EA039923B1 - Зонды для визуализации белка хантингтина - Google Patents
Зонды для визуализации белка хантингтина Download PDFInfo
- Publication number
- EA039923B1 EA039923B1 EA201790400A EA201790400A EA039923B1 EA 039923 B1 EA039923 B1 EA 039923B1 EA 201790400 A EA201790400 A EA 201790400A EA 201790400 A EA201790400 A EA 201790400A EA 039923 B1 EA039923 B1 EA 039923B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- imidazo
- pyridine
- methoxy
- methylamino
- carbonitrile
- Prior art date
Links
- 102000016252 Huntingtin Human genes 0.000 title claims abstract description 6
- 108050004784 Huntingtin Proteins 0.000 title claims abstract description 6
- 238000003384 imaging method Methods 0.000 title claims description 14
- 239000000523 sample Substances 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 160
- 150000001875 compounds Chemical class 0.000 claims abstract description 110
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 29
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 27
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 210000004556 brain Anatomy 0.000 claims abstract description 17
- 239000012216 imaging agent Substances 0.000 claims abstract description 9
- 208000037273 Pathologic Processes Diseases 0.000 claims abstract description 6
- 230000009054 pathological process Effects 0.000 claims abstract description 6
- 239000000178 monomer Substances 0.000 claims abstract description 5
- -1 methoxy, hydroxyl Chemical group 0.000 claims description 138
- 125000000217 alkyl group Chemical group 0.000 claims description 82
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 claims description 57
- 229910052757 nitrogen Inorganic materials 0.000 claims description 55
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 51
- 229910052717 sulfur Inorganic materials 0.000 claims description 49
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
- 125000005842 heteroatom Chemical group 0.000 claims description 47
- 229910052760 oxygen Inorganic materials 0.000 claims description 47
- 125000001072 heteroaryl group Chemical group 0.000 claims description 40
- 125000003545 alkoxy group Chemical group 0.000 claims description 35
- 229910052799 carbon Inorganic materials 0.000 claims description 32
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 30
- KIYOXVPZRXLLDR-UHFFFAOYSA-N imidazo[1,2-a]pyridine-7-carbonitrile Chemical compound C1=C(C#N)C=CN2C=CN=C21 KIYOXVPZRXLLDR-UHFFFAOYSA-N 0.000 claims description 30
- 125000004432 carbon atom Chemical group C* 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 21
- 238000002600 positron emission tomography Methods 0.000 claims description 21
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 20
- 208000023105 Huntington disease Diseases 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 239000003795 chemical substances by application Substances 0.000 claims description 16
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 15
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 12
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 11
- 210000004227 basal ganglia Anatomy 0.000 claims description 11
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 230000004770 neurodegeneration Effects 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 239000011737 fluorine Chemical group 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- ZHXPGZQNJIWLDI-UHFFFAOYSA-N COC1=CC=C2OC(=CC2=C1)C1=C(N(C)C)N2C=CC(=CC2=N1)C#N Chemical compound COC1=CC=C2OC(=CC2=C1)C1=C(N(C)C)N2C=CC(=CC2=N1)C#N ZHXPGZQNJIWLDI-UHFFFAOYSA-N 0.000 claims description 5
- RCFTZJKADPJHHQ-UHFFFAOYSA-N COC=1N=CC(=NC=1)COC1=CC=C(C=N1)C=1N=C2N(C=CC(=C2)C#N)C=1NC Chemical compound COC=1N=CC(=NC=1)COC1=CC=C(C=N1)C=1N=C2N(C=CC(=C2)C#N)C=1NC RCFTZJKADPJHHQ-UHFFFAOYSA-N 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- YKJICSLWCNWWFD-UHFFFAOYSA-N FC=1C=CC=2N(C=1)C(=C(N=2)C=1OC2=C(C=1)C=C(C=C2)O)NC Chemical compound FC=1C=CC=2N(C=1)C(=C(N=2)C=1OC2=C(C=1)C=C(C=C2)O)NC YKJICSLWCNWWFD-UHFFFAOYSA-N 0.000 claims description 5
- KZMRYMBBISTXTB-UHFFFAOYSA-N NC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OCCF)=CC=C2O1 Chemical compound NC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OCCF)=CC=C2O1 KZMRYMBBISTXTB-UHFFFAOYSA-N 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 238000001514 detection method Methods 0.000 claims description 5
- 150000002431 hydrogen Chemical group 0.000 claims description 5
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 5
- 125000006584 (C3-C10) heterocycloalkyl group Chemical group 0.000 claims description 4
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
- RVYYSUMYBRASNN-UHFFFAOYSA-N CN(CCOC=1C=CC2=C(C=C(O2)C=2N=C3N(C=CC(=C3)C#N)C=2NC)C=1)C Chemical compound CN(CCOC=1C=CC2=C(C=C(O2)C=2N=C3N(C=CC(=C3)C#N)C=2NC)C=1)C RVYYSUMYBRASNN-UHFFFAOYSA-N 0.000 claims description 4
- XOAVMCHKAMGNEK-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OC)=CC=C2O1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OC)=CC=C2O1 XOAVMCHKAMGNEK-UHFFFAOYSA-N 0.000 claims description 4
- ZWJAOVYQCAOPFB-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OCCF)=CC=C2O1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OCCF)=CC=C2O1 ZWJAOVYQCAOPFB-UHFFFAOYSA-N 0.000 claims description 4
- ZWENFEJTOGNBJA-UHFFFAOYSA-N CNC1=C(N=C2C=CC=CN12)C1=CC2=CC(F)=CC=C2O1 Chemical compound CNC1=C(N=C2C=CC=CN12)C1=CC2=CC(F)=CC=C2O1 ZWENFEJTOGNBJA-UHFFFAOYSA-N 0.000 claims description 4
- POEHWOYCAHVSBZ-UHFFFAOYSA-N CNC1=C(N=C2N1C=CC(=C2)C#N)C1=CC(=CC=C1)C1=NC=CN=C1 Chemical compound CNC1=C(N=C2N1C=CC(=C2)C#N)C1=CC(=CC=C1)C1=NC=CN=C1 POEHWOYCAHVSBZ-UHFFFAOYSA-N 0.000 claims description 4
- MEZXIRVFTDTRHP-UHFFFAOYSA-N COC1=CC=C2OC(=CC2=C1)C1=C(NCCN(C)C)N2C=CC(=CC2=N1)C#N Chemical compound COC1=CC=C2OC(=CC2=C1)C1=C(NCCN(C)C)N2C=CC(=CC2=N1)C#N MEZXIRVFTDTRHP-UHFFFAOYSA-N 0.000 claims description 4
- KSZOWDYOWNPZHE-UHFFFAOYSA-N OCCNC1=C(N=C2N1C=CC=C2)C=1OC2=C(C=1)C=C(C=C2)O Chemical compound OCCNC1=C(N=C2N1C=CC=C2)C=1OC2=C(C=1)C=C(C=C2)O KSZOWDYOWNPZHE-UHFFFAOYSA-N 0.000 claims description 4
- 238000012879 PET imaging Methods 0.000 claims description 4
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 4
- 238000002591 computed tomography Methods 0.000 claims description 4
- 238000002595 magnetic resonance imaging Methods 0.000 claims description 4
- ZPMWXDOTBGBOJU-UHFFFAOYSA-N 2-(5-bromo-1-benzofuran-2-yl)-3-(methylamino)imidazo[1,2-a]pyridine-7-carbonitrile Chemical compound BrC=1C=CC2=C(C=C(O2)C=2N=C3N(C=CC(=C3)C#N)C=2NC)C=1 ZPMWXDOTBGBOJU-UHFFFAOYSA-N 0.000 claims description 3
- PYKSYJJOIRRNGO-VMPITWQZSA-N 2-[(E)-2-(4-methoxyphenyl)ethenyl]-3-(methylamino)imidazo[1,2-a]pyridine-7-carbonitrile Chemical compound COC1=CC=C(C=C1)/C=C/C=1N=C2N(C=CC(=C2)C#N)C=1NC PYKSYJJOIRRNGO-VMPITWQZSA-N 0.000 claims description 3
- VJFJMCSJLDRDRR-UHFFFAOYSA-N 2-[5-[(5-methoxypyrazin-2-yl)methoxy]pyridin-2-yl]-3-(methylamino)imidazo[1,2-a]pyridine-7-carbonitrile Chemical compound COC=1N=CC(=NC=1)COC=1C=CC(=NC=1)C=1N=C2N(C=CC(=C2)C#N)C=1NC VJFJMCSJLDRDRR-UHFFFAOYSA-N 0.000 claims description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
- GSDQMGHKNLDKGS-UHFFFAOYSA-N C(#C)C1=CC=2N(C=C1)C(=C(N=2)C=1OC2=C(C=1)C=C(C=C2)OC)NC Chemical compound C(#C)C1=CC=2N(C=C1)C(=C(N=2)C=1OC2=C(C=1)C=C(C=C2)OC)NC GSDQMGHKNLDKGS-UHFFFAOYSA-N 0.000 claims description 3
- VTOJVPBRAFYQFG-UHFFFAOYSA-N C(#N)C1=CC=2N(C=C1)C(=C(N=2)C1=CC=2CN(CCC=2O1)C(=O)OC(C)(C)C)NC Chemical compound C(#N)C1=CC=2N(C=C1)C(=C(N=2)C1=CC=2CN(CCC=2O1)C(=O)OC(C)(C)C)NC VTOJVPBRAFYQFG-UHFFFAOYSA-N 0.000 claims description 3
- SJLUGUZBAJMBQF-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC(OCC2=CC=CN=C2)=CC=C1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC(OCC2=CC=CN=C2)=CC=C1 SJLUGUZBAJMBQF-UHFFFAOYSA-N 0.000 claims description 3
- RBKJEYGQBCKLGM-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(F)=CC=C2O1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(F)=CC=C2O1 RBKJEYGQBCKLGM-UHFFFAOYSA-N 0.000 claims description 3
- NPCDZMJJDWIPMB-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC=C(OC)C=C2O1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC=C(OC)C=C2O1 NPCDZMJJDWIPMB-UHFFFAOYSA-N 0.000 claims description 3
- AJYCMRRMPQDPSD-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(Br)O1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(Br)O1 AJYCMRRMPQDPSD-UHFFFAOYSA-N 0.000 claims description 3
- MPQVZUNLXDYAKW-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(C=C1)C#N Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(C=C1)C#N MPQVZUNLXDYAKW-UHFFFAOYSA-N 0.000 claims description 3
- PQAVQXOXMMLDCR-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(C=C1)C1=CN=CC=N1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(C=C1)C1=CN=CC=N1 PQAVQXOXMMLDCR-UHFFFAOYSA-N 0.000 claims description 3
- WNYMMHJVRNYABS-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(COCC2=CC=CN=C2)C=C1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(COCC2=CC=CN=C2)C=C1 WNYMMHJVRNYABS-UHFFFAOYSA-N 0.000 claims description 3
- MLMXEQIOYTVWIA-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(OCC2=CC=CN=C2)C=C1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(OCC2=CC=CN=C2)C=C1 MLMXEQIOYTVWIA-UHFFFAOYSA-N 0.000 claims description 3
- HYUHYEDKWBEMTR-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C2OC=CC2=C1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C2OC=CC2=C1 HYUHYEDKWBEMTR-UHFFFAOYSA-N 0.000 claims description 3
- XTZNLAAKBBAFNN-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C2OCCOC2=C1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C2OCCOC2=C1 XTZNLAAKBBAFNN-UHFFFAOYSA-N 0.000 claims description 3
- BWYIMJKGPSCZDS-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=NC2=C(O1)C=CC(OC)=C2 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=NC2=C(O1)C=CC(OC)=C2 BWYIMJKGPSCZDS-UHFFFAOYSA-N 0.000 claims description 3
- FGIPHZIFCKSYPL-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=NC2=CC=C(OC)C=C2S1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=NC2=CC=C(OC)C=C2S1 FGIPHZIFCKSYPL-UHFFFAOYSA-N 0.000 claims description 3
- UFIZXKXQFOMXQQ-UHFFFAOYSA-N CNC1=C(N=C2C=CC(=CN12)C#N)C1=CC2=CC(OC)=CC=C2O1 Chemical compound CNC1=C(N=C2C=CC(=CN12)C#N)C1=CC2=CC(OC)=CC=C2O1 UFIZXKXQFOMXQQ-UHFFFAOYSA-N 0.000 claims description 3
- KXLPRHZBUZUXLA-UHFFFAOYSA-N CNC1=C(N=C2C=CC(F)=CN12)C1=CC2=CC(OC)=CC=C2O1 Chemical compound CNC1=C(N=C2C=CC(F)=CN12)C1=CC2=CC(OC)=CC=C2O1 KXLPRHZBUZUXLA-UHFFFAOYSA-N 0.000 claims description 3
- LYLXYCVZZZHIKK-UHFFFAOYSA-N CNC1=C(N=C2N1C=CC(=C2)C#N)C1=CC=C(C=C1)OCC#C Chemical compound CNC1=C(N=C2N1C=CC(=C2)C#N)C1=CC=C(C=C1)OCC#C LYLXYCVZZZHIKK-UHFFFAOYSA-N 0.000 claims description 3
- KYYQKHITWXMMTA-UHFFFAOYSA-N COC1=CC=C(C=C1)C=1N=C2N(C=CC(=C2)C#N)C=1NC Chemical compound COC1=CC=C(C=C1)C=1N=C2N(C=CC(=C2)C#N)C=1NC KYYQKHITWXMMTA-UHFFFAOYSA-N 0.000 claims description 3
- GECCHUDLYZTUMC-UHFFFAOYSA-N FC1=CC=2N(C=C1)C(=C(N=2)C=1OC2=C(C=1)C=C(C=C2)O)NC Chemical compound FC1=CC=2N(C=C1)C(=C(N=2)C=1OC2=C(C=1)C=C(C=C2)O)NC GECCHUDLYZTUMC-UHFFFAOYSA-N 0.000 claims description 3
- ZHNKUPJDEJSTCM-UHFFFAOYSA-N NC1=C(N=C2N1C=CC(=C2)C#N)C=1OC2=C(C=1)C=C(C=C2)OC Chemical compound NC1=C(N=C2N1C=CC(=C2)C#N)C=1OC2=C(C=1)C=C(C=C2)OC ZHNKUPJDEJSTCM-UHFFFAOYSA-N 0.000 claims description 3
- OIKDVDYRHLAKRU-UHFFFAOYSA-N OC=1C=CC2=C(C=C(O2)C=2N=C3N(C=CC(=C3)C#N)C=2NC)C=1 Chemical compound OC=1C=CC2=C(C=C(O2)C=2N=C3N(C=CC(=C3)C#N)C=2NC)C=1 OIKDVDYRHLAKRU-UHFFFAOYSA-N 0.000 claims description 3
- SYARCGGAUZTGOC-UHFFFAOYSA-N S1C=2N(C(=C1)COC1=CC=C(C=C1)C=1N=C3N(C=CC(=C3)C#N)C=1NC)CCN=2 Chemical compound S1C=2N(C(=C1)COC1=CC=C(C=C1)C=1N=C3N(C=CC(=C3)C#N)C=1NC)CCN=2 SYARCGGAUZTGOC-UHFFFAOYSA-N 0.000 claims description 3
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 3
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- XGUYDRGNKVSGSC-UHFFFAOYSA-N COC=1C=CC(=NC=1)COC=1N=CC(=NC=1)C=1N=C2N(C=CC(=C2)C#N)C=1NC Chemical compound COC=1C=CC(=NC=1)COC=1N=CC(=NC=1)C=1N=C2N(C=CC(=C2)C#N)C=1NC XGUYDRGNKVSGSC-UHFFFAOYSA-N 0.000 claims description 2
- 206010008025 Cerebellar ataxia Diseases 0.000 claims description 2
- GOLLPWSJSDQLOI-UHFFFAOYSA-N NCC1=CC=2N(C=C1)C(=C(N=2)C=1OC2=C(C=1)C=C(C=C2)OC)NC Chemical compound NCC1=CC=2N(C=C1)C(=C(N=2)C=1OC2=C(C=1)C=C(C=C2)OC)NC GOLLPWSJSDQLOI-UHFFFAOYSA-N 0.000 claims description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 238000002059 diagnostic imaging Methods 0.000 claims description 2
- MPRMRYWPRROMHA-UHFFFAOYSA-N 2-(5-methoxy-1-methylbenzimidazol-2-yl)-3-(methylamino)imidazo[1,2-a]pyridine-7-carbonitrile Chemical compound COC1=CC2=C(N(C(=N2)C=2N=C3N(C=CC(=C3)C#N)C=2NC)C)C=C1 MPRMRYWPRROMHA-UHFFFAOYSA-N 0.000 claims 2
- XAWNDICSNACTDK-UHFFFAOYSA-N 3-(methylamino)-2-[3-(pyridin-3-ylmethoxymethyl)phenyl]imidazo[1,2-a]pyridine-7-carbonitrile Chemical compound CNC1=C(N=C2N1C=CC(=C2)C#N)C1=CC(=CC=C1)COCC=1C=NC=CC=1 XAWNDICSNACTDK-UHFFFAOYSA-N 0.000 claims 2
- CJNQWVOBLFPDRJ-UHFFFAOYSA-N CNC1=C(N=C2C=C(Br)C=CN12)C1=CC2=CC(OC)=CC=C2O1 Chemical compound CNC1=C(N=C2C=C(Br)C=CN12)C1=CC2=CC(OC)=CC=C2O1 CJNQWVOBLFPDRJ-UHFFFAOYSA-N 0.000 claims 2
- NNDKOIGQUJSQOM-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OCC3=CC=CN=C3)=CC=C2O1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OCC3=CC=CN=C3)=CC=C2O1 NNDKOIGQUJSQOM-UHFFFAOYSA-N 0.000 claims 2
- GCEJNAGPAIQGMI-UHFFFAOYSA-N CNC1=C(N=C2C=C(F)C=CN12)C1=CC2=CC(OC)=CC=C2O1 Chemical compound CNC1=C(N=C2C=C(F)C=CN12)C1=CC2=CC(OC)=CC=C2O1 GCEJNAGPAIQGMI-UHFFFAOYSA-N 0.000 claims 2
- JYTNYBNAPHPPNX-UHFFFAOYSA-N CNC1=C(N=C2C=CC=CN12)C1=CC2=CC(OC)=CC=C2O1 Chemical compound CNC1=C(N=C2C=CC=CN12)C1=CC2=CC(OC)=CC=C2O1 JYTNYBNAPHPPNX-UHFFFAOYSA-N 0.000 claims 2
- URGGSAPCZSQPLD-UHFFFAOYSA-N COC1=CC=2N(C=C1)C(=C(N=2)C=1OC2=C(C=1)C=C(C=C2)OC)NC Chemical compound COC1=CC=2N(C=C1)C(=C(N=2)C=1OC2=C(C=1)C=C(C=C2)OC)NC URGGSAPCZSQPLD-UHFFFAOYSA-N 0.000 claims 2
- JOGISKJJUIXZLP-UHFFFAOYSA-N COC=1C=CC2=C(C=C(O2)C=2N=C3N(C=CC(=C3)C#N)C=2NCCOC)C=1 Chemical compound COC=1C=CC2=C(C=C(O2)C=2N=C3N(C=CC(=C3)C#N)C=2NCCOC)C=1 JOGISKJJUIXZLP-UHFFFAOYSA-N 0.000 claims 2
- LISGSSKUVCEDJU-UHFFFAOYSA-N COC=1C=CC2=C(C=C(O2)C=2N=C3N(C=CC=C3)C=2NCCOC)C=1 Chemical compound COC=1C=CC2=C(C=C(O2)C=2N=C3N(C=CC=C3)C=2NCCOC)C=1 LISGSSKUVCEDJU-UHFFFAOYSA-N 0.000 claims 2
- VLBSNOKHTBGVSK-UHFFFAOYSA-N COC=1C=CC2=C(N(C(=N2)C=2N=C3N(C=CC(=C3)C#N)C=2NC)C)C=1 Chemical compound COC=1C=CC2=C(N(C(=N2)C=2N=C3N(C=CC(=C3)C#N)C=2NC)C)C=1 VLBSNOKHTBGVSK-UHFFFAOYSA-N 0.000 claims 2
- QALUACFZNKUXBZ-UHFFFAOYSA-N COC=1N=CC(=NC=1)COC1=CC=C(C=C1)C=1N=C2N(C=CC(=C2)C#N)C=1NC Chemical compound COC=1N=CC(=NC=1)COC1=CC=C(C=C1)C=1N=C2N(C=CC(=C2)C#N)C=1NC QALUACFZNKUXBZ-UHFFFAOYSA-N 0.000 claims 2
- TXVXTYXDJDOJBN-UHFFFAOYSA-N ClC1=CC=2N(C=C1)C(=C(N=2)C=1OC2=C(C=1)C=C(C=C2)OC)NC Chemical compound ClC1=CC=2N(C=C1)C(=C(N=2)C=1OC2=C(C=1)C=C(C=C2)OC)NC TXVXTYXDJDOJBN-UHFFFAOYSA-N 0.000 claims 2
- QQSJWOZHDPHGBZ-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=NC2=CC(OC)=CC=C2N1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=NC2=CC(OC)=CC=C2N1 QQSJWOZHDPHGBZ-UHFFFAOYSA-N 0.000 claims 1
- RPLRRHYMJPUMAU-UHFFFAOYSA-N COC=1N=CC(=NC=1)COC=1C=C(C=CC=1)C=1N=C2N(C=CC(=C2)C#N)C=1NC Chemical compound COC=1N=CC(=NC=1)COC=1C=C(C=CC=1)C=1N=C2N(C=CC(=C2)C#N)C=1NC RPLRRHYMJPUMAU-UHFFFAOYSA-N 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 claims 1
- 208000024777 Prion disease Diseases 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 1
- 150000002825 nitriles Chemical class 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 156
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 132
- 239000000203 mixture Substances 0.000 description 85
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- 239000011541 reaction mixture Substances 0.000 description 43
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- 239000000843 powder Substances 0.000 description 40
- 125000003118 aryl group Chemical group 0.000 description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- 239000000243 solution Substances 0.000 description 35
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 32
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- 239000012267 brine Substances 0.000 description 25
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 25
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
- 239000000284 extract Substances 0.000 description 23
- 238000000746 purification Methods 0.000 description 23
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 21
- 108091022884 dihydropyrimidinase Proteins 0.000 description 20
- 238000003818 flash chromatography Methods 0.000 description 20
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 20
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 20
- 125000003367 polycyclic group Chemical group 0.000 description 20
- 125000004429 atom Chemical group 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- 125000000753 cycloalkyl group Chemical group 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 18
- 239000007787 solid Substances 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 235000017557 sodium bicarbonate Nutrition 0.000 description 16
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 16
- ZRKSVHFXTRFQFL-UHFFFAOYSA-N isocyanomethane Chemical compound C[N+]#[C-] ZRKSVHFXTRFQFL-UHFFFAOYSA-N 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 238000003419 tautomerization reaction Methods 0.000 description 13
- GEEAYLFEIFJFGP-UHFFFAOYSA-N 2-aminopyridine-4-carbonitrile Chemical compound NC1=CC(C#N)=CC=N1 GEEAYLFEIFJFGP-UHFFFAOYSA-N 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 11
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 11
- 125000000392 cycloalkenyl group Chemical group 0.000 description 11
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 11
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- 235000019253 formic acid Nutrition 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- 238000002953 preparative HPLC Methods 0.000 description 9
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
- 238000007792 addition Methods 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 239000002480 mineral oil Substances 0.000 description 8
- 235000010446 mineral oil Nutrition 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- 239000012312 sodium hydride Substances 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 125000002950 monocyclic group Chemical group 0.000 description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- IZFOPMSVNDORMZ-UHFFFAOYSA-N 1-benzofuran-5-ol Chemical compound OC1=CC=C2OC=CC2=C1 IZFOPMSVNDORMZ-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 125000002619 bicyclic group Chemical group 0.000 description 6
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 239000012217 radiopharmaceutical Substances 0.000 description 6
- 229940121896 radiopharmaceutical Drugs 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 5
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000000908 ammonium hydroxide Substances 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 210000001577 neostriatum Anatomy 0.000 description 5
- 230000002799 radiopharmaceutical effect Effects 0.000 description 5
- 238000012437 strong cation exchange chromatography Methods 0.000 description 5
- 238000002305 strong-anion-exchange chromatography Methods 0.000 description 5
- 125000000547 substituted alkyl group Chemical group 0.000 description 5
- 239000003643 water by type Substances 0.000 description 5
- LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 4
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 229910052796 boron Inorganic materials 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 125000001188 haloalkyl group Chemical group 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- 210000004940 nucleus Anatomy 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 108010040003 polyglutamine Proteins 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 238000003653 radioligand binding assay Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- CNUNPQXDDJYAEE-UHFFFAOYSA-N (5-methoxypyrazin-2-yl)methanol Chemical compound COC1=CN=C(CO)C=N1 CNUNPQXDDJYAEE-UHFFFAOYSA-N 0.000 description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
- 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 3
- MUZWIMCDZKOJJW-UHFFFAOYSA-N COC1=CC=C2OC(=CC2=C1)C1=CN2C=CC(=CC2=N1)C#N Chemical compound COC1=CC=C2OC(=CC2=C1)C1=CN2C=CC(=CC2=N1)C#N MUZWIMCDZKOJJW-UHFFFAOYSA-N 0.000 description 3
- OXJOULXWVUPSAD-UHFFFAOYSA-N COC=1C=CC(=NC=1)CNC1=CC=C(C=C1)C=1N=C2N(C=CC(=C2)C#N)C=1NC Chemical compound COC=1C=CC(=NC=1)CNC1=CC=C(C=C1)C=1N=C2N(C=CC(=C2)C#N)C=1NC OXJOULXWVUPSAD-UHFFFAOYSA-N 0.000 description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 3
- 235000019502 Orange oil Nutrition 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 3
- 239000012472 biological sample Substances 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000000032 diagnostic agent Substances 0.000 description 3
- 229940039227 diagnostic agent Drugs 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 3
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 125000006574 non-aromatic ring group Chemical group 0.000 description 3
- 239000010502 orange oil Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 125000004043 oxo group Chemical group O=* 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 238000012799 strong cation exchange Methods 0.000 description 3
- 125000003107 substituted aryl group Chemical group 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 238000002211 ultraviolet spectrum Methods 0.000 description 3
- MMWRGWQTAMNAFC-UHFFFAOYSA-N 1,2-dihydropyridine Chemical compound C1NC=CC=C1 MMWRGWQTAMNAFC-UHFFFAOYSA-N 0.000 description 2
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 2
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 2
- DZOXPAYEAYNYMA-UHFFFAOYSA-N 1-(5-methoxy-1-benzofuran-2-yl)ethanone Chemical compound COC1=CC=C2OC(C(C)=O)=CC2=C1 DZOXPAYEAYNYMA-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- JTLAIKFGRHDNQM-UHFFFAOYSA-N 1-bromo-2-fluoroethane Chemical compound FCCBr JTLAIKFGRHDNQM-UHFFFAOYSA-N 0.000 description 2
- JSCFKVXPOWVVGS-UHFFFAOYSA-N 2-bromo-1-(5-methoxy-1-benzofuran-2-yl)ethanone Chemical compound COC1=CC=C2OC(C(=O)CBr)=CC2=C1 JSCFKVXPOWVVGS-UHFFFAOYSA-N 0.000 description 2
- GCNTZFIIOFTKIY-UHFFFAOYSA-N 4-hydroxypyridine Chemical compound OC1=CC=NC=C1 GCNTZFIIOFTKIY-UHFFFAOYSA-N 0.000 description 2
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
- NVNUBOSZEJYDHC-UHFFFAOYSA-N 5-methoxy-1,2-dimethylbenzimidazole Chemical compound COC1=CC=C2N(C)C(C)=NC2=C1 NVNUBOSZEJYDHC-UHFFFAOYSA-N 0.000 description 2
- ZMLZMIXKMFTTJQ-UHFFFAOYSA-N 5-methoxy-1-methylbenzimidazole-2-carbaldehyde Chemical compound COC1=CC=C2N(C)C(C=O)=NC2=C1 ZMLZMIXKMFTTJQ-UHFFFAOYSA-N 0.000 description 2
- FZHSPPYCNDYIKD-UHFFFAOYSA-N 5-methoxysalicylaldehyde Chemical compound COC1=CC=C(O)C(C=O)=C1 FZHSPPYCNDYIKD-UHFFFAOYSA-N 0.000 description 2
- BOIBGKVCSAFDSI-UHFFFAOYSA-N 6-methoxy-1,2-dimethylbenzimidazole Chemical compound COC1=CC=C2N=C(C)N(C)C2=C1 BOIBGKVCSAFDSI-UHFFFAOYSA-N 0.000 description 2
- RAFCHWOGOSKUJK-UHFFFAOYSA-N 6-methoxy-1-methylbenzimidazole-2-carbaldehyde Chemical compound COC1=CC=C2N=C(C=O)N(C)C2=C1 RAFCHWOGOSKUJK-UHFFFAOYSA-N 0.000 description 2
- ZYKVRFMMRAPHAZ-UHFFFAOYSA-N 7-fluoro-3 Chemical compound C1S(=O)(=O)CC(C=2)=CC(F)=CC=2CS(=O)(=O)CC2=CC=C1C=C2 ZYKVRFMMRAPHAZ-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 208000029402 Bulbospinal muscular atrophy Diseases 0.000 description 2
- FMQYLWULNPSPRF-UHFFFAOYSA-N C(=O)C1=CC=C(C=C1)N(C(OC(C)(C)C)=O)CC1=NC=C(C=C1)OC Chemical compound C(=O)C1=CC=C(C=C1)N(C(OC(C)(C)C)=O)CC1=NC=C(C=C1)OC FMQYLWULNPSPRF-UHFFFAOYSA-N 0.000 description 2
- WANJMVMEXUMVIB-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#C[Si](C)(C)C)C1=CC2=CC(OC)=CC=C2O1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#C[Si](C)(C)C)C1=CC2=CC(OC)=CC=C2O1 WANJMVMEXUMVIB-UHFFFAOYSA-N 0.000 description 2
- NJLFIMRWBUWHFZ-UHFFFAOYSA-N COC1=NC=C(COC2=CC=C(C=O)C=N2)N=C1 Chemical compound COC1=NC=C(COC2=CC=C(C=O)C=N2)N=C1 NJLFIMRWBUWHFZ-UHFFFAOYSA-N 0.000 description 2
- ANRFAJRLZYWULJ-UHFFFAOYSA-N COC=1N=CC(=NC=1)COC1=CC=C(C=O)C=C1 Chemical compound COC=1N=CC(=NC=1)COC1=CC=C(C=O)C=C1 ANRFAJRLZYWULJ-UHFFFAOYSA-N 0.000 description 2
- RJPMFPORUSDNOA-UHFFFAOYSA-N COCC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OC)=CC=C2O1 Chemical compound COCC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OC)=CC=C2O1 RJPMFPORUSDNOA-UHFFFAOYSA-N 0.000 description 2
- LEFHTDMVJXSWEL-UHFFFAOYSA-N CS(=O)(=O)OCC1=NC=C(N=C1)OC Chemical compound CS(=O)(=O)OCC1=NC=C(N=C1)OC LEFHTDMVJXSWEL-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 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 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 208000027747 Kennedy disease Diseases 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- JWCLUIYHOJYCNF-UHFFFAOYSA-N N1=CC(=CC=C1)COC=1C=CC2=C(C=C(O2)C=O)C=1 Chemical compound N1=CC(=CC=C1)COC=1C=CC2=C(C=C(O2)C=O)C=1 JWCLUIYHOJYCNF-UHFFFAOYSA-N 0.000 description 2
- IUPCYLCYLDVGRU-UHFFFAOYSA-N N1=CC(=CC=C1)COCC1=CC=C(C=O)C=C1 Chemical compound N1=CC(=CC=C1)COCC1=CC=C(C=O)C=C1 IUPCYLCYLDVGRU-UHFFFAOYSA-N 0.000 description 2
- NPDNZYLMBRSZAL-UHFFFAOYSA-N O1C=CC2=C1C=CC(=C2)OCC=1C=NC=CC=1 Chemical compound O1C=CC2=C1C=CC(=C2)OCC=1C=NC=CC=1 NPDNZYLMBRSZAL-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-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
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- IMHWERXSVIGCGE-UHFFFAOYSA-N S1C=2N(C(=C1)COC1=CC=C(C=O)C=C1)CCN=2 Chemical compound S1C=2N(C(=C1)COC1=CC=C(C=O)C=C1)CCN=2 IMHWERXSVIGCGE-UHFFFAOYSA-N 0.000 description 2
- 229910006074 SO2NH2 Inorganic materials 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
- AMIWTKBQVQQBBS-UHFFFAOYSA-N [1,2]oxazolo[4,5-c]pyridine Chemical compound C1=NC=C2C=NOC2=C1 AMIWTKBQVQQBBS-UHFFFAOYSA-N 0.000 description 2
- WXTRHHSZKLAHHV-UHFFFAOYSA-N [1,2]oxazolo[5,4-c]pyridine Chemical compound N1=CC=C2C=NOC2=C1 WXTRHHSZKLAHHV-UHFFFAOYSA-N 0.000 description 2
- HUMJZSMCTXGAMD-UHFFFAOYSA-N [1,2]thiazolo[4,5-c]pyridine Chemical compound C1=NC=C2C=NSC2=C1 HUMJZSMCTXGAMD-UHFFFAOYSA-N 0.000 description 2
- YBAGZQVTZXUQEU-UHFFFAOYSA-N [1,2]thiazolo[5,4-c]pyridine Chemical compound N1=CC=C2C=NSC2=C1 YBAGZQVTZXUQEU-UHFFFAOYSA-N 0.000 description 2
- ZATXVRSLQDRAHZ-UHFFFAOYSA-N [1,3]oxazolo[4,5-c]pyridine Chemical compound N1=CC=C2OC=NC2=C1 ZATXVRSLQDRAHZ-UHFFFAOYSA-N 0.000 description 2
- XRVDKIQEFCJTBZ-UHFFFAOYSA-N [1,3]oxazolo[5,4-c]pyridine Chemical compound C1=NC=C2OC=NC2=C1 XRVDKIQEFCJTBZ-UHFFFAOYSA-N 0.000 description 2
- FIPLAFRCDDWERW-UHFFFAOYSA-N [1,3]thiazolo[4,5-c]pyridine Chemical compound N1=CC=C2SC=NC2=C1 FIPLAFRCDDWERW-UHFFFAOYSA-N 0.000 description 2
- FHIMYVFGWKCROK-UHFFFAOYSA-N [1,3]thiazolo[5,4-c]pyridine Chemical compound C1=NC=C2SC=NC2=C1 FHIMYVFGWKCROK-UHFFFAOYSA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 125000005037 alkyl phenyl group Chemical group 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- 230000031018 biological processes and functions Effects 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 210000003710 cerebral cortex Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 125000004773 chlorofluoromethyl group Chemical group [H]C(F)(Cl)* 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000013256 coordination polymer Substances 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- ZYXBIOIYWUIXSM-UHFFFAOYSA-N furo[2,3-c]pyridine Chemical compound C1=NC=C2OC=CC2=C1 ZYXBIOIYWUIXSM-UHFFFAOYSA-N 0.000 description 2
- WJDMEHCIRPKRRQ-UHFFFAOYSA-N furo[3,2-c]pyridine Chemical compound N1=CC=C2OC=CC2=C1 WJDMEHCIRPKRRQ-UHFFFAOYSA-N 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 210000001905 globus pallidus Anatomy 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- AZXXFTKAVQJXCU-UHFFFAOYSA-N methyl 5-methoxypyrazine-2-carboxylate Chemical compound COC(=O)C1=CN=C(OC)C=N1 AZXXFTKAVQJXCU-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000003068 molecular probe Substances 0.000 description 2
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-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
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 2
- LBWZSUHDRDWJEC-UHFFFAOYSA-N oxadiazolo[4,5-c]pyridine Chemical compound C1=NC=CC2=C1N=NO2 LBWZSUHDRDWJEC-UHFFFAOYSA-N 0.000 description 2
- SVMOLIXMHXABPH-UHFFFAOYSA-N oxadiazolo[5,4-c]pyridine Chemical compound C1=NC=CC2=C1ON=N2 SVMOLIXMHXABPH-UHFFFAOYSA-N 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000002739 subcortical effect Effects 0.000 description 2
- 210000004281 subthalamic nucleus Anatomy 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 102000013498 tau Proteins Human genes 0.000 description 2
- 108010026424 tau Proteins Proteins 0.000 description 2
- OPKCPVXZGSRZLO-UHFFFAOYSA-N tert-butyl 2-formyl-6,7-dihydro-4h-furo[3,2-c]pyridine-5-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC2=C1C=C(C=O)O2 OPKCPVXZGSRZLO-UHFFFAOYSA-N 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- HKMXLNRHGNWKJG-UHFFFAOYSA-N thiadiazolo[4,5-c]pyridine Chemical compound C1=NC=CC2=C1N=NS2 HKMXLNRHGNWKJG-UHFFFAOYSA-N 0.000 description 2
- DNWLQCBSEZHTMF-UHFFFAOYSA-N thiadiazolo[5,4-c]pyridine Chemical compound C1=NC=CC2=C1SN=N2 DNWLQCBSEZHTMF-UHFFFAOYSA-N 0.000 description 2
- GDQBPBMIAFIRIU-UHFFFAOYSA-N thieno[2,3-c]pyridine Chemical compound C1=NC=C2SC=CC2=C1 GDQBPBMIAFIRIU-UHFFFAOYSA-N 0.000 description 2
- MKYRMMMSZSVIGD-UHFFFAOYSA-N thieno[3,2-c]pyridine Chemical compound N1=CC=C2SC=CC2=C1 MKYRMMMSZSVIGD-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 238000003325 tomography 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
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- FNQJDLTXOVEEFB-UHFFFAOYSA-N 1,2,3-benzothiadiazole Chemical compound C1=CC=C2SN=NC2=C1 FNQJDLTXOVEEFB-UHFFFAOYSA-N 0.000 description 1
- SLLFVLKNXABYGI-UHFFFAOYSA-N 1,2,3-benzoxadiazole Chemical compound C1=CC=C2ON=NC2=C1 SLLFVLKNXABYGI-UHFFFAOYSA-N 0.000 description 1
- UGUHFDPGDQDVGX-UHFFFAOYSA-N 1,2,3-thiadiazole Chemical compound C1=CSN=N1 UGUHFDPGDQDVGX-UHFFFAOYSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical compound C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 description 1
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical compound C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 description 1
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
- MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical compound C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 description 1
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 description 1
- YHIIJNLSGULWAA-UHFFFAOYSA-N 1,4-thiazinane 1-oxide Chemical compound O=S1CCNCC1 YHIIJNLSGULWAA-UHFFFAOYSA-N 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 1
- SSNMISUJOQAFRR-UHFFFAOYSA-N 2,6-naphthyridine Chemical compound N1=CC=C2C=NC=CC2=C1 SSNMISUJOQAFRR-UHFFFAOYSA-N 0.000 description 1
- HCMMECMKVPHMDE-UHFFFAOYSA-N 2,7-naphthyridine Chemical compound C1=NC=C2C=NC=CC2=C1 HCMMECMKVPHMDE-UHFFFAOYSA-N 0.000 description 1
- QQLPPRIZUPEKMV-UHFFFAOYSA-N 2-(2-phenylethenyl)-1h-benzimidazole Chemical class N=1C2=CC=CC=C2NC=1C=CC1=CC=CC=C1 QQLPPRIZUPEKMV-UHFFFAOYSA-N 0.000 description 1
- YUDJKOOHTJPAJH-UHFFFAOYSA-N 2-(chloromethyl)-5-methoxypyridine;hydrochloride Chemical compound Cl.COC1=CC=C(CCl)N=C1 YUDJKOOHTJPAJH-UHFFFAOYSA-N 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- IVHKZCSZELZKSJ-UHFFFAOYSA-N 2-hydroxyethyl sulfonate Chemical compound OCCOS(=O)=O IVHKZCSZELZKSJ-UHFFFAOYSA-N 0.000 description 1
- YVPXQMYCTGCWBE-UHFFFAOYSA-N 2-isocyano-2,4,4-trimethylpentane Chemical compound CC(C)(C)CC(C)(C)[N+]#[C-] YVPXQMYCTGCWBE-UHFFFAOYSA-N 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
- NDQQGQAFMKEMSD-UHFFFAOYSA-N 3-(bromomethyl)pyridin-1-ium;chloride Chemical compound Cl.BrCC1=CC=CN=C1 NDQQGQAFMKEMSD-UHFFFAOYSA-N 0.000 description 1
- FNHPUOJKUXFUKN-UHFFFAOYSA-N 3-(bromomethyl)pyridine;hydron;bromide Chemical compound Br.BrCC1=CC=CN=C1 FNHPUOJKUXFUKN-UHFFFAOYSA-N 0.000 description 1
- BDEIPTKOCRKKBL-UHFFFAOYSA-N 3-(chloromethyl)-5,6-dihydroimidazo[2,1-b][1,3]thiazole;hydrochloride Chemical compound Cl.C1CN2C(CCl)=CSC2=N1 BDEIPTKOCRKKBL-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- ZFHUHPNDGVGXMS-UHFFFAOYSA-N 4-(hydroxymethyl)benzaldehyde Chemical compound OCC1=CC=C(C=O)C=C1 ZFHUHPNDGVGXMS-UHFFFAOYSA-N 0.000 description 1
- WZHAXMVWLBKUOX-BJMVGYQFSA-N 4-[(e)-2-(6-iodo-1h-benzimidazol-2-yl)ethenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1\C=C\C1=NC2=CC=C(I)C=C2N1 WZHAXMVWLBKUOX-BJMVGYQFSA-N 0.000 description 1
- POILWHVDKZOXJZ-UHFFFAOYSA-N 4-hydroxypent-3-en-2-one Chemical compound CC(O)=CC(C)=O POILWHVDKZOXJZ-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- FTHJSTWDHNLSNJ-UHFFFAOYSA-N 5-[2-(dimethylamino)ethoxy]-1-benzofuran-2-carbaldehyde Chemical compound CN(C)CCOC1=CC=C2OC(C=O)=CC2=C1 FTHJSTWDHNLSNJ-UHFFFAOYSA-N 0.000 description 1
- OPAYERWEZXLSFC-UHFFFAOYSA-N 5-methoxy-1-benzofuran-2-carbaldehyde Chemical compound COC1=CC=C2OC(C=O)=CC2=C1 OPAYERWEZXLSFC-UHFFFAOYSA-N 0.000 description 1
- AFWWKZCPPRPDQK-UHFFFAOYSA-N 6-chloropyridine-3-carbaldehyde Chemical compound ClC1=CC=C(C=O)C=N1 AFWWKZCPPRPDQK-UHFFFAOYSA-N 0.000 description 1
- KZHGPDSVHSDCMX-UHFFFAOYSA-N 6-methoxy-1,3-benzothiazol-2-amine Chemical compound COC1=CC=C2N=C(N)SC2=C1 KZHGPDSVHSDCMX-UHFFFAOYSA-N 0.000 description 1
- KNQUHMCADKEUNP-UHFFFAOYSA-N 6-methoxy-2-methyl-1h-benzimidazole Chemical compound COC1=CC=C2N=C(C)NC2=C1 KNQUHMCADKEUNP-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- QHCMRXOHAMXRHR-UHFFFAOYSA-N CC(C)(C)CC(C)(C)NC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OCCF)=CC=C2O1 Chemical compound CC(C)(C)CC(C)(C)NC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OCCF)=CC=C2O1 QHCMRXOHAMXRHR-UHFFFAOYSA-N 0.000 description 1
- OLRHSKANESMYKH-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(C=C1)N(CC1=NC=C(OC)C=C1)C(=O)OC(C)(C)C Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(C=C1)N(CC1=NC=C(OC)C=C1)C(=O)OC(C)(C)C OLRHSKANESMYKH-UHFFFAOYSA-N 0.000 description 1
- PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 description 1
- WMHVHKGMBUFVHS-UHFFFAOYSA-N COC1=CC=C2OC(=CC2=C1)C1=C(CN(C)CC2=CC=CC=C2)N2C=CC(=CC2=N1)C#N Chemical compound COC1=CC=C2OC(=CC2=C1)C1=C(CN(C)CC2=CC=CC=C2)N2C=CC(=CC2=N1)C#N WMHVHKGMBUFVHS-UHFFFAOYSA-N 0.000 description 1
- SFTFBRKKWMTRPA-UHFFFAOYSA-N COC1=CC=C2OC(=CC2=C1)C1=C(N(CCN(C)C)C(=O)OC(C)(C)C)N2C=CC(=CC2=N1)C#N Chemical compound COC1=CC=C2OC(=CC2=C1)C1=C(N(CCN(C)C)C(=O)OC(C)(C)C)N2C=CC(=CC2=N1)C#N SFTFBRKKWMTRPA-UHFFFAOYSA-N 0.000 description 1
- JOKXOKRZVVGAEQ-UHFFFAOYSA-N COC=1C=CC2=C(C=C(O2)C=2N=C3N(C=CC(=C3)CNC(OC(C)(C)C)=O)C=2NC)C=1 Chemical compound COC=1C=CC2=C(C=C(O2)C=2N=C3N(C=CC(=C3)CNC(OC(C)(C)C)=O)C=2NC)C=1 JOKXOKRZVVGAEQ-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 206010008096 Cerebral atrophy Diseases 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
- OVGVJLJMXGTCCW-UHFFFAOYSA-N Cl.COc1ccc2oc(cc2c1)-c1nc2cc(ccn2c1N)C#N Chemical compound Cl.COc1ccc2oc(cc2c1)-c1nc2cc(ccn2c1N)C#N OVGVJLJMXGTCCW-UHFFFAOYSA-N 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 1
- XYFHTMMHXWAZCL-UHFFFAOYSA-N FCCOC=1C=CC2=C(C=C(O2)C=O)C=1 Chemical compound FCCOC=1C=CC2=C(C=C(O2)C=O)C=1 XYFHTMMHXWAZCL-UHFFFAOYSA-N 0.000 description 1
- DBDCWWBXKCTEDY-UHFFFAOYSA-N FCCOC=1C=CC2=C(C=CO2)C=1 Chemical compound FCCOC=1C=CC2=C(C=CO2)C=1 DBDCWWBXKCTEDY-UHFFFAOYSA-N 0.000 description 1
- 101001030705 Homo sapiens Huntingtin Proteins 0.000 description 1
- 101150043003 Htt gene Proteins 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- LWCOCAXLZIRFQE-UHFFFAOYSA-N O1C=CC2=C1C=CC(=C2)OCCN(C)C Chemical compound O1C=CC2=C1C=CC(=C2)OCCN(C)C LWCOCAXLZIRFQE-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- QPFYXYFORQJZEC-FOCLMDBBSA-N Phenazopyridine Chemical compound NC1=NC(N)=CC=C1\N=N\C1=CC=CC=C1 QPFYXYFORQJZEC-FOCLMDBBSA-N 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000003113 alkalizing effect Effects 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 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
- 229910021529 ammonia Inorganic materials 0.000 description 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- VIQRCOQXIHFJND-UHFFFAOYSA-N bicyclo[2.2.2]oct-2-ene Chemical compound C1CC2CCC1C=C2 VIQRCOQXIHFJND-UHFFFAOYSA-N 0.000 description 1
- GPRLTFBKWDERLU-UHFFFAOYSA-N bicyclo[2.2.2]octane Chemical compound C1CC2CCC1CC2 GPRLTFBKWDERLU-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000005514 but-1-yn-3-yl group Chemical group 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000001159 caudate nucleus Anatomy 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 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 1
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 210000001787 dendrite Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 description 1
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
- 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 description 1
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000005670 electromagnetic radiation Effects 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- VICYTAYPKBLQFB-UHFFFAOYSA-N ethyl 3-bromo-2-oxopropanoate Chemical compound CCOC(=O)C(=O)CBr VICYTAYPKBLQFB-UHFFFAOYSA-N 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000012757 fluorescence staining Methods 0.000 description 1
- YCKRFDGAMUMZLT-BJUDXGSMSA-N fluorine-18 atom Chemical compound [18F] YCKRFDGAMUMZLT-BJUDXGSMSA-N 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 125000004404 heteroalkyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- DOUHZFSGSXMPIE-UHFFFAOYSA-N hydroxidooxidosulfur(.) Chemical compound [O]SO DOUHZFSGSXMPIE-UHFFFAOYSA-N 0.000 description 1
- RTOFMMILZZGGNS-UHFFFAOYSA-N imidazo[1,2-a]pyridin-3-amine Chemical compound C1=CC=CN2C(N)=CN=C21 RTOFMMILZZGGNS-UHFFFAOYSA-N 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 150000005232 imidazopyridines Chemical class 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 125000003114 inden-1-yl group Chemical group [H]C1=C([H])C([H])(*)C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 208000030309 inherited neurodegenerative disease Diseases 0.000 description 1
- 230000003585 interneuronal effect Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 210000001739 intranuclear inclusion body Anatomy 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical class [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 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
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- CVVMLRFXZPKILB-UHFFFAOYSA-N methyl 5-chloropyrazine-2-carboxylate Chemical compound COC(=O)C1=CN=C(Cl)C=N1 CVVMLRFXZPKILB-UHFFFAOYSA-N 0.000 description 1
- OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical compound COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 108091005763 multidomain proteins Proteins 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 230000008587 neuronal excitability Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920000155 polyglutamine Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- DTDAQEOBFOFGGH-UHFFFAOYSA-M potassium;4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane;fluoride Chemical compound [F-].[K+].C1COCCOCCN2CCOCCOCCN1CCOCCOCC2 DTDAQEOBFOFGGH-UHFFFAOYSA-M 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 210000002637 putamen Anatomy 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 229940070891 pyridium Drugs 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 1
- 230000005258 radioactive decay Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000012857 radioactive material Substances 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 125000006413 ring segment Chemical group 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
- 239000012266 salt solution Substances 0.000 description 1
- HZXJVDYQRYYYOR-UHFFFAOYSA-K scandium(iii) trifluoromethanesulfonate Chemical compound [Sc+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F HZXJVDYQRYYYOR-UHFFFAOYSA-K 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 150000001629 stilbenes Chemical class 0.000 description 1
- 235000021286 stilbenes Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- SVQVBAUJEKSBEC-UHFFFAOYSA-N tert-butyl n-(4-formylphenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(C=O)C=C1 SVQVBAUJEKSBEC-UHFFFAOYSA-N 0.000 description 1
- JTKROKSMVFTCKQ-UHFFFAOYSA-N tert-butyl n-[(2-aminopyridin-4-yl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=NC(N)=C1 JTKROKSMVFTCKQ-UHFFFAOYSA-N 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- KLBOFRLEHJAXIU-UHFFFAOYSA-N tributylazanium;chloride Chemical compound Cl.CCCCN(CCCC)CCCC KLBOFRLEHJAXIU-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0455—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0453—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0459—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0497—Organic compounds conjugates with a carrier being an organic compounds
-
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Optics & Photonics (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Physics & Mathematics (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462043590P | 2014-08-29 | 2014-08-29 | |
| PCT/US2015/047401 WO2016033440A1 (en) | 2014-08-29 | 2015-08-28 | Probes for imaging huntingtin protein |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201790400A1 EA201790400A1 (ru) | 2017-09-29 |
| EA039923B1 true EA039923B1 (ru) | 2022-03-28 |
Family
ID=55400645
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201790400A EA039923B1 (ru) | 2014-08-29 | 2015-08-28 | Зонды для визуализации белка хантингтина |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US11104691B2 (enExample) |
| EP (1) | EP3197277B1 (enExample) |
| JP (1) | JP6754353B2 (enExample) |
| KR (1) | KR102410733B1 (enExample) |
| CN (1) | CN107105667B (enExample) |
| AU (2) | AU2015308769A1 (enExample) |
| BR (1) | BR112017004140B1 (enExample) |
| CA (1) | CA2959533C (enExample) |
| DK (1) | DK3197277T3 (enExample) |
| EA (1) | EA039923B1 (enExample) |
| ES (1) | ES2905095T3 (enExample) |
| HR (1) | HRP20220001T1 (enExample) |
| HU (1) | HUE057702T2 (enExample) |
| IL (1) | IL250802B (enExample) |
| MX (1) | MX386798B (enExample) |
| PL (1) | PL3197277T3 (enExample) |
| PT (1) | PT3197277T (enExample) |
| SG (1) | SG11201701592SA (enExample) |
| SI (1) | SI3197277T1 (enExample) |
| WO (1) | WO2016033440A1 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11104691B2 (en) | 2014-08-29 | 2021-08-31 | Chdi Foundation, Inc. | Probes for imaging huntingtin protein |
| EP3186233B8 (en) | 2014-08-29 | 2021-09-29 | CHDI Foundation, Inc. | Probes for imaging huntingtin protein |
| EA037275B1 (ru) | 2014-08-29 | 2021-03-03 | Сиэйчдиай Фаундэйшн, Инк. | Зонды для визуализации белка хантингтина |
| SG11201701580XA (en) | 2014-08-29 | 2017-03-30 | Chdi Foundation Inc | Probes for imaging huntingtin protein |
| DK3340796T3 (da) | 2015-08-28 | 2021-07-26 | Chdi Foundation Inc | Sonder til afbildning af huntingtin-protein |
| US20190381030A1 (en) * | 2017-10-12 | 2019-12-19 | University Of Kansas | Methods of treating radiation induced gastrointestinal syndrome (rigs) and related disease states using yel002/bcn057 |
| WO2020176424A1 (en) | 2019-02-25 | 2020-09-03 | Chdi Foundation, Inc. | Compounds for targeting mutant huntingtin protein and uses thereof |
| AU2020267664B2 (en) | 2019-05-09 | 2023-04-27 | F. Hoffmann-La Roche Ag | Synthesis of labeled imidazo[1,2-A]pyrimidines |
| CN114773312B (zh) * | 2021-10-29 | 2024-03-26 | 北京鑫诺康桥药物研究有限公司 | 一种盐酸阿罗洛尔中间体的制备工艺 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110065727A1 (en) * | 2008-03-21 | 2011-03-17 | Sanofi-Aventis | POLYSUBSTITUTED DERIVATIVES OF 2-HETEROARYL-6-PHENYLIMIDAZO[1,2-a]PYRIDINES, AND PREPARATION AND THERAPEUTIC USE THEREOF |
| US20110171739A1 (en) * | 2008-09-23 | 2011-07-14 | Wista Laboratories Ltd. | Ligands for aggregated tau molecules |
| WO2015044095A1 (en) * | 2013-09-26 | 2015-04-02 | F. Hoffmann-La Roche Ag | Imidazo[1,2-a]pyridin-7-amines as imaging tools |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10050663A1 (de) * | 2000-10-13 | 2002-04-18 | Gruenenthal Gmbh | Verwendung von substituierten Imidazo[1,2-a]pyridin-, -pyrimidin- und pyrazin-3-yl-amin-Derivaten zur Herstellung von Medikamenten zur NOS-Inhibierung |
| AU2004265174A1 (en) * | 2003-08-13 | 2005-02-24 | Bf Research Institute, Inc. | Probe for diseases in which amyloid accumulates, agents for staining amyloid, drugs for treatment and prophylaxis of diseases with accumulated amyloid, and probes for diagnosis of neurofibrillary tangles and agents for staining neurofibrillary tangles. |
| EP2042501B1 (en) * | 2006-06-21 | 2017-04-12 | Nihon Medi-Physics Co., Ltd. | Compound having affinity for amyloid |
| WO2008016648A2 (en) * | 2006-08-01 | 2008-02-07 | Cytokinetics, Incorporated | Certain chemical entities, compositions and methods |
| KR20090091287A (ko) * | 2006-11-17 | 2009-08-27 | 니혼 메디피직스 가부시키가이샤 | 신규 아밀로이드 친화성 화합물 |
| NZ577511A (en) * | 2006-11-30 | 2012-04-27 | Nihon Mediphysics Co Ltd | 2-Phenyl-imidazo[1,2-a]pyridine derivatives substituted with a radioactive halogen substituent |
| CA2676214A1 (en) * | 2007-01-22 | 2008-07-31 | Astrazeneca Ab | Novel heteroaryl substituted imidazo [1,2 -a] pyridine derivatives |
| WO2009057577A1 (ja) * | 2007-10-30 | 2009-05-07 | Nihon Medi-Physics Co., Ltd. | 新規アミロイド親和性化合物の使用及び製造方法 |
| WO2010011964A2 (en) * | 2008-07-24 | 2010-01-28 | Siemens Medical Solutions Usa, Inc. | Imaging agents useful for identifying ad pathology |
| WO2010141805A1 (en) * | 2009-06-05 | 2010-12-09 | Janssen Pharmaceutica Nv | Heterocyclic amides as modulators of trpa1 |
| AU2012259929B2 (en) * | 2011-05-20 | 2016-08-04 | Nihon Medi-Physics Co., Ltd. | Novel compound having affinity for amyloid |
| JP5167436B2 (ja) * | 2011-06-24 | 2013-03-21 | 日本メジフィジックス株式会社 | 新規アミロイド親和性化合物 |
| JP2013237655A (ja) * | 2012-05-17 | 2013-11-28 | Kyoto Univ | コンフォメーション病診断用分子プローブ |
| BR112015010469A2 (pt) * | 2012-11-14 | 2017-07-11 | Hoffmann La Roche | derivados de imidazopiridina |
| SI2970255T1 (sl) | 2013-03-14 | 2017-12-29 | Galapagos Nv | Spojine in farmacevtski sestavki le-teh za zdravljenje vnetnih motenj |
| EA037275B1 (ru) | 2014-08-29 | 2021-03-03 | Сиэйчдиай Фаундэйшн, Инк. | Зонды для визуализации белка хантингтина |
| SG11201701580XA (en) | 2014-08-29 | 2017-03-30 | Chdi Foundation Inc | Probes for imaging huntingtin protein |
| EP3186233B8 (en) | 2014-08-29 | 2021-09-29 | CHDI Foundation, Inc. | Probes for imaging huntingtin protein |
| US11104691B2 (en) | 2014-08-29 | 2021-08-31 | Chdi Foundation, Inc. | Probes for imaging huntingtin protein |
| DK3340796T3 (da) | 2015-08-28 | 2021-07-26 | Chdi Foundation Inc | Sonder til afbildning af huntingtin-protein |
-
2015
- 2015-08-28 US US15/507,203 patent/US11104691B2/en active Active
- 2015-08-28 CA CA2959533A patent/CA2959533C/en active Active
- 2015-08-28 ES ES15836261T patent/ES2905095T3/es active Active
- 2015-08-28 EP EP15836261.6A patent/EP3197277B1/en active Active
- 2015-08-28 SI SI201531778T patent/SI3197277T1/sl unknown
- 2015-08-28 CN CN201580058314.XA patent/CN107105667B/zh active Active
- 2015-08-28 AU AU2015308769A patent/AU2015308769A1/en not_active Abandoned
- 2015-08-28 SG SG11201701592SA patent/SG11201701592SA/en unknown
- 2015-08-28 EA EA201790400A patent/EA039923B1/ru unknown
- 2015-08-28 DK DK15836261.6T patent/DK3197277T3/da active
- 2015-08-28 BR BR112017004140-5A patent/BR112017004140B1/pt active IP Right Grant
- 2015-08-28 WO PCT/US2015/047401 patent/WO2016033440A1/en not_active Ceased
- 2015-08-28 MX MX2017002702A patent/MX386798B/es unknown
- 2015-08-28 PT PT158362616T patent/PT3197277T/pt unknown
- 2015-08-28 HU HUE15836261A patent/HUE057702T2/hu unknown
- 2015-08-28 JP JP2017511926A patent/JP6754353B2/ja active Active
- 2015-08-28 PL PL15836261T patent/PL3197277T3/pl unknown
- 2015-08-28 HR HRP20220001TT patent/HRP20220001T1/hr unknown
- 2015-08-28 KR KR1020177007881A patent/KR102410733B1/ko active Active
-
2017
- 2017-02-26 IL IL250802A patent/IL250802B/en active IP Right Grant
-
2019
- 2019-12-20 AU AU2019283999A patent/AU2019283999B2/en active Active
-
2021
- 2021-06-21 US US17/353,627 patent/US11851446B2/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110065727A1 (en) * | 2008-03-21 | 2011-03-17 | Sanofi-Aventis | POLYSUBSTITUTED DERIVATIVES OF 2-HETEROARYL-6-PHENYLIMIDAZO[1,2-a]PYRIDINES, AND PREPARATION AND THERAPEUTIC USE THEREOF |
| US20110171739A1 (en) * | 2008-09-23 | 2011-07-14 | Wista Laboratories Ltd. | Ligands for aggregated tau molecules |
| WO2015044095A1 (en) * | 2013-09-26 | 2015-04-02 | F. Hoffmann-La Roche Ag | Imidazo[1,2-a]pyridin-7-amines as imaging tools |
Non-Patent Citations (2)
| Title |
|---|
| YOUSEFI B.H. et al. "Development of an Improved Radioiodinated 2-Phenylimidazo[1,2-a]Pyridine for Non-Invasive Imaging of Amyloid Plaques", Med. Chem. Commun. 2012, vol. 3, pp 775-779, entire document, especially: abstract; pg 775, col 1, para 1; pg 776-777, table 2. * |
| ZHUANG Z.-P. et al. "Structure-Activity Relationship of Imidazo[1,2-a]pyridines as Ligands for Detecting beta-Amyloid Plaques in the Brain", J. Med. Chem. 2003, vol. 46, pp 237-243, entire document, especially: abstract; pg 237, col 1, para 2; pg 238, col 1, para 2; pg 238, scheme 1, compounds 12c, 13, 14c, 15-17 and 19. * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11851446B2 (en) | Probes for imaging Huntingtin protein | |
| US12036291B2 (en) | Probes for imaging huntingtin protein | |
| US11344637B2 (en) | Probes for imaging huntingtin protein | |
| WO2016033460A1 (en) | Probes for imaging huntingtin protein | |
| HK1241224B (en) | Probes for imaging huntingtin protein | |
| HK1240582A1 (en) | Probes for imaging huntington protein | |
| HK1240582B (en) | Probes for imaging huntington protein |