JP2005534623A

JP2005534623A - Ｅｒｂファミリーの阻害剤並びにｒａｆ及び／又はｒａｓ阻害剤を投与することを含む癌の治療法

Ｅｒｂファミリーの阻害剤並びにｒａｆ及び／又はｒａｓ阻害剤を投与することを含む癌の治療法 Download PDF

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Publication number: JP2005534623A
Authority: JP; Japan
Prior art keywords: alkyl; group; inhibitor; substituted; halo
Prior art date: 2002-04-08
Legal status : Pending

Application number

JP2003583483A

Other languages

English (en)

Japanese (ja)

Other versions

JP2005534623A5 (https=

Inventor

スペクター，ネイル，リー

シア，ウェンル

Original Assignee

スミスクラインビーチャムコーポレーション

Priority date

2002-04-08

Filing date

2003-04-08

Publication date

2005-11-17

2003-04-08 Application filed by スミスクラインビーチャムコーポレーション filed Critical スミスクラインビーチャムコーポレーション

2005-11-17 Publication of JP2005534623A publication Critical patent/JP2005534623A/ja

2006-07-06 Publication of JP2005534623A5 publication Critical patent/JP2005534623A5/ja

Status Pending legal-status Critical Current

Links

239000003112 inhibitor Substances 0.000 title claims abstract description 112
238000000034 method Methods 0.000 title claims abstract description 72
206010028980 Neoplasm Diseases 0.000 title claims abstract description 66
201000011510 cancer Diseases 0.000 title claims abstract description 55
229940078123 Ras inhibitor Drugs 0.000 title claims abstract description 17
238000011282 treatment Methods 0.000 claims abstract description 59
241000124008 Mammalia Species 0.000 claims abstract description 43
-1 3 H -imidazolyl Chemical group 0.000 claims description 335
125000000217 alkyl group Chemical group 0.000 claims description 295
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 149
229910052739 hydrogen Inorganic materials 0.000 claims description 120
125000003545 alkoxy group Chemical group 0.000 claims description 118
239000001257 hydrogen Substances 0.000 claims description 98
150000003839 salts Chemical class 0.000 claims description 95
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 75
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 70
239000012453 solvate Substances 0.000 claims description 64
125000003282 alkyl amino group Chemical group 0.000 claims description 63
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 63
125000004093 cyano group Chemical group *C#N 0.000 claims description 55
150000002431 hydrogen Chemical class 0.000 claims description 55
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 52
229910052736 halogen Inorganic materials 0.000 claims description 52
150000002367 halogens Chemical class 0.000 claims description 52
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 46
229910052757 nitrogen Inorganic materials 0.000 claims description 45
125000001309 chloro group Chemical group Cl* 0.000 claims description 41
229940125431 BRAF inhibitor Drugs 0.000 claims description 34
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 34
125000001246 bromo group Chemical group Br* 0.000 claims description 33
102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 32
108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 32
YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims description 31
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 27
229930192474 thiophene Natural products 0.000 claims description 25
125000005236 alkanoylamino group Chemical group 0.000 claims description 23
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 23
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 21
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 19
125000004414 alkyl thio group Chemical group 0.000 claims description 18
125000001475 halogen functional group Chemical group 0.000 claims description 17
102000016914 ras Proteins Human genes 0.000 claims description 17
108010014186 ras Proteins Proteins 0.000 claims description 17
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 16
239000003814 drug Substances 0.000 claims description 16
238000004519 manufacturing process Methods 0.000 claims description 16
125000003342 alkenyl group Chemical group 0.000 claims description 15
239000003795 chemical substances by application Substances 0.000 claims description 15
125000001041 indolyl group Chemical group 0.000 claims description 15
125000004076 pyridyl group Chemical group 0.000 claims description 15
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 14
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 13
125000000304 alkynyl group Chemical group 0.000 claims description 13
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 12
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 12
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 11
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 11
125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 11
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 11
239000012830 cancer therapeutic Substances 0.000 claims description 10
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 9
230000001225 therapeutic effect Effects 0.000 claims description 8
238000002560 therapeutic procedure Methods 0.000 claims description 8
230000005764 inhibitory process Effects 0.000 claims description 4
238000011275 oncology therapy Methods 0.000 abstract 1
150000001875 compounds Chemical class 0.000 description 177
125000005843 halogen group Chemical group 0.000 description 128
125000003118 aryl group Chemical group 0.000 description 120
210000004027 cell Anatomy 0.000 description 111
125000001931 aliphatic group Chemical group 0.000 description 97
235000002639 sodium chloride Nutrition 0.000 description 95
125000000623 heterocyclic group Chemical group 0.000 description 83
125000001424 substituent group Chemical group 0.000 description 68
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 67
229910052799 carbon Inorganic materials 0.000 description 64
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 58
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 57
125000002887 hydroxy group Chemical group [H]O* 0.000 description 56
239000000203 mixture Substances 0.000 description 53
229910052717 sulfur Inorganic materials 0.000 description 52
229910052760 oxygen Inorganic materials 0.000 description 49
125000005842 heteroatom Chemical group 0.000 description 48
125000001072 heteroaryl group Chemical group 0.000 description 44
239000000243 solution Substances 0.000 description 44
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 40
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 40
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 36
125000001153 fluoro group Chemical group F* 0.000 description 31
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 29
150000001408 amides Chemical class 0.000 description 27
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
150000001412 amines Chemical class 0.000 description 26
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical group C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 24
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 24
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 24
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 23
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
238000001819 mass spectrum Methods 0.000 description 22
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 21
229940124530 sulfonamide Drugs 0.000 description 21
150000003456 sulfonamides Chemical class 0.000 description 21
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 20
230000000694 effects Effects 0.000 description 20
150000002240 furans Chemical class 0.000 description 20
239000008194 pharmaceutical composition Substances 0.000 description 20
239000000047 product Substances 0.000 description 20
239000007787 solid Substances 0.000 description 19
125000004122 cyclic group Chemical group 0.000 description 18
150000002148 esters Chemical class 0.000 description 18
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 16
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 15
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
125000004432 carbon atom Chemical group C* 0.000 description 14
235000019439 ethyl acetate Nutrition 0.000 description 14
108090000623 proteins and genes Proteins 0.000 description 14
150000003536 tetrazoles Chemical class 0.000 description 14
150000003852 triazoles Chemical class 0.000 description 14
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 13
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 13
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 13
125000000753 cycloalkyl group Chemical group 0.000 description 13
238000009472 formulation Methods 0.000 description 13
125000004043 oxo group Chemical group O=* 0.000 description 13
239000000843 powder Substances 0.000 description 13
102000004169 proteins and genes Human genes 0.000 description 13
150000003457 sulfones Chemical class 0.000 description 13
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 13
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical group C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 12
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 12
150000001721 carbon Chemical group 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 12
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 12
238000006467 substitution reaction Methods 0.000 description 12
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 11
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical group C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
238000005160 1H NMR spectroscopy Methods 0.000 description 11
MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical group C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 11
125000004423 acyloxy group Chemical group 0.000 description 11
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 11
230000014509 gene expression Effects 0.000 description 11
239000001301 oxygen Substances 0.000 description 11
239000002904 solvent Substances 0.000 description 11
IWOKCMBOJXYDEE-UHFFFAOYSA-N sulfinylmethane Chemical compound C=S=O IWOKCMBOJXYDEE-UHFFFAOYSA-N 0.000 description 11
150000003462 sulfoxides Chemical class 0.000 description 11
239000000725 suspension Substances 0.000 description 11
JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 10
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 10
IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 description 10
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 10
125000002252 acyl group Chemical group 0.000 description 10
RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 10
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 10
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 10
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 10
239000002953 phosphate buffered saline Substances 0.000 description 10
230000026731 phosphorylation Effects 0.000 description 10
238000006366 phosphorylation reaction Methods 0.000 description 10
238000002360 preparation method Methods 0.000 description 10
239000000741 silica gel Substances 0.000 description 10
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CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical compound C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 description 9
KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical compound O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 description 9
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AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 9
UNTNRNUQVKDIPV-UHFFFAOYSA-N 3h-dithiazole Chemical compound N1SSC=C1 UNTNRNUQVKDIPV-UHFFFAOYSA-N 0.000 description 9
KWIVRAVCZJXOQC-UHFFFAOYSA-N 3h-oxathiazole Chemical compound N1SOC=C1 KWIVRAVCZJXOQC-UHFFFAOYSA-N 0.000 description 9
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JZFICWYCTCCINF-UHFFFAOYSA-N Thiadiazin Chemical compound S=C1SC(C)NC(C)N1CCN1C(=S)SC(C)NC1C JZFICWYCTCCINF-UHFFFAOYSA-N 0.000 description 9
239000004480 active ingredient Substances 0.000 description 9
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 9
MNQDKWZEUULFPX-UHFFFAOYSA-M dithiazanine iodide Chemical compound [I-].S1C2=CC=CC=C2[N+](CC)=C1C=CC=CC=C1N(CC)C2=CC=CC=C2S1 MNQDKWZEUULFPX-UHFFFAOYSA-M 0.000 description 9
125000004175 fluorobenzyl group Chemical group 0.000 description 9
GMQOZFVOGGIFIX-UHFFFAOYSA-N oxathiazolidine Chemical compound C1COSN1 GMQOZFVOGGIFIX-UHFFFAOYSA-N 0.000 description 9
229920006395 saturated elastomer Polymers 0.000 description 9
239000000126 substance Substances 0.000 description 9
YGNGABUJMXJPIJ-UHFFFAOYSA-N thiatriazole Chemical compound C1=NN=NS1 YGNGABUJMXJPIJ-UHFFFAOYSA-N 0.000 description 9
IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 9
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 8
BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 8
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
241000282414 Homo sapiens Species 0.000 description 8
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125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
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238000004587 chromatography analysis Methods 0.000 description 8
125000000392 cycloalkenyl group Chemical group 0.000 description 8
150000002170 ethers Chemical class 0.000 description 8
239000012091 fetal bovine serum Substances 0.000 description 8
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239000012074 organic phase Substances 0.000 description 8
239000011780 sodium chloride Substances 0.000 description 8
239000003826 tablet Substances 0.000 description 8
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 8
238000001262 western blot Methods 0.000 description 8
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125000002947 alkylene group Chemical group 0.000 description 7
238000004458 analytical method Methods 0.000 description 7
230000000118 anti-neoplastic effect Effects 0.000 description 7
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125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
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230000003381 solubilizing effect Effects 0.000 description 7
239000011593 sulfur Substances 0.000 description 7
210000001519 tissue Anatomy 0.000 description 7
125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 6
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 6
108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 description 6
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101150018665 MAPK3 gene Proteins 0.000 description 6
102000001253 Protein Kinase Human genes 0.000 description 6
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230000004913 activation Effects 0.000 description 6
229910002091 carbon monoxide Inorganic materials 0.000 description 6
239000000460 chlorine Substances 0.000 description 6
230000007423 decrease Effects 0.000 description 6
229940121647 egfr inhibitor Drugs 0.000 description 6
238000001914 filtration Methods 0.000 description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 6
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125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 6
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PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 6
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