compound FC1=CN=CC(CC=2C=C(C=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 MUKZWNKZCWLNMI-UHFFFAOYSA-N 0.000 description 3
- INPLPCQNIAEUPG-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-(furan-2-ylmethyl)benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=C1)=CC=C1CC1=CC=CO1 INPLPCQNIAEUPG-UHFFFAOYSA-N 0.000 description 3
- CSHUIIFWHQHXGQ-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-(pyridin-3-ylmethyl)benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=C1)=CC=C1CC1=CC=CN=C1 CSHUIIFWHQHXGQ-UHFFFAOYSA-N 0.000 description 3
- OYTHTBMXYHLZTP-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-(pyridin-4-ylmethyl)benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=C1)=CC=C1CC1=CC=NC=C1 OYTHTBMXYHLZTP-UHFFFAOYSA-N 0.000 description 3
- URBKEAQGINNCFB-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(2-fluoro-3-methoxyphenyl)methyl]benzamide Chemical compound COC1=CC=CC(CC=2C=CC(=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1F URBKEAQGINNCFB-UHFFFAOYSA-N 0.000 description 3
- ZZNUHICVJZHONP-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(4-fluorophenyl)methyl]benzamide Chemical compound C1=CC(F)=CC=C1CC1=CC=C(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)C=C1 ZZNUHICVJZHONP-UHFFFAOYSA-N 0.000 description 3
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 3
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 3
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 3
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 3
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 3
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 3
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 3
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 3
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 3
- 235000019345 sodium thiosulphate Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 3
- 230000009261 transgenic effect Effects 0.000 description 3
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 3
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 3
- JCKZNMSBFBPDPM-UHFFFAOYSA-N (2-fluoro-3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1F JCKZNMSBFBPDPM-UHFFFAOYSA-N 0.000 description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
- CGMPAPNASKFYLW-UHFFFAOYSA-N 2-(6-chloro-5-methyl-2-triethylsilyl-1h-indol-3-yl)ethanol Chemical compound ClC1=C(C)C=C2C(CCO)=C([Si](CC)(CC)CC)NC2=C1 CGMPAPNASKFYLW-UHFFFAOYSA-N 0.000 description 2
- WZAMCYXGPNLBRB-UHFFFAOYSA-N 2-[2-triethylsilyl-5-(trifluoromethyl)-1h-indol-3-yl]ethanol Chemical compound C1=C(C(F)(F)F)C=C2C(CCO)=C([Si](CC)(CC)CC)NC2=C1 WZAMCYXGPNLBRB-UHFFFAOYSA-N 0.000 description 2
- DVJKZOMKVLFUDW-UHFFFAOYSA-N 2-[5-(trifluoromethyl)-1h-indol-3-yl]ethanamine Chemical compound C1=C(C(F)(F)F)C=C2C(CCN)=CNC2=C1 DVJKZOMKVLFUDW-UHFFFAOYSA-N 0.000 description 2
- AZXMWQBBQWWRPJ-UHFFFAOYSA-N 2-benzyl-n-[2-(5-chloro-1h-indol-3-yl)ethyl]benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C1=CC=CC=C1CC1=CC=CC=C1 AZXMWQBBQWWRPJ-UHFFFAOYSA-N 0.000 description 2
- 125000004398 2-methyl-2-butyl group Chemical group CC(C)(CC)* 0.000 description 2
- 125000004918 2-methyl-2-pentyl group Chemical group CC(C)(CCC)* 0.000 description 2
- 125000004922 2-methyl-3-pentyl group Chemical group CC(C)C(CC)* 0.000 description 2
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
- XADIUEZKNWWRCT-UHFFFAOYSA-N 3-(3-cyanoanilino)benzoic acid Chemical compound OC(=O)C1=CC=CC(NC=2C=C(C=CC=2)C#N)=C1 XADIUEZKNWWRCT-UHFFFAOYSA-N 0.000 description 2
- DHBHGDMZFNCBSL-UHFFFAOYSA-N 3-(5-chloro-1h-indol-3-yl)propan-1-ol Chemical compound C1=C(Cl)C=C2C(CCCO)=CNC2=C1 DHBHGDMZFNCBSL-UHFFFAOYSA-N 0.000 description 2
- RPTTVZIXRSLVJG-UHFFFAOYSA-N 3-[(3-fluorophenyl)methyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(CC=2C=C(F)C=CC=2)=C1 RPTTVZIXRSLVJG-UHFFFAOYSA-N 0.000 description 2
- 125000004917 3-methyl-2-butyl group Chemical group CC(C(C)*)C 0.000 description 2
- 125000004919 3-methyl-2-pentyl group Chemical group CC(C(C)*)CC 0.000 description 2
- 125000004921 3-methyl-3-pentyl group Chemical group CC(CC)(CC)* 0.000 description 2
- 125000004920 4-methyl-2-pentyl group Chemical group CC(CC(C)*)C 0.000 description 2
- 125000005986 4-piperidonyl group Chemical group 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- WAVVVDUELKMQAZ-UHFFFAOYSA-N 4-triethylsilylbut-3-yn-1-ol Chemical compound CC[Si](CC)(CC)C#CCCO WAVVVDUELKMQAZ-UHFFFAOYSA-N 0.000 description 2
- 125000006043 5-hexenyl group Chemical group 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- 101100480712 Homo sapiens MAPT gene Proteins 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 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
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- DGKSSFUQABGKMV-UHFFFAOYSA-N [3-(2-bromoethyl)-5-(trifluoromethyl)-1h-indol-2-yl]-triethylsilane Chemical compound C1=C(C(F)(F)F)C=C2C(CCBr)=C([Si](CC)(CC)CC)NC2=C1 DGKSSFUQABGKMV-UHFFFAOYSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 150000001450 anions Chemical group 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 2
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 210000000133 brain stem Anatomy 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 2
- 150000001768 cations Chemical group 0.000 description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
- 125000003636 chemical group Chemical group 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- XGRJZXREYAXTGV-UHFFFAOYSA-N chlorodiphenylphosphine Chemical compound C=1C=CC=CC=1P(Cl)C1=CC=CC=C1 XGRJZXREYAXTGV-UHFFFAOYSA-N 0.000 description 2
- 125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
- 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 2
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- PXPSRRGMRFKFJS-UHFFFAOYSA-N diazonio-[2-[2-triethylsilyl-5-(trifluoromethyl)-1h-indol-3-yl]ethyl]azanide Chemical compound C1=C(C(F)(F)F)C=C2C(CCN=[N+]=[N-])=C([Si](CC)(CC)CC)NC2=C1 PXPSRRGMRFKFJS-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 description 2
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 102000057063 human MAPT Human genes 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 238000002991 immunohistochemical analysis Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- IQPWPZPEMSWMJE-UHFFFAOYSA-N n-[(5-chloro-1h-indol-3-yl)methyl]-4-[(3,5-difluorophenyl)methyl]benzamide Chemical compound FC1=CC(F)=CC(CC=2C=CC(=CC=2)C(=O)NCC=2C3=CC(Cl)=CC=C3NC=2)=C1 IQPWPZPEMSWMJE-UHFFFAOYSA-N 0.000 description 2
- YDGKKUBHTXFDSB-UHFFFAOYSA-N n-[2-(5,7-dichloro-2-trimethylsilyl-1h-indol-3-yl)ethyl]-3-[(3-fluorophenyl)methyl]benzamide Chemical compound C[Si](C)(C)C=1NC2=C(Cl)C=C(Cl)C=C2C=1CCNC(=O)C(C=1)=CC=CC=1CC1=CC=CC(F)=C1 YDGKKUBHTXFDSB-UHFFFAOYSA-N 0.000 description 2
- NNWUXFOVIHIJLM-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[(2-fluoro-3-methoxyphenyl)methyl]benzamide Chemical compound COC1=CC=CC(CC=2C=C(C=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1F NNWUXFOVIHIJLM-UHFFFAOYSA-N 0.000 description 2
- FZFMHJMIACRNRX-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[(3,5-difluorophenyl)methyl]benzamide Chemical compound FC1=CC(F)=CC(CC=2C=C(C=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 FZFMHJMIACRNRX-UHFFFAOYSA-N 0.000 description 2
- AQMXBAXCAHZVKQ-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[3-(trifluoromethyl)anilino]benzamide Chemical compound FC(F)(F)C1=CC=CC(NC=2C=C(C=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 AQMXBAXCAHZVKQ-UHFFFAOYSA-N 0.000 description 2
- UFCVTHHJWAJKHS-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-phenoxybenzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=1)=CC=CC=1OC1=CC=CC=C1 UFCVTHHJWAJKHS-UHFFFAOYSA-N 0.000 description 2
- AYBDGNOCMCYTCG-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(3,5-difluorophenyl)methyl]benzamide Chemical compound FC1=CC(F)=CC(CC=2C=CC(=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 AYBDGNOCMCYTCG-UHFFFAOYSA-N 0.000 description 2
- SPRKSPJSWOPKSP-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-phenoxybenzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=C1)=CC=C1OC1=CC=CC=C1 SPRKSPJSWOPKSP-UHFFFAOYSA-N 0.000 description 2
- IFNSMGPXAKLFAQ-UHFFFAOYSA-N n-[2-(5-cyano-1h-indol-3-yl)ethyl]-4-[(3-fluorophenyl)methyl]benzamide Chemical compound FC1=CC=CC(CC=2C=CC(=CC=2)C(=O)NCCC=2C3=CC(=CC=C3NC=2)C#N)=C1 IFNSMGPXAKLFAQ-UHFFFAOYSA-N 0.000 description 2
- UNWKXYRCRWYDNG-UHFFFAOYSA-N n-[2-(5-fluoro-1h-indol-3-yl)ethyl]-3-[(3-fluorophenyl)methyl]benzamide Chemical compound FC1=CC=CC(CC=2C=C(C=CC=2)C(=O)NCCC=2C3=CC(F)=CC=C3NC=2)=C1 UNWKXYRCRWYDNG-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 229940063675 spermine Drugs 0.000 description 2
- 102000013498 tau Proteins Human genes 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 2
- XDBHWPLGGBLUHH-UHFFFAOYSA-N (3-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(C#N)=C1 XDBHWPLGGBLUHH-UHFFFAOYSA-N 0.000 description 1
- KNXQDJCZSVHEIW-UHFFFAOYSA-N (3-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(F)=C1 KNXQDJCZSVHEIW-UHFFFAOYSA-N 0.000 description 1
- NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 description 1
- YQVZREHUWCCHHX-UHFFFAOYSA-N (4-chlorophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=C(Cl)C=C1 YQVZREHUWCCHHX-UHFFFAOYSA-N 0.000 description 1
- FVEDGBRHTGXPOK-UHFFFAOYSA-N (5-fluoropyridin-3-yl)boronic acid Chemical compound OB(O)C1=CN=CC(F)=C1 FVEDGBRHTGXPOK-UHFFFAOYSA-N 0.000 description 1
- 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 description 1
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
- HBWATGYSAHIWIX-UHFFFAOYSA-N 2,3-dihydrothiophen-5-ylboronic acid Chemical compound OB(O)C1=CCCS1 HBWATGYSAHIWIX-UHFFFAOYSA-N 0.000 description 1
- YJRSMJTVXWBFJJ-UHFFFAOYSA-N 2,4-dichloro-6-iodoaniline Chemical compound NC1=C(Cl)C=C(Cl)C=C1I YJRSMJTVXWBFJJ-UHFFFAOYSA-N 0.000 description 1
- ZEMZPXWZVTUONV-UHFFFAOYSA-N 2-(2-dicyclohexylphosphanylphenyl)-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 ZEMZPXWZVTUONV-UHFFFAOYSA-N 0.000 description 1
- PIZGZBUHWRRIPL-UHFFFAOYSA-N 2-(6-chloro-5-methyl-1h-indol-3-yl)ethanamine Chemical compound C1=C(Cl)C(C)=CC2=C1NC=C2CCN PIZGZBUHWRRIPL-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- FESDHLLVLYZNFY-UHFFFAOYSA-N 2-benzylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1CC1=CC=CC=C1 FESDHLLVLYZNFY-UHFFFAOYSA-N 0.000 description 1
- UKKWTZPXYIYONW-UHFFFAOYSA-N 2-iodo-4-(trifluoromethyl)aniline Chemical compound NC1=CC=C(C(F)(F)F)C=C1I UKKWTZPXYIYONW-UHFFFAOYSA-N 0.000 description 1
- LHRVIXGXFXJLTO-UHFFFAOYSA-N 3-(5-chloro-1h-indol-3-yl)propan-1-amine Chemical compound C1=C(Cl)C=C2C(CCCN)=CNC2=C1 LHRVIXGXFXJLTO-UHFFFAOYSA-N 0.000 description 1
- YCAIYRWHKSJKEB-UHFFFAOYSA-N 3-(chloromethyl)benzoyl chloride Chemical compound ClCC1=CC=CC(C(Cl)=O)=C1 YCAIYRWHKSJKEB-UHFFFAOYSA-N 0.000 description 1
- CUENIXHYORUPNP-UHFFFAOYSA-N 3-[(3-fluorophenyl)methyl]-n-[2-(5-methoxy-1h-indol-3-yl)ethyl]benzamide Chemical compound C12=CC(OC)=CC=C2NC=C1CCNC(=O)C(C=1)=CC=CC=1CC1=CC=CC(F)=C1 CUENIXHYORUPNP-UHFFFAOYSA-N 0.000 description 1
- XRCSMXVHOQYGKW-UHFFFAOYSA-N 3-[3-(trifluoromethyl)anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC(NC=2C=C(C=CC=2)C(F)(F)F)=C1 XRCSMXVHOQYGKW-UHFFFAOYSA-N 0.000 description 1
- OKEVZIMBLALLMG-UHFFFAOYSA-N 3-anilino-n-[2-(5-chloro-1h-indol-3-yl)ethyl]benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=1)=CC=CC=1NC1=CC=CC=C1 OKEVZIMBLALLMG-UHFFFAOYSA-N 0.000 description 1
- RCHSJRJPIWLNPN-UHFFFAOYSA-N 3-anilinobenzoic acid Chemical compound OC(=O)C1=CC=CC(NC=2C=CC=CC=2)=C1 RCHSJRJPIWLNPN-UHFFFAOYSA-N 0.000 description 1
- WHUFYYNKCXXKSU-UHFFFAOYSA-N 3-benzylbenzoic acid Chemical compound OC(=O)C1=CC=CC(CC=2C=CC=CC=2)=C1 WHUFYYNKCXXKSU-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
- BOPVBGZBYXBCGJ-UHFFFAOYSA-N 3-chloro-5-methyl-1h-indole Chemical compound CC1=CC=C2NC=C(Cl)C2=C1 BOPVBGZBYXBCGJ-UHFFFAOYSA-N 0.000 description 1
- RQKFYFNZSHWXAW-UHFFFAOYSA-N 3-chloro-p-toluidine Chemical compound CC1=CC=C(N)C=C1Cl RQKFYFNZSHWXAW-UHFFFAOYSA-N 0.000 description 1
- NXTDJHZGHOFSQG-UHFFFAOYSA-N 3-phenoxybenzoic acid Chemical compound OC(=O)C1=CC=CC(OC=2C=CC=CC=2)=C1 NXTDJHZGHOFSQG-UHFFFAOYSA-N 0.000 description 1
- MUYFCAZBZTUBOJ-UHFFFAOYSA-N 4-(n-methylanilino)benzoic acid Chemical compound C=1C=C(C(O)=O)C=CC=1N(C)C1=CC=CC=C1 MUYFCAZBZTUBOJ-UHFFFAOYSA-N 0.000 description 1
- YHLOOLRWHWATPU-UHFFFAOYSA-N 4-[(3-fluorophenyl)methyl]-n-[2-(5-hydroxy-1h-indol-3-yl)ethyl]benzamide Chemical compound C12=CC(O)=CC=C2NC=C1CCNC(=O)C(C=C1)=CC=C1CC1=CC=CC(F)=C1 YHLOOLRWHWATPU-UHFFFAOYSA-N 0.000 description 1
- CNBLDSDVXOUTOK-UHFFFAOYSA-N 4-[(3-fluorophenyl)methyl]-n-[2-(5-methyl-1h-indol-3-yl)ethyl]benzamide Chemical compound C12=CC(C)=CC=C2NC=C1CCNC(=O)C(C=C1)=CC=C1CC1=CC=CC(F)=C1 CNBLDSDVXOUTOK-UHFFFAOYSA-N 0.000 description 1
- TVEGKUWFJHHQAL-UHFFFAOYSA-N 4-[(3-fluorophenyl)methyl]-n-[2-(5-morpholin-4-yl-1h-indol-3-yl)ethyl]benzamide Chemical compound FC1=CC=CC(CC=2C=CC(=CC=2)C(=O)NCCC=2C3=CC(=CC=C3NC=2)N2CCOCC2)=C1 TVEGKUWFJHHQAL-UHFFFAOYSA-N 0.000 description 1
- ONDNZJADEHITIN-UHFFFAOYSA-N 4-[(benzylamino)methyl]-n-[2-(5-chloro-1h-indol-3-yl)ethyl]benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=C1)=CC=C1CNCC1=CC=CC=C1 ONDNZJADEHITIN-UHFFFAOYSA-N 0.000 description 1
- VRGNTUJJGNDAAQ-UHFFFAOYSA-N 4-anilino-n-[2-(5-chloro-1h-indol-3-yl)ethyl]benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=C1)=CC=C1NC1=CC=CC=C1 VRGNTUJJGNDAAQ-UHFFFAOYSA-N 0.000 description 1
- DPAMLADQPZFXMD-UHFFFAOYSA-N 4-anilinobenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC1=CC=CC=C1 DPAMLADQPZFXMD-UHFFFAOYSA-N 0.000 description 1
- FPHVRPCVNPHPBH-UHFFFAOYSA-N 4-benzylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CC1=CC=CC=C1 FPHVRPCVNPHPBH-UHFFFAOYSA-N 0.000 description 1
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
- RYAQFHLUEMJOMF-UHFFFAOYSA-N 4-phenoxybenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OC1=CC=CC=C1 RYAQFHLUEMJOMF-UHFFFAOYSA-N 0.000 description 1
- 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 1
- ILINOHVVKWYAFM-UHFFFAOYSA-N 5,6-dichloro-1h-indole Chemical compound C1=C(Cl)C(Cl)=CC2=C1NC=C2 ILINOHVVKWYAFM-UHFFFAOYSA-N 0.000 description 1
- VXWVFZFZYXOBTA-UHFFFAOYSA-N 5-bromo-1h-indole Chemical compound BrC1=CC=C2NC=CC2=C1 VXWVFZFZYXOBTA-UHFFFAOYSA-N 0.000 description 1
- WTQMSECCZZCDHE-UHFFFAOYSA-N 5-chloro-2-iodo-4-methylaniline Chemical compound CC1=CC(I)=C(N)C=C1Cl WTQMSECCZZCDHE-UHFFFAOYSA-N 0.000 description 1
- JTEJPPKMYBDEMY-UHFFFAOYSA-N 5-methoxytryptamine Chemical compound COC1=CC=C2NC=C(CCN)C2=C1 JTEJPPKMYBDEMY-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 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 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 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
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 238000012347 Morris Water Maze Methods 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- MDIGAZPGKJFIAH-UHFFFAOYSA-N Serotonin hydrochloride Chemical compound Cl.C1=C(O)C=C2C(CCN)=CNC2=C1 MDIGAZPGKJFIAH-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000032859 Synucleinopathies Diseases 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- 108091000117 Tyrosine 3-Monooxygenase Proteins 0.000 description 1
- 102000048218 Tyrosine 3-monooxygenases Human genes 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- LXGQHDUCNDGTDB-PAMNCVQHSA-N [2-[(8s,9r,10s,13s,14s,16s,17r)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl] acetate;[2-[(8s,9r,10s,13s,14s,16s,17r)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11, Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(C)=O)(O)[C@@]1(C)CC2O.C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COP(O)(O)=O)(O)[C@@]1(C)CC2O LXGQHDUCNDGTDB-PAMNCVQHSA-N 0.000 description 1
- NDBKVTPWTKFGPC-UHFFFAOYSA-N [3-(2-bromoethyl)-6-chloro-5-methyl-1h-indol-2-yl]-triethylsilane Chemical compound ClC1=C(C)C=C2C(CCBr)=C([Si](CC)(CC)CC)NC2=C1 NDBKVTPWTKFGPC-UHFFFAOYSA-N 0.000 description 1
- UGQUHRFBMTYPIF-UHFFFAOYSA-N [S]C1CCCS1 Chemical compound [S]C1CCCS1 UGQUHRFBMTYPIF-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 125000003302 alkenyloxy group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000005133 alkynyloxy group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 1
- AXLOCHLTNQDFFS-BESJYZOMSA-N azastene Chemical compound C([C@H]1[C@@H]2CC[C@@]([C@]2(CC[C@@H]1[C@@]1(C)C2)C)(O)C)C=C1C(C)(C)C1=C2C=NO1 AXLOCHLTNQDFFS-BESJYZOMSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 238000012742 biochemical analysis Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 229940124301 concurrent medication Drugs 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- 229940009662 edetate Drugs 0.000 description 1
- 229950008913 edisilate Drugs 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- PZJSZBJLOWMDRG-UHFFFAOYSA-N furan-2-ylboronic acid Chemical compound OB(O)C1=CC=CO1 PZJSZBJLOWMDRG-UHFFFAOYSA-N 0.000 description 1
- 229960001731 gluceptate Drugs 0.000 description 1
- KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 125000004447 heteroarylalkenyl group Chemical group 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 230000006951 hyperphosphorylation Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910001867 inorganic solvent Inorganic materials 0.000 description 1
- 239000003049 inorganic solvent Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 208000018731 motor weakness Diseases 0.000 description 1
- FMVJVHQRHHSMMD-UHFFFAOYSA-N n-[(5-chloro-1h-indol-3-yl)methyl]-4-[(3-cyanophenyl)methyl]benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CNC(=O)C(C=C1)=CC=C1CC1=CC=CC(C#N)=C1 FMVJVHQRHHSMMD-UHFFFAOYSA-N 0.000 description 1
- KSTIEIMXEDXCGP-UHFFFAOYSA-N n-[2-(5,6-dichloro-1h-indol-3-yl)ethyl]-4-[(3-fluorophenyl)methyl]benzamide Chemical compound FC1=CC=CC(CC=2C=CC(=CC=2)C(=O)NCCC=2C3=CC(Cl)=C(Cl)C=C3NC=2)=C1 KSTIEIMXEDXCGP-UHFFFAOYSA-N 0.000 description 1
- AXEZYCCDMRINIY-UHFFFAOYSA-N n-[2-(5-bromo-1h-indol-3-yl)ethyl]-4-[(3-fluorophenyl)methyl]benzamide Chemical compound FC1=CC=CC(CC=2C=CC(=CC=2)C(=O)NCCC=2C3=CC(Br)=CC=C3NC=2)=C1 AXEZYCCDMRINIY-UHFFFAOYSA-N 0.000 description 1
- OSPWIPAWSQXBRG-UHFFFAOYSA-N n-[2-(5-chloro-1-methylindol-3-yl)ethyl]-4-[(3-fluorophenyl)methyl]benzamide Chemical compound C12=CC(Cl)=CC=C2N(C)C=C1CCNC(=O)C(C=C1)=CC=C1CC1=CC=CC(F)=C1 OSPWIPAWSQXBRG-UHFFFAOYSA-N 0.000 description 1
- GWWKENBLGFRGLF-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-2-fluoro-4-[(3-fluorophenyl)methyl]benzamide Chemical compound FC1=CC=CC(CC=2C=C(F)C(C(=O)NCCC=3C4=CC(Cl)=CC=C4NC=3)=CC=2)=C1 GWWKENBLGFRGLF-UHFFFAOYSA-N 0.000 description 1
- NURKFVKLOCNXBZ-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-(3-methoxyphenoxy)benzamide Chemical compound COC1=CC=CC(OC=2C=C(C=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 NURKFVKLOCNXBZ-UHFFFAOYSA-N 0.000 description 1
- KUNOGJRORGEGLW-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-(chloromethyl)benzamide Chemical compound ClCC1=CC=CC(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 KUNOGJRORGEGLW-UHFFFAOYSA-N 0.000 description 1
- HNHGSHQBIDTPML-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-(furan-3-ylmethyl)benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=1)=CC=CC=1CC=1C=COC=1 HNHGSHQBIDTPML-UHFFFAOYSA-N 0.000 description 1
- XNJNPZRTTAILSA-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-(n-methylanilino)benzamide Chemical compound C=1C=CC(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=CC=1N(C)C1=CC=CC=C1 XNJNPZRTTAILSA-UHFFFAOYSA-N 0.000 description 1
- KUAGTXCCRHEPRW-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-(pyrazol-1-ylmethyl)benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=1)=CC=CC=1CN1C=CC=N1 KUAGTXCCRHEPRW-UHFFFAOYSA-N 0.000 description 1
- KCTFIQUVSYCYFQ-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-(thiophen-2-ylmethyl)benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=1)=CC=CC=1CC1=CC=CS1 KCTFIQUVSYCYFQ-UHFFFAOYSA-N 0.000 description 1
- HBNBPWFISBACEY-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[(2-cyanophenyl)methyl]benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=1)=CC=CC=1CC1=CC=CC=C1C#N HBNBPWFISBACEY-UHFFFAOYSA-N 0.000 description 1
- GHKIEFGDQSUEOC-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[(2-fluorophenyl)methyl]benzamide Chemical compound FC1=CC=CC=C1CC1=CC=CC(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 GHKIEFGDQSUEOC-UHFFFAOYSA-N 0.000 description 1
- JARCEOLRGSRVKY-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[(2-methoxyphenyl)methyl]benzamide Chemical compound COC1=CC=CC=C1CC1=CC=CC(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 JARCEOLRGSRVKY-UHFFFAOYSA-N 0.000 description 1
- QGIQLILTZHJVFO-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[(3-chlorophenyl)methyl]benzamide Chemical compound ClC1=CC=CC(CC=2C=C(C=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 QGIQLILTZHJVFO-UHFFFAOYSA-N 0.000 description 1
- PXQFFYZFKBCROQ-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[(3-cyanophenyl)methyl]benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=1)=CC=CC=1CC1=CC=CC(C#N)=C1 PXQFFYZFKBCROQ-UHFFFAOYSA-N 0.000 description 1
- GQWZRJGUIYNTGE-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[(3-fluorophenyl)methyl]benzamide Chemical compound FC1=CC=CC(CC=2C=C(C=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 GQWZRJGUIYNTGE-UHFFFAOYSA-N 0.000 description 1
- OJUKGYKYSNNNSA-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[(3-methylphenyl)methyl]benzamide Chemical compound CC1=CC=CC(CC=2C=C(C=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 OJUKGYKYSNNNSA-UHFFFAOYSA-N 0.000 description 1
- GPRPGLJMEFUNMD-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[(4-chlorophenyl)methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1CC1=CC=CC(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 GPRPGLJMEFUNMD-UHFFFAOYSA-N 0.000 description 1
- LDXXVLOMAJTMCS-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[(4-cyanophenyl)methyl]benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=1)=CC=CC=1CC1=CC=C(C#N)C=C1 LDXXVLOMAJTMCS-UHFFFAOYSA-N 0.000 description 1
- JBNRDPPJWNKOFR-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[(4-fluorophenyl)methyl]benzamide Chemical compound C1=CC(F)=CC=C1CC1=CC=CC(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 JBNRDPPJWNKOFR-UHFFFAOYSA-N 0.000 description 1
- UGUNKFGHNDZPTC-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[(4-methoxyphenyl)methyl]benzamide Chemical compound C1=CC(OC)=CC=C1CC1=CC=CC(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 UGUNKFGHNDZPTC-UHFFFAOYSA-N 0.000 description 1
- RZZNVAWEEKGGBY-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[(4-methylphenyl)methyl]benzamide Chemical compound C1=CC(C)=CC=C1CC1=CC=CC(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 RZZNVAWEEKGGBY-UHFFFAOYSA-N 0.000 description 1
- TYUBNVSXZSHBQK-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[(cyclohexylamino)methyl]benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=1)=CC=CC=1CNC1CCCCC1 TYUBNVSXZSHBQK-UHFFFAOYSA-N 0.000 description 1
- SIRMPUITJBVHHB-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[[3-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound FC(F)(F)C1=CC=CC(CC=2C=C(C=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 SIRMPUITJBVHHB-UHFFFAOYSA-N 0.000 description 1
- WXKINZMWRUSJIX-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-[[4-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1CC1=CC=CC(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 WXKINZMWRUSJIX-UHFFFAOYSA-N 0.000 description 1
- YIMNHRRYAINJTD-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-3-fluoro-4-[(3-fluorophenyl)methyl]benzamide Chemical compound FC1=CC=CC(CC=2C(=CC(=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)F)=C1 YIMNHRRYAINJTD-UHFFFAOYSA-N 0.000 description 1
- NTDBHDKIUXTMBE-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-(3-fluoro-n-methylanilino)benzamide Chemical compound C=1C=C(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)C=CC=1N(C)C1=CC=CC(F)=C1 NTDBHDKIUXTMBE-UHFFFAOYSA-N 0.000 description 1
- GXUDMPZWYDVEHX-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-(3-fluoroanilino)benzamide Chemical compound FC1=CC=CC(NC=2C=CC(=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 GXUDMPZWYDVEHX-UHFFFAOYSA-N 0.000 description 1
- RNXHZZQMRXNWSJ-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-(3-fluorophenoxy)benzamide Chemical compound FC1=CC=CC(OC=2C=CC(=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 RNXHZZQMRXNWSJ-UHFFFAOYSA-N 0.000 description 1
- ALVHOIYLEUAEHE-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-(furan-3-ylmethyl)benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=C1)=CC=C1CC=1C=COC=1 ALVHOIYLEUAEHE-UHFFFAOYSA-N 0.000 description 1
- UHOXOGZIKCEERN-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-(pyrazol-1-ylmethyl)benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=C1)=CC=C1CN1C=CC=N1 UHOXOGZIKCEERN-UHFFFAOYSA-N 0.000 description 1
- WCFJAYCTSWMLIM-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-(thiophen-2-ylmethyl)benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=C1)=CC=C1CC1=CC=CS1 WCFJAYCTSWMLIM-UHFFFAOYSA-N 0.000 description 1
- SNVHQIQQYXKPST-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-(thiophen-3-ylmethyl)benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=C1)=CC=C1CC=1C=CSC=1 SNVHQIQQYXKPST-UHFFFAOYSA-N 0.000 description 1
- INENGEZLUKTGNG-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(2,3-difluorophenyl)methyl]benzamide Chemical compound FC1=CC=CC(CC=2C=CC(=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1F INENGEZLUKTGNG-UHFFFAOYSA-N 0.000 description 1
- MWCNLMDSTPCHAP-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(2,5-difluorophenyl)methyl]benzamide Chemical compound FC1=CC=C(F)C(CC=2C=CC(=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 MWCNLMDSTPCHAP-UHFFFAOYSA-N 0.000 description 1
- CGELMXCEOZOWEK-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(2-chlorophenyl)methyl]benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=C1)=CC=C1CC1=CC=CC=C1Cl CGELMXCEOZOWEK-UHFFFAOYSA-N 0.000 description 1
- XFGMGJNOUXQHDJ-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(2-cyanophenyl)methyl]benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=C1)=CC=C1CC1=CC=CC=C1C#N XFGMGJNOUXQHDJ-UHFFFAOYSA-N 0.000 description 1
- YYILFEFVODHAME-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(2-fluorophenyl)methyl]benzamide Chemical compound FC1=CC=CC=C1CC1=CC=C(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)C=C1 YYILFEFVODHAME-UHFFFAOYSA-N 0.000 description 1
- YFRRJMJGLUPHQJ-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(2-methoxyphenyl)methyl]benzamide Chemical compound COC1=CC=CC=C1CC1=CC=C(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)C=C1 YFRRJMJGLUPHQJ-UHFFFAOYSA-N 0.000 description 1
- NLRGZBNZCQKPEZ-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(2-methylphenyl)methyl]benzamide Chemical compound CC1=CC=CC=C1CC1=CC=C(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)C=C1 NLRGZBNZCQKPEZ-UHFFFAOYSA-N 0.000 description 1
- BFIRPPVLSJYBBN-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(3-chlorophenyl)methyl]benzamide Chemical compound ClC1=CC=CC(CC=2C=CC(=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 BFIRPPVLSJYBBN-UHFFFAOYSA-N 0.000 description 1
- DEFGFVXXGGVRPV-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(3-cyanophenyl)methyl]benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=C1)=CC=C1CC1=CC=CC(C#N)=C1 DEFGFVXXGGVRPV-UHFFFAOYSA-N 0.000 description 1
- YBIHDEVWBQUTNB-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(3-fluorophenyl)methyl]benzamide Chemical compound FC1=CC=CC(CC=2C=CC(=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 YBIHDEVWBQUTNB-UHFFFAOYSA-N 0.000 description 1
- UBSORMUUPHCAMF-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(3-methylphenyl)methyl]benzamide Chemical compound CC1=CC=CC(CC=2C=CC(=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 UBSORMUUPHCAMF-UHFFFAOYSA-N 0.000 description 1
- PTCJFPVGGBXZRA-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(4-chlorophenyl)methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1CC1=CC=C(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)C=C1 PTCJFPVGGBXZRA-UHFFFAOYSA-N 0.000 description 1
- KQDHKWRSYIDJTJ-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(4-cyanophenyl)methyl]benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=C1)=CC=C1CC1=CC=C(C#N)C=C1 KQDHKWRSYIDJTJ-UHFFFAOYSA-N 0.000 description 1
- NGASTPOLTDYGHU-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(4-methoxyphenyl)methyl]benzamide Chemical compound C1=CC(OC)=CC=C1CC1=CC=C(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)C=C1 NGASTPOLTDYGHU-UHFFFAOYSA-N 0.000 description 1
- BKBPLOFRWREOMZ-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(4-methylphenyl)methyl]benzamide Chemical compound C1=CC(C)=CC=C1CC1=CC=C(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)C=C1 BKBPLOFRWREOMZ-UHFFFAOYSA-N 0.000 description 1
- VFCVOIQTBWJNJT-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[(cyclohexylmethylamino)methyl]benzamide Chemical compound C12=CC(Cl)=CC=C2NC=C1CCNC(=O)C(C=C1)=CC=C1CNCC1CCCCC1 VFCVOIQTBWJNJT-UHFFFAOYSA-N 0.000 description 1
- DGKMRCOBQBLUMR-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound FC(F)(F)C1=CC=CC=C1CC1=CC=C(C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)C=C1 DGKMRCOBQBLUMR-UHFFFAOYSA-N 0.000 description 1
- KRJIKDSERDFBJE-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-4-[[3-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound FC(F)(F)C1=CC=CC(CC=2C=CC(=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 KRJIKDSERDFBJE-UHFFFAOYSA-N 0.000 description 1
- JDKAVPFTYLLQFW-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-5-[(3-fluorophenyl)methyl]pyridine-2-carboxamide Chemical compound FC1=CC=CC(CC=2C=NC(=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 JDKAVPFTYLLQFW-UHFFFAOYSA-N 0.000 description 1
- KFCLTULFSMETNX-UHFFFAOYSA-N n-[2-(5-chloro-1h-indol-3-yl)ethyl]-6-[(3-fluorophenyl)methyl]pyridine-2-carboxamide Chemical compound FC1=CC=CC(CC=2N=C(C=CC=2)C(=O)NCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 KFCLTULFSMETNX-UHFFFAOYSA-N 0.000 description 1
- UJHLGHRLGWZBSY-UHFFFAOYSA-N n-[2-(5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl)ethyl]-4-[(3-fluorophenyl)methyl]benzamide Chemical compound FC1=CC=CC(CC=2C=CC(=CC=2)C(=O)NCCC=2C3=CC(Cl)=CN=C3NC=2)=C1 UJHLGHRLGWZBSY-UHFFFAOYSA-N 0.000 description 1
- OTVNTVPPKKNUEI-UHFFFAOYSA-N n-[2-(5-chloro-2-methyl-1h-indol-3-yl)ethyl]-4-[(3-fluorophenyl)methyl]benzamide Chemical compound CC=1NC2=CC=C(Cl)C=C2C=1CCNC(=O)C(C=C1)=CC=C1CC1=CC=CC(F)=C1 OTVNTVPPKKNUEI-UHFFFAOYSA-N 0.000 description 1
- FZHXBXLABVHVTC-UHFFFAOYSA-N n-[2-(5-cyano-2-triethylsilyl-1h-indol-3-yl)ethyl]-4-[(3-fluorophenyl)methyl]benzamide Chemical compound CC[Si](CC)(CC)C=1NC2=CC=C(C#N)C=C2C=1CCNC(=O)C(C=C1)=CC=C1CC1=CC=CC(F)=C1 FZHXBXLABVHVTC-UHFFFAOYSA-N 0.000 description 1
- PYUNPSUJSCJYCH-UHFFFAOYSA-N n-[2-(6-chloro-5-methyl-1h-indol-3-yl)ethyl]-4-[(3-fluorophenyl)methyl]benzamide Chemical compound C=1NC=2C=C(Cl)C(C)=CC=2C=1CCNC(=O)C(C=C1)=CC=C1CC1=CC=CC(F)=C1 PYUNPSUJSCJYCH-UHFFFAOYSA-N 0.000 description 1
- OWSGWODVDLLTQM-UHFFFAOYSA-N n-[3-(5-chloro-1h-indol-3-yl)propyl]-4-[(3-fluorophenyl)methyl]benzamide Chemical compound FC1=CC=CC(CC=2C=CC(=CC=2)C(=O)NCCCC=2C3=CC(Cl)=CC=C3NC=2)=C1 OWSGWODVDLLTQM-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 229950006327 napsilate Drugs 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002892 organic cations Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000005495 pyridazyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000010956 selective crystallization Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229950002757 teoclate Drugs 0.000 description 1
- 125000005942 tetrahydropyridyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
- 125000005032 thiofuranyl group Chemical group S1C(=CC=C1)* 0.000 description 1
- QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- 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
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- 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
- A61P25/14—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1021103.5A GB201021103D0 (en) | 2010-12-13 | 2010-12-13 | New compounds for the treatment of neurodegenerative diseases |
| GB201021103 | 2010-12-13 | ||
| PCT/EP2011/072568 WO2012080221A1 (en) | 2010-12-13 | 2011-12-13 | New compounds for the treatment of neurodegenerative diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2637288T3 true ES2637288T3 (es) | 2017-10-11 |
Family
ID=43567100
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES11805450.1T Active ES2637288T3 (es) | 2010-12-13 | 2011-12-13 | N-((1H-indol-3-il)-alquil)-4-bencil)benzamida y derivados de N-((1H-pirrolo[2,3-b]piridin-3-il)-alquil)-4-bencil)benzamida como inhibidores de la agregación de alfa-sinucleína para el tratamiento de trastornos neurodegenerativos |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US9266832B2 (https=) |
| EP (1) | EP2651888B1 (https=) |
| JP (1) | JP6050241B2 (https=) |
| CN (1) | CN103261156B (https=) |
| CA (1) | CA2819171C (https=) |
| DK (1) | DK2651888T3 (https=) |
| ES (1) | ES2637288T3 (https=) |
| GB (1) | GB201021103D0 (https=) |
| HR (1) | HRP20171186T1 (https=) |
| HU (1) | HUE033277T2 (https=) |
| SI (1) | SI2651888T1 (https=) |
| WO (1) | WO2012080221A1 (https=) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201021103D0 (en) | 2010-12-13 | 2011-01-26 | Univ Leuven Kath | New compounds for the treatment of neurodegenerative diseases |
| GB201021104D0 (en) | 2010-12-13 | 2011-01-26 | Univ Leuven Kath | Novel compounds for the treatment of neurodegenerative diseases |
| BR112016015449A8 (pt) * | 2013-12-30 | 2020-06-09 | Lifesci Pharmaceuticals Inc | compostos inibidores terapêuticos, composição farmacêutica os compreendendo e uso dos mesmos |
| EA032374B1 (ru) * | 2014-01-29 | 2019-05-31 | ЮСиБи БАЙОФАРМА СПРЛ | Гетероарильные амиды в качестве ингибиторов агрегации белков |
| CN104744353B (zh) * | 2015-03-31 | 2017-11-24 | 山东友帮生化科技有限公司 | 2‑氨基‑3‑碘‑5‑氯吡啶的合成方法 |
| CN105130978B (zh) * | 2015-07-22 | 2017-11-21 | 中国人民解放军军事医学科学院基础医学研究所 | 一种化合物及其在帕金森疾病方面的应用 |
| ES2885049T3 (es) | 2015-07-29 | 2021-12-13 | UCB Biopharma SRL | Derivados de bis-heteroarilo como moduladores de la agregación de proteínas |
| US11970486B2 (en) | 2016-10-24 | 2024-04-30 | Janssen Pharmaceutica Nv | Compounds and uses thereof |
| EA201991650A1 (ru) | 2017-01-06 | 2020-01-20 | Юманити Терапьютикс, Инк. | Способы лечения неврологических расстройств |
| US10913735B2 (en) | 2017-01-26 | 2021-02-09 | UCB Biopharma SRL | Bis-heteroaryl derivatives as modulators of protein aggregation |
| CN110167937B (zh) | 2017-01-26 | 2022-03-29 | Ucb生物制药私人有限公司 | 作为蛋白质聚集调节剂的二环双-杂芳基衍生物 |
| WO2018138085A1 (en) | 2017-01-26 | 2018-08-02 | Ucb Biopharma Sprl | Alkoxy bis-heteroaryl derivatives as modulators of protein aggregation |
| EP3589616A1 (en) | 2017-02-28 | 2020-01-08 | Universitat Autònoma de Barcelona | (nitro-phenyl)-nitropyridine compounds for treating synucleinopathies |
| WO2019025424A1 (en) | 2017-08-04 | 2019-02-07 | Universitat Autonoma De Barcelona | COMPOUNDS FOR TREATING SYNUCLEINOPATHIES |
| CA3083000A1 (en) | 2017-10-24 | 2019-05-02 | Yumanity Therapeutics, Inc. | Compounds and uses thereof |
| WO2019161917A1 (en) | 2018-02-23 | 2019-08-29 | Universitat Autonoma De Barcelona | 4-substituted 1-ethenylsulfonyl-2-nitrobenzene compounds for treating synucleinopathies |
| BR112020019191A2 (pt) | 2018-03-23 | 2021-01-05 | Yumanity Therapeutics, Inc. | Compostos e seus usos |
| JP7640458B2 (ja) | 2018-10-05 | 2025-03-05 | アンナプルナ バイオ インコーポレイテッド | Ａｐｊ受容体活性に関連する状態を処置するための化合物および組成物 |
| MX2021008903A (es) | 2019-01-24 | 2021-11-04 | Yumanity Therapeutics Inc | Compuestos y usos de los mismos. |
| WO2020198026A1 (en) * | 2019-03-22 | 2020-10-01 | Yumanity Therapeutics, Inc. | Compounds and uses thereof |
| CA3148602A1 (en) | 2019-08-02 | 2021-02-11 | Acelot, Inc. | Small molecule drugs and related methods for treatment of diseases related to tdp-43, alpha-synuclein, huntingtin's protein and tau protein oligomer formation |
| EA202192047A1 (ru) | 2019-11-13 | 2021-12-08 | Юманити Терапьютикс, Инк. | Соединения и их применение |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3202669A (en) | 1963-11-06 | 1965-08-24 | Upjohn Co | 6-methoxy-1-(3, 4, 5-trimethoxy phenyl)-9h-pyrido [3, 4-b] indole and its acid addition salts |
| IL130169A (en) | 1999-05-27 | 2006-08-20 | Neurim Pharma 1991 | Indole derivatives, and pharmaceutical preparations, skin protection preparations, and cosmetics containing them |
| US6306890B1 (en) * | 1999-08-30 | 2001-10-23 | Vanderbilt University | Esters derived from indolealkanols and novel amides derived from indolealkylamides that are selective COX-2 inhibitors |
| GB9922171D0 (en) * | 1999-09-21 | 1999-11-17 | Zeneca Ltd | Chemical compounds |
| CA2411165A1 (en) * | 2000-05-02 | 2002-12-11 | Meiji Seika Kaisha, Ltd. | Novel indole derivatives exhibiting chymase-inhibitory activities and process for preparation thereof |
| DOP2002000332A (es) * | 2001-02-14 | 2002-08-30 | Warner Lambert Co | Inhibidores de piridina de metaloproteinasas de la matriz |
| CA2517256C (en) * | 2003-02-26 | 2013-04-30 | Sugen, Inc. | Aminoheteroaryl compounds as protein kinase inhibitors |
| MX2007000150A (es) | 2004-07-01 | 2007-03-30 | Univ California | Inhibicion de moleculas pequenas de la interaccion del domini pdz. |
| US8143257B2 (en) | 2004-11-23 | 2012-03-27 | Ptc Therapeutics, Inc. | Substituted phenols as active agents inhibiting VEGF production |
| WO2007006734A1 (en) * | 2005-07-12 | 2007-01-18 | Bayer Cropscience Sa | New benzoheterocyclylethylbenzamide derivatives |
| EP2149552A1 (de) * | 2008-07-30 | 2010-02-03 | Bayer Schering Pharma AG | 5,6 substituierte Benzamid-Derivate als Modulatoren des EP2-Rezeptors |
| US20120053165A1 (en) * | 2009-03-03 | 2012-03-01 | Pfizer Inc. | Novel Phenyl Imidazoles and Phenyl Triazoles As Gamma-Secretase Modulators |
| GB0910003D0 (en) * | 2009-06-11 | 2009-07-22 | Univ Leuven Kath | Novel compounds for the treatment of neurodegenerative diseases |
| ES2360435B1 (es) * | 2009-10-30 | 2012-05-04 | Consejo Superior De Investigaciones Cientificas (Csic) (70%) | Derivados de biss (aralquil) amino y sistemas (6+5)-heteroaromaticos y su uso en el tratamiento de patologias neurodegenerativas, incluida la enfermedad de alzheimer |
| WO2012042621A1 (ja) * | 2010-09-29 | 2012-04-05 | 味の素株式会社 | 塩味増強剤 |
| AU2011329233A1 (en) * | 2010-11-15 | 2013-05-23 | Abbvie Deutschland Gmbh & Co Kg | NAMPT and ROCK inhibitors |
| GB201021104D0 (en) | 2010-12-13 | 2011-01-26 | Univ Leuven Kath | Novel compounds for the treatment of neurodegenerative diseases |
| GB201021103D0 (en) | 2010-12-13 | 2011-01-26 | Univ Leuven Kath | New compounds for the treatment of neurodegenerative diseases |
-
2010
- 2010-12-13 GB GBGB1021103.5A patent/GB201021103D0/en not_active Ceased
-
2011
- 2011-12-13 EP EP11805450.1A patent/EP2651888B1/en not_active Not-in-force
- 2011-12-13 CA CA2819171A patent/CA2819171C/en active Active
- 2011-12-13 DK DK11805450.1T patent/DK2651888T3/en active
- 2011-12-13 SI SI201131263T patent/SI2651888T1/sl unknown
- 2011-12-13 US US13/993,723 patent/US9266832B2/en active Active
- 2011-12-13 WO PCT/EP2011/072568 patent/WO2012080221A1/en not_active Ceased
- 2011-12-13 HR HRP20171186TT patent/HRP20171186T1/hr unknown
- 2011-12-13 CN CN201180059955.9A patent/CN103261156B/zh not_active Expired - Fee Related
- 2011-12-13 JP JP2013542577A patent/JP6050241B2/ja not_active Expired - Fee Related
- 2011-12-13 HU HUE11805450A patent/HUE033277T2/en unknown
- 2011-12-13 ES ES11805450.1T patent/ES2637288T3/es active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US9266832B2 (en) | 2016-02-23 |
| JP2013544872A (ja) | 2013-12-19 |
| US20130274260A1 (en) | 2013-10-17 |
| CN103261156B (zh) | 2016-12-28 |
| HRP20171186T1 (hr) | 2017-10-20 |
| HUE033277T2 (en) | 2017-11-28 |
| GB201021103D0 (en) | 2011-01-26 |
| EP2651888B1 (en) | 2017-05-17 |
| CA2819171C (en) | 2020-02-18 |
| CA2819171A1 (en) | 2012-06-21 |
| EP2651888A1 (en) | 2013-10-23 |
| CN103261156A (zh) | 2013-08-21 |
| SI2651888T1 (sl) | 2017-10-30 |
| WO2012080221A1 (en) | 2012-06-21 |
| JP6050241B2 (ja) | 2016-12-21 |
| DK2651888T3 (en) | 2017-08-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2637288T3 (es) | N-((1H-indol-3-il)-alquil)-4-bencil)benzamida y derivados de N-((1H-pirrolo[2,3-b]piridin-3-il)-alquil)-4-bencil)benzamida como inhibidores de la agregación de alfa-sinucleína para el tratamiento de trastornos neurodegenerativos | |
| JP6689805B2 (ja) | カテプシンｃの置換２−アザ−ビシクロ［２．２．１］ヘプタン−３−カルボン酸（ベンジル−シアノ−メチル）−アミド阻害剤 | |
| ES2702951T3 (es) | Inhibidores de quinasas dependientes de ciclina 7 (cdk7) | |
| CN103038229B (zh) | 杂芳基化合物及其使用方法 | |
| EP2651887B1 (en) | N-(2-(5-substituted-1H-indol-3-yl)ethyl)biphenyl-4-carboxamide derivatives and related compounds as Tau-aggregation induced toxicity inhibitors for the treatment of neurodegenerative disorders | |
| CN110437205B (zh) | 吡啶烯基哌啶衍生物及其用途 | |
| CN104725359B (zh) | 取代的哌嗪化合物及其使用方法和用途 | |
| BR112015009168B1 (pt) | Composto de fórmula estrutural xi ou um sal do mesmo, uso de um composto e composição farmacêutica | |
| BRPI0713187A2 (pt) | método de inibir rho-quinase, método de tratamento de doença mediada por rho-quinase, composto e composição farmacêutica | |
| CN104163813B (zh) | 取代的吲哚化合物及其使用方法和用途 | |
| CN105085482B (zh) | 取代的哌嗪化合物及其使用方法和用途 | |
| JP2010526027A (ja) | プリン誘導体 | |
| US9598401B2 (en) | Substituted heteroaryl compounds and methods of use thereof | |
| JP2017510657A (ja) | Ｍｉｆ阻害剤 | |
| CN121311480A (zh) | Lzk抑制剂 | |
| BR112021004999A2 (pt) | composto e método de inibição de cdk7 em um sujeito | |
| CN114728929A (zh) | 吡啶亚甲基哌啶衍生物及其用途 | |
| HK40083035B (zh) | Parp7抑制剂及其用途 | |
| TW202540096A (zh) | 靶向降解雄激素受體的雙功能嵌合體的雜環化合物及其用途 | |
| HK1192224A (en) | N-((1h-indol-3-yl)-alkyl)-4-benzyl)benzamide and n-((1h-pyrrolo[2,3-b]pyridin-3-yl)-alkyl)-4-benzyl)benzamide derivatives as alpha synuclein aggregation inhibitors for the treatment of neurodegenerative disorders | |
| HK1192224B (en) | N-((1h-indol-3-yl)-alkyl)-4-benzyl)benzamide and n-((1h-pyrrolo[2,3-b]pyridin-3-yl)-alkyl)-4-benzyl)benzamide derivatives as alpha synuclein aggregation inhibitors for the treatment of neurodegenerative disorders | |
| BR112020006456B1 (pt) | Compostos químicos, composição farmacêutica e seus usos para tratar uma infecção por vírus da hepatite b e para inibir o nível do antígeno hbe ou hbs em um hbsag de mamífero in vitro | |
| BR112020006456A2 (pt) | compostos químicos |