ES2654931T3 - Derivados de pirazolo[1,5-a]piridina y procedimientos de uso de los mismos - Google Patents

Info

Publication number

ES2654931T3

ES2654931T3 ES14824711.7T ES14824711T ES2654931T3 ES 2654931 T3 ES2654931 T3 ES 2654931T3 ES 14824711 T ES14824711 T ES 14824711T ES 2654931 T3 ES2654931 T3 ES 2654931T3

Authority

ES

Spain

Prior art keywords

fluoro

phenyl

pyridin

pyrazolo

yloxy

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.)

Active

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title claims description 188
• DVUBDHRTVYLIPA-UHFFFAOYSA-N pyrazolo[1,5-a]pyridine Chemical class C1=CC=CN2N=CC=C21 DVUBDHRTVYLIPA-UHFFFAOYSA-N 0.000 title description 7
• 150000001875 compounds Chemical class 0.000 claims abstract description 216
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 99
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 65
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 40
• 150000003839 salts Chemical class 0.000 claims abstract description 31
• 125000003118 aryl group Chemical group 0.000 claims abstract description 27
• 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 22
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 16
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 15
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 13
• 125000002947 alkylene group Chemical group 0.000 claims abstract description 10
• 125000003373 pyrazinyl group Chemical group 0.000 claims abstract description 10
• 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 10
• 125000004385 trihaloalkyl group Chemical group 0.000 claims abstract description 9
• 125000004193 piperazinyl group Chemical group 0.000 claims abstract description 8
• 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 6
• 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 6
• 125000002971 oxazolyl group Chemical group 0.000 claims abstract description 6
• 125000001786 isothiazolyl group Chemical group 0.000 claims abstract description 5
• 125000000842 isoxazolyl group Chemical group 0.000 claims abstract description 5
• 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 5
• 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 5
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 5
• 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 5
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 4
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims abstract description 4
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims abstract description 4
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims abstract description 4
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 3
• 150000002367 halogens Chemical class 0.000 claims abstract description 3
• 125000001475 halogen functional group Chemical group 0.000 claims abstract 35
• -1 [3-fluoro-4- (6-pyridin-4-yl-pyrazolo [1,5-a] pyridin-4-yloxy) -phenyl] -amide -dioxo-1,2,3,4 tetrahydro-pyrimidin-5-carboxylic Chemical compound 0.000 claims description 277
• 239000002253 acid Substances 0.000 claims description 201
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 122
• 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 claims description 45
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
• 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 17
• 206010028980 Neoplasm Diseases 0.000 claims description 15
• 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 claims description 14
• 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 claims description 11
• 201000011510 cancer Diseases 0.000 claims description 11
• RVEGSCIIXYDCJT-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CNCNC1 RVEGSCIIXYDCJT-UHFFFAOYSA-N 0.000 claims description 8
• CJYSCBSFKLJIJO-UHFFFAOYSA-N 1-(4-fluorophenyl)-2,4-dioxopyrimidine-5-carboxylic acid Chemical compound O=C1NC(=O)C(C(=O)O)=CN1C1=CC=C(F)C=C1 CJYSCBSFKLJIJO-UHFFFAOYSA-N 0.000 claims description 8
• PXPWEFRQSPWCQX-UHFFFAOYSA-N 3-(3-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxylic acid Chemical compound FC=1C=C(C=CC=1)N1C(N(C=C(C1=O)C(=O)O)C(C)C)=O PXPWEFRQSPWCQX-UHFFFAOYSA-N 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 208000005718 Stomach Neoplasms Diseases 0.000 claims description 6
• SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims description 6
• AZIKNCZQDXXEIS-UHFFFAOYSA-N 3-(4-fluorophenyl)-1-methyl-2,4-dioxopyrimidine-5-carboxylic acid Chemical compound O=C1N(C)C=C(C(O)=O)C(=O)N1C1=CC=C(F)C=C1 AZIKNCZQDXXEIS-UHFFFAOYSA-N 0.000 claims description 5
• 206010017758 gastric cancer Diseases 0.000 claims description 5
• 201000011549 stomach cancer Diseases 0.000 claims description 5
• NUPJSSQUUCZNLZ-UHFFFAOYSA-N 3-(4-fluorophenyl)-2,4-dioxo-1-(2-phenylmethoxyethyl)pyrimidine-5-carboxylic acid Chemical compound O=C1N(C=2C=CC(F)=CC=2)C(=O)C(C(=O)O)=CN1CCOCC1=CC=CC=C1 NUPJSSQUUCZNLZ-UHFFFAOYSA-N 0.000 claims description 4
• QAPUOJJJKOPDFV-UHFFFAOYSA-N 3-(4-fluorophenyl)-2,4-dioxo-1-pentylpyrimidine-5-carboxylic acid Chemical compound O=C1N(CCCCC)C=C(C(O)=O)C(=O)N1C1=CC=C(F)C=C1 QAPUOJJJKOPDFV-UHFFFAOYSA-N 0.000 claims description 4
• 206010009944 Colon cancer Diseases 0.000 claims description 4
• 208000029742 colonic neoplasm Diseases 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 201000001441 melanoma Diseases 0.000 claims description 4
• FDEAXGCAOSGCNC-UHFFFAOYSA-N 3-(4-fluorophenyl)-1-(2-hydroxyethyl)-2,4-dioxopyrimidine-5-carboxylic acid Chemical compound O=C1N(CCO)C=C(C(O)=O)C(=O)N1C1=CC=C(F)C=C1 FDEAXGCAOSGCNC-UHFFFAOYSA-N 0.000 claims description 3
• 208000003174 Brain Neoplasms Diseases 0.000 claims description 3
• 206010006187 Breast cancer Diseases 0.000 claims description 3
• 208000026310 Breast neoplasm Diseases 0.000 claims description 3
• 208000008839 Kidney Neoplasms Diseases 0.000 claims description 3
• 206010038389 Renal cancer Diseases 0.000 claims description 3
• QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims description 3
• 229910052739 hydrogen Inorganic materials 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
• YBBLOADPFWKNGS-UHFFFAOYSA-N 1,1-dimethylurea Chemical compound CN(C)C(N)=O YBBLOADPFWKNGS-UHFFFAOYSA-N 0.000 claims description 2
• OYOBTADHXXTSKP-UHFFFAOYSA-N 1-(2-ethoxyethyl)-3-(4-fluorophenyl)-2,4-dioxopyrimidine-5-carboxylic acid Chemical compound O=C1N(CCOCC)C=C(C(O)=O)C(=O)N1C1=CC=C(F)C=C1 OYOBTADHXXTSKP-UHFFFAOYSA-N 0.000 claims description 2
• YPUZOECTETYPRF-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrimidine-2-carboxylic acid Chemical compound OC(=O)C1NCC=CN1 YPUZOECTETYPRF-UHFFFAOYSA-N 0.000 claims 2
• JSYFSWSRGXNKSM-UHFFFAOYSA-N 3-fluoro-4-(6-pyrazin-2-ylpyrazolo[1,5-a]pyridin-4-yl)oxyaniline Chemical compound FC=1C=C(C=CC=1OC=1C=2N(C=C(C=1)C1=NC=CN=C1)N=CC=2)N JSYFSWSRGXNKSM-UHFFFAOYSA-N 0.000 claims 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 274
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 265
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 238
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 169
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 166
• 238000005160 1H NMR spectroscopy Methods 0.000 description 151
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 100
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-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
• 239000000203 mixture Substances 0.000 description 63
• 238000006243 chemical reaction Methods 0.000 description 61
• 239000012267 brine Substances 0.000 description 59
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 59
• 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
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
• 229910000029 sodium carbonate Inorganic materials 0.000 description 44
• 235000017550 sodium carbonate Nutrition 0.000 description 44
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 43
• 239000012299 nitrogen atmosphere Substances 0.000 description 41
• 125000005843 halogen group Chemical group 0.000 description 40
• VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 40
• 239000000243 solution Substances 0.000 description 37
• 239000007787 solid Substances 0.000 description 36
• 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 35
• 238000005481 NMR spectroscopy Methods 0.000 description 34
• 238000010168 coupling process Methods 0.000 description 31
• 239000000543 intermediate Substances 0.000 description 31
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
• 239000000741 silica gel Substances 0.000 description 27
• 229910002027 silica gel Inorganic materials 0.000 description 27
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 27
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
• 150000001408 amides Chemical class 0.000 description 26
• 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 25
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 23
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 23
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 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
• 125000002496 methyl group Chemical group [H]C([H])([H])* 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 21
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([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
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 20
• 239000002480 mineral oil Substances 0.000 description 19
• 235000010446 mineral oil Nutrition 0.000 description 19
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 19
• 238000012746 preparative thin layer chromatography Methods 0.000 description 19
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 18
• 239000006229 carbon black Substances 0.000 description 18
• 229910052763 palladium Inorganic materials 0.000 description 18
• 229910052794 bromium Inorganic materials 0.000 description 17
• 229910052801 chlorine Inorganic materials 0.000 description 17
• 230000009467 reduction Effects 0.000 description 17
• 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 16
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 16
• 229910052731 fluorine Inorganic materials 0.000 description 16
• 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 15
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 15
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 239000012312 sodium hydride Substances 0.000 description 15
• 229910000104 sodium hydride Inorganic materials 0.000 description 15
• ZXYAAVBXHKCJJB-UHFFFAOYSA-N uracil-5-carboxylic acid Chemical compound OC(=O)C1=CNC(=O)NC1=O ZXYAAVBXHKCJJB-UHFFFAOYSA-N 0.000 description 15
• 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
• 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 13
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
• 235000019341 magnesium sulphate Nutrition 0.000 description 13
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 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
• 230000000694 effects Effects 0.000 description 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
• 238000003756 stirring Methods 0.000 description 12
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
• 239000006185 dispersion Substances 0.000 description 11
• 239000002904 solvent Substances 0.000 description 11
• 239000004480 active ingredient Substances 0.000 description 10
• 238000005859 coupling reaction Methods 0.000 description 10
• 239000000546 pharmaceutical excipient Substances 0.000 description 10
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
• 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
• 230000008878 coupling Effects 0.000 description 9
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 9
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
• 108091000080 Phosphotransferase Proteins 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
• 102000020233 phosphotransferase Human genes 0.000 description 8
• LENLQGBLVGGAMF-UHFFFAOYSA-N tributyl([1,2,4]triazolo[1,5-a]pyridin-6-yl)stannane Chemical compound C1=C([Sn](CCCC)(CCCC)CCCC)C=CC2=NC=NN21 LENLQGBLVGGAMF-UHFFFAOYSA-N 0.000 description 8
• 125000005500 uronium group Chemical group 0.000 description 8
• 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 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
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 7
• 239000000725 suspension Substances 0.000 description 7
• 238000011282 treatment Methods 0.000 description 7
• 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 7
• 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 6
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 6
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 210000004027 cell Anatomy 0.000 description 6
• 150000002148 esters Chemical class 0.000 description 6
• 125000004494 ethyl ester group Chemical group 0.000 description 6
• 125000001207 fluorophenyl group Chemical group 0.000 description 6
• 238000009472 formulation Methods 0.000 description 6
• 230000014509 gene expression Effects 0.000 description 6
• 229910000027 potassium carbonate Inorganic materials 0.000 description 6
• 108090000623 proteins and genes Proteins 0.000 description 6
• GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 6
• FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 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
• 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 5
• 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
• PYOJYPBDKFTNJJ-UHFFFAOYSA-N 3-fluoro-4-(6-pyridin-3-ylpyrazolo[1,5-a]pyridin-4-yl)oxyaniline Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=C(C1)C=1C=NC=CC1)N=CC2)N PYOJYPBDKFTNJJ-UHFFFAOYSA-N 0.000 description 5
• ASKWISXSRHJZSC-UHFFFAOYSA-N 4-(4-fluorophenyl)-3,5-dioxo-2-propan-2-yl-1,2,4-triazine-6-carboxylic acid Chemical compound O=C1N(C(C)C)N=C(C(O)=O)C(=O)N1C1=CC=C(F)C=C1 ASKWISXSRHJZSC-UHFFFAOYSA-N 0.000 description 5
• 239000012298 atmosphere Substances 0.000 description 5
• 125000004432 carbon atom Chemical group C* 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
• 239000006187 pill Substances 0.000 description 5
• 235000011181 potassium carbonates Nutrition 0.000 description 5
• 102000004169 proteins and genes Human genes 0.000 description 5
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 5
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
• IMJHIMVJEFZCFP-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-iodo-2-oxopyridine-3-carbonyl chloride Chemical compound C1=CC(F)=CC=C1N1C(=O)C(C(Cl)=O)=C(I)C=C1 IMJHIMVJEFZCFP-UHFFFAOYSA-N 0.000 description 4
• UEYQJQVBUVAELZ-UHFFFAOYSA-N 2-Hydroxynicotinic acid Chemical compound OC(=O)C1=CC=CN=C1O UEYQJQVBUVAELZ-UHFFFAOYSA-N 0.000 description 4
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 4
• 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 4
• 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 4
• 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 4
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
• VAZDAKZRDPAWEJ-UHFFFAOYSA-N 6-bromo-4-(2-methyl-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-])C VAZDAKZRDPAWEJ-UHFFFAOYSA-N 0.000 description 4
• OQNFCPRIIBOCCI-UHFFFAOYSA-N 6-bromo-4-(4-nitrophenoxy)pyrazolo[1,5-a]pyridine Chemical compound BrC=1C=C(C=2N(C1)N=CC2)OC2=CC=C(C=C2)[N+](=O)[O-] OQNFCPRIIBOCCI-UHFFFAOYSA-N 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• 102100031487 Growth arrest-specific protein 6 Human genes 0.000 description 4
• 101000923005 Homo sapiens Growth arrest-specific protein 6 Proteins 0.000 description 4
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
• 102000001253 Protein Kinase Human genes 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• 238000003556 assay Methods 0.000 description 4
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
• 229910000024 caesium carbonate Inorganic materials 0.000 description 4
• 239000003054 catalyst Substances 0.000 description 4
• 208000035475 disorder Diseases 0.000 description 4
• 239000003814 drug Substances 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 238000005984 hydrogenation reaction Methods 0.000 description 4
• 230000005764 inhibitory process Effects 0.000 description 4
• 239000003446 ligand Substances 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 239000011664 nicotinic acid Substances 0.000 description 4
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
• 238000002360 preparation method Methods 0.000 description 4
• 108060006633 protein kinase Proteins 0.000 description 4
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 4
• 239000000758 substrate Substances 0.000 description 4
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
• FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 4
• HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 4
• 210000001519 tissue Anatomy 0.000 description 4
• 239000008096 xylene Substances 0.000 description 4
• 150000003738 xylenes Chemical class 0.000 description 4
• KTCNGKASVZVXHT-UHFFFAOYSA-N 1,2-dihydropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CNC1 KTCNGKASVZVXHT-UHFFFAOYSA-N 0.000 description 3
• WMKGGPCROCCUDY-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one Chemical compound C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 WMKGGPCROCCUDY-UHFFFAOYSA-N 0.000 description 3
• PFMAFXYUHZDKPY-UHFFFAOYSA-N 1-[(4-fluorophenyl)carbamoyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(F)C=CC=1NC(=O)C1(C(=O)O)CC1 PFMAFXYUHZDKPY-UHFFFAOYSA-N 0.000 description 3
• OPWIKWIRMOOCDF-UHFFFAOYSA-N 1-[4-(4-amino-2-fluorophenoxy)pyrazolo[1,5-a]pyridin-6-yl]pyrrolidin-2-one Chemical compound NC1=CC(=C(OC=2C=3N(C=C(C2)N2C(CCC2)=O)N=CC3)C=C1)F OPWIKWIRMOOCDF-UHFFFAOYSA-N 0.000 description 3
• WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical class [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 3
• KICJUQBUUHCWJE-UHFFFAOYSA-N 2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxylic acid Chemical compound CC(C)N1C=C(C(O)=O)C(=O)NC1=O KICJUQBUUHCWJE-UHFFFAOYSA-N 0.000 description 3
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 3
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
• KVLNXHPMCUNGMI-UHFFFAOYSA-N 3-[4-(4-amino-2-fluorophenoxy)pyrazolo[1,5-a]pyridin-6-yl]-1,1-dimethylurea Chemical compound NC1=CC(=C(OC=2C=3N(C=C(C2)NC(N(C)C)=O)N=CC3)C=C1)F KVLNXHPMCUNGMI-UHFFFAOYSA-N 0.000 description 3
• PBKBZMOBHQPVHD-UHFFFAOYSA-N 3-fluoro-4-[6-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]pyrazolo[1,5-a]pyridin-4-yl]oxyaniline Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=C(C1)C=1C=NC(=CC1)N1CCN(CC1)C)N=CC2)N PBKBZMOBHQPVHD-UHFFFAOYSA-N 0.000 description 3
• PQHVZUINOOKTFU-UHFFFAOYSA-N 4-(2-fluoro-4-nitrophenoxy)-6-(2-methylpyrazol-3-yl)pyrazolo[1,5-a]pyridine Chemical compound FC1=C(OC=2C=3N(C=C(C2)C=2N(N=CC2)C)N=CC3)C=CC(=C1)[N+](=O)[O-] PQHVZUINOOKTFU-UHFFFAOYSA-N 0.000 description 3
• YBKOKOJDHIDEEK-UHFFFAOYSA-N 4-[6-(1-methylimidazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyaniline Chemical compound CN1C=NC(=C1)C=1C=C(C=2N(C1)N=CC2)OC2=CC=C(C=C2)N YBKOKOJDHIDEEK-UHFFFAOYSA-N 0.000 description 3
• UHQDODDJMHIUBV-UHFFFAOYSA-N 4-pyrazolo[1,5-a]pyridin-4-yloxyaniline Chemical compound N1=CC=C2N1C=CC=C2OC2=CC=C(C=C2)N UHQDODDJMHIUBV-UHFFFAOYSA-N 0.000 description 3
• JWKDRJKHJZOYAH-UHFFFAOYSA-N 5-[6-(1-methylimidazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxypyridin-2-amine Chemical compound CN1C=NC(=C1)C=1C=C(C=2N(C1)N=CC2)OC=2C=CC(=NC2)N JWKDRJKHJZOYAH-UHFFFAOYSA-N 0.000 description 3
• UMCMLRLHQNNZDY-UHFFFAOYSA-N 6-(1-methylpyrazol-4-yl)-4-(5-nitropyridin-2-yl)oxypyrazolo[1,5-a]pyridine Chemical compound CN1N=CC(=C1)C=1C=C(C=2N(C1)N=CC2)OC2=NC=C(C=C2)[N+](=O)[O-] UMCMLRLHQNNZDY-UHFFFAOYSA-N 0.000 description 3
• ZGAMSYOMHSCSHE-UHFFFAOYSA-N 6-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxypyridin-3-amine Chemical compound CN1N=CC(=C1)C=1C=C(C=2N(C1)N=CC2)OC2=CC=C(C=N2)N ZGAMSYOMHSCSHE-UHFFFAOYSA-N 0.000 description 3
• KGHGYARWJIHKCJ-UHFFFAOYSA-N 6-bromo-4-(5-nitropyridin-2-yl)oxypyrazolo[1,5-a]pyridine Chemical compound BrC=1C=C(C=2N(C1)N=CC2)OC2=NC=C(C=C2)[N+](=O)[O-] KGHGYARWJIHKCJ-UHFFFAOYSA-N 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 102100021866 Hepatocyte growth factor Human genes 0.000 description 3
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• MERZPFXSVQDXOA-UHFFFAOYSA-N N-[4-(2-fluoro-4-nitrophenoxy)pyrazolo[1,5-a]pyridin-6-yl]acetamide Chemical compound FC1=C(OC=2C=3N(C=C(C2)NC(C)=O)N=CC3)C=CC(=C1)[N+](=O)[O-] MERZPFXSVQDXOA-UHFFFAOYSA-N 0.000 description 3
• ASEOPBMTWSKROP-UHFFFAOYSA-N N-[4-(4-amino-2-fluorophenoxy)pyrazolo[1,5-a]pyridin-6-yl]-4-methylpiperazine-1-carboxamide Chemical compound NC1=CC(=C(OC=2C=3N(C=C(C2)NC(=O)N2CCN(CC2)C)N=CC3)C=C1)F ASEOPBMTWSKROP-UHFFFAOYSA-N 0.000 description 3
• GZJNEQYGZINDKZ-UHFFFAOYSA-N N-[4-(4-amino-2-fluorophenoxy)pyrazolo[1,5-a]pyridin-6-yl]-N-methylacetamide Chemical compound NC1=CC(=C(OC=2C=3N(C=C(C2)N(C(C)=O)C)N=CC3)C=C1)F GZJNEQYGZINDKZ-UHFFFAOYSA-N 0.000 description 3
• QZYORLHJKGVQKP-UHFFFAOYSA-N N-[4-(4-amino-2-fluorophenoxy)pyrazolo[1,5-a]pyridin-6-yl]acetamide Chemical compound NC1=CC(=C(OC=2C=3N(C=C(C2)NC(C)=O)N=CC3)C=C1)F QZYORLHJKGVQKP-UHFFFAOYSA-N 0.000 description 3
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 3
• 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 3
• 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 239000007983 Tris buffer Substances 0.000 description 3
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 230000029936 alkylation Effects 0.000 description 3
• 238000005804 alkylation reaction Methods 0.000 description 3
• 230000004075 alteration Effects 0.000 description 3
• 235000019270 ammonium chloride Nutrition 0.000 description 3
• 150000001448 anilines Chemical class 0.000 description 3
• 239000012131 assay buffer Substances 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• BRYCPBJQGPFMTD-UHFFFAOYSA-N ethyl 3-(4-fluorophenyl)-2,4-dioxo-1h-pyrimidine-5-carboxylate Chemical compound O=C1C(C(=O)OCC)=CNC(=O)N1C1=CC=C(F)C=C1 BRYCPBJQGPFMTD-UHFFFAOYSA-N 0.000 description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 238000000021 kinase assay Methods 0.000 description 3
• LXOLCGVJUNWARS-UHFFFAOYSA-N methyl N-[4-(4-amino-2-fluorophenoxy)pyrazolo[1,5-a]pyridin-6-yl]carbamate Chemical compound COC(NC=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)N)F)=O LXOLCGVJUNWARS-UHFFFAOYSA-N 0.000 description 3
• 230000005012 migration Effects 0.000 description 3
• 238000013508 migration Methods 0.000 description 3
• 150000007522 mineralic acids Chemical class 0.000 description 3
• 230000035772 mutation Effects 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• 239000003921 oil Substances 0.000 description 3
• 235000019198 oils Nutrition 0.000 description 3
• 239000002245 particle Substances 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• 239000003981 vehicle Substances 0.000 description 3
• 229910052725 zinc Inorganic materials 0.000 description 3
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 2
• KQNHAXWTVPXGMP-UHFFFAOYSA-N (4-fluoroanilino)thiourea Chemical compound NC(=S)NNC1=CC=C(F)C=C1 KQNHAXWTVPXGMP-UHFFFAOYSA-N 0.000 description 2
• SYNHZTBGWVVZNZ-UHFFFAOYSA-N 1-(cyclopropylmethyl)-3-(4-fluorophenyl)-2,4-dioxopyrimidine-5-carboxylic acid Chemical compound O=C1N(C=2C=CC(F)=CC=2)C(=O)C(C(=O)O)=CN1CC1CC1 SYNHZTBGWVVZNZ-UHFFFAOYSA-N 0.000 description 2
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
• AZNKKZHZGDZSIF-UHFFFAOYSA-N 1-fluoro-2-methoxy-4-nitrobenzene Chemical compound COC1=CC([N+]([O-])=O)=CC=C1F AZNKKZHZGDZSIF-UHFFFAOYSA-N 0.000 description 2
• XUCYJGMIICONES-UHFFFAOYSA-N 1-fluoro-2-methyl-4-nitrobenzene Chemical compound CC1=CC([N+]([O-])=O)=CC=C1F XUCYJGMIICONES-UHFFFAOYSA-N 0.000 description 2
• DSVGFKBFFICWLZ-UHFFFAOYSA-N 1-fluoro-4-isocyanatobenzene Chemical compound FC1=CC=C(N=C=O)C=C1 DSVGFKBFFICWLZ-UHFFFAOYSA-N 0.000 description 2
• DFAQSHLYVFQOJM-UHFFFAOYSA-N 1-methyl-2-oxopyridine-3-carboxylic acid Chemical compound CN1C=CC=C(C(O)=O)C1=O DFAQSHLYVFQOJM-UHFFFAOYSA-N 0.000 description 2
• BFPCWYOMCDHJNZ-UHFFFAOYSA-N 2-(4-fluorophenyl)-3-oxopyridazine-4-carboxylic acid Chemical compound O=C1C(C(=O)O)=CC=NN1C1=CC=C(F)C=C1 BFPCWYOMCDHJNZ-UHFFFAOYSA-N 0.000 description 2
• DTFBBVDDPVULMK-UHFFFAOYSA-N 2-(aminomethylidene)propanedioic acid Chemical class NC=C(C(O)=O)C(O)=O DTFBBVDDPVULMK-UHFFFAOYSA-N 0.000 description 2
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
• UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 2
• MTJONRRZYZYUIV-UHFFFAOYSA-N 2-ethyl-4-(4-fluorophenyl)-3,5-dioxo-1,2,4-triazine-6-carboxylic acid Chemical compound O=C1N(CC)N=C(C(O)=O)C(=O)N1C1=CC=C(F)C=C1 MTJONRRZYZYUIV-UHFFFAOYSA-N 0.000 description 2
• PLKNGGRZZIWWLD-UHFFFAOYSA-N 3,5-dioxo-2h-1,2,4-triazine-6-carboxylic acid Chemical compound OC(=O)C1=NN=C(O)N=C1O PLKNGGRZZIWWLD-UHFFFAOYSA-N 0.000 description 2
• HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 2
• JZFILXHJJTYHBX-UHFFFAOYSA-N 3-[4-(2-fluoro-4-nitrophenoxy)pyrazolo[1,5-a]pyridin-6-yl]-1,1-dimethylurea Chemical compound FC1=C(OC=2C=3N(C=C(C2)NC(N(C)C)=O)N=CC3)C=CC(=C1)[N+](=O)[O-] JZFILXHJJTYHBX-UHFFFAOYSA-N 0.000 description 2
• 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 2
• KSTSPGCWFAVOJH-UHFFFAOYSA-N 3-fluoro-4-(6-pyrimidin-2-ylpyrazolo[1,5-a]pyridin-4-yl)oxyaniline Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=C(C1)C1=NC=CC=N1)N=CC2)N KSTSPGCWFAVOJH-UHFFFAOYSA-N 0.000 description 2
• MFILJCOKHXQDIA-UHFFFAOYSA-N 3-fluoro-4-[6-(1,2-thiazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyaniline Chemical compound FC=1C=C(C=CC=1OC=1C=2N(C=C(C=1)C=1C=NSC=1)N=CC=2)N MFILJCOKHXQDIA-UHFFFAOYSA-N 0.000 description 2
• HHWHTXUDJMFMHS-UHFFFAOYSA-N 3-fluoro-4-[6-(1,3-oxazol-5-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyaniline Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=C(C1)C1=CN=CO1)N=CC2)N HHWHTXUDJMFMHS-UHFFFAOYSA-N 0.000 description 2
• WPLNZIUSVHWTBI-UHFFFAOYSA-N 3-fluoro-4-[6-(1,3-thiazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyaniline Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=C(C1)C=1N=CSC1)N=CC2)N WPLNZIUSVHWTBI-UHFFFAOYSA-N 0.000 description 2
• IHPOSHQIAUBCBL-UHFFFAOYSA-N 3-fluoro-4-[6-(6-methylpyridin-2-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyaniline Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=C(C1)C1=NC(=CC=C1)C)N=CC2)N IHPOSHQIAUBCBL-UHFFFAOYSA-N 0.000 description 2
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
• JDHRFUKBKNHLKF-UHFFFAOYSA-N 4-(2-fluoro-4-nitrophenoxy)-6-(1-methylimidazol-4-yl)pyrazolo[1,5-a]pyridine Chemical compound FC1=C(OC=2C=3N(C=C(C2)C=2N=CN(C2)C)N=CC3)C=CC(=C1)[N+](=O)[O-] JDHRFUKBKNHLKF-UHFFFAOYSA-N 0.000 description 2
• SVZWTQUTQFLTTP-UHFFFAOYSA-N 4-(2-fluoro-4-nitrophenoxy)-6-(5-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine Chemical compound FC1=C(OC=2C=3N(C=C(C2)C=2C=NNC2C)N=CC3)C=CC(=C1)[N+](=O)[O-] SVZWTQUTQFLTTP-UHFFFAOYSA-N 0.000 description 2
• RXKXZBQJPQQVOH-UHFFFAOYSA-N 4-(2-fluoro-4-nitrophenoxy)-N,N-dimethylpyrazolo[1,5-a]pyridine-6-carboxamide Chemical compound CN(C(=O)C=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)[N+](=O)[O-])F)C RXKXZBQJPQQVOH-UHFFFAOYSA-N 0.000 description 2
• IZTJPZCKEVZPGW-UHFFFAOYSA-N 4-(2-methoxy-4-nitrophenoxy)-6-(1-methylimidazol-4-yl)pyrazolo[1,5-a]pyridine Chemical compound COC1=C(OC=2C=3N(C=C(C2)C=2N=CN(C2)C)N=CC3)C=CC(=C1)[N+](=O)[O-] IZTJPZCKEVZPGW-UHFFFAOYSA-N 0.000 description 2
• SXMNDIAECOIPRT-UHFFFAOYSA-N 4-(3-chloropyrazolo[1,5-a]pyridin-4-yl)oxy-3-fluoroaniline Chemical compound ClC=1C=NN2C1C(=CC=C2)OC2=C(C=C(C=C2)N)F SXMNDIAECOIPRT-UHFFFAOYSA-N 0.000 description 2
• BUVVJIGULSJYLF-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2h-pyridine-1-carboxylic acid Chemical compound O1C(C)(C)C(C)(C)OB1C1=CCN(C(O)=O)CC1 BUVVJIGULSJYLF-UHFFFAOYSA-N 0.000 description 2
• WDSLIKCXXPKXMT-UHFFFAOYSA-N 4-(4-amino-2-fluorophenoxy)-N-pyrimidin-2-ylpyrazolo[1,5-a]pyridin-6-amine Chemical compound NC1=CC(=C(OC=2C=3N(C=C(C2)NC2=NC=CC=N2)N=CC3)C=C1)F WDSLIKCXXPKXMT-UHFFFAOYSA-N 0.000 description 2
• YVOIRIRKJIYYQF-UHFFFAOYSA-N 4-[6-(1,1-dioxo-1,4-thiazinan-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxy-3-fluoroaniline Chemical compound O=S1(CCN(CC1)C=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)N)F)=O YVOIRIRKJIYYQF-UHFFFAOYSA-N 0.000 description 2
• VVBKNFYRFSCZKS-UHFFFAOYSA-N 4-[6-(1,5-dimethylpyrazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxy-3-fluoroaniline Chemical compound CN1N=CC(=C1C)C=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)N)F VVBKNFYRFSCZKS-UHFFFAOYSA-N 0.000 description 2
• RIRUVAJGWDJUTJ-UHFFFAOYSA-N 4-[6-(4,4-difluoropiperidin-1-yl)pyrazolo[1,5-a]pyridin-4-yl]oxy-3-fluoroaniline Chemical compound FC1(CCN(CC1)C=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)N)F)F RIRUVAJGWDJUTJ-UHFFFAOYSA-N 0.000 description 2
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 2
• WMQOSURXFLBTPC-UHFFFAOYSA-N 4-fluoro-1-nitro-2-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1C(F)(F)F WMQOSURXFLBTPC-UHFFFAOYSA-N 0.000 description 2
• KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 2
• GCNTZFIIOFTKIY-UHFFFAOYSA-N 4-hydroxypyridine Chemical compound OC1=CC=NC=C1 GCNTZFIIOFTKIY-UHFFFAOYSA-N 0.000 description 2
• SBPFINHHMJTMGM-UHFFFAOYSA-N 4-phenylmethoxypyrazolo[1,5-a]pyridine-6-carbonitrile Chemical compound C(C1=CC=CC=C1)OC=1C=2N(C=C(C1)C#N)N=CC2 SBPFINHHMJTMGM-UHFFFAOYSA-N 0.000 description 2
• VRKPAIITLKTHKO-UHFFFAOYSA-N 4-phenylmethoxypyrazolo[1,5-a]pyridine-6-carboxylic acid Chemical compound C(C1=CC=CC=C1)OC=1C=2N(C=C(C1)C(=O)O)N=CC2 VRKPAIITLKTHKO-UHFFFAOYSA-N 0.000 description 2
• JFAPKLMRQCGOCY-UHFFFAOYSA-N 5-(4-fluorophenyl)-4,6-dioxo-1-propan-2-ylpyridine-3-carboxylic acid Chemical compound FC1=CC=C(C=C1)C1C(N(C=C(C1=O)C(=O)O)C(C)C)=O JFAPKLMRQCGOCY-UHFFFAOYSA-N 0.000 description 2
• ATXXLNCPVSUCNK-UHFFFAOYSA-N 5-bromo-2-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Br)C=N1 ATXXLNCPVSUCNK-UHFFFAOYSA-N 0.000 description 2
• MJACHFMHOUJFQY-UHFFFAOYSA-N 6-(1-methylimidazol-4-yl)-4-(4-nitro-2-phenylmethoxyphenoxy)pyrazolo[1,5-a]pyridine Chemical compound C(C1=CC=CC=C1)OC1=C(OC=2C=3N(C=C(C2)C=2N=CN(C2)C)N=CC3)C=CC(=C1)[N+](=O)[O-] MJACHFMHOUJFQY-UHFFFAOYSA-N 0.000 description 2
• XJDUOAQQSQVGKB-UHFFFAOYSA-N 6-(1-methylimidazol-4-yl)-4-(4-nitrophenoxy)pyrazolo[1,5-a]pyridine Chemical compound CN1C=NC(=C1)C=1C=C(C=2N(C=1)N=CC=2)OC1=CC=C(C=C1)[N+](=O)[O-] XJDUOAQQSQVGKB-UHFFFAOYSA-N 0.000 description 2
• BEMYIVCIYSHQIJ-UHFFFAOYSA-N 6-(1-methylimidazol-4-yl)-4-(6-nitropyridin-3-yl)oxypyrazolo[1,5-a]pyridine Chemical compound CN1C=NC(=C1)C=1C=C(C=2N(C1)N=CC2)OC=2C=NC(=CC2)[N+](=O)[O-] BEMYIVCIYSHQIJ-UHFFFAOYSA-N 0.000 description 2
• ZZZOEGSDHVANLE-UHFFFAOYSA-N 6-(1-methylimidazol-4-yl)-4-[4-nitro-2-(trifluoromethyl)phenoxy]pyrazolo[1,5-a]pyridine Chemical compound CN1C=NC(=C1)C=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)[N+](=O)[O-])C(F)(F)F ZZZOEGSDHVANLE-UHFFFAOYSA-N 0.000 description 2
• YZRQRRUNWDVWFR-UHFFFAOYSA-N 6-(1-methylimidazol-4-yl)-4-[4-nitro-3-(trifluoromethyl)phenoxy]pyrazolo[1,5-a]pyridine Chemical compound CN1C=NC(=C1)C=1C=C(C=2N(C1)N=CC2)OC2=CC(=C(C=C2)[N+](=O)[O-])C(F)(F)F YZRQRRUNWDVWFR-UHFFFAOYSA-N 0.000 description 2
• RNPPLEHODREMFA-UHFFFAOYSA-N 6-[6-(1-methylimidazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxypyridin-3-amine Chemical compound CN1C=NC(=C1)C=1C=C(C=2N(C1)N=CC2)OC2=CC=C(C=N2)N RNPPLEHODREMFA-UHFFFAOYSA-N 0.000 description 2
• QATVSSGSQYNYBH-UHFFFAOYSA-N 6-bromo-4-(2-methoxy-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-])OC QATVSSGSQYNYBH-UHFFFAOYSA-N 0.000 description 2
• LGWNSTXYCHRPFH-UHFFFAOYSA-N 6-bromo-4-(6-nitropyridin-3-yl)oxypyrazolo[1,5-a]pyridine Chemical compound BrC=1C=C(C=2N(C1)N=CC2)OC=2C=NC(=CC2)[N+](=O)[O-] LGWNSTXYCHRPFH-UHFFFAOYSA-N 0.000 description 2
• WRNDAJQAVLGIQJ-UHFFFAOYSA-N 6-bromo-4-[4-nitro-2-(trifluoromethyl)phenoxy]pyrazolo[1,5-a]pyridine Chemical compound BrC=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)[N+](=O)[O-])C(F)(F)F WRNDAJQAVLGIQJ-UHFFFAOYSA-N 0.000 description 2
• GEPZZGXRSDNAMD-UHFFFAOYSA-N 6-bromo-4-[4-nitro-3-(trifluoromethyl)phenoxy]pyrazolo[1,5-a]pyridine Chemical compound BrC=1C=C(C=2N(C1)N=CC2)OC2=CC(=C(C=C2)[N+](=O)[O-])C(F)(F)F GEPZZGXRSDNAMD-UHFFFAOYSA-N 0.000 description 2
• 208000005623 Carcinogenesis Diseases 0.000 description 2
• 201000009030 Carcinoma Diseases 0.000 description 2
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• UNFUYDOHUKJRSO-UHFFFAOYSA-N FC1=C(OC=2C=3N(C=C(C2)NC(=O)N2CCN(CC2)C)N=CC3)C=CC(=C1)[N+](=O)[O-] Chemical compound FC1=C(OC=2C=3N(C=C(C2)NC(=O)N2CCN(CC2)C)N=CC3)C=CC(=C1)[N+](=O)[O-] UNFUYDOHUKJRSO-UHFFFAOYSA-N 0.000 description 2
• 239000007821 HATU Substances 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
• 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 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 206010027476 Metastases Diseases 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
• ULJHLNRRRQRXOW-UHFFFAOYSA-N N-[4-(2-fluoro-4-nitrophenoxy)pyrazolo[1,5-a]pyridin-6-yl]-1,1-diphenylmethanimine Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)=NC=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)[N+](=O)[O-])F ULJHLNRRRQRXOW-UHFFFAOYSA-N 0.000 description 2
• VYHJPVVMEWHESG-UHFFFAOYSA-N N-[4-(4-amino-2-fluorophenoxy)pyrazolo[1,5-a]pyridin-6-yl]methanesulfonamide Chemical compound NC1=CC(=C(OC=2C=3N(C=C(C2)NS(=O)(=O)C)N=CC3)C=C1)F VYHJPVVMEWHESG-UHFFFAOYSA-N 0.000 description 2
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
• 238000006619 Stille reaction Methods 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 238000006069 Suzuki reaction reaction Methods 0.000 description 2
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
• 238000005903 acid hydrolysis reaction Methods 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 230000003213 activating effect Effects 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 238000010640 amide synthesis reaction Methods 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• 230000033115 angiogenesis Effects 0.000 description 2
• 230000006907 apoptotic process Effects 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 125000003710 aryl alkyl group Chemical group 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 229960002685 biotin Drugs 0.000 description 2
• 239000011616 biotin Substances 0.000 description 2
• YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 210000000481 breast Anatomy 0.000 description 2
• 230000036952 cancer formation Effects 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 150000001735 carboxylic acids Chemical class 0.000 description 2
• 231100000504 carcinogenesis Toxicity 0.000 description 2
• 230000021164 cell adhesion Effects 0.000 description 2
• 230000003915 cell function Effects 0.000 description 2
• 230000004663 cell proliferation Effects 0.000 description 2
• 125000003636 chemical group Chemical group 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• FDKLLWKMYAMLIF-UHFFFAOYSA-N cyclopropane-1,1-dicarboxylic acid Chemical compound OC(=O)C1(C(O)=O)CC1 FDKLLWKMYAMLIF-UHFFFAOYSA-N 0.000 description 2
• 238000010511 deprotection reaction Methods 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 230000018109 developmental process Effects 0.000 description 2
• 150000004683 dihydrates Chemical class 0.000 description 2
• SXZIXHOMFPUIRK-UHFFFAOYSA-N diphenylmethanimine Chemical compound C=1C=CC=CC=1C(=N)C1=CC=CC=C1 SXZIXHOMFPUIRK-UHFFFAOYSA-N 0.000 description 2
• 231100000673 dose–response relationship Toxicity 0.000 description 2
• 229940079593 drug Drugs 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 239000012055 enteric layer Substances 0.000 description 2
• PORXVQGZLDBFFW-UHFFFAOYSA-N ethyl 4-(4-fluorophenyl)-3,5-dioxo-2h-1,2,4-triazine-6-carboxylate Chemical compound O=C1C(C(=O)OCC)=NNC(=O)N1C1=CC=C(F)C=C1 PORXVQGZLDBFFW-UHFFFAOYSA-N 0.000 description 2
• LPSVVXIBDXRFCN-UHFFFAOYSA-N ethyl 4-(4-fluorophenyl)-5-oxo-3-sulfanylidene-2h-1,2,4-triazine-6-carboxylate Chemical compound O=C1C(C(=O)OCC)=NNC(=S)N1C1=CC=C(F)C=C1 LPSVVXIBDXRFCN-UHFFFAOYSA-N 0.000 description 2
• 230000002496 gastric effect Effects 0.000 description 2
• 239000003102 growth factor Substances 0.000 description 2
• 125000001188 haloalkyl group Chemical group 0.000 description 2
• 230000036541 health Effects 0.000 description 2
• 125000005241 heteroarylamino group Chemical group 0.000 description 2
• 125000000623 heterocyclic group Chemical group 0.000 description 2
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
• 150000004678 hydrides Chemical class 0.000 description 2
• 150000003840 hydrochlorides Chemical class 0.000 description 2
• 239000001257 hydrogen Substances 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• 210000004072 lung Anatomy 0.000 description 2
• 208000020816 lung neoplasm Diseases 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 230000009401 metastasis Effects 0.000 description 2
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
• HNTILNAFXSGBIG-UHFFFAOYSA-N methyl 6-bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carboxylate Chemical compound C1=C(Br)C=C(OC)C2=C(C(=O)OC)C=NN21 HNTILNAFXSGBIG-UHFFFAOYSA-N 0.000 description 2
• OZXRLNADZJXGMV-UHFFFAOYSA-N methyl N-[4-(2-fluoro-4-nitrophenoxy)pyrazolo[1,5-a]pyridin-6-yl]carbamate Chemical compound COC(NC=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)[N+](=O)[O-])F)=O OZXRLNADZJXGMV-UHFFFAOYSA-N 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 238000002663 nebulization Methods 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 210000001672 ovary Anatomy 0.000 description 2
• 230000002018 overexpression Effects 0.000 description 2
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
• 230000003076 paracrine Effects 0.000 description 2
• 229940124531 pharmaceutical excipient Drugs 0.000 description 2
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 2
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• 230000035755 proliferation Effects 0.000 description 2
• WHYQCQRHPQBZHM-UHFFFAOYSA-N pyrazole-1-carboxylic acid Chemical compound OC(=O)N1C=CC=N1 WHYQCQRHPQBZHM-UHFFFAOYSA-N 0.000 description 2
• UYVZRUORQWAFPS-UHFFFAOYSA-N pyrazolo[1,5-a]pyridin-4-ol Chemical compound OC1=CC=CN2N=CC=C12 UYVZRUORQWAFPS-UHFFFAOYSA-N 0.000 description 2
• 239000011541 reaction mixture Substances 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 230000004083 survival effect Effects 0.000 description 2
• 208000024891 symptom Diseases 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• KIWCBBHOMONFML-UHFFFAOYSA-N tert-butyl 4-[4-(2-fluoro-4-nitrophenoxy)pyrazolo[1,5-a]pyridin-6-yl]pyrazole-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1N=CC(=C1)C=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)[N+](=O)[O-])F KIWCBBHOMONFML-UHFFFAOYSA-N 0.000 description 2
• UQWTVOIBHINIJX-UHFFFAOYSA-N tert-butyl 4-[4-(4-amino-2-fluorophenoxy)pyrazolo[1,5-a]pyridin-6-yl]piperidine-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1CCC(CC1)C=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)N)F UQWTVOIBHINIJX-UHFFFAOYSA-N 0.000 description 2
• PXCCEYYZXPAQQS-UHFFFAOYSA-N tert-butyl 4-[4-(4-amino-2-fluorophenoxy)pyrazolo[1,5-a]pyridin-6-yl]pyrazole-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1N=CC(=C1)C=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)N)F PXCCEYYZXPAQQS-UHFFFAOYSA-N 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
• 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
• 241000701447 unidentified baculovirus Species 0.000 description 2
• 239000011701 zinc Substances 0.000 description 2
• MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
• MSBGPEACXKBQSX-UHFFFAOYSA-N (4-fluorophenyl) carbonochloridate Chemical compound FC1=CC=C(OC(Cl)=O)C=C1 MSBGPEACXKBQSX-UHFFFAOYSA-N 0.000 description 1
• DHADXDMPEUWEAS-UHFFFAOYSA-N (6-methoxypyridin-3-yl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=N1 DHADXDMPEUWEAS-UHFFFAOYSA-N 0.000 description 1
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
• XJDDLMJULQGRLU-UHFFFAOYSA-N 1,3-dioxane-4,6-dione Chemical compound O=C1CC(=O)OCO1 XJDDLMJULQGRLU-UHFFFAOYSA-N 0.000 description 1
• KPKNTUUIEVXMOH-UHFFFAOYSA-N 1,4-dioxa-8-azaspiro[4.5]decane Chemical compound O1CCOC11CCNCC1 KPKNTUUIEVXMOH-UHFFFAOYSA-N 0.000 description 1
• ZLIQCQOFVHSHPX-UHFFFAOYSA-N 1,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound C1=NN(C)C(C)=C1B1OC(C)(C)C(C)(C)O1 ZLIQCQOFVHSHPX-UHFFFAOYSA-N 0.000 description 1
• CAJXQVJSWADTQZ-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-iodo-2-oxopyridine-3-carboxamide Chemical compound FC1=CC=C(C=C1)N1C(C(=C(C=C1)I)C(=O)N)=O CAJXQVJSWADTQZ-UHFFFAOYSA-N 0.000 description 1
• FNVBQTDSLIAWFA-UHFFFAOYSA-N 1-(4-fluorophenyl)-5-methyl-N-(4-pyrazolo[1,5-a]pyridin-4-yloxyphenyl)pyrazole-4-carboxamide Chemical compound N1=CC=C2N1C=CC=C2OC1=CC=C(C=C1)NC(=O)C=1C=NN(C=1C)C1=CC=C(C=C1)F FNVBQTDSLIAWFA-UHFFFAOYSA-N 0.000 description 1
• GMIUGRKFOYAXLA-UHFFFAOYSA-N 1-(4-fluorophenyl)-N-(3-fluoro-4-pyrazolo[1,5-a]pyridin-4-yloxyphenyl)-2-oxopyrrolidine-3-carboxamide Chemical compound FC=1C=C(C=CC=1OC=1C=2N(C=CC=1)N=CC=2)NC(=O)C1C(N(CC1)C1=CC=C(C=C1)F)=O GMIUGRKFOYAXLA-UHFFFAOYSA-N 0.000 description 1
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
• DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 1
• YSFIOBPLMUNQEI-UHFFFAOYSA-N 1-[(3-fluorophenyl)methyl]-2-oxopyridine-3-carboxylic acid Chemical compound O=C1C(C(=O)O)=CC=CN1CC1=CC=CC(F)=C1 YSFIOBPLMUNQEI-UHFFFAOYSA-N 0.000 description 1
• JQWTVIFNRAALHM-UHFFFAOYSA-N 1-[(4-fluorophenyl)carbamoyl]cyclopropane-1-carbonyl chloride Chemical compound C1=CC(F)=CC=C1NC(=O)C1(C(Cl)=O)CC1 JQWTVIFNRAALHM-UHFFFAOYSA-N 0.000 description 1
• ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
• UMFARKTVGBXVFH-UHFFFAOYSA-N 1-[4-(2-fluoro-4-nitrophenoxy)pyrazolo[1,5-a]pyridin-6-yl]pyrrolidin-2-one Chemical compound FC1=C(OC=2C=3N(C=C(C=2)N2C(CCC2)=O)N=CC=3)C=CC(=C1)[N+](=O)[O-] UMFARKTVGBXVFH-UHFFFAOYSA-N 0.000 description 1
• WVOJRZMURIMREU-UHFFFAOYSA-N 1-carbamoyl-2-(4-fluorophenyl)cyclopropane-1-carboxylic acid Chemical compound NC(=O)C1(C(O)=O)CC1C1=CC=C(F)C=C1 WVOJRZMURIMREU-UHFFFAOYSA-N 0.000 description 1
• ULURCCKYMHPLKC-UHFFFAOYSA-N 1-ethyl-2,4-dioxo-3-phenylpyrimidine-5-carboxylic acid Chemical compound O=C1N(CC)C=C(C(O)=O)C(=O)N1C1=CC=CC=C1 ULURCCKYMHPLKC-UHFFFAOYSA-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
• LAUAOGSIUWTVEZ-UHFFFAOYSA-N 1-fluoro-4-nitro-2-phenylmethoxybenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(OCC=2C=CC=CC=2)=C1 LAUAOGSIUWTVEZ-UHFFFAOYSA-N 0.000 description 1
• YKUZYUUESIPGMR-UHFFFAOYSA-N 1-methyl-2-oxopyridine-3-carboxamide Chemical compound CN1C=CC=C(C(N)=O)C1=O YKUZYUUESIPGMR-UHFFFAOYSA-N 0.000 description 1
• KVQXFNGVIIPCSX-UHFFFAOYSA-N 1-methyl-4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]piperazine Chemical compound C1CN(C)CCN1C1=CC=C(B2OC(C)(C)C(C)(C)O2)C=N1 KVQXFNGVIIPCSX-UHFFFAOYSA-N 0.000 description 1
• VAKOSNKAXYJZRG-UHFFFAOYSA-N 1-methyl-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CN1N=CC(C(O)=O)=C1C(F)(F)F VAKOSNKAXYJZRG-UHFFFAOYSA-N 0.000 description 1
• OKPCAONVUKBJJQ-UHFFFAOYSA-N 1-methylpyrazol-4-amine;hydrochloride Chemical compound Cl.CN1C=C(N)C=N1 OKPCAONVUKBJJQ-UHFFFAOYSA-N 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• FPYJSJDOHRDAMT-KQWNVCNZSA-N 1h-indole-5-sulfonamide, n-(3-chlorophenyl)-3-[[3,5-dimethyl-4-[(4-methyl-1-piperazinyl)carbonyl]-1h-pyrrol-2-yl]methylene]-2,3-dihydro-n-methyl-2-oxo-, (3z)- Chemical compound C=1C=C2NC(=O)\C(=C/C3=C(C(C(=O)N4CCN(C)CC4)=C(C)N3)C)C2=CC=1S(=O)(=O)N(C)C1=CC=CC(Cl)=C1 FPYJSJDOHRDAMT-KQWNVCNZSA-N 0.000 description 1
• NEUWPDLMDVINSN-UHFFFAOYSA-N 1h-pyrazol-5-ylboronic acid Chemical compound OB(O)C=1C=CNN=1 NEUWPDLMDVINSN-UHFFFAOYSA-N 0.000 description 1
• MWHAHWWOASRQKY-UHFFFAOYSA-N 2-(1-aminoethylidene)propanedioic acid Chemical compound CC(N)=C(C(O)=O)C(O)=O MWHAHWWOASRQKY-UHFFFAOYSA-N 0.000 description 1
• ZEMZPXWZVTUONV-UHFFFAOYSA-N 2-(2-dicyclohexylphosphanylphenyl)-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 ZEMZPXWZVTUONV-UHFFFAOYSA-N 0.000 description 1
• FPZWZCWUIYYYBU-UHFFFAOYSA-N 2-(2-ethoxyethoxy)ethyl acetate Chemical group CCOCCOCCOC(C)=O FPZWZCWUIYYYBU-UHFFFAOYSA-N 0.000 description 1
• ZZJNRZPPZXFTAG-UHFFFAOYSA-N 2-(2-fluoroanilino)-2-oxoacetic acid Chemical compound OC(=O)C(=O)NC1=CC=CC=C1F ZZJNRZPPZXFTAG-UHFFFAOYSA-N 0.000 description 1
• DOSGEBYQRMBTGS-UHFFFAOYSA-N 2-(3,6-dihydro-2h-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CCOCC1 DOSGEBYQRMBTGS-UHFFFAOYSA-N 0.000 description 1
• KPQPWSRTSVPWBC-UHFFFAOYSA-N 2-(4-fluorophenyl)-N-(3-fluoro-4-pyrazolo[1,5-a]pyridin-4-yloxyphenyl)acetamide Chemical compound FC1=CC=C(C=C1)CC(=O)NC1=CC(=C(C=C1)OC=1C=2N(C=CC=1)N=CC=2)F KPQPWSRTSVPWBC-UHFFFAOYSA-N 0.000 description 1
• AOUGRIHFTFSAGK-UHFFFAOYSA-N 2-(4-fluorophenyl)-N-[(3-fluoro-4-pyrazolo[1,5-a]pyridin-4-yloxyphenyl)carbamothioyl]acetamide Chemical compound FC1=CC=C(C=C1)CC(=O)NC(=S)NC1=CC(=C(C=C1)OC=1C=2N(C=CC=1)N=CC=2)F AOUGRIHFTFSAGK-UHFFFAOYSA-N 0.000 description 1
• SIOJFYRPBYGHOO-UHFFFAOYSA-N 2-(4-fluorophenyl)acetyl chloride Chemical compound FC1=CC=C(CC(Cl)=O)C=C1 SIOJFYRPBYGHOO-UHFFFAOYSA-N 0.000 description 1
• QRUMHYJVHSHYJW-UHFFFAOYSA-N 2-[3-fluoro-4-[6-(1-methylimidazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyanilino]pyridine-3-carboxylic acid Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=C(C1)C=1N=CN(C1)C)N=CC2)NC2=C(C(=O)O)C=CC=N2 QRUMHYJVHSHYJW-UHFFFAOYSA-N 0.000 description 1
• 125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
• ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
• 229940093475 2-ethoxyethanol Drugs 0.000 description 1
• XOZAJNLUAODXSP-UHFFFAOYSA-N 2-fluoro-5-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(F)N=C1 XOZAJNLUAODXSP-UHFFFAOYSA-N 0.000 description 1
• AUVALWUPUHHNQV-UHFFFAOYSA-N 2-hydroxy-3-propylbenzoic acid Chemical class CCCC1=CC=CC(C(O)=O)=C1O AUVALWUPUHHNQV-UHFFFAOYSA-N 0.000 description 1
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
• VZTSZDHBXRDVNH-UHFFFAOYSA-N 2-phenylpyridine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=C1C1=CC=CC=C1 VZTSZDHBXRDVNH-UHFFFAOYSA-N 0.000 description 1
• WMKYKQWKLILFBM-UHFFFAOYSA-N 2h-pyridine-1-carboxylic acid Chemical compound OC(=O)N1CC=CC=C1 WMKYKQWKLILFBM-UHFFFAOYSA-N 0.000 description 1
• KVTUSMPNLUCCQO-UHFFFAOYSA-N 3,3-difluoropyrrolidine Chemical compound FC1(F)CCNC1 KVTUSMPNLUCCQO-UHFFFAOYSA-N 0.000 description 1
• QEENOLBPAOCCMC-UHFFFAOYSA-N 3,5-dimethyl-1-phenyl-N-(4-pyrazolo[1,5-a]pyridin-4-yloxyphenyl)pyrazole-4-carboxamide Chemical compound N1=CC=C2N1C=CC=C2OC1=CC=C(C=C1)NC(=O)C=1C(=NN(C=1C)C1=CC=CC=C1)C QEENOLBPAOCCMC-UHFFFAOYSA-N 0.000 description 1
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
• MPIZIIRYHHOHEI-UHFFFAOYSA-N 3-bromo-5-methoxypyridin-1-ium-1-amine Chemical compound COC1=CC(Br)=C[N+](N)=C1 MPIZIIRYHHOHEI-UHFFFAOYSA-N 0.000 description 1
• QZEPCEARIYWXLW-UHFFFAOYSA-N 3-chloro-4-(2-fluoro-4-nitrophenoxy)pyrazolo[1,5-a]pyridine Chemical compound ClC=1C=NN2C1C(=CC=C2)OC2=C(C=C(C=C2)[N+](=O)[O-])F QZEPCEARIYWXLW-UHFFFAOYSA-N 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• FFNXVYXVECKMDO-UHFFFAOYSA-N 3-chloropyrazolo[1,5-a]pyridin-4-ol Chemical compound ClC=1C=NN2C1C(=CC=C2)O FFNXVYXVECKMDO-UHFFFAOYSA-N 0.000 description 1
• VFIIUOIZQZYXME-UHFFFAOYSA-N 3-fluoro-4-(6-methoxypyrazolo[1,5-a]pyridin-4-yl)oxyaniline Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=C(C1)OC)N=CC2)N VFIIUOIZQZYXME-UHFFFAOYSA-N 0.000 description 1
• JKNCSOHLXUSIPS-UHFFFAOYSA-N 3-fluoro-4-[6-(1,3-oxazol-2-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyaniline Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=C(C1)C=1OC=CN1)N=CC2)N JKNCSOHLXUSIPS-UHFFFAOYSA-N 0.000 description 1
• NJCXIIPUOYFCHE-UHFFFAOYSA-N 3-fluoro-4-[6-(1,3-thiazol-5-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyaniline Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=C(C1)C1=CN=CS1)N=CC2)N NJCXIIPUOYFCHE-UHFFFAOYSA-N 0.000 description 1
• BIRIOOTUSHFALU-UHFFFAOYSA-N 3-fluoro-4-[6-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyaniline Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=C(C1)C=1C=NNC1)N=CC2)N BIRIOOTUSHFALU-UHFFFAOYSA-N 0.000 description 1
• HPRIHAFDBCFFSO-UHFFFAOYSA-N 3-fluoro-4-[6-(3-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(C=NC1)C)N=CC2)N HPRIHAFDBCFFSO-UHFFFAOYSA-N 0.000 description 1
• MBNVGURIQDFKHW-UHFFFAOYSA-N 3-fluoro-4-[6-(4-methylpiperazin-1-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyaniline Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=C(C1)N1CCN(CC1)C)N=CC2)N MBNVGURIQDFKHW-UHFFFAOYSA-N 0.000 description 1
• MSYZDGBSLHNREU-UHFFFAOYSA-N 3-fluoro-4-[6-(oxan-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyaniline Chemical compound FC=1C=C(C=CC=1OC=1C=2N(C=C(C=1)C1CCOCC1)N=CC=2)N MSYZDGBSLHNREU-UHFFFAOYSA-N 0.000 description 1
• QQVPWYSNFKXQPS-UHFFFAOYSA-N 3-methoxy-4-[6-(1-methylimidazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyaniline Chemical compound COC=1C=C(C=CC1OC=1C=2N(C=C(C1)C=1N=CN(C1)C)N=CC2)N QQVPWYSNFKXQPS-UHFFFAOYSA-N 0.000 description 1
• LLWFWIZOFFLRKC-UHFFFAOYSA-N 3-phenylmethoxypyridine Chemical compound C=1C=CC=CC=1COC1=CC=CN=C1 LLWFWIZOFFLRKC-UHFFFAOYSA-N 0.000 description 1
• OABUKBBBSMNNPM-UHFFFAOYSA-N 4,4-difluoropiperidin-1-ium;chloride Chemical compound Cl.FC1(F)CCNCC1 OABUKBBBSMNNPM-UHFFFAOYSA-N 0.000 description 1
• MJOUJKDTBGXKIU-UHFFFAOYSA-N 4,4-difluoropiperidine Chemical compound FC1(F)CCNCC1 MJOUJKDTBGXKIU-UHFFFAOYSA-N 0.000 description 1
• LPBVIDZMUOOELU-UHFFFAOYSA-N 4-(2-fluoro-4-nitrophenoxy)-6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyridine Chemical compound FC1=C(OC=2C=3N(C=C(C2)C=2C=NN(C2)C)N=CC3)C=CC(=C1)[N+](=O)[O-] LPBVIDZMUOOELU-UHFFFAOYSA-N 0.000 description 1
• VPZJYAXTVGILTQ-UHFFFAOYSA-N 4-(2-fluoro-4-nitrophenoxy)-6-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine Chemical compound FC1=C(OC=2C=3N(C=C(C2)C=2C=NNC2)N=CC3)C=CC(=C1)[N+](=O)[O-] VPZJYAXTVGILTQ-UHFFFAOYSA-N 0.000 description 1
• FFUWGZWHNUYYFN-UHFFFAOYSA-N 4-(2-fluoro-4-nitrophenoxy)-6-pyrimidin-2-ylpyrazolo[1,5-a]pyridine Chemical compound FC1=C(OC=2C=3N(C=C(C2)C2=NC=CC=N2)N=CC3)C=CC(=C1)[N+](=O)[O-] FFUWGZWHNUYYFN-UHFFFAOYSA-N 0.000 description 1
• VWMSPOGWPDMHCU-UHFFFAOYSA-N 4-(2-fluoro-4-nitrophenoxy)-N-pyrimidin-2-ylpyrazolo[1,5-a]pyridin-6-amine Chemical compound FC1=C(OC=2C=3N(C=C(C2)NC2=NC=CC=N2)N=CC3)C=CC(=C1)[N+](=O)[O-] VWMSPOGWPDMHCU-UHFFFAOYSA-N 0.000 description 1
• IBFHUXAMFFTLKO-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-thiazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CSN=C1 IBFHUXAMFFTLKO-UHFFFAOYSA-N 0.000 description 1
• RGSHLIHXXGEXTJ-UHFFFAOYSA-N 4-(4-amino-2-fluorophenoxy)-N,N-dimethylpyrazolo[1,5-a]pyridine-6-carboxamide Chemical compound CN(C(=O)C=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)N)F)C RGSHLIHXXGEXTJ-UHFFFAOYSA-N 0.000 description 1
• UCDVBYQDANKSBM-UHFFFAOYSA-N 4-(4-amino-2-fluorophenoxy)-N-(1,5-dimethylpyrazol-4-yl)pyrazolo[1,5-a]pyridin-6-amine Chemical compound NC1=CC(=C(OC=2C=3N(C=C(C2)NC=2C=NN(C2C)C)N=CC3)C=C1)F UCDVBYQDANKSBM-UHFFFAOYSA-N 0.000 description 1
• FODNRELKGUNDIC-UHFFFAOYSA-N 4-(4-amino-2-fluorophenoxy)-N-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyridin-6-amine Chemical compound NC1=CC(=C(OC=2C=3N(C=C(C2)NC=2C=NN(C2)C)N=CC3)C=C1)F FODNRELKGUNDIC-UHFFFAOYSA-N 0.000 description 1
• SGDMCRDTTULGPB-UHFFFAOYSA-N 4-(4-amino-2-fluorophenoxy)-N-(5-fluoropyridin-2-yl)pyrazolo[1,5-a]pyridin-6-amine Chemical compound NC1=CC(=C(OC=2C=3N(C=C(C2)NC2=NC=C(C=C2)F)N=CC3)C=C1)F SGDMCRDTTULGPB-UHFFFAOYSA-N 0.000 description 1
• UAFUFRFDMFCWIU-UHFFFAOYSA-N 4-(4-amino-2-fluorophenoxy)-N-phenylpyrazolo[1,5-a]pyridin-6-amine Chemical compound NC1=CC(=C(OC=2C=3N(C=C(C2)NC2=CC=CC=C2)N=CC3)C=C1)F UAFUFRFDMFCWIU-UHFFFAOYSA-N 0.000 description 1
• OBRPEOCSDIRWIZ-UHFFFAOYSA-N 4-(4-amino-2-fluorophenoxy)-N-pyridin-2-ylpyrazolo[1,5-a]pyridin-6-amine Chemical compound NC1=CC(=C(OC=2C=3N(C=C(C2)NC2=NC=CC=C2)N=CC3)C=C1)F OBRPEOCSDIRWIZ-UHFFFAOYSA-N 0.000 description 1
• IMBBXSASDSZJSX-UHFFFAOYSA-N 4-Carboxypyrazole Chemical compound OC(=O)C=1C=NNC=1 IMBBXSASDSZJSX-UHFFFAOYSA-N 0.000 description 1
• BHCKFCNNROTKPX-UHFFFAOYSA-N 4-[4-(2-fluoro-4-nitrophenoxy)pyrazolo[1,5-a]pyridin-6-yl]morpholine Chemical compound FC1=C(OC=2C=3N(C=C(C2)N2CCOCC2)N=CC3)C=CC(=C1)[N+](=O)[O-] BHCKFCNNROTKPX-UHFFFAOYSA-N 0.000 description 1
• ZGDLVKWIZHHWIR-UHFFFAOYSA-N 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]morpholine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N2CCOCC2)N=C1 ZGDLVKWIZHHWIR-UHFFFAOYSA-N 0.000 description 1
• YIBABYPKDDYCPW-UHFFFAOYSA-N 4-[6-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)pyrazolo[1,5-a]pyridin-4-yl]oxy-3-fluoroaniline Chemical compound O1CCOC12CCN(CC2)C=2C=C(C=1N(C2)N=CC1)OC1=C(C=C(C=C1)N)F YIBABYPKDDYCPW-UHFFFAOYSA-N 0.000 description 1
• UXKGDDSWYGPVML-UHFFFAOYSA-N 4-[6-(1-methylimidazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxy-2-(trifluoromethyl)aniline Chemical compound CN1C=NC(=C1)C=1C=C(C=2N(C=1)N=CC=2)OC1=CC(=C(C=C1)N)C(F)(F)F UXKGDDSWYGPVML-UHFFFAOYSA-N 0.000 description 1
• SCOOZUUCZAYFQT-UHFFFAOYSA-N 4-[6-(1-methylimidazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxy-3-(trifluoromethyl)aniline Chemical compound CN1C=NC(=C1)C=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)N)C(F)(F)F SCOOZUUCZAYFQT-UHFFFAOYSA-N 0.000 description 1
• USFPYUZFZCNXLI-UHFFFAOYSA-N 4-[6-(1-methylimidazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxy-3-phenylmethoxyaniline Chemical compound C(C1=CC=CC=C1)OC=1C=C(C=CC1OC=1C=2N(C=C(C1)C=1N=CN(C1)C)N=CC2)N USFPYUZFZCNXLI-UHFFFAOYSA-N 0.000 description 1
• VDWLBAVFIUANAB-UHFFFAOYSA-N 4-[6-(3,5-dimethyl-1,2-oxazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxy-3-fluoroaniline Chemical compound CC1=NOC(=C1C=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)N)F)C VDWLBAVFIUANAB-UHFFFAOYSA-N 0.000 description 1
• WLKUSVNHZXUEFO-UHFFFAOYSA-N 4-fluoro-2-methoxy-1-nitrobenzene Chemical compound COC1=CC(F)=CC=C1[N+]([O-])=O WLKUSVNHZXUEFO-UHFFFAOYSA-N 0.000 description 1
• JHFOWEGCZWLHNW-UHFFFAOYSA-N 4-fluoro-2-methyl-1-nitrobenzene Chemical compound CC1=CC(F)=CC=C1[N+]([O-])=O JHFOWEGCZWLHNW-UHFFFAOYSA-N 0.000 description 1
• XQISOOQOVQCZFJ-UHFFFAOYSA-N 4-fluoro-N-[3-fluoro-4-[6-(1-methylimidazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyphenyl]benzenesulfonamide Chemical compound FC1=CC=C(C=C1)S(=O)(=O)NC1=CC(=C(C=C1)OC=1C=2N(C=C(C=1)C=1N=CN(C=1)C)N=CC=2)F XQISOOQOVQCZFJ-UHFFFAOYSA-N 0.000 description 1
• JVLQFTDZFJTXOO-UHFFFAOYSA-N 4-hydroxy-N,N-dimethylpyrazolo[1,5-a]pyridine-6-carboxamide Chemical compound CN(C(=O)C=1C=C(C=2N(C1)N=CC2)O)C JVLQFTDZFJTXOO-UHFFFAOYSA-N 0.000 description 1
• BVCUDDZWEDKTNB-UHFFFAOYSA-N 4-hydroxypyrazolo[1,5-a]pyridine-6-carboxylic acid Chemical compound OC=1C=2N(C=C(C1)C(=O)O)N=CC2 BVCUDDZWEDKTNB-UHFFFAOYSA-N 0.000 description 1
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
• IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
• UICYNPCDTZNZNQ-UHFFFAOYSA-N 5-[4-(2-fluoro-4-nitrophenoxy)pyrazolo[1,5-a]pyridin-6-yl]-1,3-oxazole Chemical compound FC1=C(OC=2C=3N(C=C(C2)C2=CN=CO2)N=CC3)C=CC(=C1)[N+](=O)[O-] UICYNPCDTZNZNQ-UHFFFAOYSA-N 0.000 description 1
• IJPFBRONCJOTTA-UHFFFAOYSA-N 5-chloro-1h-pyrazole Chemical compound ClC1=CC=NN1 IJPFBRONCJOTTA-UHFFFAOYSA-N 0.000 description 1
• MFLBIUTXXAVDIB-UHFFFAOYSA-N 5-methyl-1-phenyl-N-(4-pyrazolo[1,5-a]pyridin-4-yloxyphenyl)pyrazole-4-carboxamide Chemical compound N1=CC=C2N1C=CC=C2OC1=CC=C(C=C1)NC(=O)C=1C=NN(C=1C)C1=CC=CC=C1 MFLBIUTXXAVDIB-UHFFFAOYSA-N 0.000 description 1
• RSZXJEVGDJOJGQ-UHFFFAOYSA-N 6-(1-methylimidazol-4-yl)-4-(2-methyl-4-nitrophenoxy)pyrazolo[1,5-a]pyridine Chemical compound CN1C=NC(=C1)C=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)[N+](=O)[O-])C RSZXJEVGDJOJGQ-UHFFFAOYSA-N 0.000 description 1
• NUAMXLUERCJLTO-UHFFFAOYSA-N 6-(4,4-difluoropiperidin-1-yl)-4-(2-fluoro-4-nitrophenoxy)pyrazolo[1,5-a]pyridine Chemical compound FC1(CCN(CC1)C=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)[N+](=O)[O-])F)F NUAMXLUERCJLTO-UHFFFAOYSA-N 0.000 description 1
• KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
• NTPUGSGGQBJUFY-UHFFFAOYSA-N 6-bromo-4-(4-nitro-2-phenylmethoxyphenoxy)pyrazolo[1,5-a]pyridine Chemical compound C(C1=CC=CC=C1)OC1=C(OC=2C=3N(C=C(C2)Br)N=CC3)C=CC(=C1)[N+](=O)[O-] NTPUGSGGQBJUFY-UHFFFAOYSA-N 0.000 description 1
• WMTYPRLOKVODHN-UHFFFAOYSA-N 6-bromo-4-phenylmethoxypyrazolo[1,5-a]pyridine Chemical compound C12=CC=NN2C=C(Br)C=C1OCC1=CC=CC=C1 WMTYPRLOKVODHN-UHFFFAOYSA-N 0.000 description 1
• XRIHTJYXIHOBDQ-UHFFFAOYSA-N 6-methyl-2-oxo-1h-pyridine-3-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)C(=O)N1 XRIHTJYXIHOBDQ-UHFFFAOYSA-N 0.000 description 1
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 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 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• RMSGQBUILXEJJE-UHFFFAOYSA-N CC(C)N(C=C(C(O)=O)C(N1C(C=C2)=CC=C2F)=O)C1=O.CN1C=NC(C2=CN3N=CC=C3C(OC(C=C3)=CN=C3N)=C2)=C1 Chemical compound CC(C)N(C=C(C(O)=O)C(N1C(C=C2)=CC=C2F)=O)C1=O.CN1C=NC(C2=CN3N=CC=C3C(OC(C=C3)=CN=C3N)=C2)=C1 RMSGQBUILXEJJE-UHFFFAOYSA-N 0.000 description 1
• FHGMKMNYJGZASH-UHFFFAOYSA-N CN1N=CC=C1C=1C=CC=2N(C1)N=CC2 Chemical compound CN1N=CC=C1C=1C=CC=2N(C1)N=CC2 FHGMKMNYJGZASH-UHFFFAOYSA-N 0.000 description 1
• CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 1
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
• 229920000742 Cotton Polymers 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
• 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 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
• 206010059866 Drug resistance Diseases 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
• JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 description 1
• 102100037362 Fibronectin Human genes 0.000 description 1
• 108010067306 Fibronectins Proteins 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 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 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 108010081348 HRT1 protein Hairy Proteins 0.000 description 1
• 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 description 1
• 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 1
• 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
• 101000973901 Homo sapiens Tyrosine-protein kinase Mer Proteins 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 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 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• 206010025323 Lymphomas Diseases 0.000 description 1
• 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
• GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 206010027457 Metastases to liver Diseases 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
• SIXFKSTZFPYRGO-UHFFFAOYSA-N N'-[3-fluoro-4-[6-(1-methylimidazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyphenyl]-N-(4-fluorophenyl)oxamide Chemical compound FC=1C=C(C=CC=1OC=1C=2N(C=C(C=1)C=1N=CN(C=1)C)N=CC=2)NC(C(=O)NC1=CC=C(C=C1)F)=O SIXFKSTZFPYRGO-UHFFFAOYSA-N 0.000 description 1
• QKRSRUMJVIWHNM-UHFFFAOYSA-N N,N-dimethyl-4-phenylmethoxypyrazolo[1,5-a]pyridine-6-carboxamide Chemical compound CN(C(=O)C=1C=C(C=2N(C=1)N=CC=2)OCC1=CC=CC=C1)C QKRSRUMJVIWHNM-UHFFFAOYSA-N 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• DBHPHQAEMCBKOP-UHFFFAOYSA-N N-[4-(2-fluoro-4-nitrophenoxy)pyrazolo[1,5-a]pyridin-6-yl]methanesulfonamide Chemical compound FC1=C(OC=2C=3N(C=C(C2)NS(=O)(=O)C)N=CC3)C=CC(=C1)[N+](=O)[O-] DBHPHQAEMCBKOP-UHFFFAOYSA-N 0.000 description 1
• HWFAXKVBORANLU-UHFFFAOYSA-N N-fluoro-4-[6-(1-methylimidazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyaniline Chemical compound FNC1=CC=C(C=C1)OC=1C=2N(C=C(C=1)C=1N=CN(C=1)C)N=CC=2 HWFAXKVBORANLU-UHFFFAOYSA-N 0.000 description 1
• AKTQSHIRSZYKJS-UHFFFAOYSA-N N-methylmethanamine Chemical compound CNC.CNC AKTQSHIRSZYKJS-UHFFFAOYSA-N 0.000 description 1
• UQFQONCQIQEYPJ-UHFFFAOYSA-N N-methylpyrazole Chemical compound CN1C=CC=N1 UQFQONCQIQEYPJ-UHFFFAOYSA-N 0.000 description 1
• IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
• 108700020796 Oncogene Proteins 0.000 description 1
• 108700026244 Open Reading Frames Proteins 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 206010057249 Phagocytosis Diseases 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 108091030071 RNAI Proteins 0.000 description 1
• 208000006265 Renal cell carcinoma Diseases 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• 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 1
• 239000012317 TBTU Substances 0.000 description 1
• 208000007536 Thrombosis Diseases 0.000 description 1
• 208000033781 Thyroid carcinoma Diseases 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 101150098329 Tyro3 gene Proteins 0.000 description 1
• 102100022356 Tyrosine-protein kinase Mer Human genes 0.000 description 1
• 206010046798 Uterine leiomyoma Diseases 0.000 description 1
• 229930003448 Vitamin K Natural products 0.000 description 1
• LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
• PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 1
• KFDLHDGFDLHFRW-UHFFFAOYSA-N [O-][N+](Br)=O Chemical compound [O-][N+](Br)=O KFDLHDGFDLHFRW-UHFFFAOYSA-N 0.000 description 1
• CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
• 239000012346 acetyl chloride Substances 0.000 description 1
• 150000008065 acid anhydrides Chemical class 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 239000008135 aqueous vehicle Substances 0.000 description 1
• 150000004982 aromatic amines Chemical class 0.000 description 1
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
• 230000003416 augmentation Effects 0.000 description 1
• 230000003305 autocrine Effects 0.000 description 1
• 230000008267 autocrine signaling Effects 0.000 description 1
• 230000035578 autophosphorylation Effects 0.000 description 1
• 108010023337 axl receptor tyrosine kinase Proteins 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 239000004305 biphenyl Substances 0.000 description 1
• 239000003114 blood coagulation factor Substances 0.000 description 1
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
• 239000007853 buffer solution Substances 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 239000000378 calcium silicate Substances 0.000 description 1
• 229910052918 calcium silicate Inorganic materials 0.000 description 1
• 229960003340 calcium silicate Drugs 0.000 description 1
• 235000012241 calcium silicate Nutrition 0.000 description 1
• OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
• 239000004202 carbamide Substances 0.000 description 1
• 125000004452 carbocyclyl group Chemical group 0.000 description 1
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
• 230000020411 cell activation Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 230000009087 cell motility Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 239000003795 chemical substances by application Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 201000010989 colorectal carcinoma Diseases 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
• 239000007822 coupling agent Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 238000006114 decarboxylation reaction Methods 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 238000010520 demethylation reaction Methods 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
• ZJULYDCRWUEPTK-UHFFFAOYSA-N dichloromethyl Chemical compound Cl[CH]Cl ZJULYDCRWUEPTK-UHFFFAOYSA-N 0.000 description 1
• BSSFMHHLTVJPGW-UHFFFAOYSA-N dicyclohexyl-[2-(2-dicyclohexylphosphanylphenyl)phenyl]phosphane Chemical group C1CCCCC1P(C=1C(=CC=CC=1)C=1C(=CC=CC=1)P(C1CCCCC1)C1CCCCC1)C1CCCCC1 BSSFMHHLTVJPGW-UHFFFAOYSA-N 0.000 description 1
• LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 1
• DBKKFIIYQGGHJO-UHFFFAOYSA-N diethyl 2-oxopropanedioate Chemical compound CCOC(=O)C(=O)C(=O)OCC DBKKFIIYQGGHJO-UHFFFAOYSA-N 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 238000006471 dimerization reaction Methods 0.000 description 1
• 125000005879 dioxolanyl group Chemical group 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 230000007783 downstream signaling Effects 0.000 description 1
• 210000001198 duodenum Anatomy 0.000 description 1
• 239000008157 edible vegetable oil Substances 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 230000003511 endothelial effect Effects 0.000 description 1
• 150000002085 enols Chemical class 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 230000029578 entry into host Effects 0.000 description 1
• 230000007705 epithelial mesenchymal transition Effects 0.000 description 1
• 230000017679 epithelial-mesenchymal cell signaling Effects 0.000 description 1
• 201000004101 esophageal cancer Diseases 0.000 description 1
• PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
• KHTLNHWJZBIELS-UHFFFAOYSA-N ethyl 2-[3-fluoro-4-[6-(1-methylimidazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxyanilino]pyridine-3-carboxylate Chemical compound C(C)OC(C1=C(N=CC=C1)NC1=CC(=C(C=C1)OC=1C=2N(C=C(C=1)C=1N=CN(C=1)C)N=CC=2)F)=O KHTLNHWJZBIELS-UHFFFAOYSA-N 0.000 description 1
• PMIMPBYTPPRBGD-UHFFFAOYSA-N ethyl 2-chloropyridine-3-carboxylate Chemical compound CCOC(=O)C1=CC=CN=C1Cl PMIMPBYTPPRBGD-UHFFFAOYSA-N 0.000 description 1
• GTKPSXAZILMVIN-UHFFFAOYSA-N ethyl 3,5-dioxo-2h-1,2,4-triazine-6-carboxylate Chemical class CCOC(=O)C1=NNC(=O)NC1=O GTKPSXAZILMVIN-UHFFFAOYSA-N 0.000 description 1
• IUEASRWXJILERC-UHFFFAOYSA-N ethyl 3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxylate Chemical compound O=C1C(C(=O)OCC)=CN(C(C)C)C(=O)N1C1=CC=C(F)C=C1 IUEASRWXJILERC-UHFFFAOYSA-N 0.000 description 1
• DRPHECCUTGQVDN-UHFFFAOYSA-N ethyl 4-(4-fluorophenyl)-3,5-dioxo-2-propan-2-yl-1,2,4-triazine-6-carboxylate Chemical compound O=C1C(C(=O)OCC)=NN(C(C)C)C(=O)N1C1=CC=C(F)C=C1 DRPHECCUTGQVDN-UHFFFAOYSA-N 0.000 description 1
• WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 1
• 230000005284 excitation Effects 0.000 description 1
• 230000001815 facial effect Effects 0.000 description 1
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000020375 flavoured syrup Nutrition 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 229940014259 gelatin Drugs 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 230000009368 gene silencing by RNA Effects 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 238000000227 grinding Methods 0.000 description 1
• 125000001072 heteroaryl group Chemical group 0.000 description 1
• 239000008240 homogeneous mixture Substances 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• WICNYNXYKZNNSN-UHFFFAOYSA-N hydron;4-methylpiperazine-1-carbonyl chloride;chloride Chemical compound Cl.CN1CCN(C(Cl)=O)CC1 WICNYNXYKZNNSN-UHFFFAOYSA-N 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
• 230000003463 hyperproliferative effect Effects 0.000 description 1
• 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
• 238000010874 in vitro model Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 239000011261 inert gas Substances 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 230000015788 innate immune response Effects 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 230000008611 intercellular interaction Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 230000009545 invasion Effects 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 230000007794 irritation 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
• 239000012948 isocyanate Substances 0.000 description 1
• 150000002513 isocyanates Chemical class 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
• FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 201000010260 leiomyoma Diseases 0.000 description 1
• 238000012417 linear regression Methods 0.000 description 1
• 239000011344 liquid material Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 230000036210 malignancy Effects 0.000 description 1
• 239000011565 manganese chloride Substances 0.000 description 1
• 235000002867 manganese chloride Nutrition 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 230000014690 mesenchyme development Effects 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 230000029712 muscle cell homeostasis Effects 0.000 description 1
• 210000002464 muscle smooth vascular Anatomy 0.000 description 1
• YGGWPDLYLUHWIQ-UHFFFAOYSA-N n,n-dimethylpyridine-2-carboxamide Chemical compound CN(C)C(=O)C1=CC=CC=N1 YGGWPDLYLUHWIQ-UHFFFAOYSA-N 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
• 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
• 230000006654 negative regulation of apoptotic process Effects 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
• 230000007472 neurodevelopment Effects 0.000 description 1
• 229960003512 nicotinic acid Drugs 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• AKRYBBWYDSDZHG-UHFFFAOYSA-N nitrosobis(2-oxopropyl)amine Chemical compound CC(=O)CN(N=O)CC(C)=O AKRYBBWYDSDZHG-UHFFFAOYSA-N 0.000 description 1
• CMUOJBJRZUHRMU-UHFFFAOYSA-N nitrourea Chemical class NC(=O)N[N+]([O-])=O CMUOJBJRZUHRMU-UHFFFAOYSA-N 0.000 description 1
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 231100000590 oncogenic Toxicity 0.000 description 1
• 230000002246 oncogenic effect Effects 0.000 description 1
• 230000006548 oncogenic transformation Effects 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 238000012261 overproduction Methods 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• XEEVLJKYYUVTRC-UHFFFAOYSA-N oxomalonic acid Chemical compound OC(=O)C(=O)C(O)=O XEEVLJKYYUVTRC-UHFFFAOYSA-N 0.000 description 1
• 201000010198 papillary carcinoma Diseases 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 238000003359 percent control normalization Methods 0.000 description 1
• 125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 230000008782 phagocytosis Effects 0.000 description 1
• 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 229940081066 picolinic acid Drugs 0.000 description 1
• 125000005575 polycyclic aromatic hydrocarbon group Chemical group 0.000 description 1
• 229920001184 polypeptide Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000011056 potassium acetate Nutrition 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• 229910000160 potassium phosphate Inorganic materials 0.000 description 1
• 235000011009 potassium phosphates Nutrition 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 238000004393 prognosis Methods 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 239000003909 protein kinase inhibitor Substances 0.000 description 1
• RUUOPSRRIKJHNH-UHFFFAOYSA-N pyridazine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=N1 RUUOPSRRIKJHNH-UHFFFAOYSA-N 0.000 description 1
• ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
• QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 230000008261 resistance mechanism Effects 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 230000029058 respiratory gaseous exchange Effects 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• 239000012056 semi-solid material Substances 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 102000034285 signal transducing proteins Human genes 0.000 description 1
• 108091006024 signal transducing proteins Proteins 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 230000007781 signaling event Effects 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• VGTPCRGMBIAPIM-UHFFFAOYSA-M sodium thiocyanate Chemical compound [Na+].[S-]C#N VGTPCRGMBIAPIM-UHFFFAOYSA-M 0.000 description 1
• 239000011343 solid material Substances 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• 206010041823 squamous cell carcinoma Diseases 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000012058 sterile packaged powder Substances 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 125000001424 substituent group Chemical group 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 150000003456 sulfonamides Chemical class 0.000 description 1
• 230000000153 supplemental effect Effects 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• BEDSAXZARAKIDZ-UHFFFAOYSA-N tert-butyl 4-[4-(2-fluoro-4-nitrophenoxy)pyrazolo[1,5-a]pyridin-6-yl]-5-methylpyrazole-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1N=CC(=C1C)C=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)[N+](=O)[O-])F BEDSAXZARAKIDZ-UHFFFAOYSA-N 0.000 description 1
• UWFIXXHOQHGNGB-UHFFFAOYSA-N tert-butyl 4-[4-(4-amino-2-fluorophenoxy)pyrazolo[1,5-a]pyridin-6-yl]-5-methylpyrazole-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1N=CC(=C1C)C=1C=C(C=2N(C1)N=CC2)OC2=C(C=C(C=C2)N)F UWFIXXHOQHGNGB-UHFFFAOYSA-N 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 238000011287 therapeutic dose Methods 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 description 1
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
• 201000002510 thyroid cancer Diseases 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• 208000013077 thyroid gland carcinoma Diseases 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 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
• JJEPNAHKAMKIFE-UHFFFAOYSA-N tributyl(1H-imidazol-5-yl)stannane Chemical compound C(CCC)[Sn](C1=CN=CN1)(CCCC)CCCC JJEPNAHKAMKIFE-UHFFFAOYSA-N 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• ZBZJXHCVGLJWFG-UHFFFAOYSA-N trichloromethyl(.) Chemical compound Cl[C](Cl)Cl ZBZJXHCVGLJWFG-UHFFFAOYSA-N 0.000 description 1
• WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 108010002164 tyrosine receptor Proteins 0.000 description 1
• 238000009827 uniform distribution Methods 0.000 description 1
• 238000011144 upstream manufacturing Methods 0.000 description 1
• 201000007954 uterine fibroid Diseases 0.000 description 1
• 238000010200 validation analysis Methods 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 235000019168 vitamin K Nutrition 0.000 description 1
• 239000011712 vitamin K Substances 0.000 description 1
• 150000003721 vitamin K derivatives Chemical class 0.000 description 1
• 229940046010 vitamin k Drugs 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 1
• 239000011592 zinc chloride Substances 0.000 description 1
• 235000005074 zinc chloride Nutrition 0.000 description 1
• GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1