JP5802677B2 - プロテインキナーゼｃ阻害剤およびその使用 - Google Patents

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Publication number

JP5802677B2

JP5802677B2 JP2012542165A JP2012542165A JP5802677B2 JP 5802677 B2 JP5802677 B2 JP 5802677B2 JP 2012542165 A JP2012542165 A JP 2012542165A JP 2012542165 A JP2012542165 A JP 2012542165A JP 5802677 B2 JP5802677 B2 JP 5802677B2

Authority

JP

Japan

Prior art keywords

fluoro

ylamino

methyl

tetrazol

phenyl

Prior art date

2009-12-01

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.)

Expired - Fee Related

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• 101710175516 14 kDa zinc-binding protein Proteins 0.000 title 1
• 229940123924 Protein kinase C inhibitor Drugs 0.000 title 1
• 239000003881 protein kinase C inhibitor Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 265
• 125000000217 alkyl group Chemical group 0.000 claims description 259
• -1 amino, carboxyl Chemical group 0.000 claims description 253
• 229910052739 hydrogen Inorganic materials 0.000 claims description 208
• 239000001257 hydrogen Substances 0.000 claims description 207
• 125000000623 heterocyclic group Chemical group 0.000 claims description 157
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 151
• 125000001072 heteroaryl group Chemical group 0.000 claims description 141
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 141
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 120
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 111
• 125000003118 aryl group Chemical group 0.000 claims description 102
• 229910052736 halogen Inorganic materials 0.000 claims description 92
• 125000002252 acyl group Chemical group 0.000 claims description 91
• 150000002367 halogens Chemical class 0.000 claims description 89
• 108090000315 Protein Kinase C Proteins 0.000 claims description 79
• 102000003923 Protein Kinase C Human genes 0.000 claims description 79
• 125000003545 alkoxy group Chemical group 0.000 claims description 71
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 64
• 201000010099 disease Diseases 0.000 claims description 64
• 150000003839 salts Chemical class 0.000 claims description 59
• 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 55
• 125000000304 alkynyl group Chemical group 0.000 claims description 53
• 125000003342 alkenyl group Chemical group 0.000 claims description 51
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 49
• 208000035475 disorder Diseases 0.000 claims description 47
• 230000000694 effects Effects 0.000 claims description 47
• 125000002947 alkylene group Chemical group 0.000 claims description 40
• 229910052757 nitrogen Inorganic materials 0.000 claims description 39
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 33
• 125000001153 fluoro group Chemical group F* 0.000 claims description 32
• 125000004442 acylamino group Chemical group 0.000 claims description 29
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 29
• 230000001404 mediated effect Effects 0.000 claims description 27
• 238000011282 treatment Methods 0.000 claims description 27
• 239000012453 solvate Substances 0.000 claims description 26
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
• 239000008194 pharmaceutical composition Substances 0.000 claims description 23
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 23
• 125000004432 carbon atom Chemical group C* 0.000 claims description 21
• 241000282414 Homo sapiens Species 0.000 claims description 19
• 241001465754 Metazoa Species 0.000 claims description 19
• 230000002757 inflammatory effect Effects 0.000 claims description 18
• 229920006395 saturated elastomer Polymers 0.000 claims description 18
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 16
• 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 15
• 239000003814 drug Substances 0.000 claims description 15
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 15
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 13
• 208000023275 Autoimmune disease Diseases 0.000 claims description 12
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
• 125000004122 cyclic group Chemical group 0.000 claims description 11
• 208000030533 eye disease Diseases 0.000 claims description 10
• 125000005842 heteroatom Chemical group 0.000 claims description 10
• 230000006044 T cell activation Effects 0.000 claims description 9
• 125000004429 atom Chemical group 0.000 claims description 9
• 125000001183 hydrocarbyl group Chemical group 0.000 claims description 9
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 9
• 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 8
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 8
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 7
• 230000002491 angiogenic effect Effects 0.000 claims description 7
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 7
• 208000027866 inflammatory disease Diseases 0.000 claims description 7
• 238000004519 manufacturing process Methods 0.000 claims description 7
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
• 125000001931 aliphatic group Chemical group 0.000 claims description 6
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
• 229910052717 sulfur Chemical group 0.000 claims description 6
• JRXJIGCQQDRUIV-UHFFFAOYSA-N 1-[2-cyclopropyl-5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC=C1C1CC1 JRXJIGCQQDRUIV-UHFFFAOYSA-N 0.000 claims description 5
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 5
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
• 239000011593 sulfur Chemical group 0.000 claims description 5
• 230000002459 sustained effect Effects 0.000 claims description 5
• YCBKWEWWGGPBAM-UHFFFAOYSA-N 5-phenyl-4-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1(=CC=CC=C1)C=1C(=NC(=NC=1)N)NC1CC(NC(C1)(C)C)(C)C YCBKWEWWGGPBAM-UHFFFAOYSA-N 0.000 claims description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 4
• 239000001301 oxygen Substances 0.000 claims description 4
• 125000006413 ring segment Chemical group 0.000 claims description 4
• PUUCFGYZKZDLEA-UHFFFAOYSA-N 1-[2,6-difluoro-3-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-methyltetrazol-5-one Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C(=C(C(F)=CC=2)N2C(N(C)N=N2)=O)F)=NC=C1F PUUCFGYZKZDLEA-UHFFFAOYSA-N 0.000 claims description 3
• LOGYTIMVAIIDDY-UHFFFAOYSA-N 1-[2,6-difluoro-3-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=C(F)C=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=C1F LOGYTIMVAIIDDY-UHFFFAOYSA-N 0.000 claims description 3
• ACOKGWBSHZSKIA-UHFFFAOYSA-N 1-[2-chloro-4-fluoro-5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=C(F)C=C1Cl ACOKGWBSHZSKIA-UHFFFAOYSA-N 0.000 claims description 3
• DRKMNTMQJWMKCQ-UHFFFAOYSA-N 1-[2-chloro-5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-methyltetrazol-5-one Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(Cl)=CC=2)N2C(N(C)N=N2)=O)=NC=C1F DRKMNTMQJWMKCQ-UHFFFAOYSA-N 0.000 claims description 3
• RYANWIJWDHPLGF-UHFFFAOYSA-N 1-[2-chloro-5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-3-(trifluoromethyl)phenyl]-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC(C(F)(F)F)=C1Cl RYANWIJWDHPLGF-UHFFFAOYSA-N 0.000 claims description 3
• SQIXWDJIPSMYTO-UHFFFAOYSA-N 1-[2-chloro-5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC=C1Cl SQIXWDJIPSMYTO-UHFFFAOYSA-N 0.000 claims description 3
• SQDWRAPQUQMHEY-UHFFFAOYSA-N 1-[2-cyclopropyl-3-fluoro-5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC(F)=C1C1CC1 SQDWRAPQUQMHEY-UHFFFAOYSA-N 0.000 claims description 3
• MJAXMBPQWZSTMK-UHFFFAOYSA-N 1-[2-cyclopropyl-4-fluoro-5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-methyltetrazol-5-one Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C(=CC(=C(C=2)N2C(N(C)N=N2)=O)C2CC2)F)=NC=C1F MJAXMBPQWZSTMK-UHFFFAOYSA-N 0.000 claims description 3
• CGWRSWPWEOFYGO-VPYROQPTSA-N 1-[2-cyclopropyl-4-fluoro-5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-(trideuteriomethyl)tetrazol-5-one Chemical compound O=C1N(C([2H])([2H])[2H])N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=C(F)C=C1C1CC1 CGWRSWPWEOFYGO-VPYROQPTSA-N 0.000 claims description 3
• CGWRSWPWEOFYGO-UHFFFAOYSA-N 1-[2-cyclopropyl-4-fluoro-5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=C(F)C=C1C1CC1 CGWRSWPWEOFYGO-UHFFFAOYSA-N 0.000 claims description 3
• CIORCHOFGHDWCX-UHFFFAOYSA-N 1-[2-cyclopropyl-5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-3-(trifluoromethyl)phenyl]-4-methyltetrazol-5-one Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(C3CC3)=C(C=2)N2C(N(C)N=N2)=O)C(F)(F)F)=NC=C1F CIORCHOFGHDWCX-UHFFFAOYSA-N 0.000 claims description 3
• HWGSCFJJCINYLP-UHFFFAOYSA-N 1-[2-cyclopropyl-5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-3-(trifluoromethyl)phenyl]-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC(C(F)(F)F)=C1C1CC1 HWGSCFJJCINYLP-UHFFFAOYSA-N 0.000 claims description 3
• HLYVGISNDNHMRA-UHFFFAOYSA-N 1-[3-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-5-(oxetan-3-yloxy)phenyl]-4-methyltetrazol-5-one Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=C(OC3COC3)C=2)N2C(N(C)N=N2)=O)=NC=C1F HLYVGISNDNHMRA-UHFFFAOYSA-N 0.000 claims description 3
• KNEKNESDJHXFEK-UHFFFAOYSA-N 1-[3-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-5-(trifluoromethyl)phenyl]-4-methyltetrazol-5-one Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=C(C=2)N2C(N(C)N=N2)=O)C(F)(F)F)=NC=C1F KNEKNESDJHXFEK-UHFFFAOYSA-N 0.000 claims description 3
• AUYAEELPWLXUTR-UHFFFAOYSA-N 1-[3-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-5-methoxyphenyl]-4-methyltetrazol-5-one Chemical compound C=1C(N2C(N(C)N=N2)=O)=CC(OC)=CC=1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)N(C)C(C)(C)C1 AUYAEELPWLXUTR-UHFFFAOYSA-N 0.000 claims description 3
• AETZGBGKMCNDSF-UHFFFAOYSA-N 1-[3-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-5-(oxetan-3-yloxy)phenyl]-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC(OC2COC2)=C1 AETZGBGKMCNDSF-UHFFFAOYSA-N 0.000 claims description 3
• WXGOHMWDDPBVDZ-UHFFFAOYSA-N 1-[3-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-5-(trifluoromethyl)phenyl]-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC(C(F)(F)F)=C1 WXGOHMWDDPBVDZ-UHFFFAOYSA-N 0.000 claims description 3
• ZGKRWXRFAKVAPT-UHFFFAOYSA-N 1-[3-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-5-methoxyphenyl]-4-methyltetrazol-5-one Chemical compound C=1C(N2C(N(C)N=N2)=O)=CC(OC)=CC=1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 ZGKRWXRFAKVAPT-UHFFFAOYSA-N 0.000 claims description 3
• JBFLPWZXBJDGIR-UHFFFAOYSA-N 1-[3-chloro-5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-methylphenyl]-4-methyltetrazol-5-one Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(C)=C(Cl)C=2)N2C(N(C)N=N2)=O)=NC=C1F JBFLPWZXBJDGIR-UHFFFAOYSA-N 0.000 claims description 3
• FYCINSPFXIGRPL-UHFFFAOYSA-N 1-[3-chloro-5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-methylphenyl]-4-methyltetrazol-5-one Chemical compound C1=C(N2C(N(C)N=N2)=O)C(C)=C(Cl)C=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 FYCINSPFXIGRPL-UHFFFAOYSA-N 0.000 claims description 3
• ROQGVJRDHXKHEP-UHFFFAOYSA-N 1-[3-chloro-5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC(Cl)=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=C1 ROQGVJRDHXKHEP-UHFFFAOYSA-N 0.000 claims description 3
• FEXKZLUVFQESSZ-UHFFFAOYSA-N 1-[3-cyclopropyl-2-fluoro-5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC(C2CC2)=C1F FEXKZLUVFQESSZ-UHFFFAOYSA-N 0.000 claims description 3
• JULQRINCWYXZHC-UHFFFAOYSA-N 1-[3-cyclopropyl-5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-methyltetrazol-5-one Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=C(C=2)C2CC2)N2C(N(C)N=N2)=O)=NC=C1F JULQRINCWYXZHC-UHFFFAOYSA-N 0.000 claims description 3
• UPMRZHACVQMULL-UHFFFAOYSA-N 1-[3-cyclopropyl-5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC(C2CC2)=C1 UPMRZHACVQMULL-UHFFFAOYSA-N 0.000 claims description 3
• XSVGHNSPSGZWJL-UHFFFAOYSA-N 1-[3-fluoro-5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-methyltetrazol-5-one Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=C(F)C=2)N2C(N(C)N=N2)=O)=NC=C1F XSVGHNSPSGZWJL-UHFFFAOYSA-N 0.000 claims description 3
• NPOURDHLPUTPKN-UHFFFAOYSA-N 1-[3-fluoro-5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC(F)=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=C1 NPOURDHLPUTPKN-UHFFFAOYSA-N 0.000 claims description 3
• NIXPJPGANXTIFX-UHFFFAOYSA-N 1-[4-fluoro-3-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC=C(F)C(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=C1 NIXPJPGANXTIFX-UHFFFAOYSA-N 0.000 claims description 3
• NAARYWGPIGVOCV-HIFRSBDPSA-N 1-[4-fluoro-5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-[(1s,2s)-2-(trifluoromethyl)cyclopropyl]phenyl]-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=C(F)C=C1[C@@H]1[C@@H](C(F)(F)F)C1 NAARYWGPIGVOCV-HIFRSBDPSA-N 0.000 claims description 3
• BFIBCXLPSFGLAF-UHFFFAOYSA-N 1-[5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-(1,1,1-trifluoro-2-methylpropan-2-yl)oxyphenyl]-4-methyltetrazol-5-one Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(OC(C)(C)C(F)(F)F)=CC=2)N2C(N(C)N=N2)=O)=NC=C1F BFIBCXLPSFGLAF-UHFFFAOYSA-N 0.000 claims description 3
• LEUAPHBHGUFLAP-UHFFFAOYSA-N 1-[5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-(oxan-4-yloxy)phenyl]-4-methyltetrazol-5-one Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(OC3CCOCC3)=CC=2)N2C(N(C)N=N2)=O)=NC=C1F LEUAPHBHGUFLAP-UHFFFAOYSA-N 0.000 claims description 3
• CMXHCHOUHWIZEW-UHFFFAOYSA-N 1-[5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-methyl-3-(trifluoromethyl)phenyl]-4-methyltetrazol-5-one Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(C)=C(C=2)N2C(N(C)N=N2)=O)C(F)(F)F)=NC=C1F CMXHCHOUHWIZEW-UHFFFAOYSA-N 0.000 claims description 3
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