JP2008523018A - 脈管形成、高増殖性または神経変性疾患の治療のためのプロテインチロシンキナーゼの阻害剤としての３−アミノ−ピラゾロ［３，４ｂ］ピリジン - Google Patents

Info

Publication number

JP2008523018A

JP2008523018A JP2007544844A JP2007544844A JP2008523018A JP 2008523018 A JP2008523018 A JP 2008523018A JP 2007544844 A JP2007544844 A JP 2007544844A JP 2007544844 A JP2007544844 A JP 2007544844A JP 2008523018 A JP2008523018 A JP 2008523018A

Authority

JP

Japan

Prior art keywords

alkyl

group

phenyl

cycloalkyl

same

Prior art date

2004-12-14

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.)

Pending

Links

• Espacenet
• Global Dossier
• Discuss

• 230000033115 angiogenesis Effects 0.000 title claims description 17
• 230000004770 neurodegeneration Effects 0.000 title claims description 10
• 208000015122 neurodegenerative disease Diseases 0.000 title claims description 10
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 title abstract description 13
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 title abstract description 13
• 239000003112 inhibitor Substances 0.000 title abstract description 4
• 230000003463 hyperproliferative effect Effects 0.000 title description 2
• LUAQTQAFUORQHV-UHFFFAOYSA-N 2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C1=CC=C2C(N)=NNC2=N1 LUAQTQAFUORQHV-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 224
• 238000002360 preparation method Methods 0.000 claims abstract description 188
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 23
• 201000010099 disease Diseases 0.000 claims abstract description 22
• -1 —CH 2 —O—CH 3 Chemical group 0.000 claims description 143
• 125000001072 heteroaryl group Chemical group 0.000 claims description 112
• 125000003118 aryl group Chemical group 0.000 claims description 105
• 229910052736 halogen Inorganic materials 0.000 claims description 91
• 150000002367 halogens Chemical group 0.000 claims description 91
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 90
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 78
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 69
• 125000000217 alkyl group Chemical group 0.000 claims description 66
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 59
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 49
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 49
• 229910052757 nitrogen Inorganic materials 0.000 claims description 42
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 34
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 33
• 150000003839 salts Chemical class 0.000 claims description 33
• 229910052717 sulfur Inorganic materials 0.000 claims description 33
• 239000011593 sulfur Substances 0.000 claims description 33
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 32
• 229910052760 oxygen Inorganic materials 0.000 claims description 32
• 239000001301 oxygen Substances 0.000 claims description 32
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 31
• 125000003545 alkoxy group Chemical group 0.000 claims description 28
• 150000004677 hydrates Chemical class 0.000 claims description 28
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 28
• 125000004432 carbon atom Chemical group C* 0.000 claims description 27
• 125000004076 pyridyl group Chemical group 0.000 claims description 27
• 125000004429 atom Chemical group 0.000 claims description 26
• JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 26
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 25
• 125000000068 chlorophenyl group Chemical group 0.000 claims description 24
• 239000012453 solvate Substances 0.000 claims description 24
• 238000004519 manufacturing process Methods 0.000 claims description 23
• 239000000203 mixture Substances 0.000 claims description 23
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 21
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 20
• 239000003814 drug Substances 0.000 claims description 20
• 229910052739 hydrogen Inorganic materials 0.000 claims description 20
• 239000001257 hydrogen Substances 0.000 claims description 20
• 125000003342 alkenyl group Chemical group 0.000 claims description 19
• 125000001041 indolyl group Chemical group 0.000 claims description 16
• 229910052799 carbon Inorganic materials 0.000 claims description 15
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 15
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 15
• 125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims description 14
• 125000000623 heterocyclic group Chemical group 0.000 claims description 14
• 125000002883 imidazolyl group Chemical group 0.000 claims description 14
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 13
• 125000002757 morpholinyl group Chemical group 0.000 claims description 13
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 13
• 125000004193 piperazinyl group Chemical group 0.000 claims description 13
• 125000003386 piperidinyl group Chemical group 0.000 claims description 13
• AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical compound C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 claims description 12
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 12
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 11
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 11
• 125000001680 trimethoxyphenyl group Chemical group 0.000 claims description 10
• 230000001154 acute effect Effects 0.000 claims description 8
• 125000005336 allyloxy group Chemical group 0.000 claims description 8
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
• 230000001684 chronic effect Effects 0.000 claims description 8
• 125000002541 furyl group Chemical group 0.000 claims description 8
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 7
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 7
• 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 7
• 230000035168 lymphangiogenesis Effects 0.000 claims description 7
• 125000003944 tolyl group Chemical group 0.000 claims description 6
• 208000019553 vascular disease Diseases 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 5
• 125000004799 bromophenyl group Chemical group 0.000 claims description 5
• 125000004188 dichlorophenyl group Chemical group 0.000 claims description 5
• 125000005842 heteroatom Chemical group 0.000 claims description 5
• 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 5
• 125000001302 tertiary amino group Chemical group 0.000 claims description 5
• DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 claims description 4
• 230000000392 somatic effect Effects 0.000 claims description 4
• ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 4
• 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
• DVFXLNFDWATPMW-IWOKLKJTSA-N tert-butyldiphenylsilyl Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO[Si](C=2C=CC=CC=2)(C=2C=CC=CC=2)C(C)(C)C)[C@@H](OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](CC(O2)N2C3=NC=NC(N)=C3N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)O)C1 DVFXLNFDWATPMW-IWOKLKJTSA-N 0.000 claims description 4
• 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
• 238000009472 formulation Methods 0.000 claims description 3
• 238000000338 in vitro Methods 0.000 claims description 3
• 238000001727 in vivo Methods 0.000 claims description 3
• 239000000543 intermediate Substances 0.000 claims description 3
• 239000013067 intermediate product Substances 0.000 claims description 3
• 210000001082 somatic cell Anatomy 0.000 claims description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
• 229940110728 nitrogen / oxygen Drugs 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 21
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
• 125000004104 aryloxy group Chemical group 0.000 claims 1
• 239000000047 product Substances 0.000 description 156
• 238000005160 1H NMR spectroscopy Methods 0.000 description 147
• 239000000243 solution Substances 0.000 description 106
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 92
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 68
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 60
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
• 239000000463 material Substances 0.000 description 48
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 46
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 39
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 38
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 38
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 38
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 36
• 238000003756 stirring Methods 0.000 description 36
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 32
• 239000005695 Ammonium acetate Substances 0.000 description 32
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
• 235000019257 ammonium acetate Nutrition 0.000 description 32
• 229940043376 ammonium acetate Drugs 0.000 description 32
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 32
• AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 28
• DDZGQYREBDXECY-UHFFFAOYSA-N 1h-pyrazolo[3,4-b]pyrazine Chemical compound C1=CN=C2C=NNC2=N1 DDZGQYREBDXECY-UHFFFAOYSA-N 0.000 description 28
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
• 238000004440 column chromatography Methods 0.000 description 20
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
• PJGSXYOJTGTZAV-UHFFFAOYSA-N pinacolone Chemical compound CC(=O)C(C)(C)C PJGSXYOJTGTZAV-UHFFFAOYSA-N 0.000 description 18
• 239000000126 substance Substances 0.000 description 18
• 102000050554 Eph Family Receptors Human genes 0.000 description 17
• 108091008815 Eph receptors Proteins 0.000 description 17
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
• 239000012043 crude product Substances 0.000 description 17
• 229910052938 sodium sulfate Inorganic materials 0.000 description 17
• 235000011152 sodium sulphate Nutrition 0.000 description 17
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
• 229960000583 acetic acid Drugs 0.000 description 16
• 239000011541 reaction mixture Substances 0.000 description 16
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 15
• 238000006243 chemical reaction Methods 0.000 description 14
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 13
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
• 210000004027 cell Anatomy 0.000 description 13
• 150000002431 hydrogen Chemical class 0.000 description 13
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 12
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
• 239000012074 organic phase Substances 0.000 description 11
• 239000002244 precipitate Substances 0.000 description 11
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
• 239000012141 concentrate Substances 0.000 description 10
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 9
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
• 238000000034 method Methods 0.000 description 9
• IAVREABSGIHHMO-UHFFFAOYSA-N 3-hydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1 IAVREABSGIHHMO-UHFFFAOYSA-N 0.000 description 8
• 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 8
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
• 125000000304 alkynyl group Chemical group 0.000 description 8
• 239000012362 glacial acetic acid Substances 0.000 description 8
• FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 description 8
• 150000005229 pyrazolopyridines Chemical class 0.000 description 8
• 239000000741 silica gel Substances 0.000 description 8
• 229910002027 silica gel Inorganic materials 0.000 description 8
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
• 206010028980 Neoplasm Diseases 0.000 description 7
• 238000001816 cooling Methods 0.000 description 7
• 238000002844 melting Methods 0.000 description 7
• 230000008018 melting Effects 0.000 description 7
• 238000000746 purification Methods 0.000 description 7
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 7
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 7
• VFZRZRDOXPRTSC-UHFFFAOYSA-N 3,5-Dimethoxybenzaldehyde Chemical compound COC1=CC(OC)=CC(C=O)=C1 VFZRZRDOXPRTSC-UHFFFAOYSA-N 0.000 description 6
• 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 6
• 102100031983 Ephrin type-B receptor 4 Human genes 0.000 description 6
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 6
• 230000000844 anti-bacterial effect Effects 0.000 description 6
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 6
• 102000005962 receptors Human genes 0.000 description 6
• 108020003175 receptors Proteins 0.000 description 6
• 125000001424 substituent group Chemical group 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 5
• 229910052731 fluorine Inorganic materials 0.000 description 5
• 239000011737 fluorine Substances 0.000 description 5
• 239000000499 gel Substances 0.000 description 5
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 5
• 125000002950 monocyclic group Chemical group 0.000 description 5
• 125000006413 ring segment Chemical group 0.000 description 5
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 4
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 4
• WMQUKDQWMMOHSA-UHFFFAOYSA-N 1-pyridin-4-ylethanone Chemical compound CC(=O)C1=CC=NC=C1 WMQUKDQWMMOHSA-UHFFFAOYSA-N 0.000 description 4
• 239000001431 2-methylbenzaldehyde Substances 0.000 description 4
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 4
• 108091000080 Phosphotransferase Proteins 0.000 description 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 4
• 125000002619 bicyclic group Chemical group 0.000 description 4
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
• 108060002566 ephrin Proteins 0.000 description 4
• 102000012803 ephrin Human genes 0.000 description 4
• 125000000524 functional group Chemical group 0.000 description 4
• 239000005457 ice water Substances 0.000 description 4
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 4
• 230000003834 intracellular effect Effects 0.000 description 4
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 4
• DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 4
• 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 4
• 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 4
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
• 229910052698 phosphorus Inorganic materials 0.000 description 4
• 239000011574 phosphorus Substances 0.000 description 4
• 102000020233 phosphotransferase Human genes 0.000 description 4
• 230000008569 process Effects 0.000 description 4
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 4
• 238000010992 reflux Methods 0.000 description 4
• 229910052710 silicon Inorganic materials 0.000 description 4
• 239000010703 silicon Substances 0.000 description 4
• DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
• PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 4
• NDUDHRAPFVSFBS-UHFFFAOYSA-N 3-(3-amino-6-tert-butyl-2h-pyrazolo[3,4-b]pyridin-4-yl)-4-methylphenol Chemical compound CC1=CC=C(O)C=C1C1=CC(C(C)(C)C)=NC2=C1C(N)=NN2 NDUDHRAPFVSFBS-UHFFFAOYSA-N 0.000 description 3
• DYUMBFTYRJMAFK-UHFFFAOYSA-N 3-cyano-2-pyridone Chemical compound OC1=NC=CC=C1C#N DYUMBFTYRJMAFK-UHFFFAOYSA-N 0.000 description 3
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 3
• QWLHJVDRPZNVBS-UHFFFAOYSA-N 4-phenoxybenzaldehyde Chemical compound C1=CC(C=O)=CC=C1OC1=CC=CC=C1 QWLHJVDRPZNVBS-UHFFFAOYSA-N 0.000 description 3
• KXHGEMZWMDHDLT-UHFFFAOYSA-N 6-cyclopropyl-4-(3,4-dichlorophenyl)-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C=12C(N)=NNC2=NC(C2CC2)=CC=1C1=CC=C(Cl)C(Cl)=C1 KXHGEMZWMDHDLT-UHFFFAOYSA-N 0.000 description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
• 0 CC(C)(CN1CCOCC1)C(NC1=O)=CC(c2ccc(C)cc2)=C1C#* Chemical compound CC(C)(CN1CCOCC1)C(NC1=O)=CC(c2ccc(C)cc2)=C1C#* 0.000 description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 239000002253 acid Substances 0.000 description 3
• 239000008346 aqueous phase Substances 0.000 description 3
• 239000004305 biphenyl Substances 0.000 description 3
• 235000010290 biphenyl Nutrition 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 239000000975 dye Substances 0.000 description 3
• 230000000694 effects Effects 0.000 description 3
• 150000002148 esters Chemical class 0.000 description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
• 239000003102 growth factor Substances 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 3
• 239000003446 ligand Substances 0.000 description 3
• 125000001624 naphthyl group Chemical group 0.000 description 3
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 3
• 125000004433 nitrogen atom Chemical group N* 0.000 description 3
• 239000000825 pharmaceutical preparation Substances 0.000 description 3
• 125000006239 protecting group Chemical group 0.000 description 3
• 238000012552 review Methods 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 3
• 238000012360 testing method Methods 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• CRPTXKKKIGGDBX-UHFFFAOYSA-N (z)-but-2-ene Chemical group [CH2]C=CC CRPTXKKKIGGDBX-UHFFFAOYSA-N 0.000 description 2
• 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 2
• 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 2
• HVCFCNAITDHQFX-UHFFFAOYSA-N 1-cyclopropylethanone Chemical compound CC(=O)C1CC1 HVCFCNAITDHQFX-UHFFFAOYSA-N 0.000 description 2
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 2
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 2
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
• YJABFXKBVOOKJX-UHFFFAOYSA-N 3-(1,3-dioxolan-2-yl)-5-methoxyphenol Chemical compound COC1=CC(O)=CC(C2OCCO2)=C1 YJABFXKBVOOKJX-UHFFFAOYSA-N 0.000 description 2
• LNHOGGMCGPQPLX-UHFFFAOYSA-N 3-(3-amino-4-pyridin-4-yl-2h-pyrazolo[3,4-b]pyridin-6-yl)phenol Chemical compound C=12C(N)=NNC2=NC(C=2C=C(O)C=CC=2)=CC=1C1=CC=NC=C1 LNHOGGMCGPQPLX-UHFFFAOYSA-N 0.000 description 2
• NZZNNFHCUYSWBQ-UHFFFAOYSA-N 3-(3-amino-6-cyclohexyl-2h-pyrazolo[3,4-b]pyridin-4-yl)phenol Chemical compound C=12C(N)=NNC2=NC(C2CCCCC2)=CC=1C1=CC=CC(O)=C1 NZZNNFHCUYSWBQ-UHFFFAOYSA-N 0.000 description 2
• ZYDILZVZBMJSDC-UHFFFAOYSA-N 3-(3-amino-6-pyridin-4-yl-2h-pyrazolo[3,4-b]pyridin-4-yl)-4-methylphenol Chemical compound CC1=CC=C(O)C=C1C1=CC(C=2C=CN=CC=2)=NC2=C1C(N)=NN2 ZYDILZVZBMJSDC-UHFFFAOYSA-N 0.000 description 2
• YOCCUMKDPCZSCF-UHFFFAOYSA-N 3-(3-amino-6-pyridin-4-yl-2h-pyrazolo[3,4-b]pyridin-4-yl)-5-methoxyphenol Chemical compound COC1=CC(O)=CC(C=2C=3C(N)=NNC=3N=C(C=2)C=2C=CN=CC=2)=C1 YOCCUMKDPCZSCF-UHFFFAOYSA-N 0.000 description 2
• IMSMNGWYPSUVND-UHFFFAOYSA-N 3-(3-amino-6-pyridin-4-yl-2h-pyrazolo[3,4-b]pyridin-4-yl)phenol Chemical compound C=12C(N)=NNC2=NC(C=2C=CN=CC=2)=CC=1C1=CC=CC(O)=C1 IMSMNGWYPSUVND-UHFFFAOYSA-N 0.000 description 2
• PBMJWJWZAFFCMU-UHFFFAOYSA-N 3-(3-amino-6-tert-butyl-2h-pyrazolo[3,4-b]pyridin-4-yl)-5-methoxyphenol Chemical compound COC1=CC(O)=CC(C=2C=3C(N)=NNC=3N=C(C=2)C(C)(C)C)=C1 PBMJWJWZAFFCMU-UHFFFAOYSA-N 0.000 description 2
• WYJDWUPAHPCRSL-UHFFFAOYSA-N 3-(3-amino-6-tert-butyl-2h-pyrazolo[3,4-b]pyridin-4-yl)phenol Chemical compound C=12C(N)=NNC2=NC(C(C)(C)C)=CC=1C1=CC=CC(O)=C1 WYJDWUPAHPCRSL-UHFFFAOYSA-N 0.000 description 2
• NVLTWXMZECWWPC-UHFFFAOYSA-N 3-hydroxy-4,5-dimethoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC(O)=C1OC NVLTWXMZECWWPC-UHFFFAOYSA-N 0.000 description 2
• FGQOOHJZONJGDT-UHFFFAOYSA-N 3-hydroxy-5-methoxybenzaldehyde Chemical compound COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 2
• LUJMEECXHPYQOF-UHFFFAOYSA-N 3-hydroxyacetophenone Chemical compound CC(=O)C1=CC=CC(O)=C1 LUJMEECXHPYQOF-UHFFFAOYSA-N 0.000 description 2
• 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 2
• WMPDAIZRQDCGFH-UHFFFAOYSA-N 3-methoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1 WMPDAIZRQDCGFH-UHFFFAOYSA-N 0.000 description 2
• PERBPRKGRJLCKO-UHFFFAOYSA-N 5-(3-amino-6-tert-butyl-2h-pyrazolo[3,4-b]pyridin-4-yl)-2-methoxyphenol Chemical compound C1=C(O)C(OC)=CC=C1C1=CC(C(C)(C)C)=NC2=C1C(N)=NN2 PERBPRKGRJLCKO-UHFFFAOYSA-N 0.000 description 2
• MRIMHIHSUYAMQR-UHFFFAOYSA-N 5-(3-amino-6-tert-butyl-2h-pyrazolo[3,4-b]pyridin-4-yl)benzene-1,3-diol Chemical compound C=12C(N)=NNC2=NC(C(C)(C)C)=CC=1C1=CC(O)=CC(O)=C1 MRIMHIHSUYAMQR-UHFFFAOYSA-N 0.000 description 2
• WRBVOGCWSQDCMP-UHFFFAOYSA-N 6-tert-butyl-4-(4-nitrophenyl)-2H-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C12=C(N)NN=C2N=C(C(C)(C)C)C=C1C1=CC=C([N+]([O-])=O)C=C1 WRBVOGCWSQDCMP-UHFFFAOYSA-N 0.000 description 2
• 102100023995 Beta-nerve growth factor Human genes 0.000 description 2
• 201000009273 Endometriosis Diseases 0.000 description 2
• 108010055334 EphB2 Receptor Proteins 0.000 description 2
• 102100031968 Ephrin type-B receptor 2 Human genes 0.000 description 2
• 102000009024 Epidermal Growth Factor Human genes 0.000 description 2
• 101800003838 Epidermal growth factor Proteins 0.000 description 2
• 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
• 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• 229930186217 Glycolipid Natural products 0.000 description 2
• LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
• AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
• LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 2
• 108010025020 Nerve Growth Factor Proteins 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
• DOGVJSGOIVUKQK-UHFFFAOYSA-N [3-(5-cyano-6-oxo-4-pyridin-4-yl-1h-pyridin-2-yl)phenyl] acetate Chemical compound CC(=O)OC1=CC=CC(C=2NC(=O)C(C#N)=C(C=3C=CN=CC=3)C=2)=C1 DOGVJSGOIVUKQK-UHFFFAOYSA-N 0.000 description 2
• YHFCEKAIMHQESM-UHFFFAOYSA-N [3-(6-tert-butyl-3-cyano-2-oxo-1h-pyridin-4-yl)-5-propan-2-yloxyphenyl] acetate Chemical compound CC(C)OC1=CC(OC(C)=O)=CC(C2=C(C(=O)NC(=C2)C(C)(C)C)C#N)=C1 YHFCEKAIMHQESM-UHFFFAOYSA-N 0.000 description 2
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
• 230000002491 angiogenic effect Effects 0.000 description 2
• 230000003527 anti-angiogenesis Effects 0.000 description 2
• 230000003110 anti-inflammatory effect Effects 0.000 description 2
• 230000002785 anti-thrombosis Effects 0.000 description 2
• 238000000376 autoradiography Methods 0.000 description 2
• 125000002393 azetidinyl group Chemical group 0.000 description 2
• 125000004069 aziridinyl group Chemical group 0.000 description 2
• 125000005605 benzo group Chemical group 0.000 description 2
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• 230000000903 blocking effect Effects 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 125000005514 but-1-yn-3-yl group Chemical group 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• 239000000460 chlorine Substances 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• 125000001309 chloro group Chemical group Cl* 0.000 description 2
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 2
• 238000004891 communication Methods 0.000 description 2
• 125000004802 cyanophenyl group Chemical group 0.000 description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 125000006612 decyloxy group Chemical group 0.000 description 2
• IBDMRHDXAQZJAP-UHFFFAOYSA-N dichlorophosphorylbenzene Chemical compound ClP(Cl)(=O)C1=CC=CC=C1 IBDMRHDXAQZJAP-UHFFFAOYSA-N 0.000 description 2
• 125000000532 dioxanyl group Chemical group 0.000 description 2
• 125000005879 dioxolanyl group Chemical group 0.000 description 2
• KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 2
• 125000005883 dithianyl group Chemical group 0.000 description 2
• 239000008298 dragée Substances 0.000 description 2
• 229940116977 epidermal growth factor Drugs 0.000 description 2
• ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 2
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
• 229940126864 fibroblast growth factor Drugs 0.000 description 2
• 239000000706 filtrate Substances 0.000 description 2
• 239000000118 hair dye Substances 0.000 description 2
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 150000002430 hydrocarbons Chemical group 0.000 description 2
• 125000002632 imidazolidinyl group Chemical group 0.000 description 2
• OLNJUISKUQQNIM-UHFFFAOYSA-N indole-3-carbaldehyde Chemical compound C1=CC=C2C(C=O)=CNC2=C1 OLNJUISKUQQNIM-UHFFFAOYSA-N 0.000 description 2
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 2
• 125000001786 isothiazolyl group Chemical group 0.000 description 2
• JVTZFYYHCGSXJV-UHFFFAOYSA-N isovanillin Chemical compound COC1=CC=C(C=O)C=C1O JVTZFYYHCGSXJV-UHFFFAOYSA-N 0.000 description 2
• 125000000842 isoxazolyl group Chemical group 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 208000037841 lung tumor 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
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 229940053128 nerve growth factor Drugs 0.000 description 2
• 231100001223 noncarcinogenic Toxicity 0.000 description 2
• 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 125000001715 oxadiazolyl group Chemical group 0.000 description 2
• 125000002971 oxazolyl group Chemical group 0.000 description 2
• 125000003585 oxepinyl group Chemical group 0.000 description 2
• 125000003566 oxetanyl group Chemical group 0.000 description 2
• 125000000466 oxiranyl group Chemical group 0.000 description 2
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
• 239000012071 phase Substances 0.000 description 2
• 230000026731 phosphorylation Effects 0.000 description 2
• 238000006366 phosphorylation reaction Methods 0.000 description 2
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 2
• 239000002798 polar solvent Substances 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 102000004169 proteins and genes Human genes 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
• 125000003373 pyrazinyl group Chemical group 0.000 description 2
• 150000003217 pyrazoles Chemical class 0.000 description 2
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 2
• 125000003226 pyrazolyl group Chemical group 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
• 125000000168 pyrrolyl group Chemical group 0.000 description 2
• 230000035484 reaction time Effects 0.000 description 2
• FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
• JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
• OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 2
• 125000001113 thiadiazolyl group Chemical group 0.000 description 2
• 125000000335 thiazolyl group Chemical group 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
• 125000004306 triazinyl group Chemical group 0.000 description 2
• 125000001425 triazolyl group Chemical group 0.000 description 2
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 125000005455 trithianyl group Chemical group 0.000 description 2
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
• 229920002554 vinyl polymer Polymers 0.000 description 2
• 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 2
• CUGDYSSBTWBKII-LXGUWJNJSA-N (2r,3r,4r,5s)-6-(dimethylamino)hexane-1,2,3,4,5-pentol Chemical compound CN(C)C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO CUGDYSSBTWBKII-LXGUWJNJSA-N 0.000 description 1
• IKXCHOUDIPZROZ-LXGUWJNJSA-N (2r,3r,4r,5s)-6-(ethylamino)hexane-1,2,3,4,5-pentol Chemical compound CCNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO IKXCHOUDIPZROZ-LXGUWJNJSA-N 0.000 description 1
• 125000006527 (C1-C5) alkyl group Chemical group 0.000 description 1
• 125000006727 (C1-C6) alkenyl group Chemical group 0.000 description 1
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
• DYFBCVMPCWGVMV-UHFFFAOYSA-N 1,2-dihydropyridine-3-carbonitrile Chemical compound N#CC1=CC=CNC1 DYFBCVMPCWGVMV-UHFFFAOYSA-N 0.000 description 1
• YXNMORHRGMYQKF-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-ylmethanol Chemical compound C1CC(CO)CCC21OCCO2 YXNMORHRGMYQKF-UHFFFAOYSA-N 0.000 description 1
• HFBULKBCEFQYCJ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decane-8-carbaldehyde Chemical compound C1CC(C=O)CCC21OCCO2 HFBULKBCEFQYCJ-UHFFFAOYSA-N 0.000 description 1
• OLAMWGVYODPVAG-UHFFFAOYSA-N 1-(1,4-dioxaspiro[4.5]decan-8-yl)ethanol Chemical compound C1CC(C(O)C)CCC21OCCO2 OLAMWGVYODPVAG-UHFFFAOYSA-N 0.000 description 1
• JQOQTIDXAITFEU-UHFFFAOYSA-N 1-(1,4-dioxaspiro[4.5]decan-8-yl)ethanone Chemical compound C1CC(C(=O)C)CCC21OCCO2 JQOQTIDXAITFEU-UHFFFAOYSA-N 0.000 description 1
• ZGCHLAJIRWDGFE-UHFFFAOYSA-N 1-aminopropane-1,1-diol Chemical compound CCC(N)(O)O ZGCHLAJIRWDGFE-UHFFFAOYSA-N 0.000 description 1
• RIFKADJTWUGDOV-UHFFFAOYSA-N 1-cyclohexylethanone Chemical compound CC(=O)C1CCCCC1 RIFKADJTWUGDOV-UHFFFAOYSA-N 0.000 description 1
• DJRFJAVPROZZFL-UHFFFAOYSA-N 1975-52-6 Chemical compound CC1=CC=C([N+]([O-])=O)C=C1C(O)=O DJRFJAVPROZZFL-UHFFFAOYSA-N 0.000 description 1
• JQNWRIDXOJJUIG-UHFFFAOYSA-N 2-(3,5-dimethoxyphenyl)-1,3-dioxolane Chemical compound COC1=CC(OC)=CC(C2OCCO2)=C1 JQNWRIDXOJJUIG-UHFFFAOYSA-N 0.000 description 1
• LGMGCVGSGDCKOC-UHFFFAOYSA-N 2-(3-methoxy-5-propan-2-yloxyphenyl)-1,3-dioxolane Chemical compound COC1=CC(OC(C)C)=CC(C2OCCO2)=C1 LGMGCVGSGDCKOC-UHFFFAOYSA-N 0.000 description 1
• KJJPLEZQSCZCKE-UHFFFAOYSA-N 2-aminopropane-1,3-diol Chemical compound OCC(N)CO KJJPLEZQSCZCKE-UHFFFAOYSA-N 0.000 description 1
• NHJDXSGABOMMDA-UHFFFAOYSA-N 2-bromo-6-tert-butyl-4-(4-cyanophenyl)pyridine-3-carbonitrile Chemical compound BrC1=NC(C(C)(C)C)=CC(C=2C=CC(=CC=2)C#N)=C1C#N NHJDXSGABOMMDA-UHFFFAOYSA-N 0.000 description 1
• AGJLNWJQECLNQP-UHFFFAOYSA-N 2-bromo-6-tert-butyl-4-(4-methylphenyl)pyridine-3-carbonitrile Chemical compound C1=CC(C)=CC=C1C1=CC(C(C)(C)C)=NC(Br)=C1C#N AGJLNWJQECLNQP-UHFFFAOYSA-N 0.000 description 1
• YKNFZNXHBQWHSX-UHFFFAOYSA-N 2-chloro-6-cyclopropyl-4-(3,4-dichlorophenyl)pyridine-3-carbonitrile Chemical compound C1=C(Cl)C(Cl)=CC=C1C1=CC(C2CC2)=NC(Cl)=C1C#N YKNFZNXHBQWHSX-UHFFFAOYSA-N 0.000 description 1
• JAUPUQRPBNDMDT-UHFFFAOYSA-N 2-chloropyridine-3-carbonitrile Chemical compound ClC1=NC=CC=C1C#N JAUPUQRPBNDMDT-UHFFFAOYSA-N 0.000 description 1
• NJBCRXCAPCODGX-UHFFFAOYSA-N 2-methyl-n-(2-methylpropyl)propan-1-amine Chemical compound CC(C)CNCC(C)C NJBCRXCAPCODGX-UHFFFAOYSA-N 0.000 description 1
• BMHMKWXYXFBWMI-UHFFFAOYSA-N 3,4-Methylenedioxyacetophenone Chemical compound CC(=O)C1=CC=C2OCOC2=C1 BMHMKWXYXFBWMI-UHFFFAOYSA-N 0.000 description 1
• ZWUSBSHBFFPRNE-UHFFFAOYSA-N 3,4-dichlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1Cl ZWUSBSHBFFPRNE-UHFFFAOYSA-N 0.000 description 1
• HAQLHRYUDBKTJG-UHFFFAOYSA-N 3,5-dihydroxybenzaldehyde Chemical compound OC1=CC(O)=CC(C=O)=C1 HAQLHRYUDBKTJG-UHFFFAOYSA-N 0.000 description 1
• NNCSHALTPKCZIR-UHFFFAOYSA-N 3-(1,3-dioxolan-2-yl)-5-propan-2-yloxyphenol Chemical compound CC(C)OC1=CC(O)=CC(C2OCCO2)=C1 NNCSHALTPKCZIR-UHFFFAOYSA-N 0.000 description 1
• FQMZKCUQYVVNLQ-UHFFFAOYSA-N 3-(3-amino-6-cyclopropyl-2h-pyrazolo[3,4-b]pyridin-4-yl)phenol Chemical compound C=12C(N)=NNC2=NC(C2CC2)=CC=1C1=CC=CC(O)=C1 FQMZKCUQYVVNLQ-UHFFFAOYSA-N 0.000 description 1
• GBLPMGGDCFBKAT-UHFFFAOYSA-N 3-[tert-butyl(dimethyl)silyl]oxy-2,2-dimethylpropan-1-ol Chemical compound OCC(C)(C)CO[Si](C)(C)C(C)(C)C GBLPMGGDCFBKAT-UHFFFAOYSA-N 0.000 description 1
• PLPBSUJOMPJZJF-UHFFFAOYSA-N 3-[tert-butyl(dimethyl)silyl]oxy-2,2-dimethylpropanal Chemical compound CC(C)(C)[Si](C)(C)OCC(C)(C)C=O PLPBSUJOMPJZJF-UHFFFAOYSA-N 0.000 description 1
• YDPLFBIGFQFIDB-UHFFFAOYSA-N 3-chloropyridine-2-carbonitrile Chemical compound ClC1=CC=CN=C1C#N YDPLFBIGFQFIDB-UHFFFAOYSA-N 0.000 description 1
• HGZJJKZPPMFIBU-UHFFFAOYSA-N 3-formylbenzonitrile Chemical compound O=CC1=CC=CC(C#N)=C1 HGZJJKZPPMFIBU-UHFFFAOYSA-N 0.000 description 1
• MIQBQKAXBNXBCQ-UHFFFAOYSA-N 3-hydroxy-5-propan-2-yloxybenzaldehyde Chemical compound CC(C)OC1=CC(O)=CC(C=O)=C1 MIQBQKAXBNXBCQ-UHFFFAOYSA-N 0.000 description 1
• NQOYLEBRKVUGTN-UHFFFAOYSA-N 4-(1h-imidazol-2-yl)-6-(4-phenoxyphenyl)-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C=12C(N)=NNC2=NC(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=CC=1C1=NC=CN1 NQOYLEBRKVUGTN-UHFFFAOYSA-N 0.000 description 1
• VKHYGPXDOUAGOO-UHFFFAOYSA-N 4-(3,5-dimethoxyphenyl)-6-pyridin-4-yl-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound COC1=CC(OC)=CC(C=2C=3C(N)=NNC=3N=C(C=2)C=2C=CN=CC=2)=C1 VKHYGPXDOUAGOO-UHFFFAOYSA-N 0.000 description 1
• GNIMHOWRXPCPII-UHFFFAOYSA-N 4-(3-amino-6-cyclopropyl-2h-pyrazolo[3,4-b]pyridin-4-yl)benzonitrile Chemical compound C=12C(N)=NNC2=NC(C2CC2)=CC=1C1=CC=C(C#N)C=C1 GNIMHOWRXPCPII-UHFFFAOYSA-N 0.000 description 1
• YBHPTLNOEOKDJQ-UHFFFAOYSA-N 4-(4-chlorophenyl)-6-cyclopropyl-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C=12C(N)=NNC2=NC(C2CC2)=CC=1C1=CC=C(Cl)C=C1 YBHPTLNOEOKDJQ-UHFFFAOYSA-N 0.000 description 1
• ZPPRJSHIIUBEAF-UHFFFAOYSA-N 4-(4-chlorophenyl)-6-phenyl-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C=12C(N)=NNC2=NC(C=2C=CC=CC=2)=CC=1C1=CC=C(Cl)C=C1 ZPPRJSHIIUBEAF-UHFFFAOYSA-N 0.000 description 1
• DDGJLMAJFDZCTJ-UHFFFAOYSA-N 4-(4-methylphenyl)-6-(2-methyl-1-piperidin-1-ylpropan-2-yl)-2-(trifluoromethylsulfonyl)pyridine-3-carbonitrile Chemical compound C1=CC(C)=CC=C1C1=CC(C(C)(C)CN2CCCCC2)=NC(S(=O)(=O)C(F)(F)F)=C1C#N DDGJLMAJFDZCTJ-UHFFFAOYSA-N 0.000 description 1
• QPWJRQYXGFMUHF-UHFFFAOYSA-N 4-(4-methylphenyl)-6-(2-methyl-1-piperidin-1-ylpropan-2-yl)-2-oxo-1h-pyridine-3-carbonitrile Chemical compound C1=CC(C)=CC=C1C1=C(C#N)C(=O)NC(C(C)(C)CN2CCCCC2)=C1 QPWJRQYXGFMUHF-UHFFFAOYSA-N 0.000 description 1
• XDCOYBQVEVSNNB-UHFFFAOYSA-N 4-[(7-naphthalen-2-yl-1-benzothiophen-2-yl)methylamino]butanoic acid Chemical compound OC(=O)CCCNCc1cc2cccc(-c3ccc4ccccc4c3)c2s1 XDCOYBQVEVSNNB-UHFFFAOYSA-N 0.000 description 1
• SXYKWURBASVWFC-UHFFFAOYSA-N 4-[3-amino-6-(3-methoxyphenyl)-2h-pyrazolo[3,4-b]pyridin-4-yl]benzonitrile Chemical compound COC1=CC=CC(C=2N=C3NN=C(N)C3=C(C=3C=CC(=CC=3)C#N)C=2)=C1 SXYKWURBASVWFC-UHFFFAOYSA-N 0.000 description 1
• NQIVQNFEFYJTTP-UHFFFAOYSA-N 4-[4-[3-(dimethylamino)propoxy]phenyl]-6-(4-fluorophenyl)-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C1=CC(OCCCN(C)C)=CC=C1C1=CC(C=2C=CC(F)=CC=2)=NC2=C1C(N)=NN2 NQIVQNFEFYJTTP-UHFFFAOYSA-N 0.000 description 1
• URCLRCMVZOJCGM-UHFFFAOYSA-N 4-[5-[tert-butyl(dimethyl)silyl]oxy-2-methylphenyl]-6-pyridin-4-yl-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound CC1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1C1=CC(C=2C=CN=CC=2)=NC2=C1C(N)=NN2 URCLRCMVZOJCGM-UHFFFAOYSA-N 0.000 description 1
• VSAWBBYYMBQKIK-UHFFFAOYSA-N 4-[[3,5-bis[(3,5-ditert-butyl-4-hydroxyphenyl)methyl]-2,4,6-trimethylphenyl]methyl]-2,6-ditert-butylphenol Chemical compound CC1=C(CC=2C=C(C(O)=C(C=2)C(C)(C)C)C(C)(C)C)C(C)=C(CC=2C=C(C(O)=C(C=2)C(C)(C)C)C(C)(C)C)C(C)=C1CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 VSAWBBYYMBQKIK-UHFFFAOYSA-N 0.000 description 1
• GYJBFRTYUQNJNX-UHFFFAOYSA-N 4-[tert-butyl(dimethyl)silyl]oxy-3,3-dimethylbutan-2-ol Chemical compound CC(O)C(C)(C)CO[Si](C)(C)C(C)(C)C GYJBFRTYUQNJNX-UHFFFAOYSA-N 0.000 description 1
• XUWGYYFCOCUZIT-UHFFFAOYSA-N 4-[tert-butyl(dimethyl)silyl]oxy-3,3-dimethylbutan-2-one Chemical compound CC(=O)C(C)(C)CO[Si](C)(C)C(C)(C)C XUWGYYFCOCUZIT-UHFFFAOYSA-N 0.000 description 1
• WIFPJDJJFUSIFP-UHFFFAOYSA-N 4-aminobutane-1,2,3-triol Chemical compound NCC(O)C(O)CO WIFPJDJJFUSIFP-UHFFFAOYSA-N 0.000 description 1
• WZWIQYMTQZCSKI-UHFFFAOYSA-N 4-cyanobenzaldehyde Chemical compound O=CC1=CC=C(C#N)C=C1 WZWIQYMTQZCSKI-UHFFFAOYSA-N 0.000 description 1
• BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 description 1
• ZVTWZSXLLMNMQC-UHFFFAOYSA-N 4-phenylmethoxybenzaldehyde Chemical compound C1=CC(C=O)=CC=C1OCC1=CC=CC=C1 ZVTWZSXLLMNMQC-UHFFFAOYSA-N 0.000 description 1
• KOAHRBNAARGPCE-UHFFFAOYSA-N 5-(3-amino-6-tert-butyl-2h-pyrazolo[3,4-b]pyridin-4-yl)-2,3-dimethoxyphenol Chemical compound OC1=C(OC)C(OC)=CC(C=2C=3C(N)=NNC=3N=C(C=2)C(C)(C)C)=C1 KOAHRBNAARGPCE-UHFFFAOYSA-N 0.000 description 1
• XHRRQBFVNYADMV-UHFFFAOYSA-N 5-[3-amino-6-(4-fluorophenyl)-2h-pyrazolo[3,4-b]pyridin-4-yl]-2-methoxyphenol Chemical compound C1=C(O)C(OC)=CC=C1C1=CC(C=2C=CC(F)=CC=2)=NC2=C1C(N)=NN2 XHRRQBFVNYADMV-UHFFFAOYSA-N 0.000 description 1
• VAOPJGLZTYLDKV-UHFFFAOYSA-N 5-[tert-butyl(dimethyl)silyl]oxy-2-methylbenzaldehyde Chemical compound CC1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1C=O VAOPJGLZTYLDKV-UHFFFAOYSA-N 0.000 description 1
• XLYPHUGUKGMURE-UHFFFAOYSA-N 5-hydroxy-2-nitrobenzaldehyde Chemical compound OC1=CC=C([N+]([O-])=O)C(C=O)=C1 XLYPHUGUKGMURE-UHFFFAOYSA-N 0.000 description 1
• XXNDYAOBURFFLE-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-2-chloro-4-propan-2-ylpyridine-3-carbonitrile Chemical compound ClC1=C(C#N)C(C(C)C)=CC(C=2C=C3OCOC3=CC=2)=N1 XXNDYAOBURFFLE-UHFFFAOYSA-N 0.000 description 1
• XDSGEGZGIBXEEL-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-4-propan-2-yl-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C1=C2OCOC2=CC(C=2C=C(C=3C(N)=NNC=3N=2)C(C)C)=C1 XDSGEGZGIBXEEL-UHFFFAOYSA-N 0.000 description 1
• NGJQRDDLZOHRKP-UHFFFAOYSA-N 6-(1,4-dioxaspiro[4.5]decan-8-yl)-2-oxo-4-(4-phenoxyphenyl)-1h-pyridine-3-carbonitrile Chemical compound N#CC=1C(=O)NC(C2CCC3(CC2)OCCO3)=CC=1C(C=C1)=CC=C1OC1=CC=CC=C1 NGJQRDDLZOHRKP-UHFFFAOYSA-N 0.000 description 1
• AQTIKJBTRKFKMI-UHFFFAOYSA-N 6-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(4-methylphenyl)-2-(trifluoromethylsulfonyl)pyridine-3-carbonitrile Chemical compound C1=CC(C)=CC=C1C1=CC(C2CCC3(CC2)OCCO3)=NC(S(=O)(=O)C(F)(F)F)=C1C#N AQTIKJBTRKFKMI-UHFFFAOYSA-N 0.000 description 1
• XDTUHOVFYWQVKB-UHFFFAOYSA-N 6-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(4-methylphenyl)-2-oxo-1h-pyridine-3-carbonitrile Chemical compound C1=CC(C)=CC=C1C1=C(C#N)C(=O)NC(C2CCC3(CC2)OCCO3)=C1 XDTUHOVFYWQVKB-UHFFFAOYSA-N 0.000 description 1
• CGHNNBADUGMXMI-UHFFFAOYSA-N 6-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(4-phenoxyphenyl)-2-(trifluoromethylsulfonyl)pyridine-3-carbonitrile Chemical compound N#CC=1C(S(=O)(=O)C(F)(F)F)=NC(C2CCC3(CC2)OCCO3)=CC=1C(C=C1)=CC=C1OC1=CC=CC=C1 CGHNNBADUGMXMI-UHFFFAOYSA-N 0.000 description 1
• NWDSPQDIWDVDDC-UHFFFAOYSA-N 6-(1-hydroxy-2-methylpropan-2-yl)-2-oxo-4-(4-phenoxyphenyl)-1h-pyridine-3-carbonitrile Chemical compound O=C1NC(C(C)(CO)C)=CC(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1C#N NWDSPQDIWDVDDC-UHFFFAOYSA-N 0.000 description 1
• YMPUIDRFDWOHLM-UHFFFAOYSA-N 6-(1-hydroxy-2-methylpropan-2-yl)-4-(4-methylphenyl)-2-oxo-1h-pyridine-3-carbonitrile Chemical compound C1=CC(C)=CC=C1C1=C(C#N)C(=O)NC(C(C)(C)CO)=C1 YMPUIDRFDWOHLM-UHFFFAOYSA-N 0.000 description 1
• OFEXFYGNWAOOOM-UHFFFAOYSA-N 6-(2-methyl-1-morpholin-4-ylpropan-2-yl)-4-(4-phenoxyphenyl)-2-(trifluoromethylsulfonyl)pyridine-3-carbonitrile Chemical compound C=1C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C(C#N)C(S(=O)(=O)C(F)(F)F)=NC=1C(C)(C)CN1CCOCC1 OFEXFYGNWAOOOM-UHFFFAOYSA-N 0.000 description 1
• NTSMMMIDSGELIT-UHFFFAOYSA-N 6-(2-methyl-1-oxopropan-2-yl)-2-oxo-4-(4-phenoxyphenyl)-1h-pyridine-3-carbonitrile Chemical compound O=C1NC(C(C)(C=O)C)=CC(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1C#N NTSMMMIDSGELIT-UHFFFAOYSA-N 0.000 description 1
• LIKWLBSODRQHTN-UHFFFAOYSA-N 6-(2-methyl-1-oxopropan-2-yl)-4-(4-methylphenyl)-2-oxo-1h-pyridine-3-carbonitrile Chemical compound C1=CC(C)=CC=C1C1=C(C#N)C(=O)NC(C(C)(C)C=O)=C1 LIKWLBSODRQHTN-UHFFFAOYSA-N 0.000 description 1
• YOFIKYSDGQEFJA-UHFFFAOYSA-N 6-(3-chlorophenyl)-4-(1h-indol-3-yl)-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C=1C(C=2C3=CC=CC=C3NC=2)=C2C(N)=NNC2=NC=1C1=CC=CC(Cl)=C1 YOFIKYSDGQEFJA-UHFFFAOYSA-N 0.000 description 1
• QEKABECCVJKHGX-UHFFFAOYSA-N 6-(4-morpholin-4-ylphenyl)-4-pyridin-4-yl-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C=12C(N)=NNC2=NC(C=2C=CC(=CC=2)N2CCOCC2)=CC=1C1=CC=NC=C1 QEKABECCVJKHGX-UHFFFAOYSA-N 0.000 description 1
• QZIPBGHAUHFSKX-UHFFFAOYSA-N 6-cyclohexyl-4-(3-hydroxyphenyl)-2-oxo-1h-pyridine-3-carbonitrile Chemical compound OC1=CC=CC(C2=C(C(=O)NC(=C2)C2CCCCC2)C#N)=C1 QZIPBGHAUHFSKX-UHFFFAOYSA-N 0.000 description 1
• AEDXATKUHMMOTP-UHFFFAOYSA-N 6-cyclopropyl-4-(3,4-dichlorophenyl)-2-oxo-1h-pyridine-3-carbonitrile Chemical compound C1=C(Cl)C(Cl)=CC=C1C1=C(C#N)C(=O)NC(C2CC2)=C1 AEDXATKUHMMOTP-UHFFFAOYSA-N 0.000 description 1
• BKOZHEDXRPSYTG-UHFFFAOYSA-N 6-cyclopropyl-4-(3-nitrophenyl)-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C=12C(N)=NNC2=NC(C2CC2)=CC=1C1=CC=CC([N+]([O-])=O)=C1 BKOZHEDXRPSYTG-UHFFFAOYSA-N 0.000 description 1
• QFEDKCLCRURETN-UHFFFAOYSA-N 6-cyclopropyl-4-[4-(trifluoromethyl)phenyl]-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C=12C(N)=NNC2=NC(C2CC2)=CC=1C1=CC=C(C(F)(F)F)C=C1 QFEDKCLCRURETN-UHFFFAOYSA-N 0.000 description 1
• JMIBFTYAFVFZPY-UHFFFAOYSA-N 6-pyridin-3-yl-4-quinolin-3-yl-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C=1C(C=2C=C3C=CC=CC3=NC=2)=C2C(N)=NNC2=NC=1C1=CC=CN=C1 JMIBFTYAFVFZPY-UHFFFAOYSA-N 0.000 description 1
• GXFMTERNVDVSKJ-UHFFFAOYSA-N 6-tert-butyl-2-oxo-4-(4-phenoxyphenyl)-1h-pyridine-3-carbonitrile Chemical compound O=C1NC(C(C)(C)C)=CC(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1C#N GXFMTERNVDVSKJ-UHFFFAOYSA-N 0.000 description 1
• DXIZGRLEKLOQQI-UHFFFAOYSA-N 6-tert-butyl-4-(1h-indol-3-yl)-2-(trifluoromethylsulfonyl)pyridine-3-carbonitrile Chemical compound FC(F)(F)S(=O)(=O)C1=NC(C(C)(C)C)=CC(C=2C3=CC=CC=C3NC=2)=C1C#N DXIZGRLEKLOQQI-UHFFFAOYSA-N 0.000 description 1
• GSNVAVQQHCQTBJ-UHFFFAOYSA-N 6-tert-butyl-4-(3,5-dimethoxyphenyl)-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound COC1=CC(OC)=CC(C=2C=3C(N)=NNC=3N=C(C=2)C(C)(C)C)=C1 GSNVAVQQHCQTBJ-UHFFFAOYSA-N 0.000 description 1
• BYQXZUSKEQGIRL-UHFFFAOYSA-N 6-tert-butyl-4-(3-cyanophenyl)-2-(trifluoromethylsulfonyl)pyridine-3-carbonitrile Chemical compound FC(F)(F)S(=O)(=O)C1=NC(C(C)(C)C)=CC(C=2C=C(C=CC=2)C#N)=C1C#N BYQXZUSKEQGIRL-UHFFFAOYSA-N 0.000 description 1
• DPNDSTRXRPRGPO-UHFFFAOYSA-N 6-tert-butyl-4-(3-hydroxy-5-propan-2-yloxyphenyl)-2-oxo-1h-pyridine-3-carbonitrile Chemical compound CC(C)OC1=CC(O)=CC(C2=C(C(=O)NC(=C2)C(C)(C)C)C#N)=C1 DPNDSTRXRPRGPO-UHFFFAOYSA-N 0.000 description 1
• LDWMQMMVEYWEFJ-UHFFFAOYSA-N 6-tert-butyl-4-(3-methoxyphenyl)-2-(trifluoromethylsulfonyl)pyridine-3-carbonitrile Chemical compound COC1=CC=CC(C=2C(=C(N=C(C=2)C(C)(C)C)S(=O)(=O)C(F)(F)F)C#N)=C1 LDWMQMMVEYWEFJ-UHFFFAOYSA-N 0.000 description 1
• RTEGKCVCFYXTLK-UHFFFAOYSA-N 6-tert-butyl-4-(4-nitrophenyl)-2-(trifluoromethylsulfonyl)pyridine-3-carbonitrile Chemical compound FC(F)(F)S(=O)(=O)C1=NC(C(C)(C)C)=CC(C=2C=CC(=CC=2)[N+]([O-])=O)=C1C#N RTEGKCVCFYXTLK-UHFFFAOYSA-N 0.000 description 1
• LYRRROMRWQRPDL-UHFFFAOYSA-N 6-tert-butyl-4-(4-phenoxyphenyl)-2-(trifluoromethylsulfonyl)pyridine-3-carbonitrile Chemical compound FC(F)(F)S(=O)(=O)C1=NC(C(C)(C)C)=CC(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1C#N LYRRROMRWQRPDL-UHFFFAOYSA-N 0.000 description 1
• KUBLHBHNENZZQS-UHFFFAOYSA-N 6-tert-butyl-4-(4-phenylmethoxyphenyl)-2-(trifluoromethylsulfonyl)pyridine-3-carbonitrile Chemical compound FC(F)(F)S(=O)(=O)C1=NC(C(C)(C)C)=CC(C=2C=CC(OCC=3C=CC=CC=3)=CC=2)=C1C#N KUBLHBHNENZZQS-UHFFFAOYSA-N 0.000 description 1
• ZXHMJGBEWONFAQ-UHFFFAOYSA-N 6-tert-butyl-4-[5-[tert-butyl(dimethyl)silyl]oxy-2-methylphenyl]-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound CC1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1C1=CC(C(C)(C)C)=NC2=C1C(N)=NN2 ZXHMJGBEWONFAQ-UHFFFAOYSA-N 0.000 description 1
• 208000030507 AIDS Diseases 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
• 206010003210 Arteriosclerosis Diseases 0.000 description 1
• 102000040350 B family Human genes 0.000 description 1
• 108091072128 B family Proteins 0.000 description 1
• 208000003174 Brain Neoplasms Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• NWCJBSYZZIZPJA-UHFFFAOYSA-N CC(C)(C)C(CC(c1c[nH]c2ccccc12)=C1C#N)=NC1=O Chemical compound CC(C)(C)C(CC(c1c[nH]c2ccccc12)=C1C#N)=NC1=O NWCJBSYZZIZPJA-UHFFFAOYSA-N 0.000 description 1
• SDHDIMQNCAPPPO-UHFFFAOYSA-N CC(C)(C)C(NC1=O)=CC(c2cc(OC)cc(OC)c2)=C1C#N Chemical compound CC(C)(C)C(NC1=O)=CC(c2cc(OC)cc(OC)c2)=C1C#N SDHDIMQNCAPPPO-UHFFFAOYSA-N 0.000 description 1
• YUPHWFKKWYZEBB-UHFFFAOYSA-N CC(C)(C)C(NC1=O)=CC(c2cccc(N)c2)=C1C#N Chemical compound CC(C)(C)C(NC1=O)=CC(c2cccc(N)c2)=C1C#N YUPHWFKKWYZEBB-UHFFFAOYSA-N 0.000 description 1
• KJBGIJGZBYSWOU-UHFFFAOYSA-N CC(C)(C)C(NC1=O)=CC(c2cccc(O)c2)=C1C#N Chemical compound CC(C)(C)C(NC1=O)=CC(c2cccc(O)c2)=C1C#N KJBGIJGZBYSWOU-UHFFFAOYSA-N 0.000 description 1
• OWTIWNVBVZVWMY-UHFFFAOYSA-N CC(C)(C)c1nc([nH]nc2C)c2c(-c(cc2)ccc2Oc2ccccc2)c1 Chemical compound CC(C)(C)c1nc([nH]nc2C)c2c(-c(cc2)ccc2Oc2ccccc2)c1 OWTIWNVBVZVWMY-UHFFFAOYSA-N 0.000 description 1
• BKCISEITUMTTOB-UHFFFAOYSA-N CC(C)(CN1CCOCC1)c(cc1-c2ccc(C)cc2)nc(OS(C(F)(F)F)(=O)=O)c1C#N Chemical compound CC(C)(CN1CCOCC1)c(cc1-c2ccc(C)cc2)nc(OS(C(F)(F)F)(=O)=O)c1C#N BKCISEITUMTTOB-UHFFFAOYSA-N 0.000 description 1
• AIXIIQMLACOVNJ-UHFFFAOYSA-N CCC(C(C)c(cc1-c2ccc(C)cc2)nc(OS(C(F)(F)F)(=O)=O)c1C#N)N1CCOCC1 Chemical compound CCC(C(C)c(cc1-c2ccc(C)cc2)nc(OS(C(F)(F)F)(=O)=O)c1C#N)N1CCOCC1 AIXIIQMLACOVNJ-UHFFFAOYSA-N 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• 208000005623 Carcinogenesis Diseases 0.000 description 1
• LKRUWOXHBRZTEQ-UHFFFAOYSA-N Cc(cc1)ccc1-c1cc(C2CCCCC2)nc(OS(C(F)(F)F)(=O)=O)c1C#N Chemical compound Cc(cc1)ccc1-c1cc(C2CCCCC2)nc(OS(C(F)(F)F)(=O)=O)c1C#N LKRUWOXHBRZTEQ-UHFFFAOYSA-N 0.000 description 1
• 241001161843 Chandra Species 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• 206010012289 Dementia Diseases 0.000 description 1
• 201000004624 Dermatitis Diseases 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 102100031982 Ephrin type-B receptor 3 Human genes 0.000 description 1
• 102000003951 Erythropoietin Human genes 0.000 description 1
• 108090000394 Erythropoietin Proteins 0.000 description 1
• 229910052693 Europium Inorganic materials 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 101001064458 Homo sapiens Ephrin type-B receptor 3 Proteins 0.000 description 1
• 101000606502 Homo sapiens Protein-tyrosine kinase 6 Proteins 0.000 description 1
• 208000023105 Huntington disease Diseases 0.000 description 1
• 206010020880 Hypertrophy Diseases 0.000 description 1
• 108010001127 Insulin Receptor Proteins 0.000 description 1
• 102000003746 Insulin Receptor Human genes 0.000 description 1
• 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
• 208000008839 Kidney Neoplasms Diseases 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 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
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 206010025421 Macule Diseases 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• KZYNYJVQIHSLCQ-UHFFFAOYSA-N N#Cc(c(-c(cc1)ccc1Oc1ccccc1)cc(C(CC1)CCC11OCCO1)n1)c1OS(C(F)(F)F)(=O)=O Chemical compound N#Cc(c(-c(cc1)ccc1Oc1ccccc1)cc(C(CC1)CCC11OCCO1)n1)c1OS(C(F)(F)F)(=O)=O KZYNYJVQIHSLCQ-UHFFFAOYSA-N 0.000 description 1
• TZYWCYJVHRLUCT-VABKMULXSA-N N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 TZYWCYJVHRLUCT-VABKMULXSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• 244000061176 Nicotiana tabacum Species 0.000 description 1
• 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 208000031481 Pathologic Constriction Diseases 0.000 description 1
• 241000286209 Phasianidae Species 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 102100039810 Protein-tyrosine kinase 6 Human genes 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 description 1
• 208000017442 Retinal disease Diseases 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 108010077895 Sarcosine Proteins 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• QTLTURMWBCTZLY-UHFFFAOYSA-N [3-(3-cyano-6-cyclohexyl-2-oxo-1h-pyridin-4-yl)phenyl] acetate Chemical compound CC(=O)OC1=CC=CC(C2=C(C(=O)NC(=C2)C2CCCCC2)C#N)=C1 QTLTURMWBCTZLY-UHFFFAOYSA-N 0.000 description 1
• SROAVNWHYPLVTI-UHFFFAOYSA-N [3-(3-cyano-6-cyclopropyl-2-oxo-1h-pyridin-4-yl)phenyl] acetate Chemical compound CC(=O)OC1=CC=CC(C2=C(C(=O)NC(=C2)C2CC2)C#N)=C1 SROAVNWHYPLVTI-UHFFFAOYSA-N 0.000 description 1
• KELXGBQMJXYPPL-UHFFFAOYSA-N [3-(6-tert-butyl-3-cyano-2-oxo-1h-pyridin-4-yl)-4-nitrophenyl] acetate Chemical compound CC(=O)OC1=CC=C([N+]([O-])=O)C(C2=C(C(=O)NC(=C2)C(C)(C)C)C#N)=C1 KELXGBQMJXYPPL-UHFFFAOYSA-N 0.000 description 1
• XJXWDGHCPDJPCK-UHFFFAOYSA-N [3-(6-tert-butyl-3-cyano-2-oxo-1h-pyridin-4-yl)-5-methoxyphenyl] acetate Chemical compound COC1=CC(OC(C)=O)=CC(C2=C(C(=O)NC(=C2)C(C)(C)C)C#N)=C1 XJXWDGHCPDJPCK-UHFFFAOYSA-N 0.000 description 1
• KQFNYIPULCATOD-UHFFFAOYSA-N [3-(6-tert-butyl-3-cyano-2-oxo-1h-pyridin-4-yl)phenyl] acetate Chemical compound CC(=O)OC1=CC=CC(C2=C(C(=O)NC(=C2)C(C)(C)C)C#N)=C1 KQFNYIPULCATOD-UHFFFAOYSA-N 0.000 description 1
• VAXMWTCVAGHXAS-UHFFFAOYSA-N [3-[3-cyano-6-cyclopropyl-2-(trifluoromethylsulfonyloxy)pyridin-4-yl]phenyl] acetate Chemical compound CC(=O)OC1=CC=CC(C=2C(=C(OS(=O)(=O)C(F)(F)F)N=C(C=2)C2CC2)C#N)=C1 VAXMWTCVAGHXAS-UHFFFAOYSA-N 0.000 description 1
• ITEKTCPWEVOLNU-UHFFFAOYSA-N [3-[5-cyano-4-pyridin-4-yl-6-(trifluoromethylsulfonyloxy)pyridin-2-yl]phenyl] acetate Chemical compound CC(=O)OC1=CC=CC(C=2N=C(OS(=O)(=O)C(F)(F)F)C(C#N)=C(C=3C=CN=CC=3)C=2)=C1 ITEKTCPWEVOLNU-UHFFFAOYSA-N 0.000 description 1
• JYYFNEDNMCBEET-UHFFFAOYSA-N [3-[6-tert-butyl-3-cyano-2-(trifluoromethylsulfonyloxy)pyridin-4-yl]-4-nitrophenyl] acetate Chemical compound CC(=O)OC1=CC=C([N+]([O-])=O)C(C=2C(=C(OS(=O)(=O)C(F)(F)F)N=C(C=2)C(C)(C)C)C#N)=C1 JYYFNEDNMCBEET-UHFFFAOYSA-N 0.000 description 1
• FFJTVKRAUDJDNO-UHFFFAOYSA-N [3-[6-tert-butyl-3-cyano-2-(trifluoromethylsulfonyloxy)pyridin-4-yl]-5-methoxyphenyl] acetate Chemical compound COC1=CC(OC(C)=O)=CC(C=2C(=C(OS(=O)(=O)C(F)(F)F)N=C(C=2)C(C)(C)C)C#N)=C1 FFJTVKRAUDJDNO-UHFFFAOYSA-N 0.000 description 1
• JTLLDEMNPMFVNI-UHFFFAOYSA-N [3-[6-tert-butyl-3-cyano-2-(trifluoromethylsulfonyloxy)pyridin-4-yl]-5-propan-2-yloxyphenyl] acetate Chemical compound CC(C)OC1=CC(OC(C)=O)=CC(C=2C(=C(OS(=O)(=O)C(F)(F)F)N=C(C=2)C(C)(C)C)C#N)=C1 JTLLDEMNPMFVNI-UHFFFAOYSA-N 0.000 description 1
• ZKMZZOGBRYBQCQ-UHFFFAOYSA-N [3-[6-tert-butyl-3-cyano-2-(trifluoromethylsulfonyloxy)pyridin-4-yl]phenyl] acetate Chemical compound CC(=O)OC1=CC=CC(C=2C(=C(OS(=O)(=O)C(F)(F)F)N=C(C=2)C(C)(C)C)C#N)=C1 ZKMZZOGBRYBQCQ-UHFFFAOYSA-N 0.000 description 1
• CMCPOEWJEXSYDN-UHFFFAOYSA-N [3-acetyloxy-5-(6-tert-butyl-3-cyano-2-oxo-1h-pyridin-4-yl)phenyl] acetate Chemical compound CC(=O)OC1=CC(OC(C)=O)=CC(C2=C(C(=O)NC(=C2)C(C)(C)C)C#N)=C1 CMCPOEWJEXSYDN-UHFFFAOYSA-N 0.000 description 1
• TYYQCLWZWRBWCJ-UHFFFAOYSA-N [3-acetyloxy-5-[6-tert-butyl-3-cyano-2-(trifluoromethylsulfonyloxy)pyridin-4-yl]phenyl] acetate Chemical compound CC(=O)OC1=CC(OC(C)=O)=CC(C=2C(=C(OS(=O)(=O)C(F)(F)F)N=C(C=2)C(C)(C)C)C#N)=C1 TYYQCLWZWRBWCJ-UHFFFAOYSA-N 0.000 description 1
• BHWIFNVILWLCAM-UHFFFAOYSA-N [5-(6-tert-butyl-3-cyano-2-oxo-1h-pyridin-4-yl)-2,3-dimethoxyphenyl] acetate Chemical compound CC(=O)OC1=C(OC)C(OC)=CC(C2=C(C(=O)NC(=C2)C(C)(C)C)C#N)=C1 BHWIFNVILWLCAM-UHFFFAOYSA-N 0.000 description 1
• WCLKRHRXNQBLNG-UHFFFAOYSA-N [5-(6-tert-butyl-3-cyano-2-oxo-1h-pyridin-4-yl)-2-methoxyphenyl] acetate Chemical compound C1=C(OC(C)=O)C(OC)=CC=C1C1=C(C#N)C(=O)NC(C(C)(C)C)=C1 WCLKRHRXNQBLNG-UHFFFAOYSA-N 0.000 description 1
• RNVFJGTVDDPAFS-UHFFFAOYSA-N [5-[6-tert-butyl-3-cyano-2-(trifluoromethylsulfonyloxy)pyridin-4-yl]-2-methoxyphenyl] acetate Chemical compound C1=C(OC(C)=O)C(OC)=CC=C1C1=CC(C(C)(C)C)=NC(OS(=O)(=O)C(F)(F)F)=C1C#N RNVFJGTVDDPAFS-UHFFFAOYSA-N 0.000 description 1
• WUQIXPSESIHHRG-UHFFFAOYSA-N [5-[tert-butyl(dimethyl)silyl]oxy-2-methylphenyl]methanol Chemical compound CC1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1CO WUQIXPSESIHHRG-UHFFFAOYSA-N 0.000 description 1
• YQHSBNRHIFNBSL-UHFFFAOYSA-N [6-tert-butyl-4-[5-[tert-butyl(dimethyl)silyl]oxy-2-methylphenyl]-3-cyanopyridin-2-yl] trifluoromethanesulfonate Chemical compound CC1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1C1=CC(C(C)(C)C)=NC(OS(=O)(=O)C(F)(F)F)=C1C#N YQHSBNRHIFNBSL-UHFFFAOYSA-N 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 150000001241 acetals Chemical class 0.000 description 1
• 230000021736 acetylation Effects 0.000 description 1
• 238000006640 acetylation reaction Methods 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 150000005215 alkyl ethers Chemical class 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
• 208000007502 anemia Diseases 0.000 description 1
• 230000001772 anti-angiogenic effect Effects 0.000 description 1
• 230000000259 anti-tumor effect Effects 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 208000011775 arteriosclerosis disease Diseases 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 230000035578 autophosphorylation Effects 0.000 description 1
• 239000012752 auxiliary agent Substances 0.000 description 1
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 1
• 230000002457 bidirectional effect Effects 0.000 description 1
• 239000003613 bile acid Substances 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 102000023732 binding proteins Human genes 0.000 description 1
• 108091008324 binding proteins Proteins 0.000 description 1
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 125000005510 but-1-en-2-yl group Chemical group 0.000 description 1
• 230000036952 cancer formation Effects 0.000 description 1
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 230000033077 cellular process Effects 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000003610 charcoal Substances 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 229940099112 cornstarch Drugs 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 239000004643 cyanate ester Substances 0.000 description 1
• 238000000354 decomposition reaction Methods 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
• MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical class C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
• 238000006471 dimerization reaction Methods 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 230000013020 embryo development Effects 0.000 description 1
• 231100001129 embryonic lethality Toxicity 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 230000008202 epithelial morphogenesis Effects 0.000 description 1
• 229940105423 erythropoietin Drugs 0.000 description 1
• UXXWGBLTOSRBAY-UHFFFAOYSA-N ethyl 1,4-dioxaspiro[4.5]decane-8-carboxylate Chemical compound C1CC(C(=O)OCC)CCC21OCCO2 UXXWGBLTOSRBAY-UHFFFAOYSA-N 0.000 description 1
• PUSKHXMZPOMNTQ-UHFFFAOYSA-N ethyl 2,1,3-benzoselenadiazole-5-carboxylate Chemical compound CCOC(=O)C1=CC=C2N=[Se]=NC2=C1 PUSKHXMZPOMNTQ-UHFFFAOYSA-N 0.000 description 1
• ZXYAWONOWHSQRU-UHFFFAOYSA-N ethyl 4-oxocyclohexanecarboxylate Chemical compound CCOC(=O)C1CCC(=O)CC1 ZXYAWONOWHSQRU-UHFFFAOYSA-N 0.000 description 1
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
• 150000002391 heterocyclic compounds Chemical class 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• AKQZEFRALAUBFS-UHFFFAOYSA-N ilamine Natural products COC(C)C(O)(C(=O)OCC1=CCN2CCCC12)C(C)(C)O AKQZEFRALAUBFS-UHFFFAOYSA-N 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 239000003978 infusion fluid Substances 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 201000009019 intestinal benign neoplasm Diseases 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 238000011813 knockout mouse model Methods 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 108020001756 ligand binding domains Proteins 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• AOXPHVNMBPFOFS-UHFFFAOYSA-N methyl 2-nitrobenzoate Chemical compound COC(=O)C1=CC=CC=C1[N+]([O-])=O AOXPHVNMBPFOFS-UHFFFAOYSA-N 0.000 description 1
• XAFIGNJFTZSXSS-UHFFFAOYSA-N methyl 5-[tert-butyl(dimethyl)silyl]oxy-2-methylbenzoate Chemical compound COC(=O)C1=CC(O[Si](C)(C)C(C)(C)C)=CC=C1C XAFIGNJFTZSXSS-UHFFFAOYSA-N 0.000 description 1
• JNPZKGOLYSCSEL-UHFFFAOYSA-N methyl 5-amino-2-methylbenzoate Chemical compound COC(=O)C1=CC(N)=CC=C1C JNPZKGOLYSCSEL-UHFFFAOYSA-N 0.000 description 1
• XRTIUIMAICRVLI-UHFFFAOYSA-N methyl 5-hydroxy-2-methylbenzoate Chemical compound COC(=O)C1=CC(O)=CC=C1C XRTIUIMAICRVLI-UHFFFAOYSA-N 0.000 description 1
• 235000013336 milk Nutrition 0.000 description 1
• 239000008267 milk Substances 0.000 description 1
• 210000004080 milk Anatomy 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 230000000921 morphogenic effect Effects 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• SLCVBVWXLSEKPL-UHFFFAOYSA-N neopentyl glycol Chemical compound OCC(C)(C)CO SLCVBVWXLSEKPL-UHFFFAOYSA-N 0.000 description 1
• 210000005036 nerve Anatomy 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 230000000926 neurological effect Effects 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 125000006501 nitrophenyl group Chemical group 0.000 description 1
• 230000000771 oncological effect Effects 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 229920001515 polyalkylene glycol Polymers 0.000 description 1
• 125000003367 polycyclic group Chemical group 0.000 description 1
• OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000009443 proangiogenesis Effects 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 108091006082 receptor inhibitors Proteins 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 230000008929 regeneration Effects 0.000 description 1
• 238000011069 regeneration method Methods 0.000 description 1
• 230000009703 regulation of cell differentiation Effects 0.000 description 1
• 230000021014 regulation of cell growth Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 229940043230 sarcosine Drugs 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 229910000104 sodium hydride Inorganic materials 0.000 description 1
• RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
• 235000010288 sodium nitrite Nutrition 0.000 description 1
• QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 description 1
• 239000007787 solid Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 230000036262 stenosis Effects 0.000 description 1
• 208000037804 stenosis Diseases 0.000 description 1
• 125000000547 substituted alkyl group Chemical group 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 125000004354 sulfur functional group Chemical group 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 1
• ADQDSPAGXLPKSH-UHFFFAOYSA-N tert-butyl 4-[2-[5-cyano-4-(4-methylphenyl)-6-(trifluoromethylsulfonyloxy)pyridin-2-yl]-2-methylpropyl]piperazine-1-carboxylate Chemical compound C1=CC(C)=CC=C1C1=CC(C(C)(C)CN2CCN(CC2)C(=O)OC(C)(C)C)=NC(OS(=O)(=O)C(F)(F)F)=C1C#N ADQDSPAGXLPKSH-UHFFFAOYSA-N 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 230000005945 translocation Effects 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 230000005747 tumor angiogenesis Effects 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 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 1
• 210000005166 vasculature Anatomy 0.000 description 1
• 230000032665 vasculature development Effects 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1