CA2780759A1 - Protein kinase c inhibitors and uses thereof - Google Patents

Info

Publication number

CA2780759A1

CA2780759A1 CA2780759A CA2780759A CA2780759A1 CA 2780759 A1 CA2780759 A1 CA 2780759A1 CA 2780759 A CA2780759 A CA 2780759A CA 2780759 A CA2780759 A CA 2780759A CA 2780759 A1 CA2780759 A1 CA 2780759A1

Authority

CA

Canada

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 229940123924 Protein kinase C inhibitor Drugs 0.000 title description 2
• 239000003881 protein kinase C inhibitor Substances 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 294
• 108090000315 Protein Kinase C Proteins 0.000 claims abstract description 145
• 102000003923 Protein Kinase C Human genes 0.000 claims abstract description 145
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 108
• 238000000034 method Methods 0.000 claims abstract description 80
• 230000000694 effects Effects 0.000 claims abstract description 50
• 230000001404 mediated effect Effects 0.000 claims abstract description 31
• 238000011282 treatment Methods 0.000 claims abstract description 26
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
• 230000002459 sustained effect Effects 0.000 claims abstract description 6
• 125000000217 alkyl group Chemical group 0.000 claims description 268
• -1 amino, substituted amino, carboxyl Chemical group 0.000 claims description 218
• 229910052739 hydrogen Inorganic materials 0.000 claims description 205
• 239000001257 hydrogen Substances 0.000 claims description 204
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 172
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 158
• 125000000623 heterocyclic group Chemical group 0.000 claims description 157
• 125000001072 heteroaryl group Chemical group 0.000 claims description 142
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 122
• 229910052736 halogen Inorganic materials 0.000 claims description 98
• 125000002252 acyl group Chemical group 0.000 claims description 94
• 125000003118 aryl group Chemical group 0.000 claims description 85
• 150000002367 halogens Chemical group 0.000 claims description 85
• 125000003545 alkoxy group Chemical group 0.000 claims description 77
• 125000005415 substituted alkoxy group Chemical group 0.000 claims description 74
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 72
• 150000003839 salts Chemical class 0.000 claims description 66
• 201000010099 disease Diseases 0.000 claims description 61
• 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 59
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 59
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 57
• 125000000304 alkynyl group Chemical group 0.000 claims description 51
• 125000003342 alkenyl group Chemical group 0.000 claims description 50
• 125000005017 substituted alkenyl group Chemical group 0.000 claims description 47
• 125000004426 substituted alkynyl group Chemical group 0.000 claims description 47
• 208000035475 disorder Diseases 0.000 claims description 46
• 125000003107 substituted aryl group Chemical group 0.000 claims description 42
• 238000003556 assay Methods 0.000 claims description 39
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 38
• 125000002947 alkylene group Chemical group 0.000 claims description 38
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 37
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 32
• 125000001153 fluoro group Chemical group F* 0.000 claims description 32
• 125000004442 acylamino group Chemical group 0.000 claims description 31
• 239000012453 solvate Substances 0.000 claims description 28
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
• 230000002757 inflammatory effect Effects 0.000 claims description 22
• 210000001744 T-lymphocyte Anatomy 0.000 claims description 20
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 18
• 206010028980 Neoplasm Diseases 0.000 claims description 17
• 208000022873 Ocular disease Diseases 0.000 claims description 16
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 16
• 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 15
• 230000005764 inhibitory process Effects 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
• 239000012472 biological sample Substances 0.000 claims description 12
• 229940002612 prodrug Drugs 0.000 claims description 11
• 239000000651 prodrug Substances 0.000 claims description 11
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 9
• 230000002401 inhibitory effect Effects 0.000 claims description 9
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
• 208000028867 ischemia Diseases 0.000 claims description 8
• 201000006417 multiple sclerosis Diseases 0.000 claims description 8
• 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 7
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical class OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 7
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 7
• 230000004913 activation Effects 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 7
• 239000000523 sample Substances 0.000 claims description 7
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 6
• 159000000021 acetate salts Chemical class 0.000 claims description 6
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical class [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 6
• 208000027866 inflammatory disease Diseases 0.000 claims description 6
• 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 5
• 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 5
• OCIZSTIHTDBDFL-UHFFFAOYSA-N 1-[5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-(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=C1OC1COC1 OCIZSTIHTDBDFL-UHFFFAOYSA-N 0.000 claims description 5
• RZWDZBKHCHFJLR-UHFFFAOYSA-N 1-[5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-propan-2-yloxy-3-(trifluoromethyl)phenyl]-4-methyltetrazol-5-one Chemical compound C1=C(C(F)(F)F)C(OC(C)C)=C(N2C(N(C)N=N2)=O)C=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 RZWDZBKHCHFJLR-UHFFFAOYSA-N 0.000 claims description 5
• 208000009329 Graft vs Host Disease Diseases 0.000 claims description 5
• 206010019280 Heart failures Diseases 0.000 claims description 5
• 206010020751 Hypersensitivity Diseases 0.000 claims description 5
• 201000004681 Psoriasis Diseases 0.000 claims description 5
• 230000007815 allergy Effects 0.000 claims description 5
• 208000006673 asthma Diseases 0.000 claims description 5
• 150000001558 benzoic acid derivatives Chemical class 0.000 claims description 5
• 201000011510 cancer Diseases 0.000 claims description 5
• 208000037976 chronic inflammation Diseases 0.000 claims description 5
• 150000001860 citric acid derivatives Chemical class 0.000 claims description 5
• 150000004675 formic acid derivatives Chemical class 0.000 claims description 5
• 208000024908 graft versus host disease Diseases 0.000 claims description 5
• 150000002688 maleic acid derivatives Chemical class 0.000 claims description 5
• 208000010125 myocardial infarction Diseases 0.000 claims description 5
• 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 4
• 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 4
• DLQSAOIIZIFBSL-UHFFFAOYSA-N 1-[2-chloro-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(Cl)=C(C=2)N2C(N(C)N=N2)=O)F)=NC=C1F DLQSAOIIZIFBSL-UHFFFAOYSA-N 0.000 claims description 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
• XVXNDEPKECAPTD-UHFFFAOYSA-N 1-[5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2,3-dimethylphenyl]-4-methyltetrazol-5-one Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(C)=C(C)C=2)N2C(N(C)N=N2)=O)=NC=C1F XVXNDEPKECAPTD-UHFFFAOYSA-N 0.000 claims description 4
• 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 4
• 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 4
• XBEXCZLWOWTTAU-UHFFFAOYSA-N 1-[5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-(oxetan-3-yloxy)phenyl]-4-methyltetrazol-5-one Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(OC3COC3)=CC=2)N2C(N(C)N=N2)=O)=NC=C1F XBEXCZLWOWTTAU-UHFFFAOYSA-N 0.000 claims description 4
• 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 4
• WUFZZSSAKYWINZ-UHFFFAOYSA-N 1-[5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-propan-2-yloxy-3-(trifluoromethyl)phenyl]-4-methyltetrazol-5-one Chemical compound C1=C(C(F)(F)F)C(OC(C)C)=C(N2C(N(C)N=N2)=O)C=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)N(C)C(C)(C)C1 WUFZZSSAKYWINZ-UHFFFAOYSA-N 0.000 claims description 4
• SGYJJVFPSFIHQQ-UHFFFAOYSA-N 1-[5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2,3-dimethylphenyl]-4-methyltetrazol-5-one Chemical compound C=1C(N2C(N(C)N=N2)=O)=C(C)C(C)=CC=1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 SGYJJVFPSFIHQQ-UHFFFAOYSA-N 0.000 claims description 4
• SYDHZOULYFQDQZ-UHFFFAOYSA-N 1-[5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-(1,1,1-trifluoro-2-methylpropan-2-yl)oxyphenyl]-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=C1OC(C)(C)C(F)(F)F SYDHZOULYFQDQZ-UHFFFAOYSA-N 0.000 claims description 4
• RJPLZPMCGCGUDR-UHFFFAOYSA-N 1-[5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-(oxan-4-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=C1OC1CCOCC1 RJPLZPMCGCGUDR-UHFFFAOYSA-N 0.000 claims description 4
• MMRVAXALLLOUNL-UHFFFAOYSA-N 1-[5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-[(3-methyloxetan-3-yl)methoxy]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=C1OCC1(C)COC1 MMRVAXALLLOUNL-UHFFFAOYSA-N 0.000 claims description 4
• LFOIWZXERCSMCT-UHFFFAOYSA-N 1-[5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-methyl-3-(trifluoromethyl)phenyl]-4-methyltetrazol-5-one Chemical compound C1=C(C(F)(F)F)C(C)=C(N2C(N(C)N=N2)=O)C=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 LFOIWZXERCSMCT-UHFFFAOYSA-N 0.000 claims description 4
• YYZXGLSWGPYECZ-UHFFFAOYSA-N 1-[6-fluoro-3-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-methoxyphenyl]-4-methyltetrazol-5-one Chemical compound C1=CC(F)=C(N2C(N(C)N=N2)=O)C(OC)=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)N(C)C(C)(C)C1 YYZXGLSWGPYECZ-UHFFFAOYSA-N 0.000 claims description 4
• QYUOKBLGDCWBAS-UHFFFAOYSA-N 1-[6-fluoro-3-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-methoxyphenyl]-4-methyltetrazol-5-one Chemical compound C1=CC(F)=C(N2C(N(C)N=N2)=O)C(OC)=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 QYUOKBLGDCWBAS-UHFFFAOYSA-N 0.000 claims description 4
• FYHLVUVJUSAMCY-UHFFFAOYSA-N 2-[3-cyclopropyl-4-fluoro-5-(4-methyl-5-oxotetrazol-1-yl)anilino]-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(C#N)=CN=2)=CC(C2CC2)=C1F FYHLVUVJUSAMCY-UHFFFAOYSA-N 0.000 claims description 4
• QPTDKHVNGWZMFB-UHFFFAOYSA-N 2-[4-cyclopropyl-2-fluoro-5-(4-methyl-5-oxotetrazol-1-yl)anilino]-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile 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=C1C#N QPTDKHVNGWZMFB-UHFFFAOYSA-N 0.000 claims description 4
• HTFFZYWUFAOFBC-UHFFFAOYSA-N 2-[4-cyclopropyl-2-fluoro-5-(4-methyl-5-oxotetrazol-1-yl)anilino]-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(C#N)=CN=2)=C(F)C=C1C1CC1 HTFFZYWUFAOFBC-UHFFFAOYSA-N 0.000 claims description 4
• MINUKFGQHQKOPN-UHFFFAOYSA-N 2-[4-cyclopropyl-3-(4-methyl-5-oxotetrazol-1-yl)-5-(trifluoromethyl)anilino]-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(C#N)=CN=2)=CC(C(F)(F)F)=C1C1CC1 MINUKFGQHQKOPN-UHFFFAOYSA-N 0.000 claims description 4
• FFBXKPTUXUWNDX-UHFFFAOYSA-N 2-[4-cyclopropyl-3-fluoro-5-(4-methyl-5-oxotetrazol-1-yl)anilino]-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(C#N)=CN=2)=CC(F)=C1C1CC1 FFBXKPTUXUWNDX-UHFFFAOYSA-N 0.000 claims description 4
• FNOZOAANUAVIBR-UHFFFAOYSA-N 2-[4-cyclopropyl-3-fluoro-5-(4-methyl-5-oxotetrazol-1-yl)anilino]-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carboxamide Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(C(N)=O)=CN=2)=CC(F)=C1C1CC1 FNOZOAANUAVIBR-UHFFFAOYSA-N 0.000 claims description 4
• MUZMDCWXIKHEMB-UHFFFAOYSA-N 3-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-5-(4-methyl-5-oxotetrazol-1-yl)benzonitrile Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C=C(C=2)C#N)N2C(N(C)N=N2)=O)=NC=C1F MUZMDCWXIKHEMB-UHFFFAOYSA-N 0.000 claims description 4
• AAADLSUGXLKUOY-UHFFFAOYSA-N 3-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-5-(4-methyl-5-oxotetrazol-1-yl)benzonitrile Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC(C#N)=C1 AAADLSUGXLKUOY-UHFFFAOYSA-N 0.000 claims description 4
• GEBXEVCDUIJQCI-UHFFFAOYSA-N 4-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-(4-methyl-5-oxotetrazol-1-yl)benzonitrile Chemical compound O=C1N(C)N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=CC=C1C#N GEBXEVCDUIJQCI-UHFFFAOYSA-N 0.000 claims description 4
• IZJPJPQQYMCOOD-UHFFFAOYSA-N 5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-methyl-3-(4-methyl-5-oxotetrazol-1-yl)benzoic acid Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C(C(C)=C(C(O)=O)C=2)N2C(N(C)N=N2)=O)=NC=C1F IZJPJPQQYMCOOD-UHFFFAOYSA-N 0.000 claims description 4
• SNKYOBXFYQSUKL-UHFFFAOYSA-N 5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-n,2-dimethyl-3-(4-methyl-5-oxotetrazol-1-yl)benzamide Chemical compound C=1C(N2C(N(C)N=N2)=O)=C(C)C(C(=O)NC)=CC=1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)N(C)C(C)(C)C1 SNKYOBXFYQSUKL-UHFFFAOYSA-N 0.000 claims description 4
• PGUYSYIGCUINJJ-UHFFFAOYSA-N 5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-methyl-3-(4-methyl-5-oxotetrazol-1-yl)benzoic acid Chemical compound C1=C(N2C(N(C)N=N2)=O)C(C)=C(C(O)=O)C=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 PGUYSYIGCUINJJ-UHFFFAOYSA-N 0.000 claims description 4
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
• 208000011231 Crohn disease Diseases 0.000 claims description 4
• 206010012442 Dermatitis contact Diseases 0.000 claims description 4
• 208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 4
• 206010049567 Miller Fisher syndrome Diseases 0.000 claims description 4
• 206010052779 Transplant rejections Diseases 0.000 claims description 4
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
• 206010046851 Uveitis Diseases 0.000 claims description 4
• 206010012601 diabetes mellitus Diseases 0.000 claims description 4
• 230000003463 hyperproliferative effect Effects 0.000 claims description 4
• 208000015181 infectious disease Diseases 0.000 claims description 4
• 206010023332 keratitis Diseases 0.000 claims description 4
• 201000010666 keratoconjunctivitis Diseases 0.000 claims description 4
• HVZYQYSQBVXEHI-UHFFFAOYSA-N methyl 5-[[5-fluoro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-methyl-3-(4-methyl-5-oxotetrazol-1-yl)benzoate Chemical compound C=1C(N2C(N(C)N=N2)=O)=C(C)C(C(=O)OC)=CC=1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)N(C)C(C)(C)C1 HVZYQYSQBVXEHI-UHFFFAOYSA-N 0.000 claims description 4
• JFXGIOBPRWVFCC-UHFFFAOYSA-N methyl 5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]-2-methyl-3-(4-methyl-5-oxotetrazol-1-yl)benzoate Chemical compound C=1C(N2C(N(C)N=N2)=O)=C(C)C(C(=O)OC)=CC=1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 JFXGIOBPRWVFCC-UHFFFAOYSA-N 0.000 claims description 4
• 208000011580 syndromic disease Diseases 0.000 claims description 4
• CDLMDUOFJHDRNY-UHFFFAOYSA-N 2-[4-cyclopropyl-3-(4-methyl-5-oxotetrazol-1-yl)-5-(trifluoromethyl)anilino]-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile 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=C1C#N CDLMDUOFJHDRNY-UHFFFAOYSA-N 0.000 claims description 3
• 208000030507 AIDS Diseases 0.000 claims description 3
• 208000030090 Acute Disease Diseases 0.000 claims description 3
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
• 208000024827 Alzheimer disease Diseases 0.000 claims description 3
• 201000001320 Atherosclerosis Diseases 0.000 claims description 3
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
• 208000035473 Communicable disease Diseases 0.000 claims description 3
• 201000004624 Dermatitis Diseases 0.000 claims description 3
• 206010012438 Dermatitis atopic Diseases 0.000 claims description 3
• 208000002705 Glucose Intolerance Diseases 0.000 claims description 3
• 208000030836 Hashimoto thyroiditis Diseases 0.000 claims description 3
• 206010020772 Hypertension Diseases 0.000 claims description 3
• 206010067125 Liver injury Diseases 0.000 claims description 3
• 208000004852 Lung Injury Diseases 0.000 claims description 3
• 208000013901 Nephropathies and tubular disease Diseases 0.000 claims description 3
• 208000008589 Obesity Diseases 0.000 claims description 3
• 208000001647 Renal Insufficiency Diseases 0.000 claims description 3
• 206010063837 Reperfusion injury Diseases 0.000 claims description 3
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 3
• 206010039793 Seborrhoeic dermatitis Diseases 0.000 claims description 3
• 206010040070 Septic Shock Diseases 0.000 claims description 3
• 208000021386 Sjogren Syndrome Diseases 0.000 claims description 3
• 208000030886 Traumatic Brain injury Diseases 0.000 claims description 3
• 206010069363 Traumatic lung injury Diseases 0.000 claims description 3
• 206010044541 Traumatic shock Diseases 0.000 claims description 3
• 208000024248 Vascular System injury Diseases 0.000 claims description 3
• 208000012339 Vascular injury Diseases 0.000 claims description 3
• 206010053648 Vascular occlusion Diseases 0.000 claims description 3
• 230000001154 acute effect Effects 0.000 claims description 3
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 3
• 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 3
• 208000002029 allergic contact dermatitis Diseases 0.000 claims description 3
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 3
• 238000002399 angioplasty Methods 0.000 claims description 3
• 201000008937 atopic dermatitis Diseases 0.000 claims description 3
• 208000010668 atopic eczema Diseases 0.000 claims description 3
• 208000015114 central nervous system disease Diseases 0.000 claims description 3
• 208000037893 chronic inflammatory disorder Diseases 0.000 claims description 3
• 208000030533 eye disease Diseases 0.000 claims description 3
• 231100000753 hepatic injury Toxicity 0.000 claims description 3
• 208000001875 irritant dermatitis Diseases 0.000 claims description 3
• 201000006370 kidney failure Diseases 0.000 claims description 3
• 231100000515 lung injury Toxicity 0.000 claims description 3
• 206010028417 myasthenia gravis Diseases 0.000 claims description 3
• 235000020824 obesity Nutrition 0.000 claims description 3
• 201000008482 osteoarthritis Diseases 0.000 claims description 3
• 201000010065 polycystic ovary syndrome Diseases 0.000 claims description 3
• 201000009104 prediabetes syndrome Diseases 0.000 claims description 3
• 208000023504 respiratory system disease Diseases 0.000 claims description 3
• 208000037803 restenosis Diseases 0.000 claims description 3
• 208000008742 seborrheic dermatitis Diseases 0.000 claims description 3
• 230000036303 septic shock Effects 0.000 claims description 3
• 230000035939 shock Effects 0.000 claims description 3
• 208000017520 skin disease Diseases 0.000 claims description 3
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 3
• 230000009529 traumatic brain injury Effects 0.000 claims description 3
• 208000021331 vascular occlusion disease Diseases 0.000 claims description 3
• 208000020925 Bipolar disease Diseases 0.000 claims description 2
• 208000032843 Hemorrhage Diseases 0.000 claims description 2
• 208000006011 Stroke Diseases 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 17
• 125000005490 tosylate group Chemical class 0.000 claims 2
• 239000003112 inhibitor Substances 0.000 abstract description 16
• 230000008569 process Effects 0.000 abstract description 14
• 239000000543 intermediate Substances 0.000 abstract description 11
• 208000037765 diseases and disorders Diseases 0.000 abstract description 7
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 120
• 239000000203 mixture Substances 0.000 description 111
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 67
• 210000004027 cell Anatomy 0.000 description 60
• 125000000392 cycloalkenyl group Chemical group 0.000 description 52
• 235000019439 ethyl acetate Nutrition 0.000 description 52
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
• 239000007787 solid Substances 0.000 description 45
• 125000001424 substituent group Chemical group 0.000 description 43
• 229910001868 water Inorganic materials 0.000 description 42
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 38
• 239000000243 solution Substances 0.000 description 38
• 238000012360 testing method Methods 0.000 description 36
• 239000012044 organic layer Substances 0.000 description 35
• 238000006243 chemical reaction Methods 0.000 description 34
• 238000003786 synthesis reaction Methods 0.000 description 30
• 230000015572 biosynthetic process Effects 0.000 description 29
• 239000002904 solvent Substances 0.000 description 28
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 25
• 229910052701 rubidium Inorganic materials 0.000 description 25
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
• 239000000047 product Substances 0.000 description 24
• 125000005843 halogen group Chemical group 0.000 description 22
• 239000010410 layer Substances 0.000 description 22
• 108010029485 Protein Isoforms Proteins 0.000 description 21
• 102000001708 Protein Isoforms Human genes 0.000 description 21
• 238000005160 1H NMR spectroscopy Methods 0.000 description 20
• 239000007832 Na2SO4 Substances 0.000 description 20
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
• 229910052938 sodium sulfate Inorganic materials 0.000 description 20
• 235000011152 sodium sulphate Nutrition 0.000 description 20
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 19
• 241001465754 Metazoa Species 0.000 description 18
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 18
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 18
• 125000005309 thioalkoxy group Chemical group 0.000 description 18
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
• 241000282414 Homo sapiens Species 0.000 description 17
• 230000002829 reductive effect Effects 0.000 description 17
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 17
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 15
• XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 15
• 125000004432 carbon atom Chemical group C* 0.000 description 15
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 15
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
• 229910052757 nitrogen Inorganic materials 0.000 description 15
• 238000005481 NMR spectroscopy Methods 0.000 description 14
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 13
• 239000005977 Ethylene Substances 0.000 description 13
• 238000009472 formulation Methods 0.000 description 13
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
• 238000004809 thin layer chromatography Methods 0.000 description 13
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 12
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 12
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 12
• 239000012267 brine Substances 0.000 description 12
• 239000003814 drug Substances 0.000 description 12
• 150000002500 ions Chemical class 0.000 description 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
• 238000011160 research Methods 0.000 description 12
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 12
• 239000003981 vehicle Substances 0.000 description 12
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 11
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
• 239000007858 starting material Substances 0.000 description 11
• UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 10
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 10
• UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 10
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 10
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 10
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 10
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 10
• 125000004181 carboxyalkyl group Chemical group 0.000 description 10
• 230000003053 immunization Effects 0.000 description 10
• 238000002649 immunization Methods 0.000 description 10
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 10
• 238000002360 preparation method Methods 0.000 description 10
• 230000002062 proliferating effect Effects 0.000 description 10
• YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical compound NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 description 10
• 210000001519 tissue Anatomy 0.000 description 10
• PNWZZCRDHBFKJE-UHFFFAOYSA-N 1-(2-cyclopropyl-4-fluoro-5-nitrophenyl)-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC([N+]([O-])=O)=C(F)C=C1C1CC1 PNWZZCRDHBFKJE-UHFFFAOYSA-N 0.000 description 9
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 9
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
• 208000002250 Hematologic Neoplasms Diseases 0.000 description 9
• 108010044467 Isoenzymes Proteins 0.000 description 9
• 241000700159 Rattus Species 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 125000004423 acyloxy group Chemical group 0.000 description 9
• 150000001412 amines Chemical class 0.000 description 9
• 125000004104 aryloxy group Chemical group 0.000 description 9
• 230000037396 body weight Effects 0.000 description 9
• 239000000706 filtrate Substances 0.000 description 9
• 125000005553 heteroaryloxy group Chemical group 0.000 description 9
• 238000011534 incubation Methods 0.000 description 9
• 238000006467 substitution reaction Methods 0.000 description 9
• 239000003826 tablet Substances 0.000 description 9
• 125000005296 thioaryloxy group Chemical group 0.000 description 9
• 125000005404 thioheteroaryloxy group Chemical group 0.000 description 9
• 150000003573 thiols Chemical class 0.000 description 9
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
• 208000012526 B-cell neoplasm Diseases 0.000 description 8
• 208000017604 Hodgkin disease Diseases 0.000 description 8
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 8
• 125000004470 heterocyclooxy group Chemical group 0.000 description 8
• 239000003921 oil Substances 0.000 description 8
• 235000019198 oils Nutrition 0.000 description 8
• 150000003230 pyrimidines Chemical class 0.000 description 8
• 239000000741 silica gel Substances 0.000 description 8
• 229910002027 silica gel Inorganic materials 0.000 description 8
• 238000010561 standard procedure Methods 0.000 description 8
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 7
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 7
• 208000025317 T-cell and NK-cell neoplasm Diseases 0.000 description 7
• 239000004480 active ingredient Substances 0.000 description 7
• 125000000033 alkoxyamino group Chemical group 0.000 description 7
• 125000003277 amino group Chemical group 0.000 description 7
• 125000004429 atom Chemical group 0.000 description 7
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 7
• 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 7
• 239000002552 dosage form Substances 0.000 description 7
• 201000002491 encephalomyelitis Diseases 0.000 description 7
• 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 7
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 7
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
• 229910017604 nitric acid Inorganic materials 0.000 description 7
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 7
• PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 7
• 239000002953 phosphate buffered saline Substances 0.000 description 7
• 229910000027 potassium carbonate Inorganic materials 0.000 description 7
• 108090000765 processed proteins & peptides Proteins 0.000 description 7
• 125000006239 protecting group Chemical group 0.000 description 7
• 108090000623 proteins and genes Proteins 0.000 description 7
• 210000000130 stem cell Anatomy 0.000 description 7
• 150000003536 tetrazoles Chemical class 0.000 description 7
• 125000005323 thioketone group Chemical group 0.000 description 7
• WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 7
• GAMFOCVSHQFYPF-UHFFFAOYSA-N 1-(2-bromo-4-fluoro-5-nitrophenyl)-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC([N+]([O-])=O)=C(F)C=C1Br GAMFOCVSHQFYPF-UHFFFAOYSA-N 0.000 description 6
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• 102000001253 Protein Kinase Human genes 0.000 description 6
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
• YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 6
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 239000000284 extract Substances 0.000 description 6
• 239000012065 filter cake Substances 0.000 description 6
• 125000002541 furyl group Chemical group 0.000 description 6
• 238000004519 manufacturing process Methods 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 150000007522 mineralic acids Chemical class 0.000 description 6
• 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 6
• 150000007524 organic acids Chemical class 0.000 description 6
• 125000004043 oxo group Chemical group O=* 0.000 description 6
• 125000005255 oxyaminoacyl group Chemical group 0.000 description 6
• 239000000843 powder Substances 0.000 description 6
• 108060006633 protein kinase Proteins 0.000 description 6
• 239000011541 reaction mixture Substances 0.000 description 6
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 6
• 230000001225 therapeutic effect Effects 0.000 description 6
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 6
• SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 6
• DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 6
• 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 description 5
• OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 5
• 238000004293 19F NMR spectroscopy Methods 0.000 description 5
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 5
• VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 5
• VLRSADZEDXVUPG-UHFFFAOYSA-N 2-naphthalen-1-ylpyridine Chemical compound N1=CC=CC=C1C1=CC=CC2=CC=CC=C12 VLRSADZEDXVUPG-UHFFFAOYSA-N 0.000 description 5
• VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 5
• GDRVFDDBLLKWRI-UHFFFAOYSA-N 4H-quinolizine Chemical compound C1=CC=CN2CC=CC=C21 GDRVFDDBLLKWRI-UHFFFAOYSA-N 0.000 description 5
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 5
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 5
• 206010061187 Haematopoietic neoplasm Diseases 0.000 description 5
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 5
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 5
• 108010002350 Interleukin-2 Proteins 0.000 description 5
• 102000000588 Interleukin-2 Human genes 0.000 description 5
• 241000124008 Mammalia Species 0.000 description 5
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 5
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 5
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 5
• 239000012979 RPMI medium Substances 0.000 description 5
• 239000012980 RPMI-1640 medium Substances 0.000 description 5
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 5
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 5
• 241000700605 Viruses Species 0.000 description 5
• 230000001594 aberrant effect Effects 0.000 description 5
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 5
• 239000011575 calcium Substances 0.000 description 5
• 229910052791 calcium Inorganic materials 0.000 description 5
• 238000004440 column chromatography Methods 0.000 description 5
• 238000005859 coupling reaction Methods 0.000 description 5
• 229910052805 deuterium Inorganic materials 0.000 description 5
• 235000019441 ethanol Nutrition 0.000 description 5
• 239000012894 fetal calf serum Substances 0.000 description 5
• 230000014509 gene expression Effects 0.000 description 5
• 230000012010 growth Effects 0.000 description 5
• 150000004820 halides Chemical class 0.000 description 5
• 201000005787 hematologic cancer Diseases 0.000 description 5
• 125000005842 heteroatom Chemical group 0.000 description 5
• 150000002391 heterocyclic compounds Chemical class 0.000 description 5
• 125000001183 hydrocarbyl group Chemical group 0.000 description 5
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 5
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 5
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 5
• LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 5
• HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 5
• PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 5
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 5
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 5
• 210000001165 lymph node Anatomy 0.000 description 5
• 208000003747 lymphoid leukemia Diseases 0.000 description 5
• 208000019420 lymphoid neoplasm Diseases 0.000 description 5
• 201000000050 myeloid neoplasm Diseases 0.000 description 5
• 230000002093 peripheral effect Effects 0.000 description 5
• LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 5
• XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 5
• 125000003386 piperidinyl group Chemical group 0.000 description 5
• 235000015320 potassium carbonate Nutrition 0.000 description 5
• 210000004986 primary T-cell Anatomy 0.000 description 5
• 235000018102 proteins Nutrition 0.000 description 5
• 102000004169 proteins and genes Human genes 0.000 description 5
• CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 5
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 5
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 5
• 238000010992 reflux Methods 0.000 description 5
• 239000000829 suppository Substances 0.000 description 5
• 238000002560 therapeutic procedure Methods 0.000 description 5
• 229930192474 thiophene Natural products 0.000 description 5
• 238000002054 transplantation Methods 0.000 description 5
• 150000003852 triazoles Chemical class 0.000 description 5
• 125000004953 trihalomethyl group Chemical group 0.000 description 5
• 229940035893 uracil Drugs 0.000 description 5
• OFWRVKYSHHIRRQ-UHFFFAOYSA-N 1-(2-bromo-4-fluorophenyl)-2h-tetrazol-5-one Chemical compound BrC1=CC(F)=CC=C1N1C(=O)NN=N1 OFWRVKYSHHIRRQ-UHFFFAOYSA-N 0.000 description 4
• WHPFEQUEHBULBW-UHFFFAOYSA-N 2,4-dichloro-5-fluoropyrimidine Chemical compound FC1=CN=C(Cl)N=C1Cl WHPFEQUEHBULBW-UHFFFAOYSA-N 0.000 description 4
• DCIBUUVLQYMJPQ-UHFFFAOYSA-N 2-chloro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(Cl)=NC=C1C#N DCIBUUVLQYMJPQ-UHFFFAOYSA-N 0.000 description 4
• HNMNCBZJXFIURI-UHFFFAOYSA-N 2-cyclopropyl-4-fluoro-5-nitroaniline Chemical compound NC1=CC([N+]([O-])=O)=C(F)C=C1C1CC1 HNMNCBZJXFIURI-UHFFFAOYSA-N 0.000 description 4
• FUFZNHHSSMCXCZ-UHFFFAOYSA-N 5-piperidin-4-yl-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C1=CC=CC(C=2N=C(ON=2)C2CCNCC2)=C1 FUFZNHHSSMCXCZ-UHFFFAOYSA-N 0.000 description 4
• 208000011691 Burkitt lymphomas Diseases 0.000 description 4
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
• 229920002261 Corn starch Polymers 0.000 description 4
• 238000002965 ELISA Methods 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 4
• 206010061218 Inflammation Diseases 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
• 229930182816 L-glutamine Natural products 0.000 description 4
• 108060001084 Luciferase Proteins 0.000 description 4
• 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 4
• 102000006386 Myelin Proteins Human genes 0.000 description 4
• 108010083674 Myelin Proteins Proteins 0.000 description 4
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 4
• WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 4
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 4
• 101150077555 Ret gene Proteins 0.000 description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
• 230000006044 T cell activation Effects 0.000 description 4
• 108091008874 T cell receptors Proteins 0.000 description 4
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 4
• IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
• 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 description 4
• 101710112791 Tyrosine-protein kinase JAK2 Proteins 0.000 description 4
• 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 4
• 125000001931 aliphatic group Chemical group 0.000 description 4
• 239000003513 alkali Substances 0.000 description 4
• 206010003246 arthritis Diseases 0.000 description 4
• 125000003725 azepanyl group Chemical group 0.000 description 4
• 125000002393 azetidinyl group Chemical group 0.000 description 4
• 239000002585 base Substances 0.000 description 4
• 229940098773 bovine serum albumin Drugs 0.000 description 4
• 230000001413 cellular effect Effects 0.000 description 4
• 239000008120 corn starch Substances 0.000 description 4
• 230000007423 decrease Effects 0.000 description 4
• 239000003480 eluent Substances 0.000 description 4
• 229940088598 enzyme Drugs 0.000 description 4
• 150000002148 esters Chemical class 0.000 description 4
• 238000002474 experimental method Methods 0.000 description 4
• 239000012091 fetal bovine serum Substances 0.000 description 4
• 239000012458 free base Substances 0.000 description 4
• 201000009277 hairy cell leukemia Diseases 0.000 description 4
• 230000004054 inflammatory process Effects 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
• 235000019341 magnesium sulphate Nutrition 0.000 description 4
• 229910052751 metal Inorganic materials 0.000 description 4
• 239000002184 metal Substances 0.000 description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
• 231100000252 nontoxic Toxicity 0.000 description 4
• 230000003000 nontoxic effect Effects 0.000 description 4
• 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 4
• 238000003305 oral gavage Methods 0.000 description 4
• 239000002243 precursor Substances 0.000 description 4
• 230000002265 prevention Effects 0.000 description 4
• 230000035755 proliferation Effects 0.000 description 4
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
• 235000017557 sodium bicarbonate Nutrition 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 239000000758 substrate Substances 0.000 description 4
• 229910052717 sulfur Chemical group 0.000 description 4
• 239000006228 supernatant Substances 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• 238000010189 synthetic method Methods 0.000 description 4
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 4
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 4
• 229940124597 therapeutic agent Drugs 0.000 description 4
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
• CGXOAAMIQPDTPE-UHFFFAOYSA-N 1,2,2,6,6-pentamethylpiperidin-4-amine Chemical compound CN1C(C)(C)CC(N)CC1(C)C CGXOAAMIQPDTPE-UHFFFAOYSA-N 0.000 description 3
• TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 3
• KKHQQDMOLRKWJA-UHFFFAOYSA-N 1-(2-bromo-4-fluorophenyl)-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC=C(F)C=C1Br KKHQQDMOLRKWJA-UHFFFAOYSA-N 0.000 description 3
• VEQFGOGMGJAANN-UHFFFAOYSA-N 1-(2-cyclopropyl-4-fluoro-5-nitrophenyl)-2h-tetrazol-5-one Chemical compound C1=C(F)C([N+](=O)[O-])=CC(N2C(NN=N2)=O)=C1C1CC1 VEQFGOGMGJAANN-UHFFFAOYSA-N 0.000 description 3
• HRGUNZREDKDSPB-UHFFFAOYSA-N 1-(5-amino-2-cyclopropyl-4-fluorophenyl)-4-methyltetrazol-5-one Chemical compound O=C1N(C)N=NN1C1=CC(N)=C(F)C=C1C1CC1 HRGUNZREDKDSPB-UHFFFAOYSA-N 0.000 description 3
• FBVOIJABNHHFIF-UHFFFAOYSA-N 2-bromo-4-fluoro-5-nitroaniline Chemical compound NC1=CC([N+]([O-])=O)=C(F)C=C1Br FBVOIJABNHHFIF-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
• 208000031404 Chromosome Aberrations Diseases 0.000 description 3
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 3
• ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 3
• 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 3
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
• 239000005089 Luciferase Substances 0.000 description 3
• 208000001344 Macular Edema Diseases 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 229930195725 Mannitol Natural products 0.000 description 3
• 241000699666 Mus <mouse, genus> Species 0.000 description 3
• 241000699670 Mus sp. Species 0.000 description 3
• 208000033833 Myelomonocytic Chronic Leukemia Diseases 0.000 description 3
• GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 3
• 229930182555 Penicillin Natural products 0.000 description 3
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 3
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 3
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 3
• 208000017442 Retinal disease Diseases 0.000 description 3
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
• 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 3
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
• 208000036142 Viral infection Diseases 0.000 description 3
• 239000002253 acid Substances 0.000 description 3
• 239000000654 additive Substances 0.000 description 3
• 125000002877 alkyl aryl group Chemical group 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 210000000709 aorta Anatomy 0.000 description 3
• 238000004166 bioassay Methods 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 229910000024 caesium carbonate Inorganic materials 0.000 description 3
• 235000011089 carbon dioxide Nutrition 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 150000001768 cations Chemical class 0.000 description 3
• 230000010261 cell growth Effects 0.000 description 3
• 239000001913 cellulose Substances 0.000 description 3
• 229920002678 cellulose Polymers 0.000 description 3
• 230000001684 chronic effect Effects 0.000 description 3
• 201000010902 chronic myelomonocytic leukemia Diseases 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 239000003636 conditioned culture medium Substances 0.000 description 3
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 230000001804 emulsifying effect Effects 0.000 description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
• MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 3
• 210000002950 fibroblast Anatomy 0.000 description 3
• 239000012530 fluid Substances 0.000 description 3
• 238000002875 fluorescence polarization Methods 0.000 description 3
• 235000011187 glycerol Nutrition 0.000 description 3
• 230000002140 halogenating effect Effects 0.000 description 3
• 150000003840 hydrochlorides Chemical class 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 208000032839 leukemia Diseases 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 206010025135 lupus erythematosus Diseases 0.000 description 3
• 235000010355 mannitol Nutrition 0.000 description 3
• 239000000594 mannitol Substances 0.000 description 3
• 230000007246 mechanism Effects 0.000 description 3
• 238000010172 mouse model Methods 0.000 description 3
• 210000005012 myelin Anatomy 0.000 description 3
• 239000012038 nucleophile Substances 0.000 description 3
• 235000005985 organic acids Nutrition 0.000 description 3
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 3
• 229940049954 penicillin Drugs 0.000 description 3
• 239000000546 pharmaceutical excipient Substances 0.000 description 3
• 239000006187 pill Substances 0.000 description 3
• 229920001223 polyethylene glycol Polymers 0.000 description 3
• 229920001592 potato starch Polymers 0.000 description 3
• 239000002244 precipitate Substances 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 125000002577 pseudohalo group Chemical group 0.000 description 3
• 150000003254 radicals Chemical class 0.000 description 3
• 230000009467 reduction Effects 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 125000006413 ring segment Chemical group 0.000 description 3
• 229960005322 streptomycin Drugs 0.000 description 3
• 239000011593 sulfur Chemical group 0.000 description 3
• 230000004083 survival effect Effects 0.000 description 3
• 230000000699 topical effect Effects 0.000 description 3
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
• 230000005945 translocation Effects 0.000 description 3
• 238000001665 trituration Methods 0.000 description 3
• 230000009385 viral infection Effects 0.000 description 3
• 230000003612 virological effect Effects 0.000 description 3
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
• DDVILBOMZPOEAF-UHFFFAOYSA-N 1-(2-bromo-4-fluoro-5-nitrophenyl)-2h-tetrazol-5-one Chemical compound C1=C(F)C([N+](=O)[O-])=CC(N2C(NN=N2)=O)=C1Br DDVILBOMZPOEAF-UHFFFAOYSA-N 0.000 description 2
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
• NADZMUZERVWRKC-UHFFFAOYSA-N 1-methyl-4-[4-nitro-2-(trifluoromethyl)phenyl]piperazine Chemical compound C1CN(C)CCN1C1=CC=C([N+]([O-])=O)C=C1C(F)(F)F NADZMUZERVWRKC-UHFFFAOYSA-N 0.000 description 2
• FTVFPPFZRRKJIH-UHFFFAOYSA-N 2,2,6,6-tetramethylpiperidin-4-amine Chemical compound CC1(C)CC(N)CC(C)(C)N1 FTVFPPFZRRKJIH-UHFFFAOYSA-N 0.000 description 2
• BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 2
• IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 2
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
• PCPPHQICRFLBPM-UHFFFAOYSA-N 2-chloro-5-fluoro-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidin-4-amine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(Cl)=NC=C1F PCPPHQICRFLBPM-UHFFFAOYSA-N 0.000 description 2
• LOXQPDUWKQVKSN-UHFFFAOYSA-N 2-chloro-5-fluoro-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidin-4-amine;hydrochloride Chemical compound Cl.C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(Cl)=NC=C1F LOXQPDUWKQVKSN-UHFFFAOYSA-N 0.000 description 2
• JWQXDHKFVICOAN-UHFFFAOYSA-N 2-chloro-5-fluoro-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidin-4-amine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(Cl)=NC=C1F JWQXDHKFVICOAN-UHFFFAOYSA-N 0.000 description 2
• 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 2
• PCJSQXQRMJJBBS-UHFFFAOYSA-N 4-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-5-phenylpyrimidine-2,4-diamine Chemical compound C1(=CC=CC=C1)C=1C(=NC(=NC=1)N)NC1CC(N(C(C1)(C)C)C)(C)C PCJSQXQRMJJBBS-UHFFFAOYSA-N 0.000 description 2
• LMNPKIOZMGYQIU-UHFFFAOYSA-N 5-(trifluoromethyl)-1h-pyrimidine-2,4-dione Chemical compound FC(F)(F)C1=CNC(=O)NC1=O LMNPKIOZMGYQIU-UHFFFAOYSA-N 0.000 description 2
• LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 2
• KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 description 2
• TUARVSWVPPVUGS-UHFFFAOYSA-N 5-nitrouracil Chemical compound [O-][N+](=O)C1=CNC(=O)NC1=O TUARVSWVPPVUGS-UHFFFAOYSA-N 0.000 description 2
• 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 description 2
• GMMWNTHAIOJBSD-UHFFFAOYSA-N 6-chloro-4-n-(2,3-dimethylphenyl)-2-n,2-n-dimethylpyrimidine-2,4-diamine Chemical compound CN(C)C1=NC(Cl)=CC(NC=2C(=C(C)C=CC=2)C)=N1 GMMWNTHAIOJBSD-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 208000033496 Acute myeloid leukaemia with myelodysplasia-related features Diseases 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• 206010073478 Anaplastic large-cell lymphoma Diseases 0.000 description 2
• 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 2
• 241000208199 Buxus sempervirens Species 0.000 description 2
• 238000011749 CBA mouse Methods 0.000 description 2
• 206010007572 Cardiac hypertrophy Diseases 0.000 description 2
• 208000006029 Cardiomegaly Diseases 0.000 description 2
• 102000000503 Collagen Type II Human genes 0.000 description 2
• 108010041390 Collagen Type II Proteins 0.000 description 2
• 206010058202 Cystoid macular oedema Diseases 0.000 description 2
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
• 102000015212 Fas Ligand Protein Human genes 0.000 description 2
• 108010039471 Fas Ligand Protein Proteins 0.000 description 2
• 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 239000007995 HEPES buffer Substances 0.000 description 2
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 2
• 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 2
• 208000008839 Kidney Neoplasms Diseases 0.000 description 2
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
• 208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 description 2
• 241001139947 Mida Species 0.000 description 2
• 208000014767 Myeloproliferative disease Diseases 0.000 description 2
• 150000001204 N-oxides Chemical class 0.000 description 2
• SEQKRHFRPICQDD-UHFFFAOYSA-N N-tris(hydroxymethyl)methylglycine Chemical compound OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 description 2
• 108700020796 Oncogene Proteins 0.000 description 2
• 102000043276 Oncogene Human genes 0.000 description 2
• 208000003435 Optic Neuritis Diseases 0.000 description 2
• 206010033799 Paralysis Diseases 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• 208000009527 Refractory anemia Diseases 0.000 description 2
• 206010072684 Refractory cytopenia with unilineage dysplasia Diseases 0.000 description 2
• 206010038389 Renal cancer Diseases 0.000 description 2
• 108700008625 Reporter Genes Proteins 0.000 description 2
• 208000007014 Retinitis pigmentosa Diseases 0.000 description 2
• 206010038933 Retinopathy of prematurity Diseases 0.000 description 2
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
• 229940124639 Selective inhibitor Drugs 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 229920004890 Triton X-100 Polymers 0.000 description 2
• 239000013504 Triton X-100 Substances 0.000 description 2
• 230000003187 abdominal effect Effects 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
• DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
• 239000013543 active substance Substances 0.000 description 2
• 208000038016 acute inflammation Diseases 0.000 description 2
• 230000006022 acute inflammation Effects 0.000 description 2
• 208000016544 acute myeloid leukemia with multilineage dysplasia Diseases 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 150000001336 alkenes Chemical class 0.000 description 2
• 150000001345 alkine derivatives Chemical class 0.000 description 2
• 125000005133 alkynyloxy group Chemical group 0.000 description 2
• 230000000735 allogeneic effect Effects 0.000 description 2
• 125000003368 amide group Chemical group 0.000 description 2
• 210000000612 antigen-presenting cell Anatomy 0.000 description 2
• 230000006907 apoptotic process Effects 0.000 description 2
• 125000003710 aryl alkyl group Chemical group 0.000 description 2
• 229960005261 aspartic acid Drugs 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 238000005415 bioluminescence Methods 0.000 description 2
• 230000029918 bioluminescence Effects 0.000 description 2
• 210000003969 blast cell Anatomy 0.000 description 2
• 210000001185 bone marrow Anatomy 0.000 description 2
• 210000002168 brachiocephalic trunk Anatomy 0.000 description 2
• 239000006172 buffering agent Substances 0.000 description 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 239000002771 cell marker Substances 0.000 description 2
• 230000010307 cell transformation Effects 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 125000001309 chloro group Chemical group Cl* 0.000 description 2
• 231100000005 chromosome aberration Toxicity 0.000 description 2
• 230000006020 chronic inflammation Effects 0.000 description 2
• 229940110456 cocoa butter Drugs 0.000 description 2
• 235000019868 cocoa butter Nutrition 0.000 description 2
• 230000001186 cumulative effect Effects 0.000 description 2
• 125000006165 cyclic alkyl group Chemical group 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 2
• 201000010206 cystoid macular edema Diseases 0.000 description 2
• 230000002559 cytogenic effect Effects 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 230000018044 dehydration Effects 0.000 description 2
• 238000006297 dehydration reaction Methods 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 150000001982 diacylglycerols Chemical class 0.000 description 2
• 238000010790 dilution Methods 0.000 description 2
• 239000012895 dilution Substances 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 231100000676 disease causative agent Toxicity 0.000 description 2
• 239000003596 drug target Substances 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 238000003818 flash chromatography Methods 0.000 description 2
• 229960002949 fluorouracil Drugs 0.000 description 2
• 235000019253 formic acid Nutrition 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 102000054766 genetic haplotypes Human genes 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 239000003102 growth factor Substances 0.000 description 2
• 230000003394 haemopoietic effect Effects 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• 125000004404 heteroalkyl group Chemical group 0.000 description 2
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 2
• 238000005984 hydrogenation reaction Methods 0.000 description 2
• 210000002865 immune cell Anatomy 0.000 description 2
• 208000026278 immune system disease Diseases 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 230000008595 infiltration Effects 0.000 description 2
• 238000001764 infiltration Methods 0.000 description 2
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
• 201000010982 kidney cancer Diseases 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 150000002632 lipids Chemical class 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• 238000007726 management method Methods 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 239000012452 mother liquor Substances 0.000 description 2
• 208000017869 myelodysplastic/myeloproliferative disease Diseases 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 description 2
• 210000004287 null lymphocyte Anatomy 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• 229910052760 oxygen Inorganic materials 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• 230000036407 pain Effects 0.000 description 2
• 230000036961 partial effect Effects 0.000 description 2
• 239000008177 pharmaceutical agent Substances 0.000 description 2
• RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
• 150000004633 phorbol derivatives Chemical class 0.000 description 2
• 239000002644 phorbol ester Substances 0.000 description 2
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 210000001147 pulmonary artery Anatomy 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• 230000009257 reactivity Effects 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 230000000306 recurrent effect Effects 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 239000012047 saturated solution Substances 0.000 description 2
• 238000013207 serial dilution Methods 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• 230000019491 signal transduction Effects 0.000 description 2
• 230000011664 signaling Effects 0.000 description 2
• 239000000377 silicon dioxide Substances 0.000 description 2
• 210000002027 skeletal muscle Anatomy 0.000 description 2
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 210000004989 spleen cell Anatomy 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 230000000638 stimulation Effects 0.000 description 2
• 238000003756 stirring Methods 0.000 description 2
• 235000011149 sulphuric acid Nutrition 0.000 description 2
• 239000013589 supplement Substances 0.000 description 2
• 230000002194 synthesizing effect Effects 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
• 210000004881 tumor cell Anatomy 0.000 description 2
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
• 230000003442 weekly effect Effects 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
• 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 description 1
• CGWRSWPWEOFYGO-UICOGKGYSA-N 1-[2-cyclopropyl-4-fluoro-5-[[5-fluoro-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidin-2-yl]amino]phenyl]-4-(deuteriomethyl)tetrazol-5-one Chemical compound O=C1N(C[2H])N=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=C(F)C=C1C1CC1 CGWRSWPWEOFYGO-UICOGKGYSA-N 0.000 description 1
• DNTHMWUMRGOJRY-UHFFFAOYSA-N 1-fluoro-4-nitro-2-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(C(F)(F)F)=C1 DNTHMWUMRGOJRY-UHFFFAOYSA-N 0.000 description 1
• WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
• TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
• KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
• NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
• DZTIFMWYYHCREC-UHFFFAOYSA-N 2,4-dichloropyrimidine-5-carbonyl chloride Chemical compound ClC(=O)C1=CN=C(Cl)N=C1Cl DZTIFMWYYHCREC-UHFFFAOYSA-N 0.000 description 1
• OACCNUGECQQVLB-UHFFFAOYSA-N 2,4-dichloropyrimidine-5-carboxamide Chemical compound NC(=O)C1=CN=C(Cl)N=C1Cl OACCNUGECQQVLB-UHFFFAOYSA-N 0.000 description 1
• KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
• POVYZTLPZBUFBB-UHFFFAOYSA-N 2-bromo-4-fluoro-1-isocyanatobenzene Chemical compound FC1=CC=C(N=C=O)C(Br)=C1 POVYZTLPZBUFBB-UHFFFAOYSA-N 0.000 description 1
• YLMFXCIATJJKQL-UHFFFAOYSA-N 2-bromo-4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1Br YLMFXCIATJJKQL-UHFFFAOYSA-N 0.000 description 1
• AXZRUTPBQMAWLP-UHFFFAOYSA-N 2-bromo-4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C(Br)=C1 AXZRUTPBQMAWLP-UHFFFAOYSA-N 0.000 description 1
• MVJPGVRRYVHIKK-UHFFFAOYSA-N 2-chloro-4-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(Cl)=NC=C1C#N MVJPGVRRYVHIKK-UHFFFAOYSA-N 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• CBKDCOKSXCTDAA-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1-benzothiophene Chemical compound C1CCCC2=C1C=CS2 CBKDCOKSXCTDAA-UHFFFAOYSA-N 0.000 description 1
• 206010068532 5q minus syndrome Diseases 0.000 description 1
• XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 208000016557 Acute basophilic leukemia Diseases 0.000 description 1
• 206010000871 Acute monocytic leukaemia Diseases 0.000 description 1
• 206010000890 Acute myelomonocytic leukaemia Diseases 0.000 description 1
• 208000016585 Acute panmyelosis with myelofibrosis Diseases 0.000 description 1
• 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
• 206010001413 Adult T-cell lymphoma/leukaemia Diseases 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 102100034613 Annexin A2 Human genes 0.000 description 1
• 108090000668 Annexin A2 Proteins 0.000 description 1
• 101000719121 Arabidopsis thaliana Protein MEI2-like 1 Proteins 0.000 description 1
• 241001553178 Arachis glabrata Species 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 208000032568 B-cell prolymphocytic leukaemia Diseases 0.000 description 1
• 206010003908 B-cell small lymphocytic lymphoma Diseases 0.000 description 1
• 238000011725 BALB/c mouse Methods 0.000 description 1
• 208000033775 Basophilic Acute Leukemia Diseases 0.000 description 1
• 102000051485 Bcl-2 family Human genes 0.000 description 1
• 108700038897 Bcl-2 family Proteins 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• 206010048396 Bone marrow transplant rejection Diseases 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• LEQNPQWTSJNGPE-UHFFFAOYSA-N C(N)(=O)C=1C=NC=NC1.NC1=CC(=NC=N1)N Chemical class C(N)(=O)C=1C=NC=NC1.NC1=CC(=NC=N1)N LEQNPQWTSJNGPE-UHFFFAOYSA-N 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 241000700198 Cavia Species 0.000 description 1
• 108010001857 Cell Surface Receptors Proteins 0.000 description 1
• 102000000844 Cell Surface Receptors Human genes 0.000 description 1
• 206010008805 Chromosomal abnormalities Diseases 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
• CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
• 108700020911 DNA-Binding Proteins Proteins 0.000 description 1
• 102000052510 DNA-Binding Proteins Human genes 0.000 description 1
• CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
• 208000016192 Demyelinating disease Diseases 0.000 description 1
• 206010012305 Demyelination Diseases 0.000 description 1
• 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
• 208000003556 Dry Eye Syndromes Diseases 0.000 description 1
• 206010013774 Dry eye Diseases 0.000 description 1
• 206010058314 Dysplasia Diseases 0.000 description 1
• 238000008157 ELISA kit Methods 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 208000002460 Enteropathy-Associated T-Cell Lymphoma Diseases 0.000 description 1
• 208000036566 Erythroleukaemia Diseases 0.000 description 1
• 208000032027 Essential Thrombocythemia Diseases 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• 208000009386 Experimental Arthritis Diseases 0.000 description 1
• 206010015719 Exsanguination Diseases 0.000 description 1
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
• 208000033371 Extranodal NK/T-cell lymphoma, nasal type Diseases 0.000 description 1
• BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• 230000005526 G1 to G0 transition Effects 0.000 description 1
• 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 1
• 208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101100456320 Homo sapiens NR3C2 gene Proteins 0.000 description 1
• 101000944909 Homo sapiens Ribosomal protein S6 kinase alpha-1 Proteins 0.000 description 1
• 101000857677 Homo sapiens Runt-related transcription factor 1 Proteins 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 206010062016 Immunosuppression Diseases 0.000 description 1
• 102100023915 Insulin Human genes 0.000 description 1
• 108090001061 Insulin Proteins 0.000 description 1
• 108090000862 Ion Channels Proteins 0.000 description 1
• 102000004310 Ion Channels Human genes 0.000 description 1
• 208000010038 Ischemic Optic Neuropathy Diseases 0.000 description 1
• 206010023203 Joint destruction Diseases 0.000 description 1
• 229930194542 Keto Natural products 0.000 description 1
• 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 1
• 208000006404 Large Granular Lymphocytic Leukemia Diseases 0.000 description 1
• 201000003533 Leber congenital amaurosis Diseases 0.000 description 1
• 201000000639 Leber hereditary optic neuropathy Diseases 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
• 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
• 201000003791 MALT lymphoma Diseases 0.000 description 1
• 206010025415 Macular oedema Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 1
• 208000035490 Megakaryoblastic Acute Leukemia Diseases 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• 208000035489 Monocytic Acute Leukemia Diseases 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• 101100351501 Mus musculus Cbfb gene Proteins 0.000 description 1
• 208000033835 Myelomonocytic Acute Leukemia Diseases 0.000 description 1
• 208000037538 Myelomonocytic Juvenile Leukemia Diseases 0.000 description 1
• 206010029113 Neovascularisation Diseases 0.000 description 1
• 208000033755 Neutrophilic Chronic Leukemia Diseases 0.000 description 1
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
• 206010029461 Nodal marginal zone B-cell lymphomas Diseases 0.000 description 1
• 208000019569 Nodular lymphocyte predominant Hodgkin lymphoma Diseases 0.000 description 1
• 102000007999 Nuclear Proteins Human genes 0.000 description 1
• 108010089610 Nuclear Proteins Proteins 0.000 description 1
• 206010030113 Oedema Diseases 0.000 description 1
• 206010030924 Optic ischaemic neuropathy Diseases 0.000 description 1
• 206010061323 Optic neuropathy Diseases 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 108091082203 PKC family Proteins 0.000 description 1
• 102000042846 PKC family Human genes 0.000 description 1
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
• 206010033661 Pancytopenia Diseases 0.000 description 1
• 241001111421 Pannus Species 0.000 description 1
• 241000935974 Paralichthys dentatus Species 0.000 description 1
• 206010073286 Pathologic myopia Diseases 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 208000027190 Peripheral T-cell lymphomas Diseases 0.000 description 1
• 241000577979 Peromyscus spicilegus Species 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• 208000007452 Plasmacytoma Diseases 0.000 description 1
• 229920002732 Polyanhydride Polymers 0.000 description 1
• 206010036030 Polyarthritis Diseases 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 208000017414 Precursor T-cell acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000032758 Precursor T-lymphoblastic lymphoma/leukaemia Diseases 0.000 description 1
• 206010065857 Primary Effusion Lymphoma Diseases 0.000 description 1
• 206010036711 Primary mediastinal large B-cell lymphomas Diseases 0.000 description 1
• 208000035416 Prolymphocytic B-Cell Leukemia Diseases 0.000 description 1
• 208000033759 Prolymphocytic T-Cell Leukemia Diseases 0.000 description 1
• 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
• 102000001892 Protein Kinase C-theta Human genes 0.000 description 1
• 108010015499 Protein Kinase C-theta Proteins 0.000 description 1
• 108010010974 Proteolipids Proteins 0.000 description 1
• 102000016202 Proteolipids Human genes 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 239000007868 Raney catalyst Substances 0.000 description 1
• 229910000564 Raney nickel Inorganic materials 0.000 description 1
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
• 206010038460 Renal haemorrhage Diseases 0.000 description 1
• 201000007737 Retinal degeneration Diseases 0.000 description 1
• 206010038848 Retinal detachment Diseases 0.000 description 1
• 102100023606 Retinoic acid receptor alpha Human genes 0.000 description 1
• 206010038923 Retinopathy Diseases 0.000 description 1
• 102100033536 Ribosomal protein S6 kinase alpha-1 Human genes 0.000 description 1
• 102100025373 Runt-related transcription factor 1 Human genes 0.000 description 1
• 235000019485 Safflower oil Nutrition 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• 208000022758 Sorsby fundus dystrophy Diseases 0.000 description 1
• 208000035286 Spontaneous Remission Diseases 0.000 description 1
• 238000006619 Stille reaction Methods 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• 208000010502 Subcutaneous panniculitis-like T-cell lymphoma Diseases 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 206010042618 Surgical procedure repeated Diseases 0.000 description 1
• 238000006069 Suzuki reaction reaction Methods 0.000 description 1
• UZMAPBJVXOGOFT-UHFFFAOYSA-N Syringetin Natural products COC1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UZMAPBJVXOGOFT-UHFFFAOYSA-N 0.000 description 1
• 230000033540 T cell apoptotic process Effects 0.000 description 1
• 208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 description 1
• 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 description 1
• 206010042971 T-cell lymphoma Diseases 0.000 description 1
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 208000026651 T-cell prolymphocytic leukemia Diseases 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 239000007997 Tricine buffer Substances 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 108700005077 Viral Genes Proteins 0.000 description 1
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
• 210000003815 abdominal wall Anatomy 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 208000017733 acquired polycythemia vera Diseases 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 239000008186 active pharmaceutical agent Substances 0.000 description 1
• 208000021841 acute erythroid leukemia Diseases 0.000 description 1
• 208000013593 acute megakaryoblastic leukemia Diseases 0.000 description 1
• 208000020700 acute megakaryocytic leukemia Diseases 0.000 description 1
• 208000026784 acute myeloblastic leukemia with maturation Diseases 0.000 description 1
• 208000010816 acute myeloblastic leukemia without maturation Diseases 0.000 description 1
• 208000011912 acute myelomonocytic leukemia M4 Diseases 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 230000006978 adaptation Effects 0.000 description 1
• 208000009956 adenocarcinoma Diseases 0.000 description 1
• 230000001464 adherent effect Effects 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 208000015230 aggressive NK-cell leukemia Diseases 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 150000001335 aliphatic alkanes Chemical class 0.000 description 1
• 125000004450 alkenylene group Chemical group 0.000 description 1
• 125000005055 alkyl alkoxy group Chemical group 0.000 description 1
• 125000000278 alkyl amino alkyl group Chemical group 0.000 description 1
• 125000004414 alkyl thio group Chemical group 0.000 description 1
• 125000005275 alkylenearyl group Chemical class 0.000 description 1
• 125000004419 alkynylene group Chemical group 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 230000003872 anastomosis Effects 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 206010002449 angioimmunoblastic T-cell lymphoma Diseases 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 125000000129 anionic group Chemical group 0.000 description 1
• 201000007058 anterior ischemic optic neuropathy Diseases 0.000 description 1
• 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
• 230000003367 anti-collagen effect Effects 0.000 description 1
• 239000000427 antigen Substances 0.000 description 1
• 102000036639 antigens Human genes 0.000 description 1
• 108091007433 antigens Proteins 0.000 description 1
• 210000000702 aorta abdominal Anatomy 0.000 description 1
• 239000006286 aqueous extract Substances 0.000 description 1
• 150000004982 aromatic amines Chemical class 0.000 description 1
• 230000002917 arthritic effect Effects 0.000 description 1
• 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 1
• 150000001502 aryl halides Chemical class 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• 239000012911 assay medium Substances 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 239000003855 balanced salt solution Substances 0.000 description 1
• 239000011324 bead Substances 0.000 description 1
• 238000010009 beating Methods 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
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
• 230000027455 binding Effects 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000008827 biological function Effects 0.000 description 1
• 230000008499 blood brain barrier function Effects 0.000 description 1
• 210000001218 blood-brain barrier Anatomy 0.000 description 1
• 230000036760 body temperature Effects 0.000 description 1
• 210000002798 bone marrow cell Anatomy 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 230000005587 bubbling Effects 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 239000008366 buffered solution Substances 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 239000003560 cancer drug Substances 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 210000000845 cartilage Anatomy 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
• 238000006555 catalytic reaction Methods 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000032823 cell division Effects 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 230000023549 cell-cell signaling Effects 0.000 description 1
• 230000033077 cellular process Effects 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 210000000038 chest Anatomy 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
• 201000010903 chronic neutrophilic leukemia Diseases 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
• 229960004106 citric acid Drugs 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
• 239000005516 coenzyme A Substances 0.000 description 1
• 229940093530 coenzyme a Drugs 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 239000013066 combination product Substances 0.000 description 1
• 229940127555 combination product Drugs 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 208000010247 contact dermatitis Diseases 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 108010010201 core binding factor alpha Proteins 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 239000002285 corn oil Substances 0.000 description 1
• 230000004940 costimulation Effects 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 239000010779 crude oil Substances 0.000 description 1
• 125000004465 cycloalkenyloxy group Chemical group 0.000 description 1
• 125000000000 cycloalkoxy group Chemical group 0.000 description 1
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
• 208000024389 cytopenia Diseases 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 231100000433 cytotoxic Toxicity 0.000 description 1
• 230000001472 cytotoxic effect Effects 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
• 239000002274 desiccant Substances 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 150000001975 deuterium Chemical group 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
• 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 1
• 229910001873 dinitrogen Inorganic materials 0.000 description 1
• 238000002224 dissection Methods 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 239000006196 drop Substances 0.000 description 1
• 239000000890 drug combination Substances 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 210000003979 eosinophil Anatomy 0.000 description 1
• 230000002327 eosinophilic effect Effects 0.000 description 1
• 230000003628 erosive effect Effects 0.000 description 1
• 230000000925 erythroid effect Effects 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 125000005290 ethynyloxy group Chemical group C(#C)O* 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 210000002744 extracellular matrix Anatomy 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 235000019197 fats Nutrition 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 125000003709 fluoroalkyl group Chemical group 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 201000003444 follicular lymphoma Diseases 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 238000002825 functional assay Methods 0.000 description 1
• 230000004927 fusion Effects 0.000 description 1
• 108020001507 fusion proteins Proteins 0.000 description 1
• 102000037865 fusion proteins Human genes 0.000 description 1
• 210000004475 gamma-delta t lymphocyte Anatomy 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 239000000174 gluconic acid Substances 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• 229950006191 gluconic acid Drugs 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 230000006377 glucose transport Effects 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 210000003714 granulocyte Anatomy 0.000 description 1
• 125000004438 haloalkoxy group Chemical group 0.000 description 1
• 125000001188 haloalkyl group Chemical group 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 230000009033 hematopoietic malignancy Effects 0.000 description 1
• 210000000777 hematopoietic system Anatomy 0.000 description 1
• 230000011132 hemopoiesis Effects 0.000 description 1
• 125000004475 heteroaralkyl group Chemical group 0.000 description 1
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
• 125000005885 heterocycloalkylalkyl group Chemical group 0.000 description 1
• 125000005844 heterocyclyloxy group Chemical group 0.000 description 1
• 125000004468 heterocyclylthio group Chemical group 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 238000001794 hormone therapy Methods 0.000 description 1
• 102000055277 human IL2 Human genes 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 229940071870 hydroiodic acid Drugs 0.000 description 1
• 230000007954 hypoxia Effects 0.000 description 1
• 150000002460 imidazoles Chemical class 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 230000001900 immune effect Effects 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 230000001506 immunosuppresive effect Effects 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 125000006301 indolyl methyl group Chemical group 0.000 description 1
• 208000017532 inherited retinal dystrophy Diseases 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 150000002484 inorganic compounds Chemical class 0.000 description 1
• 229910010272 inorganic material Inorganic materials 0.000 description 1
• 229940125396 insulin Drugs 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 238000004255 ion exchange chromatography Methods 0.000 description 1
• 239000002555 ionophore Substances 0.000 description 1
• 230000000236 ionophoric effect Effects 0.000 description 1
• 230000002427 irreversible effect Effects 0.000 description 1
• 230000000302 ischemic effect Effects 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• 208000018937 joint inflammation Diseases 0.000 description 1
• 201000005992 juvenile myelomonocytic leukemia Diseases 0.000 description 1
• 125000000468 ketone group Chemical group 0.000 description 1
• 238000011813 knockout mouse model Methods 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• 210000003141 lower extremity Anatomy 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 208000037652 lymphocytic-histiocytic predominance Hodgkin lymphoma Diseases 0.000 description 1
• 210000003563 lymphoid tissue Anatomy 0.000 description 1
• 201000007919 lymphoplasmacytic lymphoma Diseases 0.000 description 1
• 239000012139 lysis buffer Substances 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 208000002780 macular degeneration Diseases 0.000 description 1
• 201000010230 macular retinal edema Diseases 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 235000014380 magnesium carbonate Nutrition 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
• 239000000347 magnesium hydroxide Substances 0.000 description 1
• 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
• YIXJRHPUWRPCBB-UHFFFAOYSA-N magnesium nitrate Inorganic materials [Mg+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O YIXJRHPUWRPCBB-UHFFFAOYSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 230000003211 malignant effect Effects 0.000 description 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 208000020968 mature T-cell and NK-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 238000012961 medicinal therapy Methods 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 108020004999 messenger RNA Proteins 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• 206010061289 metastatic neoplasm Diseases 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
• 208000037524 mixed cellularity Hodgkin lymphoma Diseases 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 210000001616 monocyte Anatomy 0.000 description 1
• 210000005087 mononuclear cell Anatomy 0.000 description 1
• 150000002772 monosaccharides Chemical class 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 201000005962 mycosis fungoides Diseases 0.000 description 1
• 108010064578 myelin proteolipid protein (139-151) Proteins 0.000 description 1
• 210000003643 myeloid progenitor cell Anatomy 0.000 description 1
• 230000002107 myocardial effect Effects 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
• 210000000822 natural killer cell Anatomy 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• 208000025275 nodular sclerosis classical Hodgkin lymphoma Diseases 0.000 description 1
• 125000006574 non-aromatic ring group Chemical group 0.000 description 1
• 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
• 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
• 230000000683 nonmetastatic effect Effects 0.000 description 1
• 239000002777 nucleoside Substances 0.000 description 1
• 150000003833 nucleoside derivatives Chemical class 0.000 description 1
• 210000004248 oligodendroglia Anatomy 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 231100000590 oncogenic Toxicity 0.000 description 1
• 230000002246 oncogenic effect Effects 0.000 description 1
• 208000020911 optic nerve disease Diseases 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 150000002892 organic cations Chemical class 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
• 239000006179 pH buffering agent Substances 0.000 description 1
• 230000037324 pain perception Effects 0.000 description 1
• 238000002559 palpation Methods 0.000 description 1
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 230000001769 paralizing effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
• 230000002688 persistence Effects 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• 229950000688 phenothiazine Drugs 0.000 description 1
• 210000004214 philadelphia chromosome Anatomy 0.000 description 1
• WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 101150031651 pkc-3 gene Proteins 0.000 description 1
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
• 229910003446 platinum oxide Inorganic materials 0.000 description 1
• 210000001778 pluripotent stem cell Anatomy 0.000 description 1
• 239000003880 polar aprotic solvent Substances 0.000 description 1
• 229920000515 polycarbonate Polymers 0.000 description 1
• 239000004417 polycarbonate Substances 0.000 description 1
• 208000037244 polycythemia vera Diseases 0.000 description 1
• 229920000728 polyester Polymers 0.000 description 1
• 239000008389 polyethoxylated castor oil Substances 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 208000017426 precursor B-cell acute lymphoblastic leukemia Diseases 0.000 description 1
• 238000012746 preparative thin layer chromatography Methods 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 208000003476 primary myelofibrosis Diseases 0.000 description 1
• 210000001948 pro-b lymphocyte Anatomy 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• TURAMGVWNUTQKH-UHFFFAOYSA-N propa-1,2-dien-1-one Chemical group C=C=C=O TURAMGVWNUTQKH-UHFFFAOYSA-N 0.000 description 1
• 239000001294 propane Substances 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 239000003586 protic polar solvent Substances 0.000 description 1
• 150000003217 pyrazoles Chemical class 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
• CSNFMBGHUOSBFU-UHFFFAOYSA-N pyrimidine-2,4,5-triamine Chemical compound NC1=NC=C(N)C(N)=N1 CSNFMBGHUOSBFU-UHFFFAOYSA-N 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 238000004451 qualitative analysis Methods 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• 238000004445 quantitative analysis Methods 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 239000000700 radioactive tracer Substances 0.000 description 1
• 238000003653 radioligand binding assay Methods 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 239000011535 reaction buffer Substances 0.000 description 1
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
• 230000014493 regulation of gene expression Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 230000010076 replication Effects 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 230000004258 retinal degeneration Effects 0.000 description 1
• 230000004264 retinal detachment Effects 0.000 description 1
• 108091008726 retinoic acid receptors α Proteins 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 102220084927 rs778740017 Human genes 0.000 description 1
• 235000005713 safflower oil Nutrition 0.000 description 1
• 239000003813 safflower oil Substances 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• UAWABSHMGXMCRK-UHFFFAOYSA-L samarium(ii) iodide Chemical compound I[Sm]I UAWABSHMGXMCRK-UHFFFAOYSA-L 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 238000007423 screening assay Methods 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 230000020341 sensory perception of pain Effects 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 238000006884 silylation reaction Methods 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• 210000004872 soft tissue Anatomy 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 229940035044 sorbitan monolaurate Drugs 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 206010062113 splenic marginal zone lymphoma Diseases 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 206010041823 squamous cell carcinoma Diseases 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 239000012258 stirred mixture Substances 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
• 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
• 150000003462 sulfoxides Chemical class 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000008961 swelling Effects 0.000 description 1
• 210000005222 synovial tissue Anatomy 0.000 description 1
• 201000004595 synovitis Diseases 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• OUOJIFQQBPKAMU-UHFFFAOYSA-N tetrazol-5-one Chemical compound O=C1N=NN=N1 OUOJIFQQBPKAMU-UHFFFAOYSA-N 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 125000000464 thioxo group Chemical group S=* 0.000 description 1
• FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 239000006208 topical dosage form Substances 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 230000001131 transforming effect Effects 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
• 150000008648 triflates Chemical class 0.000 description 1
• PBIMIGNDTBRRPI-UHFFFAOYSA-N trifluoro borate Chemical compound FOB(OF)OF PBIMIGNDTBRRPI-UHFFFAOYSA-N 0.000 description 1
• 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• JLEXUIVKURIPFI-UHFFFAOYSA-N tris phosphate Chemical compound OP(O)(O)=O.OCC(N)(CO)CO JLEXUIVKURIPFI-UHFFFAOYSA-N 0.000 description 1
• 231100000588 tumorigenic Toxicity 0.000 description 1
• 230000000381 tumorigenic effect Effects 0.000 description 1
• 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
• 201000005112 urinary bladder cancer Diseases 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 210000001631 vena cava inferior Anatomy 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 210000004885 white matter Anatomy 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1
• 229910052727 yttrium Inorganic materials 0.000 description 1