BR112021004739A2 - inibidores de o-glicoproteína-2-acetamido-2-desoxi-3-d-glucopiranosidase - Google Patents

Info

Publication number

BR112021004739A2

BR112021004739A2 BR112021004739-5A BR112021004739A BR112021004739A2 BR 112021004739 A2 BR112021004739 A2 BR 112021004739A2 BR 112021004739 A BR112021004739 A BR 112021004739A BR 112021004739 A2 BR112021004739 A2 BR 112021004739A2

Authority

BR

Brazil

Prior art keywords

methyl

acetamide

oxy

thiazol

fluoro

Prior art date

2018-09-19

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• 239000003112 inhibitor Substances 0.000 title abstract description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 393
• 150000003839 salts Chemical class 0.000 claims abstract description 115
• 238000000034 method Methods 0.000 claims abstract description 74
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
• 239000000203 mixture Substances 0.000 claims description 122
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 114
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 112
• 125000005843 halogen group Chemical group 0.000 claims description 92
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 72
• -1 4-methylpiperazinyl Chemical group 0.000 claims description 64
• 125000000623 heterocyclic group Chemical group 0.000 claims description 41
• 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 40
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 39
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 39
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 39
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
• 201000010099 disease Diseases 0.000 claims description 33
• 125000001424 substituent group Chemical group 0.000 claims description 33
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 28
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 26
• 125000004970 halomethyl group Chemical group 0.000 claims description 25
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 22
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 20
• 206010012289 Dementia Diseases 0.000 claims description 19
• 102100030122 Protein O-GlcNAcase Human genes 0.000 claims description 19
• 208000010877 cognitive disease Diseases 0.000 claims description 18
• 208000032382 Ischaemic stroke Diseases 0.000 claims description 17
• 125000001072 heteroaryl group Chemical group 0.000 claims description 16
• 208000024827 Alzheimer disease Diseases 0.000 claims description 13
• 208000027061 mild cognitive impairment Diseases 0.000 claims description 12
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 12
• 210000004556 brain Anatomy 0.000 claims description 11
• 125000004432 carbon atom Chemical group C* 0.000 claims description 11
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
• 108010045982 hexosaminidase C Proteins 0.000 claims description 11
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
• 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 10
• 201000011240 Frontotemporal dementia Diseases 0.000 claims description 9
• 208000027089 Parkinsonian disease Diseases 0.000 claims description 8
• 206010034010 Parkinsonism Diseases 0.000 claims description 8
• 229910052799 carbon Inorganic materials 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 230000006951 hyperphosphorylation Effects 0.000 claims description 8
• 125000002950 monocyclic group Chemical group 0.000 claims description 8
• 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims description 7
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• 208000034799 Tauopathies Diseases 0.000 claims description 7
• 125000004429 atom Chemical group 0.000 claims description 7
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 7
• 230000002401 inhibitory effect Effects 0.000 claims description 7
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 7
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
• 208000028698 Cognitive impairment Diseases 0.000 claims description 6
• 208000023105 Huntington disease Diseases 0.000 claims description 6
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
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• JYOIEMUTUIWZPL-GXSJLCMTSA-N N-[4-fluoro-5-[[(2S,4R)-4-(6-methoxypyrimidin-4-yl)oxy-2-methylpyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=NC=NC(=C3)OC JYOIEMUTUIWZPL-GXSJLCMTSA-N 0.000 claims description 5
• QAOQLXNGRWVWTL-WCBMZHEXSA-N N-[5-[[(2S,4R)-4-(6-chloropyrimidin-4-yl)oxy-2-methylpyrrolidin-1-yl]methyl]-4-fluoro-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=CC(=NC=N3)Cl QAOQLXNGRWVWTL-WCBMZHEXSA-N 0.000 claims description 5
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• 125000005347 halocycloalkyl group Chemical group 0.000 claims description 5
• 208000000170 postencephalitic Parkinson disease Diseases 0.000 claims description 5
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• XWMPSSJFAYHGJF-GZMMTYOYSA-N C[C@@H](C1)N(CC(SC(NC(C)=O)=N2)=C2F)C[C@@H]1OC(N=C1)=NC=C1F Chemical compound C[C@@H](C1)N(CC(SC(NC(C)=O)=N2)=C2F)C[C@@H]1OC(N=C1)=NC=C1F XWMPSSJFAYHGJF-GZMMTYOYSA-N 0.000 claims description 4
• AMVXPMAUWIZOLI-GXSJLCMTSA-N C[C@@H](C1)N(CC(SC(NC(C)=O)=N2)=C2F)C[C@@H]1OC(N=C1)=NC=C1OC Chemical compound C[C@@H](C1)N(CC(SC(NC(C)=O)=N2)=C2F)C[C@@H]1OC(N=C1)=NC=C1OC AMVXPMAUWIZOLI-GXSJLCMTSA-N 0.000 claims description 4
• LOKRLIUPFBSXPD-WCBMZHEXSA-N C[C@@H](C1)N(CC(SC(NC(C)=O)=N2)=C2F)C[C@@H]1OC(N=N1)=CC=C1F Chemical compound C[C@@H](C1)N(CC(SC(NC(C)=O)=N2)=C2F)C[C@@H]1OC(N=N1)=CC=C1F LOKRLIUPFBSXPD-WCBMZHEXSA-N 0.000 claims description 4
• GLVQUWYEGANTKB-JOYOIKCWSA-N C[C@@H](C1)N(CC(SC(NC(C)=O)=N2)=C2F)C[C@@H]1OC1=NC=NC(C(C)=O)=C1 Chemical compound C[C@@H](C1)N(CC(SC(NC(C)=O)=N2)=C2F)C[C@@H]1OC1=NC=NC(C(C)=O)=C1 GLVQUWYEGANTKB-JOYOIKCWSA-N 0.000 claims description 4
• NGPFFKQCYNTCOE-GXSJLCMTSA-N C[C@@H](C1)N(CC(SC(NC(C)=O)=N2)=C2F)C[C@@H]1OC1=NC=NC(OCC(F)(F)F)=C1 Chemical compound C[C@@H](C1)N(CC(SC(NC(C)=O)=N2)=C2F)C[C@@H]1OC1=NC=NC(OCC(F)(F)F)=C1 NGPFFKQCYNTCOE-GXSJLCMTSA-N 0.000 claims description 4
• WRVLACYEMOCHCJ-GXSJLCMTSA-N C[C@@H](C1)N(CC(SC(NC(C)=O)=N2)=C2F)C[C@@H]1OC1=NC=NC=C1OC Chemical compound C[C@@H](C1)N(CC(SC(NC(C)=O)=N2)=C2F)C[C@@H]1OC1=NC=NC=C1OC WRVLACYEMOCHCJ-GXSJLCMTSA-N 0.000 claims description 4
• 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims description 4
• 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 4
• DKJVGVNCPYLERV-XJKSGUPXSA-N N-[4-fluoro-5-[[(2S,4R)-2-methyl-4-(4-morpholin-4-ylpyridin-2-yl)oxypyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=NC=CC(=C3)N4CCOCC4 DKJVGVNCPYLERV-XJKSGUPXSA-N 0.000 claims description 4
• BPTQQFGJUANIRA-CMPLNLGQSA-N N-[4-fluoro-5-[[(2S,4R)-2-methyl-4-(5-methylpyrazin-2-yl)oxypyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=NC=C(N=C3)C BPTQQFGJUANIRA-CMPLNLGQSA-N 0.000 claims description 4
• QDYSHLPOYATPNW-GXTWGEPZSA-N N-[4-fluoro-5-[[(2S,4R)-2-methyl-4-(5-morpholin-4-ylpyrazin-2-yl)oxypyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C1N(CCOC1)C1=NC=C(O[C@@H]2C[C@@H](N(C2)CC2=C(N=C(NC(=O)C)S2)F)C)N=C1 QDYSHLPOYATPNW-GXTWGEPZSA-N 0.000 claims description 4
• IQMCVWVFIOAFTO-XJKSGUPXSA-N N-[4-fluoro-5-[[(2S,4R)-2-methyl-4-(5-morpholin-4-ylpyridin-2-yl)oxypyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C1CN(CCO1)C1=CC=C(O[C@@H]2C[C@@H](N(C2)CC2=C(N=C(NC(=O)C)S2)F)C)N=C1 IQMCVWVFIOAFTO-XJKSGUPXSA-N 0.000 claims description 4
• GLSBXHCYBGLJSD-GXTWGEPZSA-N N-[4-fluoro-5-[[(2S,4R)-2-methyl-4-(6-morpholin-4-ylpyrimidin-4-yl)oxypyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound N1(CCOCC1)C1=NC=NC(O[C@@H]2C[C@@H](N(C2)CC2=C(N=C(NC(=O)C)S2)F)C)=C1 GLSBXHCYBGLJSD-GXTWGEPZSA-N 0.000 claims description 4
• GVILVCJMPQUZFZ-WCBMZHEXSA-N N-[4-fluoro-5-[[(2S,4R)-2-methyl-4-[(6-oxo-1H-pyrimidin-4-yl)oxy]pyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound [C@H]1(OC2=NC=NC(O)=C2)CN([C@H](C1)C)CC1=C(N=C(NC(=O)C)S1)F GVILVCJMPQUZFZ-WCBMZHEXSA-N 0.000 claims description 4
• GKQNSZZMUODDFV-WMLDXEAASA-N N-[4-fluoro-5-[[(2S,4R)-2-methyl-4-[4-(4-methylpiperazin-1-yl)pyridin-2-yl]oxypyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound [C@H]1(OC2=CC(N3CCN(CC3)C)=CC=N2)CN([C@H](C1)C)CC1=C(F)N=C(NC(=O)C)S1 GKQNSZZMUODDFV-WMLDXEAASA-N 0.000 claims description 4
• OUVXMELNDVWWJK-WMLDXEAASA-N N-[4-fluoro-5-[[(2S,4R)-2-methyl-4-[5-(4-methylpiperazin-1-yl)pyridin-2-yl]oxypyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C1N(CCN(C1)C)C1=CC=C(O[C@@H]2C[C@@H](N(C2)CC2=C(N=C(NC(=O)C)S2)F)C)N=C1 OUVXMELNDVWWJK-WMLDXEAASA-N 0.000 claims description 4
• ODMXJFQHWVGXMV-WCQYABFASA-N N-[4-fluoro-5-[[(2S,4R)-2-methyl-4-[6-(1-methylazetidin-3-yl)oxypyrimidin-4-yl]oxypyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=CC(=NC=N3)OC4CN(C4)C ODMXJFQHWVGXMV-WCQYABFASA-N 0.000 claims description 4
• GBKICYZBONITNJ-CMPLNLGQSA-N N-[4-fluoro-5-[[(2S,4R)-2-methyl-4-[6-(oxetan-3-yloxy)pyrimidin-4-yl]oxypyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=CC(=NC=N3)OC4COC4 GBKICYZBONITNJ-CMPLNLGQSA-N 0.000 claims description 4
• YTKJEVFXVKTHFZ-GXSJLCMTSA-N N-[4-fluoro-5-[[(2S,4R)-2-methyl-4-pyrimidin-2-yloxypyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=NC=CC=N3 YTKJEVFXVKTHFZ-GXSJLCMTSA-N 0.000 claims description 4
• PVFLCHYWWJTDNO-GXSJLCMTSA-N N-[4-fluoro-5-[[(2S,4R)-2-methyl-4-pyrimidin-5-yloxypyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=CN=CN=C3 PVFLCHYWWJTDNO-GXSJLCMTSA-N 0.000 claims description 4
• OHKWLHVSJFXSFE-GXFFZTMASA-N N-[4-fluoro-5-[[(2S,4R)-4-(2-methoxypyridin-4-yl)oxy-2-methylpyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=CC(=NC=C3)OC OHKWLHVSJFXSFE-GXFFZTMASA-N 0.000 claims description 4
• RXRRSHOSTMIYMK-GXSJLCMTSA-N N-[4-fluoro-5-[[(2S,4R)-4-(3-fluoropyridin-2-yl)oxy-2-methylpyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=C(C=CC=N3)F RXRRSHOSTMIYMK-GXSJLCMTSA-N 0.000 claims description 4
• BEXXCVCQWNOKLJ-IINYFYTJSA-N N-[4-fluoro-5-[[(2S,4R)-4-(4-fluorophenoxy)-2-methylpyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=CC=C(C=C3)F BEXXCVCQWNOKLJ-IINYFYTJSA-N 0.000 claims description 4
• NVWUNUOWQIKRDW-JOYOIKCWSA-N N-[4-fluoro-5-[[(2S,4R)-4-(4-fluoropyridin-2-yl)oxy-2-methylpyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=NC=CC(=C3)F NVWUNUOWQIKRDW-JOYOIKCWSA-N 0.000 claims description 4
• DGNDILVIYUWWFJ-GXSJLCMTSA-N N-[4-fluoro-5-[[(2S,4R)-4-(4-methoxypyrimidin-2-yl)oxy-2-methylpyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=NC=CC(=N3)OC DGNDILVIYUWWFJ-GXSJLCMTSA-N 0.000 claims description 4
• BZKLALVUPJBUMS-JOYOIKCWSA-N N-[4-fluoro-5-[[(2S,4R)-4-(5-fluoropyridin-2-yl)oxy-2-methylpyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=NC=C(C=C3)F BZKLALVUPJBUMS-JOYOIKCWSA-N 0.000 claims description 4
• XYNIFKOBDUYFSO-GXFFZTMASA-N N-[4-fluoro-5-[[(2S,4R)-4-(5-methoxypyridin-2-yl)oxy-2-methylpyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=NC=C(C=C3)OC XYNIFKOBDUYFSO-GXFFZTMASA-N 0.000 claims description 4
• LOOIJXZCTSPTQH-JOYOIKCWSA-N N-[4-fluoro-5-[[(2S,4R)-4-(6-fluoropyridin-3-yl)oxy-2-methylpyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound O=C(NC=1SC(CN2[C@H](C[C@@H](OC3=CC=C(N=C3)F)C2)C)=C(N=1)F)C LOOIJXZCTSPTQH-JOYOIKCWSA-N 0.000 claims description 4
• UVCYPULUMMVKCP-GXSJLCMTSA-N N-[4-fluoro-5-[[(2S,4R)-4-(6-methoxypyridazin-3-yl)oxy-2-methylpyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound O=C(NC=1SC(=C(N=1)F)CN1[C@H](C[C@@H](OC2=CC=C(OC)N=N2)C1)C)C UVCYPULUMMVKCP-GXSJLCMTSA-N 0.000 claims description 4
• KQVTYEXYFPTKPV-CMPLNLGQSA-N N-[4-fluoro-5-[[(2S,4R)-4-(6-methoxypyridin-2-yl)oxy-2-methylpyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=CC=CC(=N3)OC KQVTYEXYFPTKPV-CMPLNLGQSA-N 0.000 claims description 4
• LZLVMGHURKRPBO-GXFFZTMASA-N N-[4-fluoro-5-[[(2S,4R)-4-(6-methoxypyridin-3-yl)oxy-2-methylpyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=CN=C(C=C3)OC LZLVMGHURKRPBO-GXFFZTMASA-N 0.000 claims description 4
• DSFQQPRPQOCRJZ-SWLSCSKDSA-N N-[4-fluoro-5-[[(2S,4R)-4-[4-(2-methoxyethoxy)pyridin-2-yl]oxy-2-methylpyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=NC=CC(=C3)OCCOC DSFQQPRPQOCRJZ-SWLSCSKDSA-N 0.000 claims description 4
• RXOWKTKVCURAFB-XJKSGUPXSA-N N-[4-fluoro-5-[[(2S,4R)-4-[4-[2-methoxyethyl(methyl)amino]pyridin-2-yl]oxy-2-methylpyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=NC=CC(=C3)N(C)CCOC RXOWKTKVCURAFB-XJKSGUPXSA-N 0.000 claims description 4
• FOQQEUJRIDMGEN-SWLSCSKDSA-N N-[4-fluoro-5-[[(2S,4R)-4-[5-(2-methoxyethoxy)pyridin-2-yl]oxy-2-methylpyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=NC=C(C=C3)OCCOC FOQQEUJRIDMGEN-SWLSCSKDSA-N 0.000 claims description 4
• CVFGBQHBBXVQBX-XJKSGUPXSA-N N-[4-fluoro-5-[[(2S,4R)-4-[5-[2-methoxyethyl(methyl)amino]pyridin-2-yl]oxy-2-methylpyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound N(C)(CCOC)C1=CC=C(O[C@@H]2C[C@@H](N(C2)CC=2SC(NC(=O)C)=NC=2F)C)N=C1 CVFGBQHBBXVQBX-XJKSGUPXSA-N 0.000 claims description 4
• LALHEYRNEPGUQV-GXFFZTMASA-N N-[4-fluoro-5-[[(2S,4R)-4-[6-(3-fluoroazetidin-1-yl)pyrimidin-4-yl]oxy-2-methylpyrrolidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound C(=O)(NC=1SC(=C(N=1)F)CN1[C@H](C[C@@H](OC2=NC=NC(N3CC(F)C3)=C2)C1)C)C LALHEYRNEPGUQV-GXFFZTMASA-N 0.000 claims description 4
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• ZYKVUVXFBNZNLS-WCBMZHEXSA-N N-[5-[[(2S,4R)-4-(4,5-difluoropyridin-2-yl)oxy-2-methylpyrrolidin-1-yl]methyl]-4-fluoro-1,3-thiazol-2-yl]acetamide Chemical compound C[C@H]1C[C@H](CN1CC2=C(N=C(S2)NC(=O)C)F)OC3=NC=C(C(=C3)F)F ZYKVUVXFBNZNLS-WCBMZHEXSA-N 0.000 claims description 4
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