JP2020503292A5 - - Google Patents

Info

Publication number

JP2020503292A5

JP2020503292A5 JP2019531722A JP2019531722A JP2020503292A5 JP 2020503292 A5 JP2020503292 A5 JP 2020503292A5 JP 2019531722 A JP2019531722 A JP 2019531722A JP 2019531722 A JP2019531722 A JP 2019531722A JP 2020503292 A5 JP2020503292 A5 JP 2020503292A5

Authority

JP

Japan

Prior art keywords

tautomer

compound

thiazine

amino

dihydro

Prior art date

2017-12-13

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Granted

Links

• Espacenet
• Global Dossier
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• 150000001875 compounds Chemical class 0.000 claims 51
• 150000003839 salts Chemical class 0.000 claims 23
• -1 2-propynyloxy Chemical group 0.000 claims 16
• 206010012289 Dementia Diseases 0.000 claims 8
• 125000000217 alkyl group Chemical group 0.000 claims 8
• 239000008194 pharmaceutical composition Substances 0.000 claims 5
• IRLAUZMPCLFJAE-PXNMLYILSA-N 2-amino-4-[5-[(Z)-2-(5-cyanopyridin-2-yl)-2-fluoroethenyl]-2-fluorophenyl]-4,6-dimethyl-5H-1,3-thiazine-6-carboxylic acid Chemical compound CC1(CC(C)(N=C(N)S1)c1cc(\C=C(/F)c2ccc(cn2)C#N)ccc1F)C(O)=O IRLAUZMPCLFJAE-PXNMLYILSA-N 0.000 claims 4
• GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims 4
• 208000024827 Alzheimer disease Diseases 0.000 claims 4
• 208000010877 cognitive disease Diseases 0.000 claims 4
• 239000003814 drug Substances 0.000 claims 4
• 229940079593 drug Drugs 0.000 claims 4
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
• 125000004076 pyridyl group Chemical group 0.000 claims 4
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 4
• 229920002554 vinyl polymer Polymers 0.000 claims 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
• 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 claims 2
• GDBAWUOZQRRHNL-NVNXTCNLSA-N 2-amino-4-[5-[(Z)-2-(5-chloropyridin-2-yl)-2-fluoroethenyl]-2-fluorophenyl]-4,6-dimethyl-5H-1,3-thiazine-6-carboxylic acid Chemical compound CC1(CC(C)(N=C(N)S1)c1cc(\C=C(/F)c2ccc(Cl)cn2)ccc1F)C(O)=O GDBAWUOZQRRHNL-NVNXTCNLSA-N 0.000 claims 2
• GSHVIWQGAADYSD-AUWJEWJLSA-N 2-amino-4-[5-[(Z)-2-(5-chloropyridin-2-yl)-2-fluoroethenyl]-2-fluorophenyl]-4-methyl-5,6-dihydro-1,3-thiazine-6-carboxylic acid Chemical compound CC1(CC(SC(N)=N1)C(O)=O)c1cc(\C=C(/F)c2ccc(Cl)cn2)ccc1F GSHVIWQGAADYSD-AUWJEWJLSA-N 0.000 claims 2
• WKOIVUXVVOAIDL-QHVUTBCBSA-N 6-[(Z)-2-[3-[(4S)-2-amino-4-methyl-1,3-thiazin-4-yl]-4-fluorophenyl]-1-fluoroethenyl]pyridine-3-carbonitrile Chemical compound NC=1SC=C[C@@](N=1)(C)C=1C=C(C=CC=1F)\C=C(/F)\C1=NC=C(C#N)C=C1 WKOIVUXVVOAIDL-QHVUTBCBSA-N 0.000 claims 2
• OEEHPGXMFVJORU-QHVUTBCBSA-N 6-[(Z)-2-[3-[(4S)-2-amino-4-methyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]-1-fluoroethenyl]pyridine-3-carbonitrile Chemical compound C[C@]1(CCSC(N)=N1)C1=C(F)C=CC(\C=C(/F)C2=CC=C(C=N2)C#N)=C1 OEEHPGXMFVJORU-QHVUTBCBSA-N 0.000 claims 2
• ADMYTHHAGLTLOW-UHFFFAOYSA-N C1C=C(SC=N1)C(=O)N Chemical compound C1C=C(SC=N1)C(=O)N ADMYTHHAGLTLOW-UHFFFAOYSA-N 0.000 claims 2
• 206010008111 Cerebral haemorrhage Diseases 0.000 claims 2
• 208000028698 Cognitive impairment Diseases 0.000 claims 2
• 208000011990 Corticobasal Degeneration Diseases 0.000 claims 2
• 201000010374 Down Syndrome Diseases 0.000 claims 2
• 208000018737 Parkinson disease Diseases 0.000 claims 2
• DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 claims 2
• 206010002022 amyloidosis Diseases 0.000 claims 2
• 210000004556 brain Anatomy 0.000 claims 2
• 230000002490 cerebral effect Effects 0.000 claims 2
• 210000001175 cerebrospinal fluid Anatomy 0.000 claims 2
• 229910052736 halogen Inorganic materials 0.000 claims 2
• 150000002367 halogens Chemical class 0.000 claims 2
• LCEDQNDDFOCWGG-UHFFFAOYSA-N morpholine-4-carbaldehyde Chemical compound O=CN1CCOCC1 LCEDQNDDFOCWGG-UHFFFAOYSA-N 0.000 claims 2
• 230000007505 plaque formation Effects 0.000 claims 2
• KDZXSSXGZIROJU-YHTSIIMFSA-N (4S)-4-[5-[(Z)-2-(5-chloropyridin-2-yl)-2-fluoroethenyl]-2-fluorophenyl]-4-methyl-1,3-thiazin-2-amine Chemical compound ClC=1C=CC(=NC=1)/C(=C/C=1C=CC(=C(C=1)[C@]1(N=C(SC=C1)N)C)F)/F KDZXSSXGZIROJU-YHTSIIMFSA-N 0.000 claims 1
• SUXMDOZZNWAJIB-YHTSIIMFSA-N (4S)-4-[5-[(Z)-2-(5-chloropyridin-2-yl)-2-fluoroethenyl]-2-fluorophenyl]-4-methyl-5,6-dihydro-1,3-thiazin-2-amine Chemical compound C[C@]1(CCSC(N)=N1)C1=C(F)C=CC(\C=C(/F)C2=NC=C(Cl)C=C2)=C1 SUXMDOZZNWAJIB-YHTSIIMFSA-N 0.000 claims 1
• 208000012902 Nervous system disease Diseases 0.000 claims 1
• 206010033799 Paralysis Diseases 0.000 claims 1
• 206010048327 Supranuclear palsy Diseases 0.000 claims 1
• 230000029936 alkylation Effects 0.000 claims 1
• 238000005804 alkylation reaction Methods 0.000 claims 1
• 125000004093 cyano group Chemical group *C#N 0.000 claims 1
• 125000001153 fluoro group Chemical group F* 0.000 claims 1
• 125000001072 heteroaryl group Chemical group 0.000 claims 1
• 208000027061 mild cognitive impairment Diseases 0.000 claims 1
• 201000001119 neuropathy Diseases 0.000 claims 1
• 230000007823 neuropathy Effects 0.000 claims 1
• 208000033808 peripheral neuropathy Diseases 0.000 claims 1
• 239000000546 pharmaceutical excipient Substances 0.000 claims 1
• 125000003373 pyrazinyl group Chemical group 0.000 claims 1