EA036518B1 - Производные 9h-пирролодипиридина - Google Patents
Производные 9h-пирролодипиридина Download PDFInfo
- Publication number
- EA036518B1 EA036518B1 EA201791733A EA201791733A EA036518B1 EA 036518 B1 EA036518 B1 EA 036518B1 EA 201791733 A EA201791733 A EA 201791733A EA 201791733 A EA201791733 A EA 201791733A EA 036518 B1 EA036518 B1 EA 036518B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- pyrrolo
- dipyridine
- methyl
- dipyridin
- mmol
- Prior art date
Links
- 239000012216 imaging agent Substances 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- -1 benzyl methyl group Chemical group 0.000 claims description 314
- 150000001875 compounds Chemical class 0.000 claims description 163
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims description 66
- 239000000203 mixture Substances 0.000 claims description 60
- 108010026424 tau Proteins Proteins 0.000 claims description 54
- 102000013498 tau Proteins Human genes 0.000 claims description 54
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 30
- 210000004556 brain Anatomy 0.000 claims description 28
- 230000002285 radioactive effect Effects 0.000 claims description 26
- 239000011737 fluorine Substances 0.000 claims description 23
- 229910052731 fluorine Inorganic materials 0.000 claims description 23
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 claims description 23
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 22
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 22
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 20
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 18
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 16
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 claims description 16
- 125000001153 fluoro group Chemical group F* 0.000 claims description 16
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 16
- 229910052722 tritium Inorganic materials 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 13
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 11
- IIHQNAXFIODVDU-UHFFFAOYSA-N pyrimidine-2-carbonitrile Chemical compound N#CC1=NC=CC=N1 IIHQNAXFIODVDU-UHFFFAOYSA-N 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 230000003287 optical effect Effects 0.000 claims description 10
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 9
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 claims description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 230000004770 neurodegeneration Effects 0.000 claims description 5
- NAEQZBNOUXKFFI-UHFFFAOYSA-N 11-(1H-pyrazol-4-yl)-4,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaene Chemical compound c1n[nH]cc1-c1ccc2c(n1)[nH]c1ccncc21 NAEQZBNOUXKFFI-UHFFFAOYSA-N 0.000 claims description 4
- CYLWDEZKPRWZMU-UHFFFAOYSA-N 11-(1H-pyrazol-5-yl)-4,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaene Chemical compound N1N=CC=C1C1=NC2=C(C=C1)C1=CN=CC=C1N2 CYLWDEZKPRWZMU-UHFFFAOYSA-N 0.000 claims description 4
- VSDNGHSDNIOQKJ-UHFFFAOYSA-N 11-pyridin-3-yl-4,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaene Chemical compound c1cncc(c1)-c1ccc2c(n1)[nH]c1ccncc21 VSDNGHSDNIOQKJ-UHFFFAOYSA-N 0.000 claims description 4
- LEYKWMQWDLHJTO-UHFFFAOYSA-N 11-pyridin-4-yl-4,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaene Chemical compound c1cc(ccn1)-c1ccc2c(n1)[nH]c1ccncc21 LEYKWMQWDLHJTO-UHFFFAOYSA-N 0.000 claims description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical group C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 4
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- HNEGJTWNOOWEMH-UHFFFAOYSA-N 1-fluoropropane Chemical group [CH2]CCF HNEGJTWNOOWEMH-UHFFFAOYSA-N 0.000 claims description 3
- FUMZJKNGBMBNRB-UHFFFAOYSA-N 11-(1H-pyrazol-4-yl)-5,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaene Chemical compound N1C=C(C=N1)C1=NC2=C(C=C1)C1=CC=NC=C1N2 FUMZJKNGBMBNRB-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- IBBMAWULFFBRKK-IBTRZKOZSA-N 6-tritiopyridine-2-carboxamide Chemical compound N1=C(C=CC=C1[3H])C(=O)N IBBMAWULFFBRKK-IBTRZKOZSA-N 0.000 claims description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 239000000032 diagnostic agent Substances 0.000 claims description 2
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 229910052727 yttrium Inorganic materials 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims 2
- 238000000034 method Methods 0.000 abstract description 136
- 238000001514 detection method Methods 0.000 abstract description 3
- 239000012217 radiopharmaceutical Substances 0.000 abstract description 2
- 229940121896 radiopharmaceutical Drugs 0.000 abstract description 2
- 230000002799 radiopharmaceutical effect Effects 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 description 146
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 129
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
- 239000011541 reaction mixture Substances 0.000 description 106
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 105
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 100
- 239000000243 solution Substances 0.000 description 81
- 238000005160 1H NMR spectroscopy Methods 0.000 description 76
- 230000002829 reductive effect Effects 0.000 description 69
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 62
- 238000004809 thin layer chromatography Methods 0.000 description 58
- 238000005481 NMR spectroscopy Methods 0.000 description 51
- 238000003756 stirring Methods 0.000 description 50
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 48
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- 239000002904 solvent Substances 0.000 description 42
- 125000006239 protecting group Chemical group 0.000 description 39
- 239000012043 crude product Substances 0.000 description 38
- 238000004440 column chromatography Methods 0.000 description 35
- 235000019439 ethyl acetate Nutrition 0.000 description 35
- 239000003480 eluent Substances 0.000 description 33
- 239000000741 silica gel Substances 0.000 description 33
- 229910002027 silica gel Inorganic materials 0.000 description 33
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 31
- 229910052786 argon Inorganic materials 0.000 description 31
- 239000012044 organic layer Substances 0.000 description 31
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- QCTHDAPPTWLTGR-UHFFFAOYSA-N 11-chloro-4,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaene Chemical compound Clc1ccc2c(n1)[nH]c1ccncc21 QCTHDAPPTWLTGR-UHFFFAOYSA-N 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- 235000005152 nicotinamide Nutrition 0.000 description 22
- 239000011570 nicotinamide Substances 0.000 description 22
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
- 230000027455 binding Effects 0.000 description 19
- 229960003966 nicotinamide Drugs 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 16
- 239000000543 intermediate Substances 0.000 description 15
- 229910052938 sodium sulfate Inorganic materials 0.000 description 15
- 235000011152 sodium sulphate Nutrition 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 238000006069 Suzuki reaction reaction Methods 0.000 description 14
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 208000024827 Alzheimer disease Diseases 0.000 description 12
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 11
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 10
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 9
- 235000018102 proteins Nutrition 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 238000007363 ring formation reaction Methods 0.000 description 9
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 8
- UCNGGGYMLHAMJG-UHFFFAOYSA-N 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound C1=NN(C)C=C1B1OC(C)(C)C(C)(C)O1 UCNGGGYMLHAMJG-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 101150003085 Pdcl gene Proteins 0.000 description 8
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 8
- 239000002953 phosphate buffered saline Substances 0.000 description 8
- XBBLBQZAVMHEER-UHFFFAOYSA-N (2,6-dichloropyridin-3-yl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)N=C1Cl XBBLBQZAVMHEER-UHFFFAOYSA-N 0.000 description 7
- OJBYZWHAPXIJID-UHFFFAOYSA-N (6-fluoropyridin-3-yl)boronic acid Chemical compound OB(O)C1=CC=C(F)N=C1 OJBYZWHAPXIJID-UHFFFAOYSA-N 0.000 description 7
- DNALPMZQPFKJRV-UHFFFAOYSA-N 26422-85-5 Chemical compound C1=NC=C2C3=CC=CN=C3NC2=C1 DNALPMZQPFKJRV-UHFFFAOYSA-N 0.000 description 7
- 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 7
- TVOJIBGZFYMWDT-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CNN=C1 TVOJIBGZFYMWDT-UHFFFAOYSA-N 0.000 description 7
- NCFMDIJKEYGCRD-UHFFFAOYSA-N 4-methoxy-1h-pyrazole Chemical compound COC=1C=NNC=1 NCFMDIJKEYGCRD-UHFFFAOYSA-N 0.000 description 7
- 102000010909 Monoamine Oxidase Human genes 0.000 description 7
- 108010062431 Monoamine oxidase Proteins 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 125000000217 alkyl group Chemical group 0.000 description 7
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 235000019253 formic acid Nutrition 0.000 description 7
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 7
- FNRMMDCDHWCQTH-UHFFFAOYSA-N 2-chloropyridine;3-chloropyridine;4-chloropyridine Chemical compound ClC1=CC=NC=C1.ClC1=CC=CN=C1.ClC1=CC=CC=N1 FNRMMDCDHWCQTH-UHFFFAOYSA-N 0.000 description 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 6
- 208000027089 Parkinsonian disease Diseases 0.000 description 6
- 206010034010 Parkinsonism Diseases 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 239000003643 water by type Substances 0.000 description 6
- HFSUHEWRFBAVHH-UHFFFAOYSA-N (4-nitropyridin-2-yl)methanol Chemical compound OCC1=CC([N+]([O-])=O)=CC=N1 HFSUHEWRFBAVHH-UHFFFAOYSA-N 0.000 description 5
- DPULQKXQKDFFPR-UHFFFAOYSA-N 1-(2-fluoroethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN(CCF)N=C1 DPULQKXQKDFFPR-UHFFFAOYSA-N 0.000 description 5
- ZVPORPUUZXIPEF-UHFFFAOYSA-N 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN(CC=2C=CC=CC=2)N=C1 ZVPORPUUZXIPEF-UHFFFAOYSA-N 0.000 description 5
- MBEXEUYLJHYMIR-UHFFFAOYSA-N 1-benzyl-4-methoxypyrazole Chemical compound C1=C(OC)C=NN1CC1=CC=CC=C1 MBEXEUYLJHYMIR-UHFFFAOYSA-N 0.000 description 5
- BELUNASLYMZLPW-UHFFFAOYSA-N 1-benzylpyrazol-4-ol Chemical compound C1=C(O)C=NN1CC1=CC=CC=C1 BELUNASLYMZLPW-UHFFFAOYSA-N 0.000 description 5
- MFQWQHHOOGQGLP-UHFFFAOYSA-N 2-(methoxymethyl)-4-nitropyridine Chemical compound COCC1=CC([N+]([O-])=O)=CC=N1 MFQWQHHOOGQGLP-UHFFFAOYSA-N 0.000 description 5
- KRNRQQWIGJZZAE-UHFFFAOYSA-N 2-(methoxymethyl)pyridin-4-amine Chemical compound COCC1=CC(N)=CC=N1 KRNRQQWIGJZZAE-UHFFFAOYSA-N 0.000 description 5
- YSTCMHHKDOVZDA-UHFFFAOYSA-N 2-chloro-4-nitro-1-oxidopyridin-1-ium Chemical compound [O-][N+](=O)C1=CC=[N+]([O-])C(Cl)=C1 YSTCMHHKDOVZDA-UHFFFAOYSA-N 0.000 description 5
- WQNGWPYCMHIYCR-UHFFFAOYSA-N 2-chloro-5-(2-chloropyridin-3-yl)pyridin-4-amine Chemical compound ClC1=NC=CC=C1C=1C=NC(=CC=1N)Cl WQNGWPYCMHIYCR-UHFFFAOYSA-N 0.000 description 5
- CNEWDGGPSMFWQX-UHFFFAOYSA-N 3-(1-benzyl-3,6-dihydro-2h-pyridin-4-yl)propan-1-ol Chemical compound C1CC(CCCO)=CCN1CC1=CC=CC=C1 CNEWDGGPSMFWQX-UHFFFAOYSA-N 0.000 description 5
- WHXKZLLYDRKZGI-UHFFFAOYSA-N 3-(2,6-dichloropyridin-3-yl)pyridin-2-amine Chemical compound ClC1=NC(=CC=C1C=1C(=NC=CC=1)N)Cl WHXKZLLYDRKZGI-UHFFFAOYSA-N 0.000 description 5
- HOSATWARXXDVIY-UHFFFAOYSA-N 3-(2,6-dichloropyridin-3-yl)pyridin-4-amine Chemical compound ClC1=NC(=CC=C1C=1C=NC=CC=1N)Cl HOSATWARXXDVIY-UHFFFAOYSA-N 0.000 description 5
- FJBMTFANAYFWPT-UHFFFAOYSA-N 3-bromo-2-methoxypyridin-4-amine Chemical compound COC1=NC=CC(N)=C1Br FJBMTFANAYFWPT-UHFFFAOYSA-N 0.000 description 5
- WBPLXYFTDQGSST-UHFFFAOYSA-N 3-bromo-5-(2,6-dichloropyridin-3-yl)-2-methoxypyridin-4-amine Chemical compound BrC=1C(=C(C=NC=1OC)C=1C(=NC(=CC=1)Cl)Cl)N WBPLXYFTDQGSST-UHFFFAOYSA-N 0.000 description 5
- UXWBCEIGPUSDDR-UHFFFAOYSA-N 3-bromo-5-iodo-2-methoxypyridin-4-amine Chemical compound COC1=NC=C(I)C(N)=C1Br UXWBCEIGPUSDDR-UHFFFAOYSA-N 0.000 description 5
- DBIMLJDSPUCGGY-UHFFFAOYSA-N 3-piperidin-4-ylpropan-1-ol Chemical compound OCCCC1CCNCC1 DBIMLJDSPUCGGY-UHFFFAOYSA-N 0.000 description 5
- BFSFBWOOHMBGEK-UHFFFAOYSA-N 4-(2,6-dichloropyridin-3-yl)pyridin-3-amine Chemical compound ClC1=NC(=CC=C1C1=C(C=NC=C1)N)Cl BFSFBWOOHMBGEK-UHFFFAOYSA-N 0.000 description 5
- WESFIRZDPGAYPX-UHFFFAOYSA-N 5-(2,6-dichloropyridin-3-yl)-2-(methoxymethyl)pyridin-4-amine Chemical compound ClC1=NC(=CC=C1C=1C=NC(=CC=1N)COC)Cl WESFIRZDPGAYPX-UHFFFAOYSA-N 0.000 description 5
- PBVYOFGZPFAPJY-UHFFFAOYSA-N 5-(2,6-dichloropyridin-3-yl)-2-methylpyridin-4-amine Chemical compound ClC1=NC(=CC=C1C=1C=NC(=CC=1N)C)Cl PBVYOFGZPFAPJY-UHFFFAOYSA-N 0.000 description 5
- FAMYLDMNMOLOPP-UHFFFAOYSA-N 5-iodo-2-(methoxymethyl)pyridin-4-amine Chemical compound IC=1C(=CC(=NC=1)COC)N FAMYLDMNMOLOPP-UHFFFAOYSA-N 0.000 description 5
- UJDOLPPZRSZZAS-UHFFFAOYSA-N 5-iodo-2-methylpyridin-4-amine Chemical compound CC1=CC(N)=C(I)C=N1 UJDOLPPZRSZZAS-UHFFFAOYSA-N 0.000 description 5
- 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 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 210000005013 brain tissue Anatomy 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- DLKZHMCWSUNXBC-UHFFFAOYSA-N n,n-dimethyl-4-nitro-1-oxidopyridin-1-ium-2-amine Chemical compound CN(C)C1=CC([N+]([O-])=O)=CC=[N+]1[O-] DLKZHMCWSUNXBC-UHFFFAOYSA-N 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 5
- DKORSYDQYFVQNS-UHFFFAOYSA-N propyl methanesulfonate Chemical compound CCCOS(C)(=O)=O DKORSYDQYFVQNS-UHFFFAOYSA-N 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- IRRRVCLDPODLJG-UHFFFAOYSA-N tert-butyl n-(4-bromopyridin-2-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Br)=CC=N1 IRRRVCLDPODLJG-UHFFFAOYSA-N 0.000 description 5
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- WBCBEAMZUUVBPP-UHFFFAOYSA-N 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN=C(F)C(N)=C1 WBCBEAMZUUVBPP-UHFFFAOYSA-N 0.000 description 4
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 4
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- 206010012289 Dementia Diseases 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- 201000011240 Frontotemporal dementia Diseases 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 238000013480 data collection Methods 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 238000003384 imaging method Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- LUMBLRWRRONQMO-UHFFFAOYSA-N n-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC=C1B1OC(C)(C)C(C)(C)O1 LUMBLRWRRONQMO-UHFFFAOYSA-N 0.000 description 4
- QDOXNCAIXITTKA-UHFFFAOYSA-N n-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine Chemical compound C1=NC(NC)=NC=C1B1OC(C)(C)C(C)(C)O1 QDOXNCAIXITTKA-UHFFFAOYSA-N 0.000 description 4
- 230000009871 nonspecific binding Effects 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 238000002600 positron emission tomography Methods 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- SAAGMIHGVLKZBC-UHFFFAOYSA-N tert-butyl n-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]carbamate Chemical compound C1=NC(NC(=O)OC(C)(C)C)=CC(B2OC(C)(C)C(C)(C)O2)=C1 SAAGMIHGVLKZBC-UHFFFAOYSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- NWFIPEZCROFSMT-UHFFFAOYSA-N (5-fluoropyridin-2-yl)-trimethylstannane Chemical compound C[Sn](C)(C)C1=CC=C(F)C=N1 NWFIPEZCROFSMT-UHFFFAOYSA-N 0.000 description 3
- 239000004912 1,5-cyclooctadiene Substances 0.000 description 3
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 3
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 3
- TXHBIDHOGGWIFC-UHFFFAOYSA-N 5-bromo-n-(2-methoxyethyl)pyridine-2-carboxamide Chemical compound COCCNC(=O)C1=CC=C(Br)C=N1 TXHBIDHOGGWIFC-UHFFFAOYSA-N 0.000 description 3
- MNNQIBXLAHVDDL-UHFFFAOYSA-N 5-bromopyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Br)C=N1 MNNQIBXLAHVDDL-UHFFFAOYSA-N 0.000 description 3
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 208000037259 Amyloid Plaque Diseases 0.000 description 3
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- 101000694714 Rattus norvegicus Amine oxidase [flavin-containing] A Proteins 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 102000003802 alpha-Synuclein Human genes 0.000 description 3
- 108090000185 alpha-Synuclein Proteins 0.000 description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 3
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 229910052805 deuterium Inorganic materials 0.000 description 3
- 238000011979 disease modifying therapy Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 238000002953 preparative HPLC Methods 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- PBIMIGNDTBRRPI-UHFFFAOYSA-N trifluoro borate Chemical compound FOB(OF)OF PBIMIGNDTBRRPI-UHFFFAOYSA-N 0.000 description 3
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 3
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 3
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 3
- 235000019798 tripotassium phosphate Nutrition 0.000 description 3
- 238000012800 visualization Methods 0.000 description 3
- VRDAOVQZVXYRNH-UHFFFAOYSA-N (2-chloropyridin-3-yl)boronic acid Chemical compound OB(O)C1=CC=CN=C1Cl VRDAOVQZVXYRNH-UHFFFAOYSA-N 0.000 description 2
- DHQMUJSACXTPEA-UHFFFAOYSA-N (2-methoxypyridin-4-yl)boronic acid Chemical compound COC1=CC(B(O)O)=CC=N1 DHQMUJSACXTPEA-UHFFFAOYSA-N 0.000 description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
- ZZRFDLHBMBHJTI-UHFFFAOYSA-N 1-(oxan-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=NN1C1OCCCC1 ZZRFDLHBMBHJTI-UHFFFAOYSA-N 0.000 description 2
- FZUMSWFGAAUPEI-UHFFFAOYSA-N 11-(furan-3-yl)-4,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaene Chemical compound c1cc(co1)-c1ccc2c(n1)[nH]c1ccncc21 FZUMSWFGAAUPEI-UHFFFAOYSA-N 0.000 description 2
- CQOKRSJTVWBAKI-UHFFFAOYSA-N 2-iodopyridin-3-amine Chemical compound NC1=CC=CN=C1I CQOKRSJTVWBAKI-UHFFFAOYSA-N 0.000 description 2
- UUDNBWSHTUFGDQ-UHFFFAOYSA-N 3-iodopyridin-2-amine Chemical compound NC1=NC=CC=C1I UUDNBWSHTUFGDQ-UHFFFAOYSA-N 0.000 description 2
- YJFDJTNGFPHWAM-UHFFFAOYSA-N 3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-pyrazole Chemical compound N1N=C(C)C=C1B1OC(C)(C)C(C)(C)O1 YJFDJTNGFPHWAM-UHFFFAOYSA-N 0.000 description 2
- OFDVABAUFQJWEZ-UHFFFAOYSA-N 3-pyridin-3-ylpyridine Chemical compound C1=CN=CC(C=2C=NC=CC=2)=C1 OFDVABAUFQJWEZ-UHFFFAOYSA-N 0.000 description 2
- LZPWAYBEOJRFAX-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2$l^{2}-dioxaborolane Chemical compound CC1(C)O[B]OC1(C)C LZPWAYBEOJRFAX-UHFFFAOYSA-N 0.000 description 2
- ICKDPGSQUZOIIU-UHFFFAOYSA-N 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-thiazol-2-yl]morpholine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN=C(N2CCOCC2)S1 ICKDPGSQUZOIIU-UHFFFAOYSA-N 0.000 description 2
- ZGDLVKWIZHHWIR-UHFFFAOYSA-N 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]morpholine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N2CCOCC2)N=C1 ZGDLVKWIZHHWIR-UHFFFAOYSA-N 0.000 description 2
- HZIDRGNLSOMQRH-UHFFFAOYSA-N 5,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaene Chemical compound N1=CC=C2C3=CC=CN=C3NC2=C1 HZIDRGNLSOMQRH-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 208000004051 Chronic Traumatic Encephalopathy Diseases 0.000 description 2
- 208000011990 Corticobasal Degeneration Diseases 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- 201000010374 Down Syndrome Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 101000891579 Homo sapiens Microtubule-associated protein tau Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- 102000029749 Microtubule Human genes 0.000 description 2
- 108091022875 Microtubule Proteins 0.000 description 2
- 102100040243 Microtubule-associated protein tau Human genes 0.000 description 2
- PZPPWEDCSVYBSO-UHFFFAOYSA-N N-(2-methoxyethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxamide Chemical compound COCCNC(C1=NC=C(C=C1)B1OC(C(O1)(C)C)(C)C)=O PZPPWEDCSVYBSO-UHFFFAOYSA-N 0.000 description 2
- XIPRLCRNOFSKAV-UHFFFAOYSA-M N-trimethylstannylpyridine-3-carboxamide Chemical compound C(C1=CN=CC=C1)(=O)N[Sn](C)(C)C XIPRLCRNOFSKAV-UHFFFAOYSA-M 0.000 description 2
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102100040347 TAR DNA-binding protein 43 Human genes 0.000 description 2
- 101710150875 TAR DNA-binding protein 43 Proteins 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- 125000001743 benzylic group Chemical group 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
- 239000012267 brine Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
- 125000000609 carbazolyl group Chemical class C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 2
- 210000003710 cerebral cortex Anatomy 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 230000009137 competitive binding Effects 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 208000017004 dementia pugilistica Diseases 0.000 description 2
- 238000004807 desolvation Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 210000001652 frontal lobe Anatomy 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 150000005755 iodopyridines Chemical class 0.000 description 2
- 229910052741 iridium Inorganic materials 0.000 description 2
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 2
- 230000000155 isotopic effect Effects 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 210000004688 microtubule Anatomy 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- KADXVMRYQRCLAH-UHFFFAOYSA-N n'-iodobutanediamide Chemical compound NC(=O)CCC(=O)NI KADXVMRYQRCLAH-UHFFFAOYSA-N 0.000 description 2
- ANXIFSCWAVKXIU-UHFFFAOYSA-N n-(2-methoxyethyl)pyridine-2-carboxamide Chemical compound COCCNC(=O)C1=CC=CC=N1 ANXIFSCWAVKXIU-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 239000002287 radioligand Substances 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 230000003252 repetitive effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 210000003478 temporal lobe Anatomy 0.000 description 2
- 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 2
- YODSUBUWTUTLAZ-UHFFFAOYSA-N tert-butyl 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=C(B2OC(C)(C)C(C)(C)O2)C=N1 YODSUBUWTUTLAZ-UHFFFAOYSA-N 0.000 description 2
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- KFYQOIHLZBDFBU-UHFFFAOYSA-N (2-morpholin-4-ylpyrimidin-5-yl)boronic acid Chemical compound N1=CC(B(O)O)=CN=C1N1CCOCC1 KFYQOIHLZBDFBU-UHFFFAOYSA-N 0.000 description 1
- OCWTXKZPAZAQQW-UHFFFAOYSA-N (5-fluoro-6-methoxypyridin-3-yl)boronic acid Chemical compound COC1=NC=C(B(O)O)C=C1F OCWTXKZPAZAQQW-UHFFFAOYSA-N 0.000 description 1
- KZKRRZFCAYOXQE-UHFFFAOYSA-N 1$l^{2}-azinane Chemical group C1CC[N]CC1 KZKRRZFCAYOXQE-UHFFFAOYSA-N 0.000 description 1
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 description 1
- MRBFGEHILMYPTF-UHFFFAOYSA-N 1-(2-Pyrimidyl)piperazine Chemical compound C1CNCCN1C1=NC=CC=N1 MRBFGEHILMYPTF-UHFFFAOYSA-N 0.000 description 1
- LVYJIIRJQDEGBR-UHFFFAOYSA-N 1-fluoro-2-iodoethane Chemical compound FCCI LVYJIIRJQDEGBR-UHFFFAOYSA-N 0.000 description 1
- OQZBAQXTXNIPRA-UHFFFAOYSA-N 1-pyridin-4-ylpiperazine Chemical compound C1CNCCN1C1=CC=NC=C1 OQZBAQXTXNIPRA-UHFFFAOYSA-N 0.000 description 1
- FDMOHTOITMTGNG-UHFFFAOYSA-N 11-(6-fluoropyridin-3-yl)-4,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaene Chemical compound Fc1ccc(cn1)-c1ccc2c(n1)[nH]c1ccncc21 FDMOHTOITMTGNG-UHFFFAOYSA-N 0.000 description 1
- IEXNFVCXGINZRT-UHFFFAOYSA-N 1h-dipyrido[2,3-b:3',2'-d]pyrrole Chemical compound C1=CC=C2C3=CC=CN=C3NC2=N1 IEXNFVCXGINZRT-UHFFFAOYSA-N 0.000 description 1
- 125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 description 1
- ZADWTKJOVFBKMI-UHFFFAOYSA-N 2-N,2-dimethyl-1H-pyridine-2,4-diamine Chemical compound CC1(NC=CC(=C1)N)NC ZADWTKJOVFBKMI-UHFFFAOYSA-N 0.000 description 1
- UODINHBLNPPDPD-UHFFFAOYSA-N 2-bromo-5-fluoropyridine Chemical compound FC1=CC=C(Br)N=C1 UODINHBLNPPDPD-UHFFFAOYSA-N 0.000 description 1
- LBVZINOLAFTARU-UHFFFAOYSA-N 2-bromo-n-methylacetamide Chemical compound CNC(=O)CBr LBVZINOLAFTARU-UHFFFAOYSA-N 0.000 description 1
- LIEPVGBDUYKPLC-UHFFFAOYSA-N 2-chloro-4-nitropyridine Chemical compound [O-][N+](=O)C1=CC=NC(Cl)=C1 LIEPVGBDUYKPLC-UHFFFAOYSA-N 0.000 description 1
- DEJUUKULVAIMNF-UHFFFAOYSA-N 2-chloro-5-iodopyridin-4-amine Chemical compound NC1=CC(Cl)=NC=C1I DEJUUKULVAIMNF-UHFFFAOYSA-N 0.000 description 1
- NRGGMCIBEHEAIL-UHFFFAOYSA-N 2-ethylpyridine Chemical compound CCC1=CC=CC=N1 NRGGMCIBEHEAIL-UHFFFAOYSA-N 0.000 description 1
- FURHRJBOFNDYTG-UHFFFAOYSA-N 2-fluoroethanamine Chemical compound NCCF FURHRJBOFNDYTG-UHFFFAOYSA-N 0.000 description 1
- CCZWSTFVHJPCEM-UHFFFAOYSA-N 2-iodopyridine Chemical compound IC1=CC=CC=N1 CCZWSTFVHJPCEM-UHFFFAOYSA-N 0.000 description 1
- QOGNDJLSYMJGPP-UHFFFAOYSA-N 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound C1=NC(OC)=CC=C1B1OC(C)(C)C(C)(C)O1 QOGNDJLSYMJGPP-UHFFFAOYSA-N 0.000 description 1
- BMIBJCFFZPYJHF-UHFFFAOYSA-N 2-methoxy-5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound COC1=NC=C(C)C=C1B1OC(C)(C)C(C)(C)O1 BMIBJCFFZPYJHF-UHFFFAOYSA-N 0.000 description 1
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
- SVEQHRSELNPKJJ-UHFFFAOYSA-N 2-methoxypyridin-4-amine Chemical compound COC1=CC(N)=CC=N1 SVEQHRSELNPKJJ-UHFFFAOYSA-N 0.000 description 1
- FTTIAVRPJGCXAC-UHFFFAOYSA-N 2-methyl-4-nitro-1-oxidopyridin-1-ium Chemical compound CC1=CC([N+]([O-])=O)=CC=[N+]1[O-] FTTIAVRPJGCXAC-UHFFFAOYSA-N 0.000 description 1
- GNCLPNMQEGMNTG-UHFFFAOYSA-N 2-methylpyridin-4-amine Chemical compound CC1=CC(N)=CC=N1 GNCLPNMQEGMNTG-UHFFFAOYSA-N 0.000 description 1
- ZJRSKTXMSIVNAU-UHFFFAOYSA-N 3-amino-4-iodopyridine Chemical compound NC1=CN=CC=C1I ZJRSKTXMSIVNAU-UHFFFAOYSA-N 0.000 description 1
- OAEDVIUUNHFXLJ-UHFFFAOYSA-N 3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN=C(N)C(F)=C1 OAEDVIUUNHFXLJ-UHFFFAOYSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- ZGOCEDVVZKFHSY-UHFFFAOYSA-N 3-iodopyridin-4-amine Chemical compound NC1=CC=NC=C1I ZGOCEDVVZKFHSY-UHFFFAOYSA-N 0.000 description 1
- AIOUQYUFHADEHR-UHFFFAOYSA-N 3-methylpyridine-2-carboxamide Chemical compound CC1=CC=CN=C1C(N)=O AIOUQYUFHADEHR-UHFFFAOYSA-N 0.000 description 1
- PZVZGDBCMQBRMA-UHFFFAOYSA-N 3-pyridin-4-ylpropan-1-ol Chemical compound OCCCC1=CC=NC=C1 PZVZGDBCMQBRMA-UHFFFAOYSA-N 0.000 description 1
- BAQKUNMKVAPWGU-UHFFFAOYSA-N 4-bromopyridin-2-amine Chemical compound NC1=CC(Br)=CC=N1 BAQKUNMKVAPWGU-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- SYJMHOBGFXCKRG-UHFFFAOYSA-N 4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine Chemical compound CC1=NC(N)=NC=C1B1OC(C)(C)C(C)(C)O1 SYJMHOBGFXCKRG-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
- WAUWXCUPDOXYKS-UHFFFAOYSA-N 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-pyridin-2-one Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(O)N=C1 WAUWXCUPDOXYKS-UHFFFAOYSA-N 0.000 description 1
- KJQVHJSIJTVCMN-UHFFFAOYSA-N 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine-2-carbonitrile Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN=C(C#N)N=C1 KJQVHJSIJTVCMN-UHFFFAOYSA-N 0.000 description 1
- CLYOMCMDBNNGSM-UHFFFAOYSA-N 5-bromo-2-fluoropyridin-3-amine Chemical compound NC1=CC(Br)=CN=C1F CLYOMCMDBNNGSM-UHFFFAOYSA-N 0.000 description 1
- UDQGIOYIJKRLFH-UHFFFAOYSA-N 5-bromo-n-methylpyrimidin-2-amine Chemical compound CNC1=NC=C(Br)C=N1 UDQGIOYIJKRLFH-UHFFFAOYSA-N 0.000 description 1
- JHFJFJHQZAIQLE-UHFFFAOYSA-N 6-bromo-n-methylpyridine-3-carboxamide Chemical compound CNC(=O)C1=CC=C(Br)N=C1 JHFJFJHQZAIQLE-UHFFFAOYSA-N 0.000 description 1
- PGBXHSHENWASTH-UHFFFAOYSA-N 6-fluoropyridine-3-carboxamide Chemical compound NC(=O)C1=CC=C(F)N=C1 PGBXHSHENWASTH-UHFFFAOYSA-N 0.000 description 1
- BZHCVCNZIJZMRN-UHFFFAOYSA-N 9h-pyridazino[3,4-b]indole Chemical class N1=CC=C2C3=CC=CC=C3NC2=N1 BZHCVCNZIJZMRN-UHFFFAOYSA-N 0.000 description 1
- 208000023697 ABri amyloidosis Diseases 0.000 description 1
- 208000017227 ADan amyloidosis Diseases 0.000 description 1
- 102100034452 Alternative prion protein Human genes 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 241001071161 Asclepias Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- VHAFLGCHWIGIRL-UHFFFAOYSA-N CC1(OB(OC1C)C=1C=NC(=NC=1)N1CCOCC1)C Chemical compound CC1(OB(OC1C)C=1C=NC(=NC=1)N1CCOCC1)C VHAFLGCHWIGIRL-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 1
- 241001198387 Escherichia coli BL21(DE3) Species 0.000 description 1
- 206010018341 Gliosis Diseases 0.000 description 1
- 102000019054 Group II Phospholipases A2 Human genes 0.000 description 1
- 108010026929 Group II Phospholipases A2 Proteins 0.000 description 1
- 101000694718 Homo sapiens Amine oxidase [flavin-containing] A Proteins 0.000 description 1
- 201000000162 ITM2B-related cerebral amyloid angiopathy 1 Diseases 0.000 description 1
- 201000000194 ITM2B-related cerebral amyloid angiopathy 2 Diseases 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 description 1
- 208000036626 Mental retardation Diseases 0.000 description 1
- 206010068871 Myotonic dystrophy Diseases 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 108091006657 SLC9A6 Proteins 0.000 description 1
- 102000005473 Secretory Phospholipases A2 Human genes 0.000 description 1
- 108010031873 Secretory Phospholipases A2 Proteins 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 102100029972 Sodium/hydrogen exchanger 6 Human genes 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- 108010076818 TEV protease Proteins 0.000 description 1
- 206010044688 Trisomy 21 Diseases 0.000 description 1
- 208000007930 Type C Niemann-Pick Disease Diseases 0.000 description 1
- 102220594896 Vasopressin-neurophysin 2-copeptin_M20A_mutation Human genes 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N benzo-alpha-pyrone Chemical class C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- 125000000332 coumarinyl group Chemical class O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 239000011903 deuterated solvents Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229960001985 dextromethorphan Drugs 0.000 description 1
- 238000002059 diagnostic imaging Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
- IWMMXPNBCHCFCY-UHFFFAOYSA-M dicyclohexyl-[3,6-dimethoxy-2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane;palladium(2+);2-phenylethanamine;chloride Chemical compound [Pd+]Cl.NCCC1=CC=CC=[C-]1.COC1=CC=C(OC)C(C=2C(=CC(=CC=2C(C)C)C(C)C)C(C)C)=C1P(C1CCCCC1)C1CCCCC1 IWMMXPNBCHCFCY-UHFFFAOYSA-M 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004424 eye movement Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002213 flavones Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- CYEFKCRAAGLNHW-UHFFFAOYSA-N furan-3-ylboronic acid Chemical compound OB(O)C=1C=COC=1 CYEFKCRAAGLNHW-UHFFFAOYSA-N 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 230000007387 gliosis Effects 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000006951 hyperphosphorylation Effects 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- SCKBPXUWGMKLDM-UHFFFAOYSA-N n-(2-aminoethyl)-5-(3-fluorophenyl)-1,3-thiazole-4-carboxamide Chemical compound N1=CSC(C=2C=C(F)C=CC=2)=C1C(=O)NCCN SCKBPXUWGMKLDM-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 230000009635 nitrosylation Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- LVSJDHGRKAEGLX-UHFFFAOYSA-N oxolane;2,2,2-trifluoroacetic acid Chemical compound C1CCOC1.OC(=O)C(F)(F)F LVSJDHGRKAEGLX-UHFFFAOYSA-N 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- RJQRCOMHVBLQIH-UHFFFAOYSA-M pentane-1-sulfonate Chemical compound CCCCCS([O-])(=O)=O RJQRCOMHVBLQIH-UHFFFAOYSA-M 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 102000035123 post-translationally modified proteins Human genes 0.000 description 1
- 108091005626 post-translationally modified proteins Proteins 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000011085 pressure filtration Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
- QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 229930185107 quinolinone Chemical class 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- WRTMQOHKMFDUKX-UHFFFAOYSA-N triiodide Chemical compound I[I-]I WRTMQOHKMFDUKX-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
- C07D471/12—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 three hetero rings
- C07D471/14—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- 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
- A61K51/0459—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
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0463—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/002—Heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15153448 | 2015-02-02 | ||
| PCT/EP2016/051993 WO2016124508A1 (en) | 2015-02-02 | 2016-01-29 | 9h-pyrrolo-dipyridine derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201791733A1 EA201791733A1 (ru) | 2018-01-31 |
| EA036518B1 true EA036518B1 (ru) | 2020-11-18 |
Family
ID=52477553
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201791733A EA036518B1 (ru) | 2015-02-02 | 2016-01-29 | Производные 9h-пирролодипиридина |
Country Status (17)
| Country | Link |
|---|---|
| US (3) | US20180022748A1 (enExample) |
| EP (1) | EP3253762B1 (enExample) |
| JP (1) | JP6579670B2 (enExample) |
| KR (1) | KR102621513B1 (enExample) |
| CN (1) | CN107207508B (enExample) |
| AU (1) | AU2016214537B2 (enExample) |
| BR (1) | BR112017016311A2 (enExample) |
| CA (1) | CA2973648C (enExample) |
| CL (1) | CL2017001923A1 (enExample) |
| DK (1) | DK3253762T3 (enExample) |
| EA (1) | EA036518B1 (enExample) |
| ES (1) | ES2875734T3 (enExample) |
| IL (1) | IL253381B (enExample) |
| MX (1) | MX378155B (enExample) |
| MY (1) | MY191590A (enExample) |
| SG (1) | SG11201705727TA (enExample) |
| WO (1) | WO2016124508A1 (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL2247558T5 (pl) | 2008-02-14 | 2024-10-14 | Eli Lilly And Company | Nowe środki obrazujące do wykrywania czynnościowych zaburzeń neurologicznych |
| SG11201705727TA (en) * | 2015-02-02 | 2017-08-30 | Ucb Biopharma Sprl | 9h-pyrrolo-dipyridine derivatives |
| CN115650982A (zh) * | 2016-07-22 | 2023-01-31 | Ac免疫有限公司 | 用于成像tau蛋白聚集体的化合物 |
| EP3487545A1 (en) | 2016-07-22 | 2019-05-29 | AC Immune S.A. | Compounds for imaging tau protein aggregates |
| ES2847903T3 (es) * | 2016-09-09 | 2021-08-04 | Hoffmann La Roche | Procedimiento para la preparación de 2-(6-nitropiridin-3-il)-9H-dipirido[2,3-b;3',4'-d]pirrol |
| KR20230127371A (ko) * | 2016-11-01 | 2023-08-31 | 아비나스 오퍼레이션스, 인코포레이티드 | 타우(Tau)-단백질 표적화 프로탁(PROTAC) 및 관련 사용 방법 |
| US11660287B2 (en) | 2017-06-02 | 2023-05-30 | Fujifilm Toyama Chemical Co., Ltd. | Agent for preventing or treating spinocerebellar ataxia |
| MX393052B (es) | 2017-06-02 | 2025-03-24 | Fujifilm Toyama Chemical Co Ltd | Agente para prevenir o tratar atrofia cerebral. |
| WO2018221731A1 (ja) * | 2017-06-02 | 2018-12-06 | 富山化学工業株式会社 | タウオパチー予防または治療剤 |
| EP3636262A4 (en) | 2017-06-02 | 2020-06-10 | FUJIFILM Toyama Chemical Co., Ltd. | AGENT FOR PREVENTING OR TREATING ALZHEIMER-LIKE DEMENTIA |
| BR112019024983A2 (pt) | 2017-06-02 | 2020-06-23 | Fujifilm Toyama Chemical Co., Ltd. | Agente para reduzir a quantidade de proteína b amiloide |
| EP3705121B1 (en) | 2017-10-30 | 2023-08-30 | FUJIFILM Toyama Chemical Co., Ltd. | Emopamil binding protein binding agent and use thereof |
| CN111868062B (zh) * | 2018-01-24 | 2023-07-07 | Ac免疫有限公司 | 制备显像化合物的方法 |
| EP3743426A1 (en) * | 2018-01-24 | 2020-12-02 | AC Immune SA | Azacarboline compounds for the detection of tau aggregates |
| EP3743423A1 (en) | 2018-01-24 | 2020-12-02 | AC Immune SA | Gamma-carboline compounds for the detection of tau aggregates |
| US11912699B2 (en) | 2019-07-17 | 2024-02-27 | Arvinas Operations, Inc. | Tau-protein targeting compounds and associated |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008132454A1 (en) * | 2007-04-26 | 2008-11-06 | Ge Healthcare Limited | Carbolines and their use as imaging agents |
| WO2009102498A1 (en) * | 2008-02-14 | 2009-08-20 | Siemens Medical Solutions Usa, Inc. | Novel imaging agents for detecting neurological dysfunction |
| WO2013176698A1 (en) * | 2012-05-22 | 2013-11-28 | Eli Lilly And Company | Carboline and carbazole based imaging agents for detecting neurological dysfunction |
| WO2015052105A1 (en) * | 2013-10-08 | 2015-04-16 | F. Hoffmann-La Roche Ag | Diazacarbazole derivatives as tau-pet-ligands |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1268771A (en) | 1968-03-15 | 1972-03-29 | Glaxo Lab Ltd | Azacarbazoles |
| JP5557849B2 (ja) * | 2008-12-19 | 2014-07-23 | ブリストル−マイヤーズ スクイブ カンパニー | カルバゾールおよびカルボリンキナーゼ阻害剤 |
| US20160115162A1 (en) * | 2013-05-31 | 2016-04-28 | The General Hospital Corporation | Radiosynthesis of Tau Radiopharmaceuticals |
| US9774356B2 (en) * | 2013-07-24 | 2017-09-26 | Telefonaktiebolaget Lm Ericsson (Publ) | Method and apparatus relating to reception of radio signals |
| WO2015110263A1 (en) * | 2014-01-21 | 2015-07-30 | Ac Immune Sa | Carbazole and carboline compounds for use in the diagnosis, treatment, alleviation or prevention of disorders associated with amyloid or amyolid-like proteins |
| SG11201705727TA (en) * | 2015-02-02 | 2017-08-30 | Ucb Biopharma Sprl | 9h-pyrrolo-dipyridine derivatives |
-
2016
- 2016-01-29 SG SG11201705727TA patent/SG11201705727TA/en unknown
- 2016-01-29 BR BR112017016311A patent/BR112017016311A2/pt not_active Application Discontinuation
- 2016-01-29 DK DK16702121.1T patent/DK3253762T3/da active
- 2016-01-29 KR KR1020177024371A patent/KR102621513B1/ko active Active
- 2016-01-29 US US15/547,980 patent/US20180022748A1/en not_active Abandoned
- 2016-01-29 EA EA201791733A patent/EA036518B1/ru not_active IP Right Cessation
- 2016-01-29 MY MYPI2017702668A patent/MY191590A/en unknown
- 2016-01-29 MX MX2017009505A patent/MX378155B/es unknown
- 2016-01-29 AU AU2016214537A patent/AU2016214537B2/en active Active
- 2016-01-29 EP EP16702121.1A patent/EP3253762B1/en active Active
- 2016-01-29 JP JP2017540724A patent/JP6579670B2/ja active Active
- 2016-01-29 ES ES16702121T patent/ES2875734T3/es active Active
- 2016-01-29 CN CN201680008314.3A patent/CN107207508B/zh active Active
- 2016-01-29 CA CA2973648A patent/CA2973648C/en active Active
- 2016-01-29 WO PCT/EP2016/051993 patent/WO2016124508A1/en not_active Ceased
-
2017
- 2017-07-10 IL IL253381A patent/IL253381B/en active IP Right Grant
- 2017-07-27 CL CL2017001923A patent/CL2017001923A1/es unknown
-
2020
- 2020-01-22 US US16/749,537 patent/US11312716B2/en active Active
-
2022
- 2022-03-21 US US17/700,075 patent/US12006316B2/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008132454A1 (en) * | 2007-04-26 | 2008-11-06 | Ge Healthcare Limited | Carbolines and their use as imaging agents |
| WO2009102498A1 (en) * | 2008-02-14 | 2009-08-20 | Siemens Medical Solutions Usa, Inc. | Novel imaging agents for detecting neurological dysfunction |
| WO2013176698A1 (en) * | 2012-05-22 | 2013-11-28 | Eli Lilly And Company | Carboline and carbazole based imaging agents for detecting neurological dysfunction |
| WO2015052105A1 (en) * | 2013-10-08 | 2015-04-16 | F. Hoffmann-La Roche Ag | Diazacarbazole derivatives as tau-pet-ligands |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107207508A (zh) | 2017-09-26 |
| CL2017001923A1 (es) | 2018-02-16 |
| CA2973648C (en) | 2023-09-26 |
| EA201791733A1 (ru) | 2018-01-31 |
| US20220213103A1 (en) | 2022-07-07 |
| JP6579670B2 (ja) | 2019-09-25 |
| MX2017009505A (es) | 2017-11-02 |
| US12006316B2 (en) | 2024-06-11 |
| BR112017016311A2 (pt) | 2018-03-27 |
| KR102621513B1 (ko) | 2024-01-04 |
| CA2973648A1 (en) | 2016-08-11 |
| MX378155B (es) | 2025-03-10 |
| ES2875734T3 (es) | 2021-11-11 |
| CN107207508B (zh) | 2020-02-28 |
| EP3253762B1 (en) | 2021-05-05 |
| EP3253762A1 (en) | 2017-12-13 |
| JP2018503673A (ja) | 2018-02-08 |
| MY191590A (en) | 2022-06-30 |
| AU2016214537A1 (en) | 2017-08-03 |
| SG11201705727TA (en) | 2017-08-30 |
| US11312716B2 (en) | 2022-04-26 |
| IL253381A0 (en) | 2017-09-28 |
| US20180022748A1 (en) | 2018-01-25 |
| WO2016124508A1 (en) | 2016-08-11 |
| DK3253762T3 (da) | 2021-07-19 |
| IL253381B (en) | 2020-10-29 |
| KR20170113607A (ko) | 2017-10-12 |
| AU2016214537B2 (en) | 2018-05-10 |
| US20210047326A1 (en) | 2021-02-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US12006316B2 (en) | 9H-pyrrolo-dipyridine derivatives | |
| AU2022221446B2 (en) | Rho-associated protein kinase inhibitor, pharmaceutical composition comprising same, and preparation method and use thereof | |
| JP6513107B2 (ja) | 神経原線維濃縮体のイメージング剤としてのピロロ［２，３−ｃ］ピリジン | |
| AU2011253058A1 (en) | Heteroaryloxycarbocyclyl compounds as PDE10 inhibitors | |
| JP6680774B2 (ja) | ＰＩ３Ｋ阻害剤としてのピリド［１，２−ａ］ピリミドン類似体 | |
| JP2018507883A (ja) | 抗がん剤としての置換２−ｈ−ピラゾール誘導体 | |
| RS56315B2 (sr) | P2x7 modulatori | |
| CA2904618A1 (en) | Substituted 2-azabicycles and their use as orexin receptor modulators | |
| TW201326173A (zh) | ５，７－經取代之－咪唑并［１，２－ｃ］嘧啶 | |
| KR20150126695A (ko) | 치환된 7-아자바이사이클 및 오렉신 수용체 조절제로서의 이의 용도 | |
| TW201333005A (zh) | １,５－萘啶衍生物與含此之ｍｅｌｋ抑制劑 | |
| WO2019074809A1 (en) | INDAZOLYL-SPIRO [2.2] PENTANE-CARBONITRILE DERIVATIVES AS LRRK2 INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF | |
| JP7604067B2 (ja) | ジアシルグリセロールキナーゼ阻害剤としての複素環化合物及びその用途 | |
| WO2024186584A2 (en) | Alpha-synuclein binders and methods of use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG TJ TM |