EA032458B1 - Гетероарилы и их применение - Google Patents

Info

Publication number

EA032458B1

EA032458B1 EA201691421A EA201691421A EA032458B1 EA 032458 B1 EA032458 B1 EA 032458B1 EA 201691421 A EA201691421 A EA 201691421A EA 201691421 A EA201691421 A EA 201691421A EA 032458 B1 EA032458 B1 EA 032458B1

Authority

EA

Eurasian Patent Office

Prior art keywords

mmol

pharmaceutically acceptable

compound

acceptable salt

methyl

Prior art date

2014-01-14

Links

• Espacenet
• Global Dossier
• Discuss

• 125000001072 heteroaryl group Chemical group 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 190
• 150000003839 salts Chemical class 0.000 claims abstract description 37
• 230000002062 proliferating effect Effects 0.000 claims abstract description 11
• -1 aliphatic radical Chemical class 0.000 claims description 182
• 239000000126 substance Substances 0.000 claims description 45
• 229940079593 drug Drugs 0.000 claims description 42
• 239000003814 drug Substances 0.000 claims description 42
• 229910052757 nitrogen Inorganic materials 0.000 claims description 27
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
• 201000010099 disease Diseases 0.000 claims description 17
• 229910052739 hydrogen Inorganic materials 0.000 claims description 14
• 239000001257 hydrogen Substances 0.000 claims description 13
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
• 239000000460 chlorine Substances 0.000 claims description 10
• 239000003937 drug carrier Substances 0.000 claims description 9
• 125000000217 alkyl group Chemical group 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
• 150000002431 hydrogen Chemical class 0.000 claims description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
• 229910052700 potassium Inorganic materials 0.000 claims description 3
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims description 2
• 239000005483 tyrosine kinase inhibitor Substances 0.000 claims description 2
• 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 claims description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 8
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 7
• 125000001424 substituent group Chemical group 0.000 claims 7
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 5
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 5
• 229910052801 chlorine Inorganic materials 0.000 claims 5
• 229910052731 fluorine Inorganic materials 0.000 claims 5
• 239000011737 fluorine Substances 0.000 claims 5
• 229910052799 carbon Inorganic materials 0.000 claims 4
• 125000004432 carbon atom Chemical group C* 0.000 claims 4
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims 3
• 229910052736 halogen Inorganic materials 0.000 claims 3
• 150000002367 halogens Chemical group 0.000 claims 3
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
• 125000004076 pyridyl group Chemical group 0.000 claims 3
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
• 125000001309 chloro group Chemical group Cl* 0.000 claims 2
• 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 2
• 125000001153 fluoro group Chemical group F* 0.000 claims 2
• 125000001624 naphthyl group Chemical group 0.000 claims 2
• 125000004433 nitrogen atom Chemical group N* 0.000 claims 2
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 2
• FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims 1
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 1
• 239000005977 Ethylene Substances 0.000 claims 1
• 125000002947 alkylene group Chemical group 0.000 claims 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
• 125000002883 imidazolyl group Chemical group 0.000 claims 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims 1
• 125000003226 pyrazolyl group Chemical group 0.000 claims 1
• 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 1
• 239000003112 inhibitor Substances 0.000 abstract description 8
• 208000024172 Cardiovascular disease Diseases 0.000 abstract description 3
• 208000027866 inflammatory disease Diseases 0.000 abstract description 3
• 230000002757 inflammatory effect Effects 0.000 abstract description 3
• 101000605630 Homo sapiens Phosphatidylinositol 3-kinase catalytic subunit type 3 Proteins 0.000 abstract 1
• 102100038329 Phosphatidylinositol 3-kinase catalytic subunit type 3 Human genes 0.000 abstract 1
• 239000011541 reaction mixture Substances 0.000 description 263
• 239000000203 mixture Substances 0.000 description 216
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 190
• 239000000243 solution Substances 0.000 description 167
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 157
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 151
• 239000003153 chemical reaction reagent Substances 0.000 description 124
• 238000003756 stirring Methods 0.000 description 122
• 238000004440 column chromatography Methods 0.000 description 121
• 239000012043 crude product Substances 0.000 description 103
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
• 239000012074 organic phase Substances 0.000 description 96
• 235000002639 sodium chloride Nutrition 0.000 description 92
• 239000007787 solid Substances 0.000 description 88
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 87
• 229920006395 saturated elastomer Polymers 0.000 description 84
• 239000007858 starting material Substances 0.000 description 83
• 239000011780 sodium chloride Substances 0.000 description 75
• 239000007864 aqueous solution Substances 0.000 description 74
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 72
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 62
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 60
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 58
• 238000005481 NMR spectroscopy Methods 0.000 description 55
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
• 239000002904 solvent Substances 0.000 description 51
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 48
• 238000006243 chemical reaction Methods 0.000 description 45
• 229910000027 potassium carbonate Inorganic materials 0.000 description 43
• 238000000034 method Methods 0.000 description 40
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 39
• 230000015572 biosynthetic process Effects 0.000 description 35
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 34
• 238000003786 synthesis reaction Methods 0.000 description 33
• 229960001686 afatinib Drugs 0.000 description 32
• ULXXDDBFHOBEHA-CWDCEQMOSA-N afatinib Chemical compound N1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ULXXDDBFHOBEHA-CWDCEQMOSA-N 0.000 description 32
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
• 239000000706 filtrate Substances 0.000 description 30
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 30
• 239000005551 L01XE03 - Erlotinib Substances 0.000 description 29
• AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 29
• 229960001433 erlotinib Drugs 0.000 description 28
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• 230000005855 radiation Effects 0.000 description 27
• 235000011181 potassium carbonates Nutrition 0.000 description 26
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 24
• 239000000725 suspension Substances 0.000 description 23
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 22
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
• 210000004027 cell Anatomy 0.000 description 22
• 238000010992 reflux Methods 0.000 description 21
• 229910052938 sodium sulfate Inorganic materials 0.000 description 20
• 235000011152 sodium sulphate Nutrition 0.000 description 20
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
• LXSZMGQQXZXQKX-UHFFFAOYSA-N n-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide Chemical compound C1=NC(NC(=O)C)=CC(B2OC(C)(C)C(C)(C)O2)=C1 LXSZMGQQXZXQKX-UHFFFAOYSA-N 0.000 description 18
• 238000000746 purification Methods 0.000 description 18
• 238000001914 filtration Methods 0.000 description 17
• 235000015320 potassium carbonate Nutrition 0.000 description 17
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
• 239000000047 product Substances 0.000 description 16
• 239000011734 sodium Substances 0.000 description 16
• 239000008346 aqueous phase Substances 0.000 description 15
• 239000000843 powder Substances 0.000 description 15
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
• 238000004128 high performance liquid chromatography Methods 0.000 description 14
• 239000003921 oil Substances 0.000 description 14
• 235000019198 oils Nutrition 0.000 description 14
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 14
• 239000002244 precipitate Substances 0.000 description 14
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 13
• LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 13
• 238000002953 preparative HPLC Methods 0.000 description 13
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 12
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
• 239000012071 phase Substances 0.000 description 12
• 206010028980 Neoplasm Diseases 0.000 description 11
• 229910052786 argon Inorganic materials 0.000 description 11
• 230000004048 modification Effects 0.000 description 11
• 238000012986 modification Methods 0.000 description 11
• 229940124530 sulfonamide Drugs 0.000 description 11
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 10
• CBAXYISWNGGXOZ-UHFFFAOYSA-N 5-bromo-2-methylpyridin-3-amine Chemical compound CC1=NC=C(Br)C=C1N CBAXYISWNGGXOZ-UHFFFAOYSA-N 0.000 description 10
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 10
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 10
• 239000000543 intermediate Substances 0.000 description 10
• 239000000546 pharmaceutical excipient Substances 0.000 description 10
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 9
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
• 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 9
• 229910000024 caesium carbonate Inorganic materials 0.000 description 9
• 239000000945 filler Substances 0.000 description 9
• 239000007789 gas Substances 0.000 description 9
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 9
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
• 235000019341 magnesium sulphate Nutrition 0.000 description 9
• 238000002156 mixing Methods 0.000 description 9
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 8
• ITPSFLLGFGUUQH-UHFFFAOYSA-N 5-bromo-2-chloro-4-methylpyridin-3-amine Chemical compound CC1=C(N)C(Cl)=NC=C1Br ITPSFLLGFGUUQH-UHFFFAOYSA-N 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• 235000019441 ethanol Nutrition 0.000 description 8
• 235000019253 formic acid Nutrition 0.000 description 8
• 230000005764 inhibitory process Effects 0.000 description 8
• 239000000463 material Substances 0.000 description 8
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
• 235000011056 potassium acetate Nutrition 0.000 description 8
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 7
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
• 238000004458 analytical method Methods 0.000 description 7
• 239000002585 base Substances 0.000 description 7
• 238000000576 coating method Methods 0.000 description 7
• 238000002648 combination therapy Methods 0.000 description 7
• 239000002552 dosage form Substances 0.000 description 7
• 239000002480 mineral oil Substances 0.000 description 7
• 235000010446 mineral oil Nutrition 0.000 description 7
• 239000012299 nitrogen atmosphere Substances 0.000 description 7
• 239000003208 petroleum Substances 0.000 description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
• 239000000741 silica gel Substances 0.000 description 7
• 229910002027 silica gel Inorganic materials 0.000 description 7
• 229910000104 sodium hydride Inorganic materials 0.000 description 7
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 7
• 239000003826 tablet Substances 0.000 description 7
• FJSAJUXIHJIAMD-UHFFFAOYSA-N 2,4-difluorobenzenesulfonyl chloride Chemical compound FC1=CC=C(S(Cl)(=O)=O)C(F)=C1 FJSAJUXIHJIAMD-UHFFFAOYSA-N 0.000 description 6
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• 201000011510 cancer Diseases 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 238000006880 cross-coupling reaction Methods 0.000 description 6
• 239000012065 filter cake Substances 0.000 description 6
• 238000010438 heat treatment Methods 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• JVJPZDXQLQOSTP-UHFFFAOYSA-N n-(4-iodo-5-methylpyridin-2-yl)cyclopropanecarboxamide Chemical compound C1=C(I)C(C)=CN=C1NC(=O)C1CC1 JVJPZDXQLQOSTP-UHFFFAOYSA-N 0.000 description 6
• 229920001223 polyethylene glycol Polymers 0.000 description 6
• 238000002390 rotary evaporation Methods 0.000 description 6
• 235000017557 sodium bicarbonate Nutrition 0.000 description 6
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
• 229910000029 sodium carbonate Inorganic materials 0.000 description 6
• 239000012312 sodium hydride Substances 0.000 description 6
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
• 238000012360 testing method Methods 0.000 description 6
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
• RAMMAUFNZRRUIV-UHFFFAOYSA-N 2-chloro-5-[2-[(2-cyclopropylpyrimidin-4-yl)amino]pyridin-4-yl]-4-methylpyridine-3-carboxylic acid Chemical compound ClC1=NC=C(C(=C1C(=O)O)C)C1=CC(=NC=C1)NC1=NC(=NC=C1)C1CC1 RAMMAUFNZRRUIV-UHFFFAOYSA-N 0.000 description 5
• BAQKUNMKVAPWGU-UHFFFAOYSA-N 4-bromopyridin-2-amine Chemical compound NC1=CC(Br)=CC=N1 BAQKUNMKVAPWGU-UHFFFAOYSA-N 0.000 description 5
• KTXDLMQWUZXRPA-UHFFFAOYSA-N 5-bromo-2-methylpyridin-3-ol Chemical compound CC1=NC=C(Br)C=C1O KTXDLMQWUZXRPA-UHFFFAOYSA-N 0.000 description 5
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 5
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
• LHHCXVFVFZFMRV-UHFFFAOYSA-N N-[4-[5-(1,3-oxazol-2-ylamino)pyridin-3-yl]pyridin-2-yl]acetamide Chemical compound O1C(=NC=C1)NC=1C=C(C=NC1)C1=CC(=NC=C1)NC(C)=O LHHCXVFVFZFMRV-UHFFFAOYSA-N 0.000 description 5
• ZMOXSKHLHDDQMH-UHFFFAOYSA-N N-[4-[6-chloro-5-[(4-cyclopropyl-2-fluorophenyl)sulfonylamino]-4-methylpyridin-3-yl]pyridin-2-yl]acetamide Chemical compound ClC1=C(C(=C(C=N1)C1=CC(=NC=C1)NC(C)=O)C)NS(=O)(=O)C1=C(C=C(C=C1)C1CC1)F ZMOXSKHLHDDQMH-UHFFFAOYSA-N 0.000 description 5
• QMHAHUAQAJVBIW-UHFFFAOYSA-N [methyl(sulfamoyl)amino]methane Chemical compound CN(C)S(N)(=O)=O QMHAHUAQAJVBIW-UHFFFAOYSA-N 0.000 description 5
• 238000010521 absorption reaction Methods 0.000 description 5
• 239000000654 additive Substances 0.000 description 5
• 230000008485 antagonism Effects 0.000 description 5
• 239000012300 argon atmosphere Substances 0.000 description 5
• 239000012298 atmosphere Substances 0.000 description 5
• 239000002775 capsule Substances 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 239000008101 lactose Substances 0.000 description 5
• 239000006187 pill Substances 0.000 description 5
• 229910000160 potassium phosphate Inorganic materials 0.000 description 5
• 235000011009 potassium phosphates Nutrition 0.000 description 5
• 239000007909 solid dosage form Substances 0.000 description 5
• 238000004808 supercritical fluid chromatography Methods 0.000 description 5
• 239000006228 supernatant Substances 0.000 description 5
• 239000001993 wax Substances 0.000 description 5
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
• CSTIHEUAYBOTIY-UHFFFAOYSA-N (5-bromo-2-methylpyridin-3-yl)-piperidin-1-ylmethanone Chemical compound BrC=1C=C(C(=NC1)C)C(=O)N1CCCCC1 CSTIHEUAYBOTIY-UHFFFAOYSA-N 0.000 description 4
• DMWKCFBSPIWNAU-UHFFFAOYSA-N 2-(5-bromo-2-methylpyridin-3-yl)-1,2,6-thiadiazinane 1,1-dioxide Chemical compound BrC=1C=C(C(=NC1)C)N1S(NCCC1)(=O)=O DMWKCFBSPIWNAU-UHFFFAOYSA-N 0.000 description 4
• OJAQETILCUMTDO-UHFFFAOYSA-N 2-(5-bromo-2-methylpyridin-3-yl)-6-methyl-1,2,6-thiadiazinane 1,1-dioxide Chemical compound BrC=1C=C(C(=NC1)C)N1S(N(CCC1)C)(=O)=O OJAQETILCUMTDO-UHFFFAOYSA-N 0.000 description 4
• STZLIXFJZRNZAT-UHFFFAOYSA-N 2-methyl-5-[2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl]pyridine-3-carboxylic acid Chemical compound CC1=C(C=C(C=N1)C1=CC(=NC=C1)NC1=NC(=NC=C1)C)C(=O)O STZLIXFJZRNZAT-UHFFFAOYSA-N 0.000 description 4
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 4
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
• MDQXGHBCDCOOSM-UHFFFAOYSA-N 5-bromopyridin-3-amine Chemical compound NC1=CN=CC(Br)=C1 MDQXGHBCDCOOSM-UHFFFAOYSA-N 0.000 description 4
• YRGMYJUKFJPNPD-UHFFFAOYSA-N 5-bromopyridine-2,3-diamine Chemical compound NC1=CC(Br)=CN=C1N YRGMYJUKFJPNPD-UHFFFAOYSA-N 0.000 description 4
• TXOJCWWMKARMDB-UHFFFAOYSA-N 6-benzyl-3-[2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl]-7,8-dihydro-1,6-naphthyridin-5-one Chemical compound C(C1=CC=CC=C1)N1C(C=2C=C(C=NC2CC1)C1=CC(=NC=C1)NC1=NC(=NC=C1)C)=O TXOJCWWMKARMDB-UHFFFAOYSA-N 0.000 description 4
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
• 239000005695 Ammonium acetate Substances 0.000 description 4
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
• GBRMWCSOJTYVLY-UHFFFAOYSA-N N-[2-chloro-5-[5-fluoro-2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl]-4-methylpyridin-3-yl]-2,4-difluorobenzenesulfonamide Chemical compound ClC1=C(C(=C(C=N1)C1=CC(=NC=C1F)NC1=NC(=NC=C1)C)C)NS(=O)(=O)C1=C(C=C(C=C1)F)F GBRMWCSOJTYVLY-UHFFFAOYSA-N 0.000 description 4
• PQYVHMSWCMUNQD-UHFFFAOYSA-N N-[4-(5-amino-6-methylpyridin-3-yl)pyridin-2-yl]acetamide Chemical compound NC=1C=C(C=NC1C)C1=CC(=NC=C1)NC(C)=O PQYVHMSWCMUNQD-UHFFFAOYSA-N 0.000 description 4
• NVZNRMFABIGXOG-UHFFFAOYSA-N N-[4-[5-(1,1-dioxo-1,2-thiazolidin-2-yl)pyridin-3-yl]pyridin-2-yl]acetamide Chemical compound O=S1(N(CCC1)C=1C=C(C=NC1)C1=CC(=NC=C1)NC(C)=O)=O NVZNRMFABIGXOG-UHFFFAOYSA-N 0.000 description 4
• SOPLBMOCJINBES-UHFFFAOYSA-N N-[4-[5-(1,3-benzoxazol-2-ylamino)-6-methylpyridin-3-yl]pyridin-2-yl]acetamide Chemical compound O1C(=NC2=C1C=CC=C2)NC=2C=C(C=NC2C)C2=CC(=NC=C2)NC(C)=O SOPLBMOCJINBES-UHFFFAOYSA-N 0.000 description 4
• ASDMODQFWDOSKD-UHFFFAOYSA-N N-[4-[5-[4-(dimethylamino)-1,1-dioxo-1,2-thiazolidin-2-yl]-6-methylpyridin-3-yl]pyridin-2-yl]acetamide Chemical compound CN(C1CN(S(C1)(=O)=O)C=1C=C(C=NC1C)C1=CC(=NC=C1)NC(C)=O)C ASDMODQFWDOSKD-UHFFFAOYSA-N 0.000 description 4
• XOLJSGCMIOJJED-UHFFFAOYSA-N N-[4-[6-amino-5-(cyclopropylmethylamino)pyridin-3-yl]pyridin-2-yl]acetamide Chemical compound NC1=C(C=C(C=N1)C1=CC(=NC=C1)NC(C)=O)NCC1CC1 XOLJSGCMIOJJED-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• 229920002472 Starch Polymers 0.000 description 4
• 229930006000 Sucrose Natural products 0.000 description 4
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
• CHKQALUEEULCPZ-UHFFFAOYSA-N amino 2,4,6-trimethylbenzenesulfonate Chemical compound CC1=CC(C)=C(S(=O)(=O)ON)C(C)=C1 CHKQALUEEULCPZ-UHFFFAOYSA-N 0.000 description 4
• 235000019257 ammonium acetate Nutrition 0.000 description 4
• 229940043376 ammonium acetate Drugs 0.000 description 4
• 235000019270 ammonium chloride Nutrition 0.000 description 4
• GQDPCLBRMGXZJR-UHFFFAOYSA-N azetidin-1-yl-[2-methyl-5-[2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl]pyridin-3-yl]methanone Chemical compound N1(CCC1)C(=O)C=1C=C(C=NC1C)C1=CC(=NC=C1)NC1=NC(=NC=C1)C GQDPCLBRMGXZJR-UHFFFAOYSA-N 0.000 description 4
• IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 4
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 4
• 239000006172 buffering agent Substances 0.000 description 4
• 229910002091 carbon monoxide Inorganic materials 0.000 description 4
• 230000030833 cell death Effects 0.000 description 4
• 238000004587 chromatography analysis Methods 0.000 description 4
• AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 description 4
• 230000003111 delayed effect Effects 0.000 description 4
• 238000013461 design Methods 0.000 description 4
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 239000005457 ice water Substances 0.000 description 4
• 239000003701 inert diluent Substances 0.000 description 4
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
• 239000000314 lubricant Substances 0.000 description 4
• AZBXJWQTYFWWRI-UHFFFAOYSA-N methyl 2-chloro-5-[2-[(2-cyclopropylpyrimidin-4-yl)amino]pyridin-4-yl]-4-methylpyridine-3-carboxylate Chemical compound ClC1=NC=C(C(=C1C(=O)OC)C)C1=CC(=NC=C1)NC1=NC(=NC=C1)C1CC1 AZBXJWQTYFWWRI-UHFFFAOYSA-N 0.000 description 4
• LZSLMCNKLYHEPM-UHFFFAOYSA-N methyl N-[4-[6-amino-5-(dimethylsulfamoyl)pyridin-3-yl]pyridin-2-yl]carbamate Chemical compound NC1=C(C=C(C=N1)C1=CC(=NC=C1)NC(OC)=O)S(N(C)C)(=O)=O LZSLMCNKLYHEPM-UHFFFAOYSA-N 0.000 description 4
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 4
• RVKAEGMFPJIRGY-UHFFFAOYSA-N methyl n-(4-trimethylstannylpyridin-2-yl)carbamate Chemical compound COC(=O)NC1=CC([Sn](C)(C)C)=CC=N1 RVKAEGMFPJIRGY-UHFFFAOYSA-N 0.000 description 4
• MSSXBFTYUJPDDR-UHFFFAOYSA-N n-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]cyclopropanecarboxamide Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=NC(NC(=O)C2CC2)=C1 MSSXBFTYUJPDDR-UHFFFAOYSA-N 0.000 description 4
• 229920000642 polymer Polymers 0.000 description 4
• 239000000523 sample Substances 0.000 description 4
• 238000000926 separation method Methods 0.000 description 4
• 235000019698 starch Nutrition 0.000 description 4
• 239000005720 sucrose Substances 0.000 description 4
• 230000004083 survival effect Effects 0.000 description 4
• 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 4
• 230000035899 viability Effects 0.000 description 4
• LNTWKHVDGFZRES-UHFFFAOYSA-N 1-(2-amino-5-bromopyridin-3-yl)pyrrolidin-2-one Chemical compound NC1=NC=C(C=C1N1C(CCC1)=O)Br LNTWKHVDGFZRES-UHFFFAOYSA-N 0.000 description 3
• KSYLOEKCZPHIOR-UHFFFAOYSA-N 1-(5-bromo-2-methylpyridin-3-yl)-1,3-diazinan-2-one Chemical compound BrC=1C=C(C(=NC1)C)N1C(NCCC1)=O KSYLOEKCZPHIOR-UHFFFAOYSA-N 0.000 description 3
• UBCLAKYYJXTIKU-UHFFFAOYSA-N 1-(5-bromo-2-methylpyridin-3-yl)-3-(3-chloropropyl)urea Chemical compound BrC=1C=C(C(=NC1)C)NC(=O)NCCCCl UBCLAKYYJXTIKU-UHFFFAOYSA-N 0.000 description 3
• WVMVRXXYNPDVBK-UHFFFAOYSA-N 2,5-dichloropyridine-3-sulfonyl chloride Chemical compound ClC1=CN=C(Cl)C(S(Cl)(=O)=O)=C1 WVMVRXXYNPDVBK-UHFFFAOYSA-N 0.000 description 3
• BEGNSALZEYHRFN-UHFFFAOYSA-N 2-(5-bromo-2-methylpyridin-3-yl)-3H-1,2-thiazole 1,1-dioxide Chemical compound BrC=1C=C(C(=NC1)C)N1S(C=CC1)(=O)=O BEGNSALZEYHRFN-UHFFFAOYSA-N 0.000 description 3
• FLZXEHBPYYGTOC-UHFFFAOYSA-N 2-(5-bromo-2-methylpyridin-3-yl)-N,N-dimethyl-1,1-dioxo-1,2-thiazolidin-4-amine Chemical compound BrC=1C=C(C(=NC1)C)N1S(CC(C1)N(C)C)(=O)=O FLZXEHBPYYGTOC-UHFFFAOYSA-N 0.000 description 3
• VVJASOVQRRZHLO-UHFFFAOYSA-N 2-(5-bromopyridin-3-yl)-6-methyl-1,2,6-thiadiazinane 1,1-dioxide Chemical compound BrC=1C=C(C=NC1)N1S(N(CCC1)C)(=O)=O VVJASOVQRRZHLO-UHFFFAOYSA-N 0.000 description 3
• COCONHAJXGRUOC-UHFFFAOYSA-N 2-(benzylamino)acetonitrile Chemical compound N#CCNCC1=CC=CC=C1 COCONHAJXGRUOC-UHFFFAOYSA-N 0.000 description 3
• HHOMGTXSVLXUEV-UHFFFAOYSA-N 2-[(4-bromopyridin-2-yl)amino]-1,3-oxazole-5-carboxylic acid Chemical compound BrC1=CC(=NC=C1)NC=1OC(=CN1)C(=O)O HHOMGTXSVLXUEV-UHFFFAOYSA-N 0.000 description 3
• BUBAIZHUKPAINV-UHFFFAOYSA-N 2-amino-5-bromopyridine-3-sulfonohydrazide Chemical compound NNS(=O)(=O)C1=CC(Br)=CN=C1N BUBAIZHUKPAINV-UHFFFAOYSA-N 0.000 description 3
• DMQJKPQOXFIXFG-UHFFFAOYSA-N 2-amino-5-bromopyridine-3-sulfonyl chloride Chemical compound NC1=NC=C(Br)C=C1S(Cl)(=O)=O DMQJKPQOXFIXFG-UHFFFAOYSA-N 0.000 description 3
• FYBCWIILJHUXBE-UHFFFAOYSA-N 2-bromo-5-chloropyridine-3-sulfonyl chloride Chemical compound ClC1=CN=C(Br)C(S(Cl)(=O)=O)=C1 FYBCWIILJHUXBE-UHFFFAOYSA-N 0.000 description 3
• TWBPWBPGNQWFSJ-UHFFFAOYSA-N 2-phenylaniline Chemical group NC1=CC=CC=C1C1=CC=CC=C1 TWBPWBPGNQWFSJ-UHFFFAOYSA-N 0.000 description 3
• NXXDJFCUDQRLLL-UHFFFAOYSA-N 3-[2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl]-7,8-dihydro-6H-1,6-naphthyridin-5-one Chemical compound CC1=NC=CC(=N1)NC1=NC=CC(=C1)C=1C=NC=2CCNC(C2C1)=O NXXDJFCUDQRLLL-UHFFFAOYSA-N 0.000 description 3
• LQKLVOWNBKJRJE-UHFFFAOYSA-N 3-bicyclo[1.1.1]pentanylazanium;chloride Chemical compound Cl.C1C2CC1(N)C2 LQKLVOWNBKJRJE-UHFFFAOYSA-N 0.000 description 3
• MLWBQWSDSCHCHN-UHFFFAOYSA-N 3-bromo-5-methylsulfonyl-1-oxidopyridin-1-ium Chemical compound BrC=1C=[N+](C=C(C1)S(=O)(=O)C)[O-] MLWBQWSDSCHCHN-UHFFFAOYSA-N 0.000 description 3
• IRDYUEIXLCUPBK-UHFFFAOYSA-N 3-chloro-5-[(4-fluoro-2,3-dihydro-1H-inden-1-yl)oxy]pyridine Chemical compound ClC=1C=NC=C(C1)OC1CCC2=C(C=CC=C12)F IRDYUEIXLCUPBK-UHFFFAOYSA-N 0.000 description 3
• MLTDNPHNRXQQFJ-UHFFFAOYSA-N 4-(1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-2-amine Chemical compound N1N=CC=2C1=NC=C(C2)C2=CC(=NC=C2)N MLTDNPHNRXQQFJ-UHFFFAOYSA-N 0.000 description 3
• HJNZXANJTKKPLA-UHFFFAOYSA-N 4-(4-bromopyridin-2-yl)-2-methyl-3H-pyridine-3,4-diamine Chemical compound BrC1=CC(=NC=C1)C1(C(C(=NC=C1)C)N)N HJNZXANJTKKPLA-UHFFFAOYSA-N 0.000 description 3
• ZUEFYGMUWHCUOX-UHFFFAOYSA-N 4-amino-6-bromopyrazolo[1,5-a]pyridine-3-carboxylic acid Chemical compound NC=1C=2N(C=C(C1)Br)N=CC2C(=O)O ZUEFYGMUWHCUOX-UHFFFAOYSA-N 0.000 description 3
• JAYNXQOCFNFJQP-UHFFFAOYSA-N 5-(2-acetamidopyridin-4-yl)-2-aminopyridine-3-sulfonic acid Chemical compound C(C)(=O)NC1=NC=CC(=C1)C=1C=NC(=C(C1)S(=O)(=O)O)N JAYNXQOCFNFJQP-UHFFFAOYSA-N 0.000 description 3
• QSHKMZHQTJIDND-UHFFFAOYSA-N 5-bromo-1H-pyrrolo[2,3-b]pyridine-3-sulfonyl chloride Chemical compound BrC=1C=C2C(=NC1)NC=C2S(=O)(=O)Cl QSHKMZHQTJIDND-UHFFFAOYSA-N 0.000 description 3
• LPTVWZSQAIDCEB-UHFFFAOYSA-N 5-bromo-1h-pyrrolo[2,3-b]pyridine Chemical compound BrC1=CN=C2NC=CC2=C1 LPTVWZSQAIDCEB-UHFFFAOYSA-N 0.000 description 3
• FEJYHXKMEDXPBE-UHFFFAOYSA-N 5-bromo-2,4-dimethyl-3-nitropyridine Chemical compound CC1=NC=C(Br)C(C)=C1[N+]([O-])=O FEJYHXKMEDXPBE-UHFFFAOYSA-N 0.000 description 3
• USTIQRHYARIVMJ-UHFFFAOYSA-N 5-bromo-2,4-dimethylpyridin-3-amine Chemical compound BrC=1C(=C(C(=NC1)C)N)C USTIQRHYARIVMJ-UHFFFAOYSA-N 0.000 description 3
• WSVUADXXEYJFRX-UHFFFAOYSA-N 5-bromo-2-(dimethylamino)pyridine-3-carboxylic acid Chemical compound CN(C)C1=NC=C(Br)C=C1C(O)=O WSVUADXXEYJFRX-UHFFFAOYSA-N 0.000 description 3
• XNDNUKRIGYUPOK-UHFFFAOYSA-N 5-bromo-2-chloro-4-ethyl-3-nitropyridine Chemical compound BrC=1C(=C(C(=NC1)Cl)[N+](=O)[O-])CC XNDNUKRIGYUPOK-UHFFFAOYSA-N 0.000 description 3
• QITWMKWIURJTQJ-UHFFFAOYSA-N 5-bromo-2-chloro-4-ethylpyridin-3-amine Chemical compound BrC=1C(=C(C(=NC1)Cl)N)CC QITWMKWIURJTQJ-UHFFFAOYSA-N 0.000 description 3
• BRHJJZJWSDPQBJ-UHFFFAOYSA-N 5-bromo-3-ethoxy-2-methylpyridine Chemical compound CCOC1=CC(Br)=CN=C1C BRHJJZJWSDPQBJ-UHFFFAOYSA-N 0.000 description 3
• OIQFOJOLDCDHSI-UHFFFAOYSA-N 5-bromo-3-phenylsulfanyl-1h-pyrrolo[2,3-b]pyridine Chemical compound C12=CC(Br)=CN=C2NC=C1SC1=CC=CC=C1 OIQFOJOLDCDHSI-UHFFFAOYSA-N 0.000 description 3
• UTMFPWMQFRRHQH-UHFFFAOYSA-N 5-bromo-4-ethyl-3-nitro-1H-pyridin-2-one Chemical compound BrC=1C(=C(C(NC1)=O)[N+](=O)[O-])CC UTMFPWMQFRRHQH-UHFFFAOYSA-N 0.000 description 3
• BODGSAKNSPPOHD-UHFFFAOYSA-N 5-bromo-4-ethyl-3-nitropyridin-2-amine Chemical compound BrC=1C(=C(C(=NC1)N)[N+](=O)[O-])CC BODGSAKNSPPOHD-UHFFFAOYSA-N 0.000 description 3
• MHTDGXBHFCKWTD-UHFFFAOYSA-N 5-bromo-4-ethylpyridin-2-amine Chemical compound CCC1=CC(N)=NC=C1Br MHTDGXBHFCKWTD-UHFFFAOYSA-N 0.000 description 3
• DROXFHXHKVMPHZ-UHFFFAOYSA-M 5-bromopyridin-1-ium-1,3-diamine 2,4,6-trimethylbenzenesulfonate Chemical compound CC1=C(C(=CC(=C1)C)C)S(=O)(=O)[O-].N[N+]1=CC(=CC(=C1)Br)N DROXFHXHKVMPHZ-UHFFFAOYSA-M 0.000 description 3
• DIONPYCYVWCDIG-UHFFFAOYSA-N 5-chloro-3-iodopyridin-2-amine Chemical compound NC1=NC=C(Cl)C=C1I DIONPYCYVWCDIG-UHFFFAOYSA-N 0.000 description 3
• VIYINXDAPKGARM-UHFFFAOYSA-N 6-benzyl-3-bromo-7,8-dihydro-1,6-naphthyridin-5-one Chemical compound C(C1=CC=CC=C1)N1C(C=2C=C(C=NC2CC1)Br)=O VIYINXDAPKGARM-UHFFFAOYSA-N 0.000 description 3
• ZUOPKGGHOJFWGO-UHFFFAOYSA-N 6-bromo-1-cyclopropylsulfonylpyrazolo[4,3-b]pyridine Chemical compound BrC=1C=C2C(=NC1)C=NN2S(=O)(=O)C2CC2 ZUOPKGGHOJFWGO-UHFFFAOYSA-N 0.000 description 3
• GHOQJMQIVBAXQG-UHFFFAOYSA-N 6-bromopyrazolo[1,5-a]pyridin-4-amine Chemical compound BrC=1C=C(C=2N(C1)N=CC2)N GHOQJMQIVBAXQG-UHFFFAOYSA-N 0.000 description 3
• LENYWTQYOHGJLB-UHFFFAOYSA-N 6-chloro-8-iodo-[1,2,4]triazolo[1,5-a]pyridine Chemical compound C1=C(Cl)C=C(I)C2=NC=NN21 LENYWTQYOHGJLB-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• 206010006187 Breast cancer Diseases 0.000 description 3
• 208000026310 Breast neoplasm Diseases 0.000 description 3
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 3
• 206010009944 Colon cancer Diseases 0.000 description 3
• 206010013710 Drug interaction Diseases 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• IYMUDTOWAIBHQF-UHFFFAOYSA-N N-(1-bicyclo[1.1.1]pentanyl)-2-(dimethylamino)-N-methyl-5-[2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl]pyridine-3-carboxamide Chemical compound C12(CC(C1)C2)N(C(=O)C=2C=C(C=NC2N(C)C)C2=CC(=NC=C2)NC2=NC(=NC=C2)C)C IYMUDTOWAIBHQF-UHFFFAOYSA-N 0.000 description 3
• GLVGLJUGZOGRSN-UHFFFAOYSA-N N-(4-bromopyridin-2-yl)pyrrolidine-1-carboxamide Chemical compound BrC1=CC(=NC=C1)NC(=O)N1CCCC1 GLVGLJUGZOGRSN-UHFFFAOYSA-N 0.000 description 3
• FVNPRLQUHKNDOQ-UHFFFAOYSA-N N-(6-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-2,4-difluorobenzenesulfonamide Chemical compound ClC=1C=C(C=2N(C1)N=CN2)NS(=O)(=O)C2=C(C=C(C=C2)F)F FVNPRLQUHKNDOQ-UHFFFAOYSA-N 0.000 description 3
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
• NXEAMZULBMRWDK-UHFFFAOYSA-N N-[4-(1,1-dioxo-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-8-yl)pyridin-2-yl]acetamide Chemical compound O=S1(C2=C(OCCN1)N=CC(=C2)C2=CC(=NC=C2)NC(C)=O)=O NXEAMZULBMRWDK-UHFFFAOYSA-N 0.000 description 3
• PGMLLNMHSMXQMK-UHFFFAOYSA-N N-[4-(1-cyclopropylsulfonylpyrazolo[4,3-b]pyridin-6-yl)pyridin-2-yl]acetamide Chemical compound C1(CC1)S(=O)(=O)N1N=CC2=NC=C(C=C21)C2=CC(=NC=C2)NC(C)=O PGMLLNMHSMXQMK-UHFFFAOYSA-N 0.000 description 3
• MVEKEVLTHHIPEB-UHFFFAOYSA-N N-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-2-yl]acetamide Chemical compound N1N=CC=2C1=NC=C(C2)C2=CC(=NC=C2)NC(C)=O MVEKEVLTHHIPEB-UHFFFAOYSA-N 0.000 description 3
• SAZBGGKGICJTBV-UHFFFAOYSA-N N-[4-(5-bromopyridin-3-yl)pyridin-2-yl]acetamide Chemical compound BrC=1C=C(C=NC1)C1=CC(=NC=C1)NC(C)=O SAZBGGKGICJTBV-UHFFFAOYSA-N 0.000 description 3
• PCFHPNSIWKOJKS-UHFFFAOYSA-N N-[4-(5-methylsulfonyl-1-oxidopyridin-1-ium-3-yl)pyridin-2-yl]acetamide Chemical compound CS(=O)(=O)C=1C=C(C=[N+](C1)[O-])C1=CC(=NC=C1)NC(C)=O PCFHPNSIWKOJKS-UHFFFAOYSA-N 0.000 description 3
• ZORGKBDLRUZVHN-UHFFFAOYSA-N N-[4-(6-amino-5-methylsulfonylpyridin-3-yl)pyridin-2-yl]acetamide Chemical compound NC1=C(C=C(C=N1)C1=CC(=NC=C1)NC(C)=O)S(=O)(=O)C ZORGKBDLRUZVHN-UHFFFAOYSA-N 0.000 description 3
• AJWQWRXLZJYTMZ-UHFFFAOYSA-N N-[4-[1-(cyclopropylmethyl)imidazo[4,5-b]pyridin-6-yl]pyridin-2-yl]acetamide Chemical compound C1(CC1)CN1C=NC2=NC=C(C=C21)C2=CC(=NC=C2)NC(C)=O AJWQWRXLZJYTMZ-UHFFFAOYSA-N 0.000 description 3
• YAXQZBOBMGGLQN-UHFFFAOYSA-N N-[4-[5-(6-methyl-1,1-dioxo-1,2,6-thiadiazinan-2-yl)pyridin-3-yl]pyridin-2-yl]acetamide Chemical compound CN1CCCN(S1(=O)=O)C=1C=C(C=NC1)C1=CC(=NC=C1)NC(C)=O YAXQZBOBMGGLQN-UHFFFAOYSA-N 0.000 description 3
• NJGYCVDFIFBTQK-UHFFFAOYSA-N N-[4-[6-(methylamino)-5-[methyl(methylsulfonyl)amino]pyridin-3-yl]pyridin-2-yl]acetamide Chemical compound CNC1=C(C=C(C=N1)C1=CC(=NC=C1)NC(C)=O)N(S(=O)(=O)C)C NJGYCVDFIFBTQK-UHFFFAOYSA-N 0.000 description 3
• MXPPCUMHPHYZJS-UHFFFAOYSA-N N-[4-[6-amino-5-(2-oxopyrrolidin-1-yl)pyridin-3-yl]pyridin-2-yl]acetamide Chemical compound NC1=C(C=C(C=N1)C1=CC(=NC=C1)NC(C)=O)N1C(CCC1)=O MXPPCUMHPHYZJS-UHFFFAOYSA-N 0.000 description 3
• CUSNPYAULLUKDQ-UHFFFAOYSA-N N-[4-[6-amino-5-(dimethylsulfamoyl)pyridin-3-yl]pyridin-2-yl]acetamide Chemical compound NC1=C(C=C(C=N1)C1=CC(=NC=C1)NC(C)=O)S(N(C)C)(=O)=O CUSNPYAULLUKDQ-UHFFFAOYSA-N 0.000 description 3
• PGUAHYPVGKHZHU-UHFFFAOYSA-N N-[4-[6-amino-5-[methyl(methylsulfonyl)amino]pyridin-3-yl]pyridin-2-yl]acetamide Chemical compound NC1=C(C=C(C=N1)C1=CC(=NC=C1)NC(C)=O)N(S(=O)(=O)C)C PGUAHYPVGKHZHU-UHFFFAOYSA-N 0.000 description 3
• CPRITTZZVZQRHC-UHFFFAOYSA-N N-[5-(2-acetamidopyridin-4-yl)pyridin-3-yl]-2,4-difluoro-N-methylbenzamide Chemical compound C(C)(=O)NC1=NC=CC(=C1)C=1C=NC=C(C1)N(C(C1=C(C=C(C=C1)F)F)=O)C CPRITTZZVZQRHC-UHFFFAOYSA-N 0.000 description 3
• IJICEZSIPATIBS-UHFFFAOYSA-N N-[5-(2-acetamidopyridin-4-yl)pyridin-3-yl]benzamide Chemical compound C(C)(=O)NC1=NC=CC(=C1)C=1C=NC=C(C1)NC(C1=CC=CC=C1)=O IJICEZSIPATIBS-UHFFFAOYSA-N 0.000 description 3
• 229910019142 PO4 Inorganic materials 0.000 description 3
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• 239000007983 Tris buffer Substances 0.000 description 3
• 240000008042 Zea mays Species 0.000 description 3
• WVMDSNGINQNHLN-UHFFFAOYSA-N [(2-methylpropan-2-yl)oxycarbonylamino] 2,4,6-trimethylbenzenesulfonate Chemical compound CC1=CC(C)=C(S(=O)(=O)ONC(=O)OC(C)(C)C)C(C)=C1 WVMDSNGINQNHLN-UHFFFAOYSA-N 0.000 description 3
• 239000002253 acid Substances 0.000 description 3
• 239000004480 active ingredient Substances 0.000 description 3
• 239000013543 active substance Substances 0.000 description 3
• 230000000996 additive effect Effects 0.000 description 3
• 235000010443 alginic acid Nutrition 0.000 description 3
• 229920000615 alginic acid Polymers 0.000 description 3
• 230000001028 anti-proliverative effect Effects 0.000 description 3
• IVAPYYPVIZZLSZ-UHFFFAOYSA-N azetidin-1-yl-(5-bromo-2-methylpyridin-3-yl)methanone Chemical compound N1(CCC1)C(=O)C=1C(=NC=C(C1)Br)C IVAPYYPVIZZLSZ-UHFFFAOYSA-N 0.000 description 3
• HYXRQJLZLKEASW-UHFFFAOYSA-N azetidin-1-yl-[2-chloro-5-[2-[(2-cyclopropylpyrimidin-4-yl)amino]pyridin-4-yl]-4-methylpyridin-3-yl]methanone Chemical compound N1(CCC1)C(=O)C=1C(=C(C=NC1Cl)C1=CC(=NC=C1)NC1=NC(=NC=C1)C1CC1)C HYXRQJLZLKEASW-UHFFFAOYSA-N 0.000 description 3
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 3
• 238000009835 boiling Methods 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
• 239000011248 coating agent Substances 0.000 description 3
• 208000029742 colonic neoplasm Diseases 0.000 description 3
• 238000001816 cooling Methods 0.000 description 3
• 239000013058 crude material Substances 0.000 description 3
• 235000014113 dietary fatty acids Nutrition 0.000 description 3
• 230000000694 effects Effects 0.000 description 3
• 239000003995 emulsifying agent Substances 0.000 description 3
• XSAVUNZYENKZAU-UHFFFAOYSA-N ethyl 2-[(4-bromopyridin-2-yl)amino]-1,3-oxazole-5-carboxylate Chemical compound BrC1=CC(=NC=C1)NC=1OC(=CN1)C(=O)OCC XSAVUNZYENKZAU-UHFFFAOYSA-N 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• 239000000194 fatty acid Substances 0.000 description 3
• 229930195729 fatty acid Natural products 0.000 description 3
• 239000008187 granular material Substances 0.000 description 3
• 208000015181 infectious disease Diseases 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
• PLDIAMANHQVSOP-UHFFFAOYSA-N methyl N-(4-bromopyridin-2-yl)carbamate Chemical compound BrC1=CC(=NC=C1)NC(OC)=O PLDIAMANHQVSOP-UHFFFAOYSA-N 0.000 description 3
• NAMRZWSNLHWGHO-UHFFFAOYSA-N n-(2-amino-5-bromopyridin-3-yl)methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC(Br)=CN=C1N NAMRZWSNLHWGHO-UHFFFAOYSA-N 0.000 description 3
• LFMGMKPLBDZJLP-UHFFFAOYSA-N n-(4-bromopyridin-2-yl)acetamide Chemical compound CC(=O)NC1=CC(Br)=CC=N1 LFMGMKPLBDZJLP-UHFFFAOYSA-N 0.000 description 3
• KBXDYISZXRQXMW-UHFFFAOYSA-N n-(4-bromopyridin-2-yl)cyclopropanecarboxamide Chemical compound BrC1=CC=NC(NC(=O)C2CC2)=C1 KBXDYISZXRQXMW-UHFFFAOYSA-N 0.000 description 3
• WEMICCVLQRGHBC-UHFFFAOYSA-N n-[5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]cyclopropanecarboxamide Chemical compound C1=C(B2OC(C)(C)C(C)(C)O2)C(C)=CN=C1NC(=O)C1CC1 WEMICCVLQRGHBC-UHFFFAOYSA-N 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• 201000002528 pancreatic cancer Diseases 0.000 description 3
• 208000008443 pancreatic carcinoma Diseases 0.000 description 3
• 229960001972 panitumumab Drugs 0.000 description 3
• 235000021317 phosphate Nutrition 0.000 description 3
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
• 238000000634 powder X-ray diffraction Methods 0.000 description 3
• 238000002360 preparation method Methods 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 239000012047 saturated solution Substances 0.000 description 3
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
• 235000010288 sodium nitrite Nutrition 0.000 description 3
• 239000008107 starch Substances 0.000 description 3
• NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 3
• 239000000829 suppository Substances 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
• 238000005406 washing Methods 0.000 description 3
• UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical group CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 3
• ZPWQJUMCZOZNQB-UHFFFAOYSA-N (5-bromopyridin-3-yl)-cyclopropylmethanone Chemical compound BrC1=CN=CC(C(=O)C2CC2)=C1 ZPWQJUMCZOZNQB-UHFFFAOYSA-N 0.000 description 2
• PPVMCMWRHQQOFE-LZCJLJQNSA-N (E)-3-(5-bromopyridin-3-yl)-1-(4-fluorophenyl)prop-2-en-1-one Chemical compound BrC=1C=C(C=NC1)/C=C/C(=O)C1=CC=C(C=C1)F PPVMCMWRHQQOFE-LZCJLJQNSA-N 0.000 description 2
• DEVUYWTZRXOMSI-UHFFFAOYSA-N (sulfamoylamino)benzene Chemical compound NS(=O)(=O)NC1=CC=CC=C1 DEVUYWTZRXOMSI-UHFFFAOYSA-N 0.000 description 2
• 0 *C(Nc1cc(-c2cnc(*s([n]3)(N4*CCC4)=O)c3c2C2*C2)ccn1)=O Chemical compound *C(Nc1cc(-c2cnc(*s([n]3)(N4*CCC4)=O)c3c2C2*C2)ccn1)=O 0.000 description 2
• SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
• LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 2
• KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 2
• ACTKAGSPIFDCMF-UHFFFAOYSA-N 1,3-oxazol-2-amine Chemical compound NC1=NC=CO1 ACTKAGSPIFDCMF-UHFFFAOYSA-N 0.000 description 2
• SVQGOJUBYPMYAV-UHFFFAOYSA-N 1-(4-bromopyridin-2-yl)-4-methylimidazo[4,5-c]pyridine Chemical compound BrC1=CC(=NC=C1)N1C=NC=2C(=NC=CC21)C SVQGOJUBYPMYAV-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• VTOMXVXQWHAJMY-UHFFFAOYSA-N 2,4-difluoro-n-[2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]benzenesulfonamide Chemical compound CC1=NC=C(B2OC(C)(C)C(C)(C)O2)C=C1NS(=O)(=O)C1=CC=C(F)C=C1F VTOMXVXQWHAJMY-UHFFFAOYSA-N 0.000 description 2
• JSWRVDNTKPAJLB-UHFFFAOYSA-N 2,4-difluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C(F)=C1 JSWRVDNTKPAJLB-UHFFFAOYSA-N 0.000 description 2
• DQCORRQVBKBFLB-UHFFFAOYSA-N 2,4-dimethylpyridine-3-sulfonamide Chemical compound CC1=CC=NC(C)=C1S(N)(=O)=O DQCORRQVBKBFLB-UHFFFAOYSA-N 0.000 description 2
• MPQHBWNDIOJYNP-UHFFFAOYSA-N 2,6-dimethylpyridine-3-carboxamide Chemical compound CC1=CC=C(C(N)=O)C(C)=N1 MPQHBWNDIOJYNP-UHFFFAOYSA-N 0.000 description 2
• PJGSLZLTBQSPOI-UHFFFAOYSA-N 2-(5-bromopyridin-3-yl)-1,2-thiazolidine 1,1-dioxide Chemical compound BrC=1C=NC=C(C1)N1S(CCC1)(=O)=O PJGSLZLTBQSPOI-UHFFFAOYSA-N 0.000 description 2
• IEPDTLRHISNBLB-UHFFFAOYSA-N 2-amino-5-bromopyridine-3-carboxylic acid Chemical compound NC1=NC=C(Br)C=C1C(O)=O IEPDTLRHISNBLB-UHFFFAOYSA-N 0.000 description 2
• XFEUCMSMNHQVAJ-UHFFFAOYSA-N 2-amino-5-bromopyridine-3-sulfonic acid Chemical compound NC1=NC=C(Br)C=C1S(O)(=O)=O XFEUCMSMNHQVAJ-UHFFFAOYSA-N 0.000 description 2
• VPCCSTKCGRUAQF-UHFFFAOYSA-N 2-amino-N-(1-bicyclo[1.1.1]pentanyl)-5-bromo-N-methylpyridine-3-carboxamide Chemical compound NC1=C(C(=O)N(C)C23CC(C2)C3)C=C(C=N1)Br VPCCSTKCGRUAQF-UHFFFAOYSA-N 0.000 description 2
• BXAHKRQLBBUNGK-UHFFFAOYSA-N 2-methyl-1,2,6-thiadiazinane 1,1-dioxide Chemical compound CN1CCCNS1(=O)=O BXAHKRQLBBUNGK-UHFFFAOYSA-N 0.000 description 2
• CMCPVHGIYCIIAX-UHFFFAOYSA-N 2-methyl-6-[2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]-1,2,6-thiadiazinane 1,1-dioxide Chemical compound CN1S(N(CCC1)C=1C(=NC=C(C1)B1OC(C(O1)(C)C)(C)C)C)(=O)=O CMCPVHGIYCIIAX-UHFFFAOYSA-N 0.000 description 2
• KSFORUTXEPGVOW-UHFFFAOYSA-N 2-phenylpyrimidin-4-amine Chemical compound NC1=CC=NC(C=2C=CC=CC=2)=N1 KSFORUTXEPGVOW-UHFFFAOYSA-N 0.000 description 2
• SOSPMXMEOFGPIM-UHFFFAOYSA-N 3,5-dibromopyridine Chemical compound BrC1=CN=CC(Br)=C1 SOSPMXMEOFGPIM-UHFFFAOYSA-N 0.000 description 2
• MTLLYIYLWHKZEN-UHFFFAOYSA-N 3-(benzenesulfonyl)-5-bromo-1H-pyrrolo[2,3-b]pyridine Chemical compound BrC=1C=C2C(=NC1)NC=C2S(=O)(=O)C2=CC=CC=C2 MTLLYIYLWHKZEN-UHFFFAOYSA-N 0.000 description 2
• YTEIHWVCQJZNEN-UHFFFAOYSA-N 3-pyridin-4-ylpyridine Chemical compound C1=CN=CC(C=2C=CN=CC=2)=C1 YTEIHWVCQJZNEN-UHFFFAOYSA-N 0.000 description 2
• AEYWBYHIMXSYEI-UHFFFAOYSA-N 5-bromo-2-(methylamino)pyridine-3-sulfonyl chloride Chemical compound CNC1=NC=C(Br)C=C1S(Cl)(=O)=O AEYWBYHIMXSYEI-UHFFFAOYSA-N 0.000 description 2
• PNSXWHZPEYYEBN-UHFFFAOYSA-N 5-bromo-2-chloro-4-methylpyridine-3-sulfonyl chloride Chemical compound BrC=1C(=C(C(=NC1)Cl)S(=O)(=O)Cl)C PNSXWHZPEYYEBN-UHFFFAOYSA-N 0.000 description 2
• WQIMBKKSDPMLLE-UHFFFAOYSA-N 5-bromo-2-ethylpyridin-3-amine Chemical compound CCC1=NC=C(Br)C=C1N WQIMBKKSDPMLLE-UHFFFAOYSA-N 0.000 description 2
• VUGXRWXIIOSMCF-UHFFFAOYSA-N 5-bromo-2-fluoropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC(Br)=CN=C1F VUGXRWXIIOSMCF-UHFFFAOYSA-N 0.000 description 2
• WOVLKYARFQYAMN-UHFFFAOYSA-N 5-bromo-2-methylpyridine-3-carboxylic acid Chemical compound CC1=NC=C(Br)C=C1C(O)=O WOVLKYARFQYAMN-UHFFFAOYSA-N 0.000 description 2
• FURYLVOQEVHNSE-UHFFFAOYSA-N 5-bromo-3-(2-methylpiperidin-1-yl)pyridine-2-carbonitrile Chemical compound BrC=1C=C(C(=NC1)C#N)N1C(CCCC1)C FURYLVOQEVHNSE-UHFFFAOYSA-N 0.000 description 2
• CGEDRSBMDJCUKO-UHFFFAOYSA-N 5-bromo-3-(cyclopropylmethoxy)-2-methylpyridine Chemical compound BrC=1C=C(C(=NC1)C)OCC1CC1 CGEDRSBMDJCUKO-UHFFFAOYSA-N 0.000 description 2
• RTFLWLRVBQGAPQ-UHFFFAOYSA-N 5-bromo-3-methylsulfonylpyridin-2-amine Chemical compound CS(=O)(=O)C1=CC(Br)=CN=C1N RTFLWLRVBQGAPQ-UHFFFAOYSA-N 0.000 description 2
• SMSUOOVCJYHRJW-UHFFFAOYSA-N 6-bromo-1-(cyclopropylmethyl)imidazo[4,5-b]pyridine Chemical compound BrC=1C=C2C(=NC1)N=CN2CC2CC2 SMSUOOVCJYHRJW-UHFFFAOYSA-N 0.000 description 2
• PCGRTLODNRIQLR-UHFFFAOYSA-N 6-bromo-2-cyclopropylsulfonylpyrazolo[4,3-b]pyridine Chemical compound BrC1=CC=2C(N=C1)=CN(N2)S(=O)(=O)C2CC2 PCGRTLODNRIQLR-UHFFFAOYSA-N 0.000 description 2
• UQGVKOABQVMENO-UHFFFAOYSA-N 6-bromo-2-methyl-1h-imidazo[4,5-b]pyridine Chemical compound C1=C(Br)C=C2NC(C)=NC2=N1 UQGVKOABQVMENO-UHFFFAOYSA-N 0.000 description 2
• 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 2
• QJXCAVMPOXHWPH-UHFFFAOYSA-N 7-bromo-2-methyl-3,4-dihydropyrido[2,3-e][1,2,4]thiadiazine 1,1-dioxide Chemical compound BrC1=CC2=C(NCN(S2(=O)=O)C)N=C1 QJXCAVMPOXHWPH-UHFFFAOYSA-N 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• FQPQOWSBGMKWRO-UHFFFAOYSA-N BrC1=CC(=[N+](C=C1)[O-])NC(C)=O Chemical compound BrC1=CC(=[N+](C=C1)[O-])NC(C)=O FQPQOWSBGMKWRO-UHFFFAOYSA-N 0.000 description 2
• ZQSJKGCYSAXQKL-UHFFFAOYSA-N C12(CC(C1)C2)N(C(=O)C=2C=C(C=NC2N(C)C)B(O)O)C Chemical compound C12(CC(C1)C2)N(C(=O)C=2C=C(C=NC2N(C)C)B(O)O)C ZQSJKGCYSAXQKL-UHFFFAOYSA-N 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• 101100270233 Dictyostelium discoideum arrH gene Proteins 0.000 description 2
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
• GUUVPOWQJOLRAS-UHFFFAOYSA-N Diphenyl disulfide Chemical compound C=1C=CC=CC=1SSC1=CC=CC=C1 GUUVPOWQJOLRAS-UHFFFAOYSA-N 0.000 description 2
• 101100520660 Drosophila melanogaster Poc1 gene Proteins 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 239000004705 High-molecular-weight polyethylene Substances 0.000 description 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
• 239000005517 L01XE01 - Imatinib Substances 0.000 description 2
• 239000002136 L01XE07 - Lapatinib Substances 0.000 description 2
• 239000005536 L01XE08 - Nilotinib Substances 0.000 description 2
• 239000003798 L01XE11 - Pazopanib Substances 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• 241000699660 Mus musculus Species 0.000 description 2
• KRTWZZIERITXLR-UHFFFAOYSA-N N-(1-bicyclo[1.1.1]pentanyl)-5-bromo-2-fluoro-N-methylpyridine-3-carboxamide Chemical compound C12(CC(C1)C2)N(C(C2=C(N=CC(=C2)Br)F)=O)C KRTWZZIERITXLR-UHFFFAOYSA-N 0.000 description 2
• OMKIOTCYFXYXNV-UHFFFAOYSA-N N-(4-bromopyridin-2-yl)-2-methyl-3-nitropyridin-4-amine Chemical compound BrC1=CC(=NC=C1)NC1=C(C(=NC=C1)C)[N+](=O)[O-] OMKIOTCYFXYXNV-UHFFFAOYSA-N 0.000 description 2
• PRVCJQHNMKVXRO-UHFFFAOYSA-N N-(4-bromopyridin-2-yl)-3-oxobutanamide Chemical compound BrC1=CC(=NC=C1)NC(CC(C)=O)=O PRVCJQHNMKVXRO-UHFFFAOYSA-N 0.000 description 2
• LPNXAPUVCMSTEM-UHFFFAOYSA-N N-(4-chloropyridin-2-yl)-2-methylpyrimidin-4-amine Chemical compound ClC1=CC(=NC=C1)NC1=NC(=NC=C1)C LPNXAPUVCMSTEM-UHFFFAOYSA-N 0.000 description 2
• PWUPPUBERIAYMS-UHFFFAOYSA-N N-(5-bromo-2,4-dimethylpyridin-3-yl)-2,4-difluorobenzenesulfonamide Chemical compound BrC=1C(=C(C(=NC1)C)NS(=O)(=O)C1=C(C=C(C=C1)F)F)C PWUPPUBERIAYMS-UHFFFAOYSA-N 0.000 description 2
• XAOHLXHJUIYNTF-UHFFFAOYSA-N N-(5-bromo-2-methyl-1-oxidopyridin-1-ium-3-yl)-2,4-difluorobenzenesulfonamide Chemical compound BrC=1C=C(C(=[N+](C1)[O-])C)NS(=O)(=O)C1=C(C=C(C=C1)F)F XAOHLXHJUIYNTF-UHFFFAOYSA-N 0.000 description 2
• HDXHBOUVXSFNJV-UHFFFAOYSA-N N-(5-bromo-2-methylpyridin-3-yl)-3,3-difluoroazetidine-1-carboxamide Chemical compound BrC=1C=C(C(=NC1)C)NC(=O)N1CC(C1)(F)F HDXHBOUVXSFNJV-UHFFFAOYSA-N 0.000 description 2
• NGHWQEFDZWWSLW-UHFFFAOYSA-N N-(5-bromopyridin-3-yl)-2,4-difluoro-N-methylbenzamide Chemical compound BrC=1C=C(C=NC1)N(C(C1=C(C=C(C=C1)F)F)=O)C NGHWQEFDZWWSLW-UHFFFAOYSA-N 0.000 description 2
• YGUYVTYVRXWTOJ-UHFFFAOYSA-N N-(5-bromopyridin-3-yl)-2,4-difluorobenzamide Chemical compound BrC=1C=C(C=NC1)NC(C1=C(C=C(C=C1)F)F)=O YGUYVTYVRXWTOJ-UHFFFAOYSA-N 0.000 description 2
• DMXAFYLVPUBJJA-UHFFFAOYSA-N N-[4-(2-cyclopropylsulfonylpyrazolo[4,3-b]pyridin-6-yl)pyridin-2-yl]acetamide Chemical compound C1(CC1)S(=O)(=O)N1N=C2C(N=CC(=C2)C2=CC(=NC=C2)NC(C)=O)=C1 DMXAFYLVPUBJJA-UHFFFAOYSA-N 0.000 description 2
• LWSVPXUPRRRYDG-UHFFFAOYSA-N N-[4-[1-(benzenesulfonyl)pyrrolo[3,2-b]pyridin-6-yl]pyridin-2-yl]acetamide Chemical compound C1(=CC=CC=C1)S(=O)(=O)N1C=CC2=NC=C(C=C21)C2=CC(=NC=C2)NC(C)=O LWSVPXUPRRRYDG-UHFFFAOYSA-N 0.000 description 2
• NXVTUYWYAKOGMS-UHFFFAOYSA-N N-[4-[3-(benzenesulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]pyridin-2-yl]acetamide Chemical compound C1(=CC=CC=C1)S(=O)(=O)C1=CNC2=NC=C(C=C21)C2=CC(=NC=C2)NC(C)=O NXVTUYWYAKOGMS-UHFFFAOYSA-N 0.000 description 2
• LMVKYSFJRVLXQV-UHFFFAOYSA-N N-[4-[3-(dimethylsulfamoyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]pyridin-2-yl]acetamide Chemical compound CN(S(=O)(=O)C1=CNC2=NC=C(C=C21)C2=CC(=NC=C2)NC(C)=O)C LMVKYSFJRVLXQV-UHFFFAOYSA-N 0.000 description 2
• NSOMIPRUYFQANJ-UHFFFAOYSA-N N-[4-[3-(pyrrolidin-1-ylmethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]pyridin-2-yl]acetamide Chemical compound N1(CCCC1)CC1=CNC2=NC=C(C=C21)C2=CC(=NC=C2)NC(C)=O NSOMIPRUYFQANJ-UHFFFAOYSA-N 0.000 description 2
• ZPGYUGAWJUVIKW-UHFFFAOYSA-N N-[4-[5-(1-bicyclo[1.1.1]pentanylsulfamoyl)-6-methylpyridin-3-yl]pyridin-2-yl]acetamide Chemical compound C12(CC(C1)C2)NS(=O)(=O)C=2C=C(C=NC2C)C2=CC(=NC=C2)NC(C)=O ZPGYUGAWJUVIKW-UHFFFAOYSA-N 0.000 description 2
• QXESFJPBQIJNRG-UHFFFAOYSA-N N-[4-[5-(cyclopropanecarbonyl)pyridin-3-yl]pyridin-2-yl]acetamide Chemical compound C1(CC1)C(=O)C=1C=C(C=NC1)C1=CC(=NC=C1)NC(C)=O QXESFJPBQIJNRG-UHFFFAOYSA-N 0.000 description 2
• YCAKSNBHAZQTCI-UHFFFAOYSA-N N-[4-[5-[(2-chloro-4-fluorophenyl)sulfonylamino]-6-methylpyridin-3-yl]pyridin-2-yl]acetamide Chemical compound ClC1=C(C=CC(=C1)F)S(=O)(=O)NC=1C=C(C=NC1C)C1=CC(=NC=C1)NC(C)=O YCAKSNBHAZQTCI-UHFFFAOYSA-N 0.000 description 2
• JGWXATAHBKXIAP-UHFFFAOYSA-N N-[4-[6-methyl-5-(2-oxo-1,3-diazinan-1-yl)pyridin-3-yl]pyridin-2-yl]acetamide Chemical compound CC1=C(C=C(C=N1)C1=CC(=NC=C1)NC(C)=O)N1C(NCCC1)=O JGWXATAHBKXIAP-UHFFFAOYSA-N 0.000 description 2
• OMISYSMIJLAHIY-UHFFFAOYSA-N N-[4-[8-[(2,4-difluorophenyl)sulfonylamino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]pyridin-2-yl]acetamide Chemical compound FC1=C(C=CC(=C1)F)S(=O)(=O)NC=1C=2N(C=C(C1)C1=CC(=NC=C1)NC(C)=O)N=CN2 OMISYSMIJLAHIY-UHFFFAOYSA-N 0.000 description 2
• 229930040373 Paraformaldehyde Natural products 0.000 description 2
• 108091000080 Phosphotransferase Proteins 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 2
• 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 2
• 101100520662 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PBA1 gene Proteins 0.000 description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
• RUNFBRJBLANXKA-UHFFFAOYSA-N [5-(azetidine-1-carbonyl)-6-methylpyridin-3-yl]boronic acid Chemical compound N1(CCC1)C(=O)C=1C=C(C=NC1C)B(O)O RUNFBRJBLANXKA-UHFFFAOYSA-N 0.000 description 2
• HZEMWTAHHQUTOA-UHFFFAOYSA-N [6-amino-5-[1-bicyclo[1.1.1]pentanyl(methyl)carbamoyl]pyridin-3-yl]boronic acid Chemical compound NC1=C(C=C(C=N1)B(O)O)C(N(C)C12CC(C1)C2)=O HZEMWTAHHQUTOA-UHFFFAOYSA-N 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• 239000000783 alginic acid Substances 0.000 description 2
• 229960001126 alginic acid Drugs 0.000 description 2
• 150000004781 alginic acids Chemical class 0.000 description 2
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
• NKZLZZFOPCGYKY-UHFFFAOYSA-N azetidin-1-yl-[2-methyl-5-[2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl]pyridin-3-yl]methanethione Chemical compound N1(CCC1)C(=S)C=1C=C(C=NC1C)C1=CC(=NC=C1)NC1=NC(=NC=C1)C NKZLZZFOPCGYKY-UHFFFAOYSA-N 0.000 description 2
• SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 229920002988 biodegradable polymer Polymers 0.000 description 2
• 239000004621 biodegradable polymer Substances 0.000 description 2
• 239000012472 biological sample Substances 0.000 description 2
• 239000004305 biphenyl Substances 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 2
• 235000019437 butane-1,3-diol Nutrition 0.000 description 2
• 150000003857 carboxamides Chemical class 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 230000006364 cellular survival Effects 0.000 description 2
• 229960005395 cetuximab Drugs 0.000 description 2
• 239000003610 charcoal Substances 0.000 description 2
• XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 2
• 238000004140 cleaning Methods 0.000 description 2
• 229940110456 cocoa butter Drugs 0.000 description 2
• 235000019868 cocoa butter Nutrition 0.000 description 2
• OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
• BERDEBHAJNAUOM-UHFFFAOYSA-N copper(i) oxide Chemical compound [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 2
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
• 235000005822 corn Nutrition 0.000 description 2
• 235000012343 cottonseed oil Nutrition 0.000 description 2
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 2
• ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 2
• PFWWSGFPICCWGU-UHFFFAOYSA-N cyclopropanesulfonyl chloride Chemical compound ClS(=O)(=O)C1CC1 PFWWSGFPICCWGU-UHFFFAOYSA-N 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• HQPCXBJVDSZYMM-UHFFFAOYSA-N dimethyl 2-(5-bromo-4-methyl-3-nitropyridin-2-yl)propanedioate Chemical compound BrC=1C(=C(C(=NC1)C(C(=O)OC)C(=O)OC)[N+](=O)[O-])C HQPCXBJVDSZYMM-UHFFFAOYSA-N 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 238000004090 dissolution Methods 0.000 description 2
• 239000008298 dragée Substances 0.000 description 2
• 239000006196 drop Substances 0.000 description 2
• 239000000890 drug combination Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 239000002702 enteric coating Substances 0.000 description 2
• 238000009505 enteric coating Methods 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• FYJIXXPWJDWVNW-UHFFFAOYSA-N ethyl N-(4-chloropyridin-2-yl)carbamate Chemical compound ClC1=CC(=NC=C1)NC(OCC)=O FYJIXXPWJDWVNW-UHFFFAOYSA-N 0.000 description 2
• MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 235000019197 fats Nutrition 0.000 description 2
• 150000004665 fatty acids Chemical class 0.000 description 2
• XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 238000007429 general method Methods 0.000 description 2
• 239000011521 glass Substances 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• 235000011187 glycerol Nutrition 0.000 description 2
• 201000010536 head and neck cancer Diseases 0.000 description 2
• 208000014829 head and neck neoplasm Diseases 0.000 description 2
• FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
• 210000000936 intestine Anatomy 0.000 description 2
• 229910052742 iron Inorganic materials 0.000 description 2
• 229960004891 lapatinib Drugs 0.000 description 2
• BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 238000002514 liquid chromatography mass spectrum Methods 0.000 description 2
• 239000008297 liquid dosage form Substances 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• AXEVDVLWIOCRRC-UHFFFAOYSA-N methyl 4-amino-6-bromopyrazolo[1,5-a]pyridine-3-carboxylate Chemical compound NC=1C=2N(C=C(C1)Br)N=CC2C(=O)OC AXEVDVLWIOCRRC-UHFFFAOYSA-N 0.000 description 2
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 2
• 239000004530 micro-emulsion Substances 0.000 description 2
• 230000003020 moisturizing effect Effects 0.000 description 2
• JFCHSQDLLFJHOA-UHFFFAOYSA-N n,n-dimethylsulfamoyl chloride Chemical compound CN(C)S(Cl)(=O)=O JFCHSQDLLFJHOA-UHFFFAOYSA-N 0.000 description 2
• CVFWTKBRRTYVHC-UHFFFAOYSA-N n-(3-chloropropyl)sulfamoyl chloride Chemical compound ClCCCNS(Cl)(=O)=O CVFWTKBRRTYVHC-UHFFFAOYSA-N 0.000 description 2
• BPINVZNJXFKXPJ-UHFFFAOYSA-N n-(5-bromopyridin-3-yl)benzamide Chemical compound BrC1=CN=CC(NC(=O)C=2C=CC=CC=2)=C1 BPINVZNJXFKXPJ-UHFFFAOYSA-N 0.000 description 2
• HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 description 2
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
• 239000000346 nonvolatile oil Substances 0.000 description 2
• 238000011580 nude mouse model Methods 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 239000004006 olive oil Substances 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 2
• 229920002866 paraformaldehyde Polymers 0.000 description 2
• CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 102000020233 phosphotransferase Human genes 0.000 description 2
• 229920001592 potato starch Polymers 0.000 description 2
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 2
• 229960004063 propylene glycol Drugs 0.000 description 2
• 238000005956 quaternization reaction Methods 0.000 description 2
• 239000011535 reaction buffer Substances 0.000 description 2
• 238000001953 recrystallisation Methods 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 239000008159 sesame oil Substances 0.000 description 2
• 235000011803 sesame oil Nutrition 0.000 description 2
• 238000009097 single-agent therapy Methods 0.000 description 2
• 150000003385 sodium Chemical class 0.000 description 2
• 239000001632 sodium acetate Substances 0.000 description 2
• 235000017281 sodium acetate Nutrition 0.000 description 2
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
• 239000008247 solid mixture Substances 0.000 description 2
• 241000894007 species Species 0.000 description 2
• VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical compound COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 2
• 206010041823 squamous cell carcinoma Diseases 0.000 description 2
• 150000003456 sulfonamides Chemical class 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• 230000004614 tumor growth Effects 0.000 description 2
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
• 238000010792 warming Methods 0.000 description 2
• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 2
• 229910052727 yttrium Inorganic materials 0.000 description 2
• JRHPOFJADXHYBR-HTQZYQBOSA-N (1r,2r)-1-n,2-n-dimethylcyclohexane-1,2-diamine Chemical compound CN[C@@H]1CCCC[C@H]1NC JRHPOFJADXHYBR-HTQZYQBOSA-N 0.000 description 1
• QOWBXWFYRXSBAS-UHFFFAOYSA-N (2,4-dimethoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C(OC)=C1 QOWBXWFYRXSBAS-UHFFFAOYSA-N 0.000 description 1
• JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
• JZKMIPDOAWBAHE-NVQRDWNXSA-N (2r,3r,4s,5r)-2-[6-[cyclohexyl(prop-2-enyl)amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N(CC=C)C3CCCCC3)=C2N=C1 JZKMIPDOAWBAHE-NVQRDWNXSA-N 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• HUPVIAINOSTNBJ-HWKANZROSA-N (e)-3-ethoxyprop-2-enenitrile Chemical compound CCO\C=C\C#N HUPVIAINOSTNBJ-HWKANZROSA-N 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• SJQBHNHASPQACB-UHFFFAOYSA-N 1,2-dimethoxyethene Chemical compound COC=COC SJQBHNHASPQACB-UHFFFAOYSA-N 0.000 description 1
• 229940058015 1,3-butylene glycol Drugs 0.000 description 1
• RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 1
• ZDPAWHACYDRYIW-UHFFFAOYSA-N 1-(4-fluorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(F)C=C1 ZDPAWHACYDRYIW-UHFFFAOYSA-N 0.000 description 1
• RQAVSDINDRNIKL-UHFFFAOYSA-N 1-chloro-3-isocyanatopropane Chemical compound ClCCCN=C=O RQAVSDINDRNIKL-UHFFFAOYSA-N 0.000 description 1
• DEHXIHUIYSXZNH-UHFFFAOYSA-N 1-chloro-4-(isothiocyanatomethyl)benzene Chemical compound ClC1=CC=C(CN=C=S)C=C1 DEHXIHUIYSXZNH-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• RMYQCXRSGWBYOX-UHFFFAOYSA-N 2,3-dihydroxy-1-(oxan-2-yl)propan-1-one Chemical compound O1C(CCCC1)C(=O)C(CO)O RMYQCXRSGWBYOX-UHFFFAOYSA-N 0.000 description 1
• PVJZBZSCGJAWNG-UHFFFAOYSA-N 2,4,6-trimethylbenzenesulfonyl chloride Chemical compound CC1=CC(C)=C(S(Cl)(=O)=O)C(C)=C1 PVJZBZSCGJAWNG-UHFFFAOYSA-N 0.000 description 1
• CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
• PCMMSLVJMKQWMQ-UHFFFAOYSA-N 2,4-dibromopyridine Chemical compound BrC1=CC=NC(Br)=C1 PCMMSLVJMKQWMQ-UHFFFAOYSA-N 0.000 description 1
• PTHLPYKPCQLAOF-UHFFFAOYSA-N 2,4-difluorobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(F)C=C1F PTHLPYKPCQLAOF-UHFFFAOYSA-N 0.000 description 1
• INVWHYJKLSRVJP-UHFFFAOYSA-N 2-(1-bicyclo[1.1.1]pentanyl)-5-bromopyridine-3-carboxamide Chemical compound C12(CC(C1)C2)C1=C(C(=O)N)C=C(C=N1)Br INVWHYJKLSRVJP-UHFFFAOYSA-N 0.000 description 1
• NNWUEBIEOFQMSS-UHFFFAOYSA-N 2-Methylpiperidine Chemical compound CC1CCCCN1 NNWUEBIEOFQMSS-UHFFFAOYSA-N 0.000 description 1
• FQLVTUWFVIPUOF-UHFFFAOYSA-N 2-amino-N-(1-bicyclo[1.1.1]pentanyl)-5-bromopyridine-3-carboxamide Chemical compound NC1=C(C(=O)NC23CC(C2)C3)C=C(C=N1)Br FQLVTUWFVIPUOF-UHFFFAOYSA-N 0.000 description 1
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 1
• SURKZMFXICWLHU-UHFFFAOYSA-N 2-bromo-4-chloropyridine Chemical compound ClC1=CC=NC(Br)=C1 SURKZMFXICWLHU-UHFFFAOYSA-N 0.000 description 1
• AZOXQBMBDRLSCQ-UHFFFAOYSA-N 2-bromo-5-chloropyridin-3-amine Chemical compound NC1=CC(Cl)=CN=C1Br AZOXQBMBDRLSCQ-UHFFFAOYSA-N 0.000 description 1
• LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 1
• BBVQDWDBTWSGHQ-UHFFFAOYSA-N 2-chloro-1,3-benzoxazole Chemical compound C1=CC=C2OC(Cl)=NC2=C1 BBVQDWDBTWSGHQ-UHFFFAOYSA-N 0.000 description 1
• FCFPJKHVCHKCMP-UHFFFAOYSA-N 2-chloro-4-fluorobenzenesulfonyl chloride Chemical compound FC1=CC=C(S(Cl)(=O)=O)C(Cl)=C1 FCFPJKHVCHKCMP-UHFFFAOYSA-N 0.000 description 1
• SZIFAVKTNFCBPC-UHFFFAOYSA-N 2-chloroethanol Chemical compound OCCCl SZIFAVKTNFCBPC-UHFFFAOYSA-N 0.000 description 1
• IIUUNXSYGPXQGX-UHFFFAOYSA-N 2-cyclopropylpyrimidin-4-amine Chemical compound NC1=CC=NC(C2CC2)=N1 IIUUNXSYGPXQGX-UHFFFAOYSA-N 0.000 description 1
• RVBFWXYFXKDVKG-UHFFFAOYSA-N 2-ethoxyprop-2-enenitrile Chemical compound CCOC(=C)C#N RVBFWXYFXKDVKG-UHFFFAOYSA-N 0.000 description 1
• BVKQLNXPPQEELX-UHFFFAOYSA-N 2-fluoro-4-iodo-5-methylpyridine Chemical compound CC1=CN=C(F)C=C1I BVKQLNXPPQEELX-UHFFFAOYSA-N 0.000 description 1
• AOSOZARHUJMBLZ-UHFFFAOYSA-N 2-fluoro-5-methylpyridine Chemical compound CC1=CC=C(F)N=C1 AOSOZARHUJMBLZ-UHFFFAOYSA-N 0.000 description 1
• PWMOQGXCXFHJMF-UHFFFAOYSA-N 2-methyl-3-nitropyridin-4-amine Chemical compound CC1=NC=CC(N)=C1[N+]([O-])=O PWMOQGXCXFHJMF-UHFFFAOYSA-N 0.000 description 1
• JRYYVMDEUJQWRO-UHFFFAOYSA-N 2-methylnicotinamide Chemical compound CC1=NC=CC=C1C(N)=O JRYYVMDEUJQWRO-UHFFFAOYSA-N 0.000 description 1
• GKVDLTTVBNOGNJ-UHFFFAOYSA-N 2-methylpyrimidin-4-amine Chemical compound CC1=NC=CC(N)=N1 GKVDLTTVBNOGNJ-UHFFFAOYSA-N 0.000 description 1
• FZIABZQRRYQFBB-UHFFFAOYSA-N 2-phenylpyridine-3-sulfonamide Chemical compound NS(=O)(=O)C1=CC=CN=C1C1=CC=CC=C1 FZIABZQRRYQFBB-UHFFFAOYSA-N 0.000 description 1
• BTMCCOMLYMKBFL-UHFFFAOYSA-N 2-propylpyrimidin-4-amine Chemical compound CCCC1=NC=CC(N)=N1 BTMCCOMLYMKBFL-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• CDBAEFXTCRKJPZ-UHFFFAOYSA-N 3,3-difluoroazetidine;hydron;chloride Chemical compound Cl.FC1(F)CNC1 CDBAEFXTCRKJPZ-UHFFFAOYSA-N 0.000 description 1
• JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
• XIRXNRUKEJDEGM-UHFFFAOYSA-N 3-(1,3-oxazol-2-yl)pyridin-2-amine Chemical compound O1C(=NC=C1)C=1C(=NC=CC=1)N XIRXNRUKEJDEGM-UHFFFAOYSA-N 0.000 description 1
• GPKDGVXBXQTHRY-UHFFFAOYSA-N 3-chloropropane-1-sulfonyl chloride Chemical compound ClCCCS(Cl)(=O)=O GPKDGVXBXQTHRY-UHFFFAOYSA-N 0.000 description 1
• RGDQRXPEZUNWHX-UHFFFAOYSA-N 3-methylpyridin-2-amine Chemical compound CC1=CC=CN=C1N RGDQRXPEZUNWHX-UHFFFAOYSA-N 0.000 description 1
• GVGBSVGEHHSTIB-UHFFFAOYSA-N 4-(cyclopropylmethyl)pyridine-2,3-diamine Chemical compound NC1=NC=CC(CC2CC2)=C1N GVGBSVGEHHSTIB-UHFFFAOYSA-N 0.000 description 1
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
• PTPTZLXZHPPVKG-UHFFFAOYSA-N 4-bromo-2-fluoropyridine Chemical compound FC1=CC(Br)=CC=N1 PTPTZLXZHPPVKG-UHFFFAOYSA-N 0.000 description 1
• LRTRXDSAJLSRTG-UHFFFAOYSA-N 4-bromobutanoyl chloride Chemical compound ClC(=O)CCCBr LRTRXDSAJLSRTG-UHFFFAOYSA-N 0.000 description 1
• IKKMKJOVXQEEHS-UHFFFAOYSA-N 4-chloro-6-methylpyridin-2-amine Chemical compound CC1=CC(Cl)=CC(N)=N1 IKKMKJOVXQEEHS-UHFFFAOYSA-N 0.000 description 1
• RQMWVVBHJMUJNZ-UHFFFAOYSA-N 4-chloropyridin-2-amine Chemical compound NC1=CC(Cl)=CC=N1 RQMWVVBHJMUJNZ-UHFFFAOYSA-N 0.000 description 1
• NNMYRMGMVLMQAY-UHFFFAOYSA-N 4-chloropyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC(Cl)=CC=N1 NNMYRMGMVLMQAY-UHFFFAOYSA-N 0.000 description 1
• SJWHILBZPGQBJE-UHFFFAOYSA-N 4-ethylpyridin-2-amine Chemical compound CCC1=CC=NC(N)=C1 SJWHILBZPGQBJE-UHFFFAOYSA-N 0.000 description 1
• HOMSJDBZHCPYHY-UHFFFAOYSA-N 4-fluoro-2,3-dihydroinden-1-one Chemical compound FC1=CC=CC2=C1CCC2=O HOMSJDBZHCPYHY-UHFFFAOYSA-N 0.000 description 1
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
• ICGLPKIVTVWCFT-UHFFFAOYSA-N 4-methylbenzenesulfonohydrazide Chemical compound CC1=CC=C(S(=O)(=O)NN)C=C1 ICGLPKIVTVWCFT-UHFFFAOYSA-N 0.000 description 1
• WJCIDYMLQBPVLE-UHFFFAOYSA-N 5-(2-acetamidopyridin-4-yl)-N-(1-bicyclo[1.1.1]pentanyl)-2-(dimethylamino)pyridine-3-carboxamide Chemical compound C(C)(=O)NC1=NC=CC(=C1)C=1C=NC(=C(C1)C(=O)NC12CC(C1)C2)N(C)C WJCIDYMLQBPVLE-UHFFFAOYSA-N 0.000 description 1
• BASYLPMLKGQZOG-UHFFFAOYSA-N 5-bromo-1h-pyrazolo[3,4-b]pyridine Chemical compound BrC1=CN=C2NN=CC2=C1 BASYLPMLKGQZOG-UHFFFAOYSA-N 0.000 description 1
• BLJOCKNDWUTFEN-UHFFFAOYSA-N 5-bromo-2-chloro-4-methyl-3-nitropyridine Chemical compound CC1=C(Br)C=NC(Cl)=C1[N+]([O-])=O BLJOCKNDWUTFEN-UHFFFAOYSA-N 0.000 description 1
• JLAAMVKIARIWSL-UHFFFAOYSA-N 5-bromo-2-chloro-n-cyclobutylpyridine-3-sulfonamide Chemical compound ClC1=NC=C(Br)C=C1S(=O)(=O)NC1CCC1 JLAAMVKIARIWSL-UHFFFAOYSA-N 0.000 description 1
• ZRVOONOBKHYCNV-UHFFFAOYSA-N 5-bromo-2-chloropyridine-3-sulfonyl chloride Chemical compound ClC1=NC=C(Br)C=C1S(Cl)(=O)=O ZRVOONOBKHYCNV-UHFFFAOYSA-N 0.000 description 1
• JDMZSVDTYPUKEX-UHFFFAOYSA-N 5-bromo-2-ethyl-3-nitropyridine Chemical compound CCC1=NC=C(Br)C=C1[N+]([O-])=O JDMZSVDTYPUKEX-UHFFFAOYSA-N 0.000 description 1
• HJOOFLFWIISCAI-UHFFFAOYSA-N 5-bromo-2-methoxypyridin-3-amine Chemical compound COC1=NC=C(Br)C=C1N HJOOFLFWIISCAI-UHFFFAOYSA-N 0.000 description 1
• ZVWLOUCMPVTUOY-UHFFFAOYSA-N 5-bromo-3-(pyrrolidin-1-ylmethyl)-1H-pyrrolo[2,3-b]pyridine Chemical compound BrC=1C=C2C(=NC1)NC=C2CN2CCCC2 ZVWLOUCMPVTUOY-UHFFFAOYSA-N 0.000 description 1
• HMURQOFNWZWERT-UHFFFAOYSA-N 5-bromo-3-fluoropyridine-2-carbonitrile Chemical compound FC1=CC(Br)=CN=C1C#N HMURQOFNWZWERT-UHFFFAOYSA-N 0.000 description 1
• YWTGVFDGOFXIPM-UHFFFAOYSA-N 5-bromo-n-methoxy-n-methylpyridine-3-carboxamide Chemical compound CON(C)C(=O)C1=CN=CC(Br)=C1 YWTGVFDGOFXIPM-UHFFFAOYSA-N 0.000 description 1
• NGUVGKAEOFPLDT-UHFFFAOYSA-N 5-bromopyridine-3-carbaldehyde Chemical compound BrC1=CN=CC(C=O)=C1 NGUVGKAEOFPLDT-UHFFFAOYSA-N 0.000 description 1
• FQIUCPGDKPXSLL-UHFFFAOYSA-N 5-bromopyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=CC(Br)=C1 FQIUCPGDKPXSLL-UHFFFAOYSA-N 0.000 description 1
• MAXBVGJEFDMHNV-UHFFFAOYSA-N 5-chloropyridin-2-amine Chemical compound NC1=CC=C(Cl)C=N1 MAXBVGJEFDMHNV-UHFFFAOYSA-N 0.000 description 1
• TUIDQYRZDZRHPQ-UHFFFAOYSA-N 5-chloropyridin-3-ol Chemical compound OC1=CN=CC(Cl)=C1 TUIDQYRZDZRHPQ-UHFFFAOYSA-N 0.000 description 1
• CBEAKBPDDGYXND-UHFFFAOYSA-N 5-pyridin-4-ylpyridine-3-carboxamide Chemical compound NC(=O)C1=CN=CC(C=2C=CN=CC=2)=C1 CBEAKBPDDGYXND-UHFFFAOYSA-N 0.000 description 1
• QUTSXTCRDNMESC-UHFFFAOYSA-N 6-bromo-1-(cyclopropylmethyl)pyrrolo[3,2-b]pyridine Chemical compound BrC=1C=C2C(=NC1)C=CN2CC2CC2 QUTSXTCRDNMESC-UHFFFAOYSA-N 0.000 description 1
• XPHWCAKVRKUXLK-UHFFFAOYSA-N 6-bromo-1h-imidazo[4,5-b]pyridine Chemical compound BrC1=CN=C2N=CNC2=C1 XPHWCAKVRKUXLK-UHFFFAOYSA-N 0.000 description 1
• FONNZZMIJPHSJP-UHFFFAOYSA-N 6-bromo-1h-pyrazolo[4,3-b]pyridine Chemical compound BrC1=CN=C2C=NNC2=C1 FONNZZMIJPHSJP-UHFFFAOYSA-N 0.000 description 1
• OJFFFCVPCVATIV-UHFFFAOYSA-N 6-bromo-1h-pyrrolo[3,2-b]pyridine Chemical compound BrC1=CN=C2C=CNC2=C1 OJFFFCVPCVATIV-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• ULXXDDBFHOBEHA-ONEGZZNKSA-N Afatinib Chemical compound N1=CN=C2C=C(OC3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ULXXDDBFHOBEHA-ONEGZZNKSA-N 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 101100025420 Arabidopsis thaliana XI-C gene Proteins 0.000 description 1
• 235000017060 Arachis glabrata Nutrition 0.000 description 1
• 244000105624 Arachis hypogaea Species 0.000 description 1
• 235000010777 Arachis hypogaea Nutrition 0.000 description 1
• 235000018262 Arachis monticola Nutrition 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 1
• 101000718601 Bacillus subtilis (strain 168) RNA polymerase sigma-E factor Proteins 0.000 description 1
• 101100488915 Bacillus subtilis (strain 168) yppE gene Proteins 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• SAMRRJILHLYVIO-UHFFFAOYSA-N BrC=1C=C(C(=NC=1)C)N1SN(CCC1)C Chemical compound BrC=1C=C(C(=NC=1)C)N1SN(CCC1)C SAMRRJILHLYVIO-UHFFFAOYSA-N 0.000 description 1
• 208000003174 Brain Neoplasms Diseases 0.000 description 1
• FZRNONMOZONJQG-UHFFFAOYSA-N C1(CC1)C1=NC=CC(=N1)NC1=NC=CC(=C1)B1OC(C(O1)(C)C)(C)C Chemical compound C1(CC1)C1=NC=CC(=N1)NC1=NC=CC(=C1)B1OC(C(O1)(C)C)(C)C FZRNONMOZONJQG-UHFFFAOYSA-N 0.000 description 1
• GKIADQVQEGUAIH-UHFFFAOYSA-N C1(CC1)CC=1C(=C(C(=NC=1)N)N)CC1CC1 Chemical compound C1(CC1)CC=1C(=C(C(=NC=1)N)N)CC1CC1 GKIADQVQEGUAIH-UHFFFAOYSA-N 0.000 description 1
• ZSOHNMRYIJXFLS-UHFFFAOYSA-N CC1=NC=C(C=C1)C2=CC(=NC=C2)NC3=NC(=NC=C3)C Chemical compound CC1=NC=C(C=C1)C2=CC(=NC=C2)NC3=NC(=NC=C3)C ZSOHNMRYIJXFLS-UHFFFAOYSA-N 0.000 description 1
• 101100324465 Caenorhabditis elegans arr-1 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 206010057248 Cell death Diseases 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 1
• 206010052360 Colorectal adenocarcinoma Diseases 0.000 description 1
• 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 1
• ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 1
• 240000008570 Digitaria exilis Species 0.000 description 1
• 235000005459 Digitaria exilis Nutrition 0.000 description 1
• 101710109733 ECF RNA polymerase sigma-E factor Proteins 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 241000206672 Gelidium Species 0.000 description 1
• 208000032612 Glial tumor Diseases 0.000 description 1
• 206010018338 Glioma Diseases 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 244000060234 Gmelina philippensis Species 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
• 101001095320 Homo sapiens Serine/threonine-protein phosphatase PP1-beta catalytic subunit Proteins 0.000 description 1
• 101000689199 Homo sapiens Src-like-adapter Proteins 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 208000008839 Kidney Neoplasms Diseases 0.000 description 1
• 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
• 239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
• 239000002118 L01XE12 - Vandetanib Substances 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 240000003183 Manihot esculenta Species 0.000 description 1
• 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 239000004909 Moisturizer Substances 0.000 description 1
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
• ZFJIXCDMHZEQIY-UHFFFAOYSA-N N-(1-bicyclo[1.1.1]pentanyl)-2,5-dichloropyridine-3-sulfonamide Chemical compound C12(CC(C1)C2)NS(=O)(=O)C=2C(=NC=C(C2)Cl)Cl ZFJIXCDMHZEQIY-UHFFFAOYSA-N 0.000 description 1
• UPTWIFSKYCUICE-UHFFFAOYSA-N N-(1-bicyclo[1.1.1]pentanyl)-5-bromo-2-(dimethylamino)-N-methylpyridine-3-carboxamide Chemical compound C12(CC(C1)C2)N(C(C2=C(N=CC(=C2)Br)N(C)C)=O)C UPTWIFSKYCUICE-UHFFFAOYSA-N 0.000 description 1
• RNJCKMHGCFURPU-UHFFFAOYSA-N N-(1-bicyclo[1.1.1]pentanyl)-5-bromo-2-(dimethylamino)pyridine-3-carboxamide Chemical compound C12(CC(C1)C2)NC(C2=C(N=CC(=C2)Br)N(C)C)=O RNJCKMHGCFURPU-UHFFFAOYSA-N 0.000 description 1
• SJLPCTURUVIQND-UHFFFAOYSA-N N-(1-bicyclo[1.1.1]pentanyl)-5-bromo-2-fluoropyridine-3-carboxamide Chemical compound C12(CC(C1)C2)NC(C2=C(N=CC(=C2)Br)F)=O SJLPCTURUVIQND-UHFFFAOYSA-N 0.000 description 1
• OREQJYUKFPADRG-UHFFFAOYSA-N N-(1-bicyclo[1.1.1]pentanyl)-5-chloro-2-methylpyridine-3-sulfonamide Chemical compound C12(CC(C1)C2)NS(=O)(=O)C=2C(=NC=C(C2)Cl)C OREQJYUKFPADRG-UHFFFAOYSA-N 0.000 description 1
• BKMSFOZFSOWSEP-UHFFFAOYSA-N N-(4-bromopyridin-2-yl)-1,3-oxazol-2-amine Chemical compound BrC1=CC(=NC=C1)NC=1OC=CN1 BKMSFOZFSOWSEP-UHFFFAOYSA-N 0.000 description 1
• IUBUAFVWNXWELZ-UHFFFAOYSA-N N-(4-chloro-5-fluoropyridin-2-yl)-2-methylpyrimidin-4-amine Chemical compound ClC1=CC(=NC=C1F)NC1=NC(=NC=C1)C IUBUAFVWNXWELZ-UHFFFAOYSA-N 0.000 description 1
• YQJRXDLABDSQMC-UHFFFAOYSA-N N-(4-chloropyridin-2-yl)-2-methoxypyrimidin-4-amine Chemical compound ClC1=CC(=NC=C1)NC1=NC(=NC=C1)OC YQJRXDLABDSQMC-UHFFFAOYSA-N 0.000 description 1
• GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
• LDUPIVXCCNMVPG-UHFFFAOYSA-N N-[2-chloro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]-2,4-difluorobenzenesulfonamide Chemical compound ClC1=NC=C(C(=C1NS(=O)(=O)C1=C(C=C(C=C1)F)F)C)B1OC(C(O1)(C)C)(C)C LDUPIVXCCNMVPG-UHFFFAOYSA-N 0.000 description 1
• NMUBLECCSXKUTB-UHFFFAOYSA-N N-[4-(2-methyl-1,1-dioxo-3,4-dihydropyrido[2,3-e][1,2,4]thiadiazin-7-yl)pyridin-2-yl]acetamide Chemical compound CN1S(C2=C(NC1)N=CC(=C2)C2=CC(=NC=C2)NC(C)=O)(=O)=O NMUBLECCSXKUTB-UHFFFAOYSA-N 0.000 description 1
• DKXGITBUJSVVNV-UHFFFAOYSA-N N-[4-(6-methyl-5-sulfamoylpyridin-3-yl)pyridin-2-yl]acetamide Chemical compound CC1=C(C=C(C=N1)C1=CC(=NC=C1)NC(C)=O)S(N)(=O)=O DKXGITBUJSVVNV-UHFFFAOYSA-N 0.000 description 1
• NXZZWGJETRFDHU-UHFFFAOYSA-N N-[4-[5-(8-fluoro-1,1-dioxo-3,4-dihydro-5,1lambda6,2-benzoxathiazepin-2-yl)pyridin-3-yl]pyridin-2-yl]acetamide Chemical compound FC1=CC2=C(OCCN(S2(=O)=O)C=2C=C(C=NC2)C2=CC(=NC=C2)NC(C)=O)C=C1 NXZZWGJETRFDHU-UHFFFAOYSA-N 0.000 description 1
• PWLVQVXQTFBKGU-UHFFFAOYSA-N N-[4-[5-(tert-butylsulfamoyl)-6-chloro-4-methylpyridin-3-yl]pyridin-2-yl]acetamide Chemical compound C(C)(C)(C)NS(=O)(=O)C=1C(=C(C=NC1Cl)C1=CC(=NC=C1)NC(C)=O)C PWLVQVXQTFBKGU-UHFFFAOYSA-N 0.000 description 1
• BZCNQOANJOIXBP-UHFFFAOYSA-N N-[4-[5-[(2,4-difluorophenyl)sulfonyl-(2-hydroxyethyl)amino]pyridin-3-yl]pyridin-2-yl]acetamide Chemical compound FC1=C(C=CC(=C1)F)S(=O)(=O)N(C=1C=C(C=NC1)C1=CC(=NC=C1)NC(C)=O)CCO BZCNQOANJOIXBP-UHFFFAOYSA-N 0.000 description 1
• IXOXCJQTOBWAKI-FARCUNLSSA-N N-[4-[5-[(E)-3-(4-fluorophenyl)-3-oxoprop-1-enyl]pyridin-3-yl]pyridin-2-yl]acetamide Chemical compound FC1=CC=C(C=C1)C(/C=C/C=1C=C(C=NC1)C1=CC(=NC=C1)NC(C)=O)=O IXOXCJQTOBWAKI-FARCUNLSSA-N 0.000 description 1
• QOSHBDGWRQBXFE-UHFFFAOYSA-N N-[4-[5-[cyclopropylsulfonyl(methyl)amino]-6-methylpyridin-3-yl]pyridin-2-yl]acetamide Chemical compound C1(CC1)S(=O)(=O)N(C=1C=C(C=NC1C)C1=CC(=NC=C1)NC(C)=O)C QOSHBDGWRQBXFE-UHFFFAOYSA-N 0.000 description 1
• NJFIWXMIPGGMPP-UHFFFAOYSA-N N-[4-[6-chloro-5-(2-hydroxyethylsulfamoyl)pyridin-3-yl]pyridin-2-yl]acetamide Chemical compound ClC1=C(C=C(C=N1)C1=CC(=NC=C1)NC(C)=O)S(NCCO)(=O)=O NJFIWXMIPGGMPP-UHFFFAOYSA-N 0.000 description 1
• LQVMJURNDSXAPM-UHFFFAOYSA-N N-[5-[2-[(2-cyclopropylpyrimidin-4-yl)amino]pyridin-4-yl]-2-methylpyridin-3-yl]-3,3-difluoroazetidine-1-carboxamide Chemical compound C1(CC1)C1=NC=CC(=N1)NC1=NC=CC(=C1)C=1C=NC(=C(C1)NC(=O)N1CC(C1)(F)F)C LQVMJURNDSXAPM-UHFFFAOYSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
• 240000007817 Olea europaea Species 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
• 229920002732 Polyanhydride Polymers 0.000 description 1
• 229920000954 Polyglycolide Polymers 0.000 description 1
• 229920001710 Polyorthoester Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 102000007327 Protamines Human genes 0.000 description 1
• 108010007568 Protamines Proteins 0.000 description 1
• 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
• 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 235000010575 Pueraria lobata Nutrition 0.000 description 1
• 108050006002 RNA polymerase sigma factor FliA Proteins 0.000 description 1
• 101710097492 RNA polymerase sigma factor RpoS Proteins 0.000 description 1
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
• 206010038389 Renal cancer Diseases 0.000 description 1
• 235000004443 Ricinus communis Nutrition 0.000 description 1
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
• 102100037764 Serine/threonine-protein phosphatase PP1-beta catalytic subunit Human genes 0.000 description 1
• XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
• 102100024519 Src-like-adapter Human genes 0.000 description 1
• SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
• 208000005718 Stomach Neoplasms Diseases 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 235000019486 Sunflower oil Nutrition 0.000 description 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
• 229910052776 Thorium Inorganic materials 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
• 108010046377 Whey Proteins Proteins 0.000 description 1
• MZLRLIAQRLDZPF-UHFFFAOYSA-N [2-benzylidene-4-[1,3-bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene]-1,3-dichlorocyclohexyl]-dicyclohexylphosphane Chemical compound CC1=C(C(=CC(=C1)C)C)N1C(N(CC1)C1=C(C=C(C=C1C)C)C)=C1C(C(C(CC1)(P(C1CCCCC1)C1CCCCC1)Cl)=CC1=CC=CC=C1)Cl MZLRLIAQRLDZPF-UHFFFAOYSA-N 0.000 description 1
• FQCLJBPBUGYVLJ-UHFFFAOYSA-N [4-[6-amino-5-(dimethylsulfamoyl)pyridin-3-yl]pyridin-2-yl] carbamate Chemical compound C(N)(OC1=NC=CC(=C1)C=1C=NC(=C(C=1)S(N(C)C)(=O)=O)N)=O FQCLJBPBUGYVLJ-UHFFFAOYSA-N 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• 239000003655 absorption accelerator Substances 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
• 229940063655 aluminum stearate Drugs 0.000 description 1
• DQPBABKTKYNPMH-UHFFFAOYSA-N amino hydrogen sulfate Chemical compound NOS(O)(=O)=O DQPBABKTKYNPMH-UHFFFAOYSA-N 0.000 description 1
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
• 235000011114 ammonium hydroxide Nutrition 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 125000003118 aryl group Chemical group 0.000 description 1
• 125000005228 aryl sulfonate group Chemical group 0.000 description 1
• 230000004900 autophagic degradation Effects 0.000 description 1
• 229960003005 axitinib Drugs 0.000 description 1
• RITAVMQDGBJQJZ-FMIVXFBMSA-N axitinib Chemical compound CNC(=O)C1=CC=CC=C1SC1=CC=C(C(\C=C\C=2N=CC=CC=2)=NN2)C2=C1 RITAVMQDGBJQJZ-FMIVXFBMSA-N 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 239000000440 bentonite Substances 0.000 description 1
• 229910000278 bentonite Inorganic materials 0.000 description 1
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
• PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
• 229960002903 benzyl benzoate Drugs 0.000 description 1
• PNPBGYBHLCEVMK-UHFFFAOYSA-N benzylidene(dichloro)ruthenium;tricyclohexylphosphanium Chemical compound Cl[Ru](Cl)=CC1=CC=CC=C1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1 PNPBGYBHLCEVMK-UHFFFAOYSA-N 0.000 description 1
• FCDPQMAOJARMTG-UHFFFAOYSA-M benzylidene-[1,3-bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene]-dichlororuthenium;tricyclohexylphosphanium Chemical compound C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1.CC1=CC(C)=CC(C)=C1N(CCN1C=2C(=CC(C)=CC=2C)C)C1=[Ru](Cl)(Cl)=CC1=CC=CC=C1 FCDPQMAOJARMTG-UHFFFAOYSA-M 0.000 description 1
• UNOMOKBVBBHHMU-UHFFFAOYSA-N benzylidene-dicyclohexyl-(4,4-dichlorocyclohexyl)-lambda5-phosphane ruthenium Chemical compound [Ru].ClC1(Cl)CCC(CC1)P(=Cc1ccccc1)(C1CCCCC1)C1CCCCC1 UNOMOKBVBBHHMU-UHFFFAOYSA-N 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 238000001574 biopsy Methods 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000001124 body fluid Anatomy 0.000 description 1
• 239000010839 body fluid Substances 0.000 description 1
• 230000036760 body temperature Effects 0.000 description 1
• 125000005621 boronate group Chemical class 0.000 description 1
• 125000005620 boronic acid group Chemical class 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 230000006652 catabolic pathway Effects 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• 201000010881 cervical cancer Diseases 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 description 1
• 239000004927 clay Substances 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 239000002285 corn oil Substances 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• NFAZOGXQOWEWBM-UHFFFAOYSA-N cyclobutanamine;hydrochloride Chemical compound Cl.NC1CCC1 NFAZOGXQOWEWBM-UHFFFAOYSA-N 0.000 description 1
• TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 description 1
• JMYVMOUINOAAPA-UHFFFAOYSA-N cyclopropanecarbaldehyde Chemical compound O=CC1CC1 JMYVMOUINOAAPA-UHFFFAOYSA-N 0.000 description 1
• JRYOZJIRAVZGMV-UHFFFAOYSA-N cyclopropanecarboximidamide;hydron;chloride Chemical compound Cl.NC(=N)C1CC1 JRYOZJIRAVZGMV-UHFFFAOYSA-N 0.000 description 1
• IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 1
• GUDMZGLFZNLYEY-UHFFFAOYSA-N cyclopropylmethanol Chemical compound OCC1CC1 GUDMZGLFZNLYEY-UHFFFAOYSA-N 0.000 description 1
• 231100000433 cytotoxic Toxicity 0.000 description 1
• 230000001472 cytotoxic effect Effects 0.000 description 1
• 229960002448 dasatinib Drugs 0.000 description 1
• 238000007405 data analysis Methods 0.000 description 1
• 238000013480 data collection Methods 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 1
• WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
• 235000019700 dicalcium phosphate Nutrition 0.000 description 1
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
• GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
• BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 1
• AXAZMDOAUQTMOW-UHFFFAOYSA-N dimethylzinc Chemical compound C[Zn]C AXAZMDOAUQTMOW-UHFFFAOYSA-N 0.000 description 1
• SBQIJPBUMNWUKN-UHFFFAOYSA-M diphenyliodanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.C=1C=CC=CC=1[I+]C1=CC=CC=C1 SBQIJPBUMNWUKN-UHFFFAOYSA-M 0.000 description 1
• GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
• 235000019797 dipotassium phosphate Nutrition 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• 230000008406 drug-drug interaction Effects 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 239000003221 ear drop Substances 0.000 description 1
• 229940047652 ear drops Drugs 0.000 description 1
• 239000003792 electrolyte Substances 0.000 description 1
• 239000012039 electrophile Substances 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 229940082789 erbitux Drugs 0.000 description 1
• 229940071111 erlotinib 25 mg Drugs 0.000 description 1
• 201000004101 esophageal cancer Diseases 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 239000012259 ether extract Substances 0.000 description 1
• PFHIAOXOWQOLLW-UHFFFAOYSA-N ethyl 2-[(2-bromopyridin-4-yl)amino]-1,3-oxazole-5-carboxylate Chemical compound BrC1=NC=CC(=C1)NC=1OC(=CN1)C(=O)OCC PFHIAOXOWQOLLW-UHFFFAOYSA-N 0.000 description 1
• UHUDJKCNXFBBHU-UHFFFAOYSA-N ethyl 2-amino-1,3-oxazole-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(N)O1 UHUDJKCNXFBBHU-UHFFFAOYSA-N 0.000 description 1
• 229940093499 ethyl acetate Drugs 0.000 description 1
• XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 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
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 125000001207 fluorophenyl group Chemical group 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 102000037865 fusion proteins Human genes 0.000 description 1
• 108020001507 fusion proteins Proteins 0.000 description 1
• 206010017758 gastric cancer Diseases 0.000 description 1
• 229940087158 gilotrif Drugs 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
• 229960002449 glycine Drugs 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 239000011984 grubbs catalyst Substances 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• 239000002638 heterogeneous catalyst Substances 0.000 description 1
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
• GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• 238000003384 imaging method Methods 0.000 description 1
• KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
• 229960002411 imatinib Drugs 0.000 description 1
• YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 1
• 238000009169 immunotherapy Methods 0.000 description 1
• 239000000411 inducer Substances 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
• 238000005342 ion exchange Methods 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 239000000644 isotonic solution Substances 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 201000010982 kidney cancer Diseases 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
• 239000006194 liquid suspension Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 238000004020 luminiscence type Methods 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 210000003712 lysosome Anatomy 0.000 description 1
• 230000001868 lysosomic effect Effects 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
• 239000000347 magnesium hydroxide Substances 0.000 description 1
• 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
• 239000000391 magnesium silicate Substances 0.000 description 1
• 235000019793 magnesium trisilicate Nutrition 0.000 description 1
• 229940099273 magnesium trisilicate Drugs 0.000 description 1
• 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
• VFZXMEQGIIWBFJ-UHFFFAOYSA-M magnesium;cyclopropane;bromide Chemical compound [Mg+2].[Br-].C1C[CH-]1 VFZXMEQGIIWBFJ-UHFFFAOYSA-M 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 108010082117 matrigel Proteins 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 239000000155 melt Substances 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 1
• NWYCAFBQGIOHDB-UHFFFAOYSA-N methyl N-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-2-yl]carbamate Chemical compound N1N=CC=2C1=NC=C(C2)C2=CC(=NC=C2)NC(OC)=O NWYCAFBQGIOHDB-UHFFFAOYSA-N 0.000 description 1
• LCGLNKUTAGEVQW-UHFFFAOYSA-N methyl monoether Natural products COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
• IMAKHNTVDGLIRY-UHFFFAOYSA-N methyl prop-2-ynoate Chemical compound COC(=O)C#C IMAKHNTVDGLIRY-UHFFFAOYSA-N 0.000 description 1
• 230000011987 methylation Effects 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 239000003094 microcapsule Substances 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 230000001333 moisturizer Effects 0.000 description 1
• CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
• PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 1
• QHJABUZHRJTCAR-UHFFFAOYSA-N n'-methylpropane-1,3-diamine Chemical compound CNCCCN QHJABUZHRJTCAR-UHFFFAOYSA-N 0.000 description 1
• APSPMQPBKCRLDJ-UHFFFAOYSA-N n-(4-chloropyridin-2-yl)cyclobutanecarboxamide Chemical compound ClC1=CC=NC(NC(=O)C2CCC2)=C1 APSPMQPBKCRLDJ-UHFFFAOYSA-N 0.000 description 1
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
• IFYDWYVPVAMGRO-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]tetradecanamide Chemical compound CCCCCCCCCCCCCC(=O)NCCCN(C)C IFYDWYVPVAMGRO-UHFFFAOYSA-N 0.000 description 1
• HUFOZJXAKZVRNJ-UHFFFAOYSA-N n-[3-[[2-[4-(4-acetylpiperazin-1-yl)-2-methoxyanilino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]phenyl]prop-2-enamide Chemical compound COC1=CC(N2CCN(CC2)C(C)=O)=CC=C1NC(N=1)=NC=C(C(F)(F)F)C=1NC1=CC=CC(NC(=O)C=C)=C1 HUFOZJXAKZVRNJ-UHFFFAOYSA-N 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
• DXTVLPGBNZIAMV-UHFFFAOYSA-N n-[5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide Chemical compound C1=NC(NC(=O)C)=CC(B2OC(C)(C)C(C)(C)O2)=C1C DXTVLPGBNZIAMV-UHFFFAOYSA-N 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-M nicotinate Chemical compound [O-]C(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-M 0.000 description 1
• 229960001346 nilotinib Drugs 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 235000015097 nutrients Nutrition 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 229940023490 ophthalmic product Drugs 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
• LVSJDHGRKAEGLX-UHFFFAOYSA-N oxolane;2,2,2-trifluoroacetic acid Chemical compound C1CCOC1.OC(=O)C(F)(F)F LVSJDHGRKAEGLX-UHFFFAOYSA-N 0.000 description 1
• 238000004806 packaging method and process Methods 0.000 description 1
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 229960000639 pazopanib Drugs 0.000 description 1
• 235000020232 peanut Nutrition 0.000 description 1
• 235000021400 peanut butter Nutrition 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 239000002745 poly(ortho ester) Substances 0.000 description 1
• 229920000058 polyacrylate Polymers 0.000 description 1
• 229920001451 polypropylene glycol Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 239000004302 potassium sorbate Substances 0.000 description 1
• 235000010241 potassium sorbate Nutrition 0.000 description 1
• 229940069338 potassium sorbate Drugs 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 229950008679 protamine sulfate Drugs 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 235000018102 proteins Nutrition 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 1
• 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
• 125000001453 quaternary ammonium group Chemical group 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 229950009855 rociletinib Drugs 0.000 description 1
• 229910052707 ruthenium Inorganic materials 0.000 description 1
• 210000003296 saliva Anatomy 0.000 description 1
• 210000000582 semen Anatomy 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 150000004760 silicates Chemical class 0.000 description 1
• RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
• 229910052710 silicon Inorganic materials 0.000 description 1
• 239000010703 silicon Substances 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 description 1
• 229940071536 silver acetate Drugs 0.000 description 1
• 208000000649 small cell carcinoma Diseases 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
• 235000009518 sodium iodide Nutrition 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• 229960003787 sorafenib Drugs 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 239000003206 sterilizing agent Substances 0.000 description 1
• 239000012258 stirred mixture Substances 0.000 description 1
• 201000011549 stomach cancer Diseases 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 238000000967 suction filtration Methods 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
• 239000002600 sunflower oil Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 229940120982 tarceva Drugs 0.000 description 1
• 229940069905 tasigna Drugs 0.000 description 1
• 230000009967 tasteless effect Effects 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• DRDVJQOGFWAVLH-UHFFFAOYSA-N tert-butyl n-hydroxycarbamate Chemical compound CC(C)(C)OC(=O)NO DRDVJQOGFWAVLH-UHFFFAOYSA-N 0.000 description 1
• YJBKVPRVZAQTPY-UHFFFAOYSA-J tetrachlorostannane;dihydrate Chemical compound O.O.Cl[Sn](Cl)(Cl)Cl YJBKVPRVZAQTPY-UHFFFAOYSA-J 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 201000002510 thyroid cancer Diseases 0.000 description 1
• 208000013077 thyroid gland carcinoma Diseases 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 102000027257 transmembrane receptors Human genes 0.000 description 1
• 108091008578 transmembrane receptors Proteins 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
• SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
• 201000005112 urinary bladder cancer Diseases 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• 229960000241 vandetanib Drugs 0.000 description 1
• UHTHHESEBZOYNR-UHFFFAOYSA-N vandetanib Chemical compound COC1=CC(C(/N=CN2)=N/C=3C(=CC(Br)=CC=3)F)=C2C=C1OCC1CCN(C)CC1 UHTHHESEBZOYNR-UHFFFAOYSA-N 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 239000003039 volatile agent Substances 0.000 description 1
• 229940069559 votrient Drugs 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000010497 wheat germ oil Substances 0.000 description 1
• 235000021119 whey protein Nutrition 0.000 description 1
• 210000002268 wool Anatomy 0.000 description 1
• 239000008096 xylene Substances 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1
• IKVDXUFZJARKPF-UHFFFAOYSA-M zinc;cyclopropane;bromide Chemical compound Br[Zn+].C1C[CH-]1 IKVDXUFZJARKPF-UHFFFAOYSA-M 0.000 description 1
• CZPRKINNVBONSF-UHFFFAOYSA-M zinc;dioxido(oxo)phosphanium Chemical compound [Zn+2].[O-][P+]([O-])=O CZPRKINNVBONSF-UHFFFAOYSA-M 0.000 description 1