KR20160110390A - 피라졸로[1,5-a]피리딘 유도체 및 그의 용도 - Google Patents

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Publication number

KR20160110390A

KR20160110390A KR1020167019605A KR20167019605A KR20160110390A KR 20160110390 A KR20160110390 A KR 20160110390A KR 1020167019605 A KR1020167019605 A KR 1020167019605A KR 20167019605 A KR20167019605 A KR 20167019605A KR 20160110390 A KR20160110390 A KR 20160110390A

Authority

KR

South Korea

Prior art keywords

alkyl

fluoro

pyrazolo

pyridin

optionally substituted

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.)

Withdrawn

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• 238000000034 method Methods 0.000 title claims description 151
• DVUBDHRTVYLIPA-UHFFFAOYSA-N pyrazolo[1,5-a]pyridine Chemical class C1=CC=CN2N=CC=C21 DVUBDHRTVYLIPA-UHFFFAOYSA-N 0.000 title abstract description 4
• 150000001875 compounds Chemical class 0.000 claims description 279
• -1 substituted Chemical class 0.000 claims description 259
• 125000000217 alkyl group Chemical group 0.000 claims description 168
• 125000003118 aryl group Chemical group 0.000 claims description 34
• 229910052757 nitrogen Inorganic materials 0.000 claims description 31
• 125000003545 alkoxy group Chemical group 0.000 claims description 29
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 27
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
• 150000003839 salts Chemical class 0.000 claims description 17
• 206010028980 Neoplasm Diseases 0.000 claims description 14
• 125000004076 pyridyl group Chemical group 0.000 claims description 12
• 201000011510 cancer Diseases 0.000 claims description 10
• 229910052799 carbon Inorganic materials 0.000 claims description 10
• 229910052739 hydrogen Inorganic materials 0.000 claims description 10
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 10
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 10
• 125000004385 trihaloalkyl group Chemical group 0.000 claims description 9
• 125000002947 alkylene group Chemical group 0.000 claims description 8
• 208000005718 Stomach Neoplasms Diseases 0.000 claims description 7
• 206010017758 gastric cancer Diseases 0.000 claims description 7
• 201000011549 stomach cancer Diseases 0.000 claims description 7
• 125000002757 morpholinyl group Chemical group 0.000 claims description 6
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 6
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 6
• 208000026310 Breast neoplasm Diseases 0.000 claims description 5
• 125000002883 imidazolyl group Chemical group 0.000 claims description 5
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 5
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
• 125000002971 oxazolyl group Chemical group 0.000 claims description 5
• 125000004193 piperazinyl group Chemical group 0.000 claims description 5
• 125000003386 piperidinyl group Chemical group 0.000 claims description 5
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 5
• 125000000335 thiazolyl group Chemical group 0.000 claims description 5
• 206010006187 Breast cancer Diseases 0.000 claims description 4
• 208000008839 Kidney Neoplasms Diseases 0.000 claims description 4
• 206010038389 Renal cancer Diseases 0.000 claims description 4
• 201000010982 kidney cancer Diseases 0.000 claims description 4
• 201000001441 melanoma Diseases 0.000 claims description 4
• 208000003174 Brain Neoplasms Diseases 0.000 claims description 3
• 206010009944 Colon cancer Diseases 0.000 claims description 3
• 208000029742 colonic neoplasm 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
• 125000001475 halogen functional group Chemical group 0.000 claims 35
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 3
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
• 229940043355 kinase inhibitor Drugs 0.000 abstract description 2
• 239000003757 phosphotransferase inhibitor Substances 0.000 abstract description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 278
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 250
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 186
• 238000005481 NMR spectroscopy Methods 0.000 description 179
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 166
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 160
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 147
• 239000000243 solution Substances 0.000 description 107
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 90
• 239000000203 mixture Substances 0.000 description 74
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 68
• 239000000047 product Substances 0.000 description 68
• 238000006243 chemical reaction Methods 0.000 description 67
• 235000019439 ethyl acetate Nutrition 0.000 description 63
• 238000002360 preparation method Methods 0.000 description 61
• 239000012267 brine Substances 0.000 description 60
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 60
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 58
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 51
• 229910052938 sodium sulfate Inorganic materials 0.000 description 51
• 235000011152 sodium sulphate Nutrition 0.000 description 51
• 239000011664 nicotinic acid Substances 0.000 description 44
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
• 125000005843 halogen group Chemical group 0.000 description 42
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
• 239000007787 solid Substances 0.000 description 37
• 229910000029 sodium carbonate Inorganic materials 0.000 description 34
• 239000012299 nitrogen atmosphere Substances 0.000 description 32
• 239000000543 intermediate Substances 0.000 description 30
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
• 239000000741 silica gel Substances 0.000 description 26
• 229910002027 silica gel Inorganic materials 0.000 description 26
• 150000001408 amides Chemical class 0.000 description 24
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 24
• 125000002496 methyl group Chemical group [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
• 230000015572 biosynthetic process Effects 0.000 description 21
• 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 20
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 20
• 229910052763 palladium Inorganic materials 0.000 description 20
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 20
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
• 238000010168 coupling process Methods 0.000 description 19
• 238000003786 synthesis reaction Methods 0.000 description 19
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 19
• 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 18
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 18
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 18
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 18
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 18
• 239000012312 sodium hydride Substances 0.000 description 18
• 229910000104 sodium hydride Inorganic materials 0.000 description 18
• 239000006229 carbon black Substances 0.000 description 17
• 229910052801 chlorine Inorganic materials 0.000 description 17
• 229910052731 fluorine Inorganic materials 0.000 description 17
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 16
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 15
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 15
• 239000002480 mineral oil Substances 0.000 description 15
• 235000010446 mineral oil Nutrition 0.000 description 15
• 239000002904 solvent Substances 0.000 description 15
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 14
• 125000001624 naphthyl group Chemical group 0.000 description 14
• 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 13
• 230000009467 reduction Effects 0.000 description 13
• VDFROLGDZZETHN-UHFFFAOYSA-N 3-fluoro-4-pyrazolo[1,5-a]pyridin-4-yloxyaniline Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=CC1)N=CC2)N VDFROLGDZZETHN-UHFFFAOYSA-N 0.000 description 12
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
• 239000011734 sodium Substances 0.000 description 12
• 238000003756 stirring Methods 0.000 description 12
• 239000002253 acid Substances 0.000 description 11
• 230000000694 effects Effects 0.000 description 11
• 239000000546 pharmaceutical excipient Substances 0.000 description 11
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
• 108091000080 Phosphotransferase Proteins 0.000 description 10
• 239000004480 active ingredient Substances 0.000 description 10
• 102000020233 phosphotransferase Human genes 0.000 description 10
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
• 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 description 9
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
• 239000002552 dosage form Substances 0.000 description 8
• 239000010410 layer 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
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 8
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 8
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-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
• 238000009472 formulation Methods 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• 125000005500 uronium group Chemical group 0.000 description 7
• KDSGRFDWQSNHMH-UHFFFAOYSA-N 3-fluoro-4-(6-morpholin-4-ylpyrazolo[1,5-a]pyridin-4-yl)oxyaniline Chemical compound FC=1C=C(C=CC1OC=1C=2N(C=C(C1)N1CCOCC1)N=CC2)N KDSGRFDWQSNHMH-UHFFFAOYSA-N 0.000 description 6
• ULSHXIWEAIWUOL-UHFFFAOYSA-N 4-(2-fluoro-4-nitrophenoxy)pyrazolo[1,5-a]pyridin-6-amine Chemical compound FC1=C(OC=2C=3N(C=C(C2)N)N=CC3)C=CC(=C1)[N+](=O)[O-] ULSHXIWEAIWUOL-UHFFFAOYSA-N 0.000 description 6
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
• 0 C=C(CCCC(C=*)N)Nc(cc1F)ccc1ClC(CN)=C Chemical compound C=C(CCCC(C=*)N)Nc(cc1F)ccc1ClC(CN)=C 0.000 description 6
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 6
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 239000000725 suspension Substances 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
• ZXYAAVBXHKCJJB-UHFFFAOYSA-N uracil-5-carboxylic acid Chemical compound OC(=O)C1=CNC(=O)NC1=O ZXYAAVBXHKCJJB-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
• 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 5
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
• 239000002585 base Substances 0.000 description 5
• 125000004432 carbon atom Chemical group C* 0.000 description 5
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• 230000014509 gene expression Effects 0.000 description 5
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• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 5
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Substances [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• JTZSVYCKAYMNCT-UHFFFAOYSA-N 3-(4-fluorophenyl)-2,4-dioxo-1h-pyrimidine-5-carboxylic acid Chemical compound O=C1C(C(=O)O)=CNC(=O)N1C1=CC=C(F)C=C1 JTZSVYCKAYMNCT-UHFFFAOYSA-N 0.000 description 4
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
• KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 4
• 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 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
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• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
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• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 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
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• 230000037396 body weight Effects 0.000 description 4
• 239000000872 buffer Substances 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
• 210000004027 cell Anatomy 0.000 description 4
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• 125000001207 fluorophenyl group Chemical group 0.000 description 4
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
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• UYVZRUORQWAFPS-UHFFFAOYSA-N pyrazolo[1,5-a]pyridin-4-ol Chemical compound OC1=CC=CN2N=CC=C12 UYVZRUORQWAFPS-UHFFFAOYSA-N 0.000 description 4
• 238000006467 substitution reaction Methods 0.000 description 4
• 210000001519 tissue Anatomy 0.000 description 4
• 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
• 238000005160 1H NMR spectroscopy Methods 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
• 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 3
• 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 3
• 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 3
• 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 3
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