AU2014370186A1 - Pyrazolo[1,5-a]pyridine derivatives and methods of their use - Google Patents

Info

Publication number

AU2014370186A1

AU2014370186A1 AU2014370186A AU2014370186A AU2014370186A1 AU 2014370186 A1 AU2014370186 A1 AU 2014370186A1 AU 2014370186 A AU2014370186 A AU 2014370186A AU 2014370186 A AU2014370186 A AU 2014370186A AU 2014370186 A1 AU2014370186 A1 AU 2014370186A1

Authority

AU

Australia

Prior art keywords

fluoro

compound

pyrazolo

alkyl

phenyl

Prior art date

2013-12-26

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
• Discuss

• 238000000034 method Methods 0.000 title claims description 189
• DVUBDHRTVYLIPA-UHFFFAOYSA-N pyrazolo[1,5-a]pyridine Chemical class C1=CC=CN2N=CC=C21 DVUBDHRTVYLIPA-UHFFFAOYSA-N 0.000 title abstract description 7
• 150000001875 compounds Chemical class 0.000 claims description 287
• -1 substituted Chemical class 0.000 claims description 111
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 72
• 229910052757 nitrogen Inorganic materials 0.000 claims description 55
• 125000003118 aryl group Chemical group 0.000 claims description 31
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 17
• 206010028980 Neoplasm Diseases 0.000 claims description 16
• 150000003839 salts Chemical class 0.000 claims description 16
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 14
• 201000011510 cancer Diseases 0.000 claims description 12
• 125000004076 pyridyl group Chemical group 0.000 claims description 12
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 10
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 10
• 125000004385 trihaloalkyl group Chemical group 0.000 claims description 9
• 208000005718 Stomach Neoplasms Diseases 0.000 claims description 7
• 125000002757 morpholinyl group Chemical group 0.000 claims description 6
• 125000004193 piperazinyl group Chemical group 0.000 claims description 6
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 6
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 6
• 206010017758 gastric cancer Diseases 0.000 claims description 5
• 125000002883 imidazolyl group Chemical group 0.000 claims description 5
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 5
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
• 125000002971 oxazolyl group Chemical group 0.000 claims description 5
• 125000003386 piperidinyl group Chemical group 0.000 claims description 5
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
• 201000011549 stomach cancer Diseases 0.000 claims description 5
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 5
• 125000000335 thiazolyl group Chemical group 0.000 claims description 5
• 206010006187 Breast cancer Diseases 0.000 claims description 4
• 208000026310 Breast neoplasm Diseases 0.000 claims description 4
• 206010009944 Colon cancer Diseases 0.000 claims description 4
• 201000001441 melanoma Diseases 0.000 claims description 4
• 208000003174 Brain Neoplasms Diseases 0.000 claims description 3
• 208000008839 Kidney Neoplasms Diseases 0.000 claims description 3
• 206010038389 Renal cancer Diseases 0.000 claims description 3
• 208000029742 colonic neoplasm Diseases 0.000 claims description 3
• 201000010982 kidney cancer Diseases 0.000 claims description 3
• 208000032839 leukemia Diseases 0.000 claims description 3
• 201000007270 liver cancer Diseases 0.000 claims description 3
• 208000014018 liver neoplasm Diseases 0.000 claims description 3
• 229910052799 carbon Inorganic materials 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims 33
• 229940043355 kinase inhibitor Drugs 0.000 abstract description 2
• 239000003757 phosphotransferase inhibitor Substances 0.000 abstract description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 276
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 271
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 236
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 189
• 238000005160 1H NMR spectroscopy Methods 0.000 description 182
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 171
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 166
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 103
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 98
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 92
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 88
• 239000000047 product Substances 0.000 description 69
• 235000019439 ethyl acetate Nutrition 0.000 description 65
• WPJGHIVGAOVUAT-UHFFFAOYSA-N 1-(4-fluorophenyl)-2-oxopyridine-3-carboxylic acid Chemical compound O=C1C(C(=O)O)=CC=CN1C1=CC=C(F)C=C1 WPJGHIVGAOVUAT-UHFFFAOYSA-N 0.000 description 61
• 238000006243 chemical reaction Methods 0.000 description 60
• 239000012267 brine Substances 0.000 description 59
• 239000000203 mixture Substances 0.000 description 59
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 59
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 52
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 50
• 229910052938 sodium sulfate Inorganic materials 0.000 description 50
• 235000011152 sodium sulphate Nutrition 0.000 description 50
• GDDMXXIYSLJCRK-UHFFFAOYSA-N 3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxylic acid Chemical compound O=C1N(C(C)C)C=C(C(O)=O)C(=O)N1C1=CC=C(F)C=C1 GDDMXXIYSLJCRK-UHFFFAOYSA-N 0.000 description 49
• IGIJOGBLFJFFHO-UHFFFAOYSA-N 1-ethyl-3-(4-fluorophenyl)-2,4-dioxopyrimidine-5-carboxylic acid Chemical compound O=C1N(CC)C=C(C(O)=O)C(=O)N1C1=CC=C(F)C=C1 IGIJOGBLFJFFHO-UHFFFAOYSA-N 0.000 description 47
• 239000012298 atmosphere Substances 0.000 description 46
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 45
• 229910000029 sodium carbonate Inorganic materials 0.000 description 44
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 43
• 125000005843 halogen group Chemical group 0.000 description 41
• 239000000243 solution Substances 0.000 description 39
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 38
• 229940093499 ethyl acetate Drugs 0.000 description 36
• 239000007787 solid Substances 0.000 description 35
• 239000000543 intermediate Substances 0.000 description 34
• 150000001408 amides Chemical class 0.000 description 33
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
• 238000010168 coupling process Methods 0.000 description 32
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
• 239000000741 silica gel Substances 0.000 description 26
• 229910002027 silica gel Inorganic materials 0.000 description 26
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 24
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 23
• 239000002253 acid Substances 0.000 description 23
• 101000807561 Homo sapiens Tyrosine-protein kinase receptor UFO Proteins 0.000 description 22
• 102100037236 Tyrosine-protein kinase receptor UFO Human genes 0.000 description 22
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 22
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 21
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 21
• COJCNRWONZZIHV-UHFFFAOYSA-N 6-bromo-4-(2-fluoro-4-nitrophenoxy)pyrazolo[1,5-a]pyridine Chemical compound BrC=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)[N+](=O)[O-])F COJCNRWONZZIHV-UHFFFAOYSA-N 0.000 description 20
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 20
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 20
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 20
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 20
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 20
• ZXFBBQJGPRZCHS-UHFFFAOYSA-N 6-bromopyrazolo[1,5-a]pyridin-4-ol Chemical compound OC1=CC(Br)=CN2N=CC=C12 ZXFBBQJGPRZCHS-UHFFFAOYSA-N 0.000 description 19
• 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 19
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 19
• 239000006229 carbon black Substances 0.000 description 18
• 239000002480 mineral oil Substances 0.000 description 18
• 235000010446 mineral oil Nutrition 0.000 description 18
• 230000009467 reduction Effects 0.000 description 18
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
• 229910052801 chlorine Inorganic materials 0.000 description 17
• BTPCWSQBSXUYHV-UHFFFAOYSA-N 1-(4-fluorophenyl)-6-methyl-2-oxopyridine-3-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)C(=O)N1C1=CC=C(F)C=C1 BTPCWSQBSXUYHV-UHFFFAOYSA-N 0.000 description 16
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
• 229910052731 fluorine Inorganic materials 0.000 description 16
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 15
• 239000012312 sodium hydride Substances 0.000 description 15
• 229910000104 sodium hydride Inorganic materials 0.000 description 15
• NSIBFUPUJYMBJZ-UHFFFAOYSA-N 3-fluoro-4-[6-(1-methylimidazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyaniline Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=C(C1)C=1N=CN(C1)C)N=CC2)N NSIBFUPUJYMBJZ-UHFFFAOYSA-N 0.000 description 14
• 125000001624 naphthyl group Chemical group 0.000 description 14
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
• ZXYAAVBXHKCJJB-UHFFFAOYSA-N uracil-5-carboxylic acid Chemical class OC(=O)C1=CNC(=O)NC1=O ZXYAAVBXHKCJJB-UHFFFAOYSA-N 0.000 description 13
• VDFROLGDZZETHN-UHFFFAOYSA-N 3-fluoro-4-pyrazolo[1,5-a]pyridin-4-yloxyaniline Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=CC1)N=CC2)N VDFROLGDZZETHN-UHFFFAOYSA-N 0.000 description 12
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
• 238000005859 coupling reaction Methods 0.000 description 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
• 230000008878 coupling Effects 0.000 description 11
• 239000002904 solvent Substances 0.000 description 11
• 238000003756 stirring Methods 0.000 description 11
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
• 241000282414 Homo sapiens Species 0.000 description 10
• 108091000080 Phosphotransferase Proteins 0.000 description 10
• 239000004480 active ingredient Substances 0.000 description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
• 230000000694 effects Effects 0.000 description 10
• 102000020233 phosphotransferase Human genes 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• 125000000217 alkyl group Chemical group 0.000 description 9
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 9
• 239000000546 pharmaceutical excipient Substances 0.000 description 9
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• 239000006185 dispersion Substances 0.000 description 8
• 239000002552 dosage form Substances 0.000 description 8
• 239000000463 material Substances 0.000 description 8
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 8
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 8
• JTZSVYCKAYMNCT-UHFFFAOYSA-N 3-(4-fluorophenyl)-2,4-dioxo-1h-pyrimidine-5-carboxylic acid Chemical compound O=C1C(C(=O)O)=CNC(=O)N1C1=CC=C(F)C=C1 JTZSVYCKAYMNCT-UHFFFAOYSA-N 0.000 description 7
• KDSGRFDWQSNHMH-UHFFFAOYSA-N 3-fluoro-4-(6-morpholin-4-ylpyrazolo[1,5-a]pyridin-4-yl)oxyaniline Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=C(C1)N1CCOCC1)N=CC2)N KDSGRFDWQSNHMH-UHFFFAOYSA-N 0.000 description 7
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 7
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 7
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
• 238000004587 chromatography analysis Methods 0.000 description 7
• 201000010099 disease Diseases 0.000 description 7
• 239000010410 layer Substances 0.000 description 7
• 239000011664 nicotinic acid Substances 0.000 description 7
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 7
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 7
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 7
• FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 7
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 6
• RUBQQRMAWLSCCJ-UHFFFAOYSA-N 1,2-difluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(F)=C1 RUBQQRMAWLSCCJ-UHFFFAOYSA-N 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• AZFWMMGMSUYQNX-UHFFFAOYSA-N 3-fluoro-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyaniline Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=C(C1)C=1C=NN(C1)C)N=CC2)N AZFWMMGMSUYQNX-UHFFFAOYSA-N 0.000 description 6
• ULSHXIWEAIWUOL-UHFFFAOYSA-N 4-(2-fluoro-4-nitrophenoxy)pyrazolo[1,5-a]pyridin-6-amine Chemical compound FC1=C(OC=2C=3N(C=C(C2)N)N=CC3)C=CC(=C1)[N+](=O)[O-] ULSHXIWEAIWUOL-UHFFFAOYSA-N 0.000 description 6
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
• KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• 125000002947 alkylene group Chemical group 0.000 description 6
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
• 210000004027 cell Anatomy 0.000 description 6
• FDKLLWKMYAMLIF-UHFFFAOYSA-N cyclopropane-1,1-dicarboxylic acid Chemical compound OC(=O)C1(C(O)=O)CC1 FDKLLWKMYAMLIF-UHFFFAOYSA-N 0.000 description 6
• 230000014509 gene expression Effects 0.000 description 6
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
• 229910000027 potassium carbonate Inorganic materials 0.000 description 6
• WCEWCRAPSCLFOV-UHFFFAOYSA-N tributyl-(1-methylimidazol-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CN(C)C=N1 WCEWCRAPSCLFOV-UHFFFAOYSA-N 0.000 description 6
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
• 125000005500 uronium group Chemical group 0.000 description 6
• CGDDRASYDFHWHN-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-iodo-2-oxopyridine-3-carboxylic acid Chemical compound O=C1C(C(=O)O)=C(I)C=CN1C1=CC=C(F)C=C1 CGDDRASYDFHWHN-UHFFFAOYSA-N 0.000 description 5
• RTPBRNZVUVGGAV-UHFFFAOYSA-N 3-methyl-4-[6-(1-methylimidazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyaniline Chemical compound CC=1C=C(C=CC1OC=1C=2N(C=C(C1)C=1N=CN(C1)C)N=CC2)N RTPBRNZVUVGGAV-UHFFFAOYSA-N 0.000 description 5
• PINWVNBVTATDRD-UHFFFAOYSA-N 4-(6-bromopyrazolo[1,5-a]pyridin-4-yl)oxy-3-fluoroaniline Chemical compound BrC=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)N)F PINWVNBVTATDRD-UHFFFAOYSA-N 0.000 description 5
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• 125000004432 carbon atom Chemical group C* 0.000 description 5
• QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 5
• 238000009472 formulation Methods 0.000 description 5
• 239000008194 pharmaceutical composition Substances 0.000 description 5
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 5
• IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 description 5
• 239000000725 suspension Substances 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• 238000011282 treatment Methods 0.000 description 5
• KTCNGKASVZVXHT-UHFFFAOYSA-N 1,2-dihydropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CNC1 KTCNGKASVZVXHT-UHFFFAOYSA-N 0.000 description 4
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