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

Info

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 (enExample

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
229910002027 silica gel Inorganic materials 0.000 description 10
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
BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 9
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
DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 description 9
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
108091054455 MAP kinase family Proteins 0.000 description 8
102000043136 MAP kinase family Human genes 0.000 description 8
150000004657 carbamic acid derivatives Chemical class 0.000 description 8
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
230000022131 cell cycle Effects 0.000 description 8
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
125000004433 nitrogen atom Chemical group N* 0.000 description 8
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
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 7
108091000080 Phosphotransferase Proteins 0.000 description 7
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 7
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 7
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
229940079593 drug Drugs 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
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 7
102000020233 phosphotransferase Human genes 0.000 description 7
BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical compound C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 description 7
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
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
101150018665 MAPK3 gene Proteins 0.000 description 6
102000001253 Protein Kinase Human genes 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
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
239000012528 membrane Substances 0.000 description 6
239000003921 oil Substances 0.000 description 6
230000002018 overexpression Effects 0.000 description 6
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 6
108060006633 protein kinase Proteins 0.000 description 6
PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 6
241000894007 species Species 0.000 description 6
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 6
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 6
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 5
JOSBKHSFMWFNIR-UHFFFAOYSA-N 4-methylbenzenesulfonic acid;hydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1 JOSBKHSFMWFNIR-UHFFFAOYSA-N 0.000 description 5
101710088194 Dehydrogenase Proteins 0.000 description 5
102100029974 GTPase HRas Human genes 0.000 description 5
101000584633 Homo sapiens GTPase HRas Proteins 0.000 description 5
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 5
229930182816 L-glutamine Natural products 0.000 description 5
101150024075 Mapk1 gene Proteins 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
125000005115 alkyl carbamoyl group Chemical group 0.000 description 5
229940034982 antineoplastic agent Drugs 0.000 description 5
229910052786 argon Inorganic materials 0.000 description 5
239000012298 atmosphere Substances 0.000 description 5
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 5
238000004113 cell culture Methods 0.000 description 5
230000004663 cell proliferation Effects 0.000 description 5
239000006071 cream Substances 0.000 description 5
201000010099 disease Diseases 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
239000000284 extract Substances 0.000 description 5
238000003780 insertion Methods 0.000 description 5
230000037431 insertion Effects 0.000 description 5
239000007788 liquid Substances 0.000 description 5
230000002438 mitochondrial effect Effects 0.000 description 5
125000002950 monocyclic group Chemical group 0.000 description 5
239000008188 pellet Substances 0.000 description 5
239000000546 pharmaceutical excipient Substances 0.000 description 5
230000035755 proliferation Effects 0.000 description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
108700042226 ras Genes Proteins 0.000 description 5
230000002829 reductive effect Effects 0.000 description 5
150000003335 secondary amines Chemical class 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
238000003756 stirring Methods 0.000 description 5
230000004083 survival effect Effects 0.000 description 5
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 4
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
HZKVHNJIBUDOPD-UHFFFAOYSA-N N-[5-(5-piperidin-4-yl-2-pyridin-4-ylfuran-3-yl)-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2CCNCC2)OC=1C1=CC=NC=C1 HZKVHNJIBUDOPD-UHFFFAOYSA-N 0.000 description 4
150000007945 N-acyl ureas Chemical class 0.000 description 4
MLSAQOINCGAULQ-UHFFFAOYSA-N N-{5-[2-{4-[2-(dimethylamino)ethoxy]phenyl}-4-(pyridin-4-yl)-1H-imidazol-5-yl]-2,3-dihydro-1H-inden-1-ylidene}hydroxylamine Chemical compound C1=CC(OCCN(C)C)=CC=C1C1=NC(C=2C=C3CCC(C3=CC=2)=NO)=C(C=2C=CN=CC=2)N1 MLSAQOINCGAULQ-UHFFFAOYSA-N 0.000 description 4
206010061902 Pancreatic neoplasm Diseases 0.000 description 4
239000012980 RPMI-1640 medium Substances 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
239000002253 acid Substances 0.000 description 4
125000003277 amino group Chemical group 0.000 description 4
235000011114 ammonium hydroxide Nutrition 0.000 description 4
239000002585 base Substances 0.000 description 4
239000011230 binding agent Substances 0.000 description 4
239000002775 capsule Substances 0.000 description 4
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 4
238000000576 coating method Methods 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
239000003937 drug carrier Substances 0.000 description 4
239000001963 growth medium Substances 0.000 description 4
125000001188 haloalkyl group Chemical group 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
150000002430 hydrocarbons Chemical group 0.000 description 4
JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 4
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 4
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
208000015486 malignant pancreatic neoplasm Diseases 0.000 description 4
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 4
231100000252 nontoxic Toxicity 0.000 description 4
230000003000 nontoxic effect Effects 0.000 description 4
235000019198 oils Nutrition 0.000 description 4
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 4
201000002528 pancreatic cancer Diseases 0.000 description 4
208000008443 pancreatic carcinoma Diseases 0.000 description 4
230000037361 pathway Effects 0.000 description 4
229920000642 polymer Polymers 0.000 description 4
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000011121 sodium hydroxide Nutrition 0.000 description 4
239000008107 starch Substances 0.000 description 4
235000019698 starch Nutrition 0.000 description 4
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 4
125000001544 thienyl group Chemical group 0.000 description 4
230000035899 viability Effects 0.000 description 4
LMXYVLFTZRPNRV-KMKOMSMNSA-N (3z)-3-[(3,5-dibromo-4-hydroxyphenyl)methylidene]-5-iodo-1h-indol-2-one Chemical compound C1=C(Br)C(O)=C(Br)C=C1\C=C/1C2=CC(I)=CC=C2NC\1=O LMXYVLFTZRPNRV-KMKOMSMNSA-N 0.000 description 3
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 3
125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 description 3
125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 3
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 3
125000005955 1H-indazolyl group Chemical group 0.000 description 3
ZDPSJASIRJASEV-UHFFFAOYSA-N 5-[2-[4-[2-(dimethylamino)ethoxy]phenyl]-5-pyridin-4-yl-1h-imidazol-4-yl]-2,3-dihydroinden-1-one Chemical compound C1=CC(OCCN(C)C)=CC=C1C1=NC(C=2C=C3CCC(=O)C3=CC=2)=C(C=2C=CN=CC=2)N1 ZDPSJASIRJASEV-UHFFFAOYSA-N 0.000 description 3
UVCWLJMIKDQVBS-UHFFFAOYSA-N 5-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]quinazolin-6-yl]furan-2-carbaldehyde;4-methylbenzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.FC1=CC=CC(COC=2C(=CC(NC=3C4=CC(=CC=C4N=CN=3)C=3OC(C=O)=CC=3)=CC=2)Cl)=C1 UVCWLJMIKDQVBS-UHFFFAOYSA-N 0.000 description 3
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 3
206010006187 Breast cancer Diseases 0.000 description 3
208000026310 Breast neoplasm Diseases 0.000 description 3
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 3
101710146526 Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 3
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
229930194542 Keto Natural products 0.000 description 3
229940124647 MEK inhibitor Drugs 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
KCVIVFUGMDCUHW-UHFFFAOYSA-N N-[5-[5-[1-[2-(4-chlorophenoxy)ethyl]piperidin-4-yl]-2-pyridin-4-ylfuran-3-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2CCN(CCOC=3C=CC(Cl)=CC=3)CC2)OC=1C1=CC=NC=C1 KCVIVFUGMDCUHW-UHFFFAOYSA-N 0.000 description 3
0 NC1=NC2=CI=*C=C2C(N[U])=N1 Chemical compound NC1=NC2=CI=*C=C2C(N[U])=N1 0.000 description 3
229940124158 Protease/peptidase inhibitor Drugs 0.000 description 3
239000012083 RIPA buffer Substances 0.000 description 3
GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 3
125000004442 acylamino group Chemical group 0.000 description 3
125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
150000008064 anhydrides Chemical class 0.000 description 3
230000006907 apoptotic process Effects 0.000 description 3
125000003435 aroyl group Chemical group 0.000 description 3
125000005333 aroyloxy group Chemical group 0.000 description 3
125000003710 aryl alkyl group Chemical group 0.000 description 3
125000004658 aryl carbonyl amino group Chemical group 0.000 description 3
125000005161 aryl oxy carbonyl group Chemical group 0.000 description 3
125000004104 aryloxy group Chemical group 0.000 description 3
238000003556 assay Methods 0.000 description 3
XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
125000002619 bicyclic group Chemical group 0.000 description 3
230000033228 biological regulation Effects 0.000 description 3
239000012267 brine Substances 0.000 description 3
KWEDUNSJJZVRKR-UHFFFAOYSA-N carbononitridic azide Chemical compound [N-]=[N+]=NC#N KWEDUNSJJZVRKR-UHFFFAOYSA-N 0.000 description 3
230000032823 cell division Effects 0.000 description 3
239000011248 coating agent Substances 0.000 description 3
239000002299 complementary DNA Substances 0.000 description 3
239000013058 crude material Substances 0.000 description 3
125000000000 cycloalkoxy group Chemical group 0.000 description 3
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
230000001086 cytosolic effect Effects 0.000 description 3
229940009976 deoxycholate Drugs 0.000 description 3
KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 3
125000004989 dicarbonyl group Chemical group 0.000 description 3
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 3
125000005879 dioxolanyl group Chemical group 0.000 description 3
239000007884 disintegrant Substances 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
230000003828 downregulation Effects 0.000 description 3
230000007717 exclusion Effects 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
125000002541 furyl group Chemical group 0.000 description 3
239000000499 gel Substances 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
239000008187 granular material Substances 0.000 description 3
238000000227 grinding Methods 0.000 description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
125000002346 iodo group Chemical group I* 0.000 description 3
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
125000000468 ketone group Chemical group 0.000 description 3
239000000314 lubricant Substances 0.000 description 3
238000002156 mixing Methods 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
125000001624 naphthyl group Chemical group 0.000 description 3
239000006072 paste Substances 0.000 description 3
239000000137 peptide hydrolase inhibitor Substances 0.000 description 3
238000000746 purification Methods 0.000 description 3
125000000714 pyrimidinyl group Chemical group 0.000 description 3
238000010992 reflux Methods 0.000 description 3
230000019491 signal transduction Effects 0.000 description 3
239000011775 sodium fluoride Substances 0.000 description 3
235000013024 sodium fluoride Nutrition 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
239000006188 syrup Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
238000011200 topical administration Methods 0.000 description 3
IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 3
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 3
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
239000001993 wax Substances 0.000 description 3
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 2
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
MYHBJJIFLLKXFR-UHFFFAOYSA-N 1-methoxyimino-2,3-dihydroindene-5-carbaldehyde Chemical compound O=CC1=CC=C2C(=NOC)CCC2=C1 MYHBJJIFLLKXFR-UHFFFAOYSA-N 0.000 description 2
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 2
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 2
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 2
MXLHVLGZXNCMKA-UHFFFAOYSA-N 5-[2-[4-[3-(dimethylamino)propoxy]phenyl]-5-pyridin-4-yl-1h-imidazol-4-yl]-2,3-dihydroinden-1-one Chemical compound C1=CC(OCCCN(C)C)=CC=C1C1=NC(C=2C=C3CCC(=O)C3=CC=2)=C(C=2C=CN=CC=2)N1 MXLHVLGZXNCMKA-UHFFFAOYSA-N 0.000 description 2
XQPZOUAAXRXPAM-UHFFFAOYSA-N 5-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]quinazolin-6-yl]furan-2-carbaldehyde Chemical compound FC1=CC=CC(COC=2C(=CC(NC=3C4=CC(=CC=C4N=CN=3)C=3OC(C=O)=CC=3)=CC=2)Cl)=C1 XQPZOUAAXRXPAM-UHFFFAOYSA-N 0.000 description 2
LRXSVYIRRDZVNQ-UHFFFAOYSA-N 5-pyridin-3-yl-1,3-dihydroindol-2-one Chemical compound C=1C=C2NC(=O)CC2=CC=1C1=CC=CN=C1 LRXSVYIRRDZVNQ-UHFFFAOYSA-N 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
244000215068 Acacia senegal Species 0.000 description 2
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
229920001817 Agar Polymers 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
238000009010 Bradford assay Methods 0.000 description 2
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 2
102000001301 EGF receptor Human genes 0.000 description 2
108060006698 EGF receptor Proteins 0.000 description 2
YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 2
YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 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
239000004471 Glycine Substances 0.000 description 2
102000009465 Growth Factor Receptors Human genes 0.000 description 2
108010009202 Growth Factor Receptors Proteins 0.000 description 2
229920000084 Gum arabic Polymers 0.000 description 2
238000009015 Human TaqMan MicroRNA Assay kit Methods 0.000 description 2
102000004877 Insulin Human genes 0.000 description 2
108090001061 Insulin Proteins 0.000 description 2
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
XNRVGTHNYCNCFF-UHFFFAOYSA-N Lapatinib ditosylate monohydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.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 XNRVGTHNYCNCFF-UHFFFAOYSA-N 0.000 description 2
108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 2
102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 2
102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
OMRXHUAFSSDKSO-UHFFFAOYSA-N N-[5-[5-[1-(2-methoxyethyl)piperidin-4-yl]-2-pyridin-4-ylfuran-3-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C1CN(CCOC)CCC1C1=CC(C=2C=C3CCC(C3=CC=2)=NO)=C(C=2C=CN=CC=2)O1 OMRXHUAFSSDKSO-UHFFFAOYSA-N 0.000 description 2
150000001204 N-oxides Chemical class 0.000 description 2
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
239000000020 Nitrocellulose Substances 0.000 description 2
229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
102000001788 Proto-Oncogene Proteins c-raf Human genes 0.000 description 2
108010029869 Proto-Oncogene Proteins c-raf Proteins 0.000 description 2
102000006382 Ribonucleases Human genes 0.000 description 2
108010083644 Ribonucleases Proteins 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
235000010489 acacia gum Nutrition 0.000 description 2
239000000205 acacia gum Substances 0.000 description 2
DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
239000013543 active substance Substances 0.000 description 2
208000009956 adenocarcinoma Diseases 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
239000008272 agar Substances 0.000 description 2
235000010419 agar Nutrition 0.000 description 2
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
239000002246 antineoplastic agent Substances 0.000 description 2
230000001640 apoptogenic effect Effects 0.000 description 2
125000005239 aroylamino group Chemical group 0.000 description 2
238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
239000000440 bentonite Substances 0.000 description 2
235000012216 bentonite Nutrition 0.000 description 2
229910000278 bentonite Inorganic materials 0.000 description 2
SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
125000005605 benzo group Chemical group 0.000 description 2
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
239000004305 biphenyl Substances 0.000 description 2
235000010290 biphenyl Nutrition 0.000 description 2
230000037396 body weight Effects 0.000 description 2
210000000481 breast Anatomy 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 2
239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
239000008112 carboxymethyl-cellulose Substances 0.000 description 2
230000030833 cell death Effects 0.000 description 2
230000010261 cell growth Effects 0.000 description 2
230000036755 cellular response Effects 0.000 description 2
206010008118 cerebral infarction Diseases 0.000 description 2
CWBLXJCKFLHZEE-UHFFFAOYSA-N chembl586863 Chemical compound C1=CC(OCCCN(C)C)=CC=C1C1=NC(C=2C=C3CCC(C3=CC=2)=NO)=C(C=2C=CN=CC=2)N1 CWBLXJCKFLHZEE-UHFFFAOYSA-N 0.000 description 2
238000000451 chemical ionisation Methods 0.000 description 2
238000002512 chemotherapy Methods 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
210000001072 colon Anatomy 0.000 description 2
239000003086 colorant Substances 0.000 description 2
238000001816 cooling Methods 0.000 description 2
125000004966 cyanoalkyl group Chemical group 0.000 description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
230000003831 deregulation Effects 0.000 description 2
125000004663 dialkyl amino group Chemical group 0.000 description 2
238000009826 distribution Methods 0.000 description 2
238000000132 electrospray ionisation Methods 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
238000011049 filling Methods 0.000 description 2
125000001207 fluorophenyl group Chemical group 0.000 description 2
239000006260 foam Substances 0.000 description 2
235000013355 food flavoring agent Nutrition 0.000 description 2
235000003599 food sweetener Nutrition 0.000 description 2
239000008103 glucose Substances 0.000 description 2
230000012010 growth Effects 0.000 description 2
239000003102 growth factor Substances 0.000 description 2
125000004438 haloalkoxy group Chemical group 0.000 description 2
150000004677 hydrates Chemical class 0.000 description 2
229960000890 hydrocortisone Drugs 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 2
125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 2
125000002883 imidazolyl group Chemical group 0.000 description 2
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
239000007924 injection Substances 0.000 description 2
238000002347 injection Methods 0.000 description 2
229940125396 insulin Drugs 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
230000000302 ischemic effect Effects 0.000 description 2
239000002502 liposome Substances 0.000 description 2
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
238000011068 loading method Methods 0.000 description 2
235000020121 low-fat milk Nutrition 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
238000005259 measurement Methods 0.000 description 2
239000002609 medium Substances 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
239000002207 metabolite Substances 0.000 description 2
150000004702 methyl esters Chemical class 0.000 description 2
125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
150000004682 monohydrates Chemical class 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
UHFPFDMMKYQMLC-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-iodoquinazolin-4-amine Chemical compound FC1=CC=CC(COC=2C(=CC(NC=3C4=CC(I)=CC=C4N=CN=3)=CC=2)Cl)=C1 UHFPFDMMKYQMLC-UHFFFAOYSA-N 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
PDUSWJORWQPNRP-UHFFFAOYSA-N n-propan-2-ylacetamide Chemical compound CC(C)NC(C)=O PDUSWJORWQPNRP-UHFFFAOYSA-N 0.000 description 2
230000001537 neural effect Effects 0.000 description 2
150000002825 nitriles Chemical class 0.000 description 2
229920001220 nitrocellulos Polymers 0.000 description 2
125000006574 non-aromatic ring group Chemical group 0.000 description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
239000002674 ointment Substances 0.000 description 2
125000001715 oxadiazolyl group Chemical group 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
239000012188 paraffin wax Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
239000002861 polymer material Substances 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 2
125000003373 pyrazinyl group Chemical group 0.000 description 2
USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 2
125000000168 pyrrolyl group Chemical group 0.000 description 2
238000011002 quantification Methods 0.000 description 2
102000009929 raf Kinases Human genes 0.000 description 2
108010077182 raf Kinases Proteins 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
230000021014 regulation of cell growth Effects 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
238000011160 research Methods 0.000 description 2
230000035945 sensitivity Effects 0.000 description 2
239000002893 slag Substances 0.000 description 2
239000002002 slurry Substances 0.000 description 2
RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 2
JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 2
239000007921 spray Substances 0.000 description 2
238000010186 staining Methods 0.000 description 2
239000000758 substrate Substances 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical class S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 description 2
239000003765 sweetening 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
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
125000003831 tetrazolyl group Chemical group 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
150000003568 thioethers Chemical class 0.000 description 2
125000005505 thiomorpholino group Chemical group 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
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
238000001890 transfection Methods 0.000 description 2
125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 2
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
239000002691 unilamellar liposome Substances 0.000 description 2
PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 2
CRYXXTXWUCPIMU-WNQIDUERSA-N (2s)-2-aminobutanediamide;phenol Chemical compound OC1=CC=CC=C1.NC(=O)[C@@H](N)CC(N)=O CRYXXTXWUCPIMU-WNQIDUERSA-N 0.000 description 1
MLLMAIJXIZOSFS-LURJTMIESA-N (2s)-n,n-dimethylpyrrolidine-2-carboxamide Chemical group CN(C)C(=O)[C@@H]1CCCN1 MLLMAIJXIZOSFS-LURJTMIESA-N 0.000 description 1
125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 description 1
125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 description 1
125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 1
125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
BVOMRRWJQOJMPA-UHFFFAOYSA-N 1,2,3-trithiane Chemical compound C1CSSSC1 BVOMRRWJQOJMPA-UHFFFAOYSA-N 0.000 description 1
VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical group C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
CSJXMGWIFCRNGY-UHFFFAOYSA-N 1-(1-methoxyimino-2,3-dihydroinden-5-yl)-2-pyridin-4-ylethane-1,2-diol Chemical compound C=1C=C2C(=NOC)CCC2=CC=1C(O)C(O)C1=CC=NC=C1 CSJXMGWIFCRNGY-UHFFFAOYSA-N 0.000 description 1
GUPVAYODPWPSIM-UHFFFAOYSA-N 1-(1-methoxyimino-2,3-dihydroinden-5-yl)-2-pyridin-4-ylethane-1,2-dione Chemical compound C=1C=C2C(=NOC)CCC2=CC=1C(=O)C(=O)C1=CC=NC=C1 GUPVAYODPWPSIM-UHFFFAOYSA-N 0.000 description 1
IJRGJHKHDNEQRY-UHFFFAOYSA-N 1-(2-methoxyethyl)piperidin-1-ium-4-carboxylate Chemical compound COCCN1CCC(C(O)=O)CC1 IJRGJHKHDNEQRY-UHFFFAOYSA-N 0.000 description 1
VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
QRKFHQZNHFPBTJ-UHFFFAOYSA-N 1-[3-[4-(1-hydroxyimino-2,3-dihydroinden-5-yl)-5-pyridin-4-ylfuran-2-yl]piperidin-1-yl]-2-morpholin-4-ylethanone Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2CN(CCC2)C(=O)CN2CCOCC2)OC=1C1=CC=NC=C1 QRKFHQZNHFPBTJ-UHFFFAOYSA-N 0.000 description 1
ZANXFLNJCSZDJV-UHFFFAOYSA-N 1-[4-[5-(1-hydroxyimino-2,3-dihydroinden-5-yl)-4-pyridin-4-ylfuran-2-yl]piperidin-1-yl]-2-morpholin-4-ylethanone Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1OC(C2CCN(CC2)C(=O)CN2CCOCC2)=CC=1C1=CC=NC=C1 ZANXFLNJCSZDJV-UHFFFAOYSA-N 0.000 description 1
AAHFONQSIRRSCN-UHFFFAOYSA-N 1-[4-[5-(1-hydroxyimino-2,3-dihydroinden-5-yl)-4-pyridin-4-ylfuran-2-yl]piperidin-1-yl]-2-piperazin-1-ylethanone Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1OC(C2CCN(CC2)C(=O)CN2CCNCC2)=CC=1C1=CC=NC=C1 AAHFONQSIRRSCN-UHFFFAOYSA-N 0.000 description 1
YWHIFFVKDRIAGU-UHFFFAOYSA-N 1-[4-[5-(1-hydroxyimino-2,3-dihydroinden-5-yl)-4-pyridin-4-ylfuran-2-yl]piperidin-1-yl]-2-piperidin-1-ylethanone Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1OC(C2CCN(CC2)C(=O)CN2CCCCC2)=CC=1C1=CC=NC=C1 YWHIFFVKDRIAGU-UHFFFAOYSA-N 0.000 description 1
125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
WUIJTQZXUURFQU-UHFFFAOYSA-N 1-methylsulfonylethene Chemical compound CS(=O)(=O)C=C WUIJTQZXUURFQU-UHFFFAOYSA-N 0.000 description 1
KKVYYGGCHJGEFJ-UHFFFAOYSA-N 1-n-(4-chlorophenyl)-6-methyl-5-n-[3-(7h-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine Chemical compound N=1C=CC2=C(NC=3C(=CC=CN=3)C=3C=4N=CNC=4N=CN=3)C(C)=CC=C2C=1NC1=CC=C(Cl)C=C1 KKVYYGGCHJGEFJ-UHFFFAOYSA-N 0.000 description 1
125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 1
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
JSDNWOUCHKCGBM-UHFFFAOYSA-N 2-(4-chlorophenoxy)acetaldehyde Chemical compound ClC1=CC=C(OCC=O)C=C1 JSDNWOUCHKCGBM-UHFFFAOYSA-N 0.000 description 1
QJVDELVLMBKOIP-UHFFFAOYSA-N 2-(dimethylamino)-1-[4-[4-(1-hydroxyimino-2,3-dihydroinden-5-yl)-5-pyridin-4-ylfuran-2-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)CN(C)C)CCC1C1=CC(C=2C=C3CCC(C3=CC=2)=NO)=C(C=2C=CN=CC=2)O1 QJVDELVLMBKOIP-UHFFFAOYSA-N 0.000 description 1
IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
KYSZSACCZCQBOT-UHFFFAOYSA-N 2-[4-[4-(1-methoxyimino-2,3-dihydroinden-5-yl)-5-pyridin-4-yl-1h-imidazol-2-yl]phenoxy]-n,n-dimethylethanamine Chemical compound C=1C=C2C(=NOC)CCC2=CC=1C=1N=C(C=2C=CC(OCCN(C)C)=CC=2)NC=1C1=CC=NC=C1 KYSZSACCZCQBOT-UHFFFAOYSA-N 0.000 description 1
JYRKSRMJTSHDDH-UHFFFAOYSA-N 2-[4-[5-(1-hydroxyimino-2,3-dihydroinden-5-yl)-4-pyridin-4-ylfuran-2-yl]piperidin-1-yl]acetonitrile Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1OC(C2CCN(CC#N)CC2)=CC=1C1=CC=NC=C1 JYRKSRMJTSHDDH-UHFFFAOYSA-N 0.000 description 1
OHTZWXWQCDKTCQ-UHFFFAOYSA-N 2-[4-[5-(1-hydroxyimino-2,3-dihydroinden-5-yl)-4-pyridin-4-ylfuran-2-yl]piperidin-1-yl]ethanol Chemical compound C1CN(CCO)CCC1C1=CC(C=2C=CN=CC=2)=C(C=2C=C3CCC(C3=CC=2)=NO)O1 OHTZWXWQCDKTCQ-UHFFFAOYSA-N 0.000 description 1
JGUKCUUOQNQOBB-UHFFFAOYSA-N 2-[[5-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]quinazolin-6-yl]furan-2-yl]methyl-(2-methylsulfonylethyl)amino]acetonitrile Chemical compound O1C(CN(CC#N)CCS(=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 JGUKCUUOQNQOBB-UHFFFAOYSA-N 0.000 description 1
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
FWMBEYDLDLJTDP-UHFFFAOYSA-N 2-iodoquinazoline Chemical class C1=CC=CC2=NC(I)=NC=C21 FWMBEYDLDLJTDP-UHFFFAOYSA-N 0.000 description 1
YSEFYOVWKJXNCH-UHFFFAOYSA-N 2-methoxyacetaldehyde Chemical compound COCC=O YSEFYOVWKJXNCH-UHFFFAOYSA-N 0.000 description 1
OPJKGTJXHVPYIM-UHFFFAOYSA-N 2-methylprop-2-enamide;phenol Chemical compound CC(=C)C(N)=O.OC1=CC=CC=C1 OPJKGTJXHVPYIM-UHFFFAOYSA-N 0.000 description 1
SDNXQWUJWNTDCC-UHFFFAOYSA-N 2-methylsulfonylethanamine Chemical compound CS(=O)(=O)CCN SDNXQWUJWNTDCC-UHFFFAOYSA-N 0.000 description 1
DHFKENKHVSIOCO-UHFFFAOYSA-N 2-propan-2-ylsulfonylethanamine;hydrochloride Chemical compound Cl.CC(C)S(=O)(=O)CCN DHFKENKHVSIOCO-UHFFFAOYSA-N 0.000 description 1
125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
QMEQBOSUJUOXMX-UHFFFAOYSA-N 2h-oxadiazine Chemical compound N1OC=CC=N1 QMEQBOSUJUOXMX-UHFFFAOYSA-N 0.000 description 1
KDQKHCKKBOMKLQ-UHFFFAOYSA-N 3-[(3,5-dibromo-4-hydroxyphenyl)methylidene]-5-(3-methylbutanoyl)-1h-indol-2-one Chemical compound C12=CC(C(=O)CC(C)C)=CC=C2NC(=O)C1=CC1=CC(Br)=C(O)C(Br)=C1 KDQKHCKKBOMKLQ-UHFFFAOYSA-N 0.000 description 1
JDWFRUYIIDYGAA-UHFFFAOYSA-N 3-[(3,5-dibromo-4-hydroxyphenyl)methylidene]-5-(pyridine-4-carbonyl)-1h-indol-2-one Chemical compound C1=C(Br)C(O)=C(Br)C=C1C=C1C2=CC(C(=O)C=3C=CN=CC=3)=CC=C2NC1=O JDWFRUYIIDYGAA-UHFFFAOYSA-N 0.000 description 1
CAEMFFVPJFULIV-UHFFFAOYSA-N 3-[(3,5-dibromo-4-hydroxyphenyl)methylidene]-5-pyridin-3-yl-1h-indol-2-one Chemical compound C1=C(Br)C(O)=C(Br)C=C1C=C1C2=CC(C=3C=NC=CC=3)=CC=C2NC1=O CAEMFFVPJFULIV-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
CBOKAZFQZOQTOC-UHFFFAOYSA-N 4-[2-(dimethylamino)ethoxy]benzaldehyde Chemical compound CN(C)CCOC1=CC=C(C=O)C=C1 CBOKAZFQZOQTOC-UHFFFAOYSA-N 0.000 description 1
ZYOHTXKOHWSJMZ-UHFFFAOYSA-N 4-[3-(dimethylamino)propoxy]benzaldehyde Chemical compound CN(C)CCCOC1=CC=C(C=O)C=C1 ZYOHTXKOHWSJMZ-UHFFFAOYSA-N 0.000 description 1
JVTKTAQKFYKAFR-UHFFFAOYSA-N 4-[4-(1-hydroxyimino-2,3-dihydroinden-5-yl)-5-pyridin-4-ylfuran-2-yl]piperidin-4-ol Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2(O)CCNCC2)OC=1C1=CC=NC=C1 JVTKTAQKFYKAFR-UHFFFAOYSA-N 0.000 description 1
BDAIUOPDSRAOKI-UHFFFAOYSA-N 4-chloro-6-iodoquinazoline Chemical compound C1=C(I)C=C2C(Cl)=NC=NC2=C1 BDAIUOPDSRAOKI-UHFFFAOYSA-N 0.000 description 1
125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 1
125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
JFRFROAKFMUGLR-UHFFFAOYSA-N 5-(2-methyl-1,3-thiazol-4-yl)-1,3-dihydroindol-2-one Chemical compound S1C(C)=NC(C=2C=C3CC(=O)NC3=CC=2)=C1 JFRFROAKFMUGLR-UHFFFAOYSA-N 0.000 description 1
ZSACGSRVFHVLJK-UHFFFAOYSA-N 5-(2-phenyl-5-pyridin-4-yl-1h-imidazol-4-yl)-2,3-dihydroinden-1-one Chemical compound C=1C=C2C(=O)CCC2=CC=1C=1N=C(C=2C=CC=CC=2)NC=1C1=CC=NC=C1 ZSACGSRVFHVLJK-UHFFFAOYSA-N 0.000 description 1
DAPDCLNXHFSYLO-UHFFFAOYSA-N 5-(2-pyridin-3-yl-5-pyridin-4-yl-1h-imidazol-4-yl)-2,3-dihydroinden-1-one Chemical compound C=1C=C2C(=O)CCC2=CC=1C=1N=C(C=2C=NC=CC=2)NC=1C1=CC=NC=C1 DAPDCLNXHFSYLO-UHFFFAOYSA-N 0.000 description 1
OOIAZINONBTABX-UHFFFAOYSA-N 5-(5-piperidin-4-yl-2-pyridin-4-ylfuran-3-yl)-2,3-dihydroinden-1-one Chemical compound C=1C=C2C(=O)CCC2=CC=1C=1C=C(C2CCNCC2)OC=1C1=CC=NC=C1 OOIAZINONBTABX-UHFFFAOYSA-N 0.000 description 1
KMGNGTFMPWKDRC-UHFFFAOYSA-N 5-[2-[4-(2-morpholin-4-ylethoxy)phenyl]-5-pyridin-4-yl-1h-imidazol-4-yl]-2,3-dihydroinden-1-one Chemical compound C=1C=C2C(=O)CCC2=CC=1C=1N=C(C=2C=CC(OCCN3CCOCC3)=CC=2)NC=1C1=CC=NC=C1 KMGNGTFMPWKDRC-UHFFFAOYSA-N 0.000 description 1
AZALJURLJNWAGN-UHFFFAOYSA-N 5-[5-[1-[2-(4-chlorophenoxy)ethyl]piperidin-4-yl]-2-pyridin-4-ylfuran-3-yl]-2,3-dihydroinden-1-one Chemical compound C1=CC(Cl)=CC=C1OCCN1CCC(C=2OC(=C(C=2)C=2C=C3CCC(=O)C3=CC=2)C=2C=CN=CC=2)CC1 AZALJURLJNWAGN-UHFFFAOYSA-N 0.000 description 1
KSONICAHAPRCMV-UHFFFAOYSA-N 5-bromo-2,3-dihydroinden-1-one Chemical compound BrC1=CC=C2C(=O)CCC2=C1 KSONICAHAPRCMV-UHFFFAOYSA-N 0.000 description 1
JAVMRYUQNRFNMQ-UHFFFAOYSA-N 5-bromo-n-methoxy-2,3-dihydroinden-1-imine Chemical compound BrC1=CC=C2C(=NOC)CCC2=C1 JAVMRYUQNRFNMQ-UHFFFAOYSA-N 0.000 description 1
FAIHEVFTQPMOLE-UHFFFAOYSA-N 5-iodo-1,3-dihydroindol-2-one Chemical compound IC1=CC=C2NC(=O)CC2=C1 FAIHEVFTQPMOLE-UHFFFAOYSA-N 0.000 description 1
FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
101150019464 ARAF gene Proteins 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
206010052747 Adenocarcinoma pancreas Diseases 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
102000051485 Bcl-2 family Human genes 0.000 description 1
108700038897 Bcl-2 family Proteins 0.000 description 1
GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
201000006474 Brain Ischemia Diseases 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 description 1
KPDKNBPAHYOKOG-UHFFFAOYSA-N C1CN(C)CCC1N(C)CC(OC=1C=2C=C3CCC(C3=CC=2)=NO)=CC=1C1=CC=NC=C1 Chemical compound C1CN(C)CCC1N(C)CC(OC=1C=2C=C3CCC(C3=CC=2)=NO)=CC=1C1=CC=NC=C1 KPDKNBPAHYOKOG-UHFFFAOYSA-N 0.000 description 1
AHEYGDPFPGKZDJ-UHFFFAOYSA-N C1CN(C)CCN1CC(=O)N1CC(C=2OC(=C(C=2)C=2C=C3CCC(C3=CC=2)=NO)C=2C=CN=CC=2)CCC1 Chemical compound C1CN(C)CCN1CC(=O)N1CC(C=2OC(=C(C=2)C=2C=C3CCC(C3=CC=2)=NO)C=2C=CN=CC=2)CCC1 AHEYGDPFPGKZDJ-UHFFFAOYSA-N 0.000 description 1
IYHRUBISIPZDIW-UHFFFAOYSA-N C1CN(C)CCN1CC1=CC(C=2C=CN=CC=2)=C(C=2C=C3CCC(C3=CC=2)=NO)O1 Chemical compound C1CN(C)CCN1CC1=CC(C=2C=CN=CC=2)=C(C=2C=C3CCC(C3=CC=2)=NO)O1 IYHRUBISIPZDIW-UHFFFAOYSA-N 0.000 description 1
CSGRUMKMBMMKDR-UHFFFAOYSA-N C1CN(CC)CCN1CC1=CC(C=2C=CN=CC=2)=C(C=2C=C3CCC(C3=CC=2)=NO)O1 Chemical compound C1CN(CC)CCN1CC1=CC(C=2C=CN=CC=2)=C(C=2C=C3CCC(C3=CC=2)=NO)O1 CSGRUMKMBMMKDR-UHFFFAOYSA-N 0.000 description 1
PQOMANPODNHARE-UHFFFAOYSA-N C1CN(CCO)CCN1CC1=CC(C=2C=CN=CC=2)=C(C=2C=C3CCC(C3=CC=2)=NO)O1 Chemical compound C1CN(CCO)CCN1CC1=CC(C=2C=CN=CC=2)=C(C=2C=C3CCC(C3=CC=2)=NO)O1 PQOMANPODNHARE-UHFFFAOYSA-N 0.000 description 1
ALXKTBIZECECSF-UHFFFAOYSA-N C1CN(CCOC)CCC1(O)C1=CC(C=2C=C3CCC(C3=CC=2)=NO)=C(C=2C=CN=CC=2)O1 Chemical compound C1CN(CCOC)CCC1(O)C1=CC(C=2C=C3CCC(C3=CC=2)=NO)=C(C=2C=CN=CC=2)O1 ALXKTBIZECECSF-UHFFFAOYSA-N 0.000 description 1
LZJQCWUGSQEFHA-UHFFFAOYSA-N C1CN(CCOC)CCN1CC1=CC(C=2C=CN=CC=2)=C(C=2C=C3CCC(C3=CC=2)=NO)O1 Chemical compound C1CN(CCOC)CCN1CC1=CC(C=2C=CN=CC=2)=C(C=2C=C3CCC(C3=CC=2)=NO)O1 LZJQCWUGSQEFHA-UHFFFAOYSA-N 0.000 description 1
OUPYNUUMQKBRBM-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C(=C(C=1)C=2C=CN=CC=2)OC=1CN(CC1)CCC1N1CCCC1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C(=C(C=1)C=2C=CN=CC=2)OC=1CN(CC1)CCC1N1CCCC1 OUPYNUUMQKBRBM-UHFFFAOYSA-N 0.000 description 1
SERGLEOUTQCZDJ-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C(=C(C=1)C=2C=CN=CC=2)OC=1CN1CCCC1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C(=C(C=1)C=2C=CN=CC=2)OC=1CN1CCCC1 SERGLEOUTQCZDJ-UHFFFAOYSA-N 0.000 description 1
CVAGRLJWSONJOD-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C(=C(C=1)C=2C=CN=CC=2)OC=1CN1CCCCC1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C(=C(C=1)C=2C=CN=CC=2)OC=1CN1CCCCC1 CVAGRLJWSONJOD-UHFFFAOYSA-N 0.000 description 1
UPTYLCYGLGBBLW-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C(=C(C=1)C=2C=CN=CC=2)OC=1CN1CCNCC1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C(=C(C=1)C=2C=CN=CC=2)OC=1CN1CCNCC1 UPTYLCYGLGBBLW-UHFFFAOYSA-N 0.000 description 1
XJHCAWMMDLDXDD-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C(=C(C=1)C=2C=CN=CC=2)OC=1CN1CCOCC1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C(=C(C=1)C=2C=CN=CC=2)OC=1CN1CCOCC1 XJHCAWMMDLDXDD-UHFFFAOYSA-N 0.000 description 1
WEQSMABWXSZBCX-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C(=C(C=1)C=2C=CN=CC=2)OC=1CN1CCS(=O)(=O)CC1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C(=C(C=1)C=2C=CN=CC=2)OC=1CN1CCS(=O)(=O)CC1 WEQSMABWXSZBCX-UHFFFAOYSA-N 0.000 description 1
ZNNNNNKYLJYWOH-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C(=C(C=1)C=2C=CN=CC=2)OC=1CNCCN1CCOCC1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C(=C(C=1)C=2C=CN=CC=2)OC=1CNCCN1CCOCC1 ZNNNNNKYLJYWOH-UHFFFAOYSA-N 0.000 description 1
RRUSNRKSYJZFMI-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C(=C(O1)C=2C=CN=CC=2)C=C1CN1CCCC1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C(=C(O1)C=2C=CN=CC=2)C=C1CN1CCCC1 RRUSNRKSYJZFMI-UHFFFAOYSA-N 0.000 description 1
FRGYVLQMRNMRMJ-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C(=C(O1)C=2C=CN=CC=2)C=C1CN1CCCCC1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C(=C(O1)C=2C=CN=CC=2)C=C1CN1CCCCC1 FRGYVLQMRNMRMJ-UHFFFAOYSA-N 0.000 description 1
IMHLXCWOHNQDNB-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C(=C(O1)C=2C=CN=CC=2)C=C1CN1CCNCC1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C(=C(O1)C=2C=CN=CC=2)C=C1CN1CCNCC1 IMHLXCWOHNQDNB-UHFFFAOYSA-N 0.000 description 1
XUZKCHWXGPOLAL-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C(=C(O1)C=2C=CN=CC=2)C=C1CN1CCS(=O)(=O)CC1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C(=C(O1)C=2C=CN=CC=2)C=C1CN1CCS(=O)(=O)CC1 XUZKCHWXGPOLAL-UHFFFAOYSA-N 0.000 description 1
KNSOKLXZIMKJGW-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2(O)CCN(CC3CC3)CC2)OC=1C1=CC=NC=C1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2(O)CCN(CC3CC3)CC2)OC=1C1=CC=NC=C1 KNSOKLXZIMKJGW-UHFFFAOYSA-N 0.000 description 1
SAANUQNXXHPBFA-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2CCN(CC2)C(=O)CCN2CCCCC2)OC=1C1=CC=NC=C1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2CCN(CC2)C(=O)CCN2CCCCC2)OC=1C1=CC=NC=C1 SAANUQNXXHPBFA-UHFFFAOYSA-N 0.000 description 1
OOJRPYIRIVXTFC-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2CCN(CC2)C2CCCC2)OC=1C1=CC=NC=C1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2CCN(CC2)C2CCCC2)OC=1C1=CC=NC=C1 OOJRPYIRIVXTFC-UHFFFAOYSA-N 0.000 description 1
BJSXGEKBPNNUMQ-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2CCN(CC3CC3)CC2)OC=1C1=CC=NC=C1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2CCN(CC3CC3)CC2)OC=1C1=CC=NC=C1 BJSXGEKBPNNUMQ-UHFFFAOYSA-N 0.000 description 1
TXKUQOKEQRBNNN-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2CCN(CCN3CCOCC3)CC2)OC=1C1=CC=NC=C1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2CCN(CCN3CCOCC3)CC2)OC=1C1=CC=NC=C1 TXKUQOKEQRBNNN-UHFFFAOYSA-N 0.000 description 1
LVUPQRROUUSZRZ-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2CN(CCC2)C(=O)CN2CCCC2)OC=1C1=CC=NC=C1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2CN(CCC2)C(=O)CN2CCCC2)OC=1C1=CC=NC=C1 LVUPQRROUUSZRZ-UHFFFAOYSA-N 0.000 description 1
KVCDECVDUCIYJV-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2CN(CCC2)C(=O)CN2CCCCC2)OC=1C1=CC=NC=C1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2CN(CCC2)C(=O)CN2CCCCC2)OC=1C1=CC=NC=C1 KVCDECVDUCIYJV-UHFFFAOYSA-N 0.000 description 1
GIWPLGGJGREFLF-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C=1OC(C2CCN(CC2)C2CCCC2)=CC=1C1=CC=NC=C1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1OC(C2CCN(CC2)C2CCCC2)=CC=1C1=CC=NC=C1 GIWPLGGJGREFLF-UHFFFAOYSA-N 0.000 description 1
PBDBDBYCZVYDOC-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C=1OC(C2CCN(CC3CC3)CC2)=CC=1C1=CC=NC=C1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1OC(C2CCN(CC3CC3)CC2)=CC=1C1=CC=NC=C1 PBDBDBYCZVYDOC-UHFFFAOYSA-N 0.000 description 1
UZVSJUYWNXGHFQ-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C=1OC(C2CCN(CCOC=3C=CC(Cl)=CC=3)CC2)=CC=1C1=CC=NC=C1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1OC(C2CCN(CCOC=3C=CC(Cl)=CC=3)CC2)=CC=1C1=CC=NC=C1 UZVSJUYWNXGHFQ-UHFFFAOYSA-N 0.000 description 1
DECDKZIDFUSEGQ-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C=1OC(CN(C)C)=CC=1C1=CC=NC=C1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1OC(CN(C)C)=CC=1C1=CC=NC=C1 DECDKZIDFUSEGQ-UHFFFAOYSA-N 0.000 description 1
IGNZAVOGUIFWKZ-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C=1OC(CN(C)CCOC)=CC=1C1=CC=NC=C1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1OC(CN(C)CCOC)=CC=1C1=CC=NC=C1 IGNZAVOGUIFWKZ-UHFFFAOYSA-N 0.000 description 1
BTBVJHCWUUDGJR-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C=1OC(CN(CC)CC)=CC=1C1=CC=NC=C1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1OC(CN(CC)CC)=CC=1C1=CC=NC=C1 BTBVJHCWUUDGJR-UHFFFAOYSA-N 0.000 description 1
QZHYFZMCRIBFOD-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C=1OC(CN(CCOC)C(C)C)=CC=1C1=CC=NC=C1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1OC(CN(CCOC)C(C)C)=CC=1C1=CC=NC=C1 QZHYFZMCRIBFOD-UHFFFAOYSA-N 0.000 description 1
TUDLZLOMMBDMPD-UHFFFAOYSA-N C=1C=C2C(=NO)CCC2=CC=1C=1OC(CNCCOC)=CC=1C1=CC=NC=C1 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1OC(CNCCOC)=CC=1C1=CC=NC=C1 TUDLZLOMMBDMPD-UHFFFAOYSA-N 0.000 description 1
VQBJMVRCTLBZSB-UHFFFAOYSA-N CN(C(C=C1)=C=O)C1=O Chemical compound CN(C(C=C1)=C=O)C1=O VQBJMVRCTLBZSB-UHFFFAOYSA-N 0.000 description 1
DOEJWPYGEYQYDC-UHFFFAOYSA-N CS(=O)(=O)NCCNN(C)CC(=O)N Chemical compound CS(=O)(=O)NCCNN(C)CC(=O)N DOEJWPYGEYQYDC-UHFFFAOYSA-N 0.000 description 1
LESVRDRPDYAYRW-XTCLZLMSSA-N CS(N(CC1)CC=C1c1cc(-c(cc2)cc(CC3)c2/C3=N/O)c(-c2ccncc2)[o]1)(=O)=O Chemical compound CS(N(CC1)CC=C1c1cc(-c(cc2)cc(CC3)c2/C3=N/O)c(-c2ccncc2)[o]1)(=O)=O LESVRDRPDYAYRW-XTCLZLMSSA-N 0.000 description 1
DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 1
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
102000053642 Catalytic RNA Human genes 0.000 description 1
108090000994 Catalytic RNA Proteins 0.000 description 1
102000000844 Cell Surface Receptors Human genes 0.000 description 1
108010001857 Cell Surface Receptors Proteins 0.000 description 1
206010008120 Cerebral ischaemia Diseases 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 1
208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
206010009944 Colon cancer Diseases 0.000 description 1
206010010904 Convulsion Diseases 0.000 description 1
229920001651 Cyanoacrylate Polymers 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
108020004414 DNA Proteins 0.000 description 1
230000004544 DNA amplification Effects 0.000 description 1
206010012289 Dementia Diseases 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
102100023266 Dual specificity mitogen-activated protein kinase kinase 2 Human genes 0.000 description 1
101710146529 Dual specificity mitogen-activated protein kinase kinase 2 Proteins 0.000 description 1
239000004278 EU approved seasoning Substances 0.000 description 1
241000792859 Enema Species 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
102000007317 Farnesyltranstransferase Human genes 0.000 description 1
108010007508 Farnesyltranstransferase Proteins 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
229910004373 HOAc Inorganic materials 0.000 description 1
206010019196 Head injury Diseases 0.000 description 1
208000010496 Heart Arrest Diseases 0.000 description 1
101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
206010020880 Hypertrophy Diseases 0.000 description 1
WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
239000007760 Iscove's Modified Dulbecco's Medium Substances 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
VLJNHYLEOZPXFW-BYPYZUCNSA-N L-prolinamide Chemical compound NC(=O)[C@@H]1CCCN1 VLJNHYLEOZPXFW-BYPYZUCNSA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
102000018697 Membrane Proteins Human genes 0.000 description 1
108010052285 Membrane Proteins Proteins 0.000 description 1
208000019695 Migraine disease Diseases 0.000 description 1
101100381978 Mus musculus Braf gene Proteins 0.000 description 1
208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
JECAEPVJIGSRRT-UHFFFAOYSA-N N'-hydroxy-2-[3-[4-(1-hydroxyimino-2,3-dihydroinden-5-yl)-5-pyridin-4-ylfuran-2-yl]piperidin-1-yl]ethanimidamide Chemical compound C1N(CC(=N)NO)CCCC1C1=CC(C=2C=C3CCC(C3=CC=2)=NO)=C(C=2C=CN=CC=2)O1 JECAEPVJIGSRRT-UHFFFAOYSA-N 0.000 description 1
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
ZVNHZLUWQFRVFQ-UHFFFAOYSA-N N-[2-[4-(1-hydroxyimino-2,3-dihydroinden-5-yl)-5-pyridin-4-yl-1H-imidazol-2-yl]-2-methylpropyl]-1-(2-methoxyethyl)piperidine-4-carboxamide Chemical compound C1CN(CCOC)CCC1C(=O)NCC(C)(C)C1=NC(C=2C=CN=CC=2)=C(C=2C=C3CCC(C3=CC=2)=NO)N1 ZVNHZLUWQFRVFQ-UHFFFAOYSA-N 0.000 description 1
KZSAHWNTHDQGCV-UHFFFAOYSA-N N-[2-[4-(1-hydroxyimino-2,3-dihydroinden-5-yl)-5-pyridin-4-yl-1H-imidazol-2-yl]-2-methylpropyl]methanesulfonamide Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1NC(C(C)(CNS(C)(=O)=O)C)=NC=1C1=CC=NC=C1 KZSAHWNTHDQGCV-UHFFFAOYSA-N 0.000 description 1
MNNXRVSQOABRRP-UHFFFAOYSA-N N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[2-[(2-methylsulfonylethylamino)methyl]-4-thiazolyl]-4-quinazolinamine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2C=C3C(NC=4C=C(Cl)C(OCC=5C=C(F)C=CC=5)=CC=4)=NC=NC3=CC=2)=C1 MNNXRVSQOABRRP-UHFFFAOYSA-N 0.000 description 1
VSBSSDLCXXCVJB-UHFFFAOYSA-N N-[5-(2-phenyl-5-pyridin-4-yl-1H-imidazol-4-yl)-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1N=C(C=2C=CC=CC=2)NC=1C1=CC=NC=C1 VSBSSDLCXXCVJB-UHFFFAOYSA-N 0.000 description 1
IGDWIDWJAUNPDV-UHFFFAOYSA-N N-[5-(2-pyridin-3-yl-5-pyridin-4-yl-1H-imidazol-4-yl)-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1N=C(C=2C=NC=CC=2)NC=1C1=CC=NC=C1 IGDWIDWJAUNPDV-UHFFFAOYSA-N 0.000 description 1
PUKFMGDWOKDNHW-UHFFFAOYSA-N N-[5-(5-piperidin-3-yl-2-pyridin-4-ylfuran-3-yl)-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2CNCCC2)OC=1C1=CC=NC=C1 PUKFMGDWOKDNHW-UHFFFAOYSA-N 0.000 description 1
BNJHWKKFYYOPQV-UHFFFAOYSA-N N-[5-(5-piperidin-4-yl-3-pyridin-4-ylfuran-2-yl)-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1OC(C2CCNCC2)=CC=1C1=CC=NC=C1 BNJHWKKFYYOPQV-UHFFFAOYSA-N 0.000 description 1
LDEBZDNGSPAYOQ-UHFFFAOYSA-N N-[5-[2-(1-amino-2-methylpropan-2-yl)-5-pyridin-4-yl-1H-imidazol-4-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound N1C(C(C)(CN)C)=NC(C=2C=C3CCC(C3=CC=2)=NO)=C1C1=CC=NC=C1 LDEBZDNGSPAYOQ-UHFFFAOYSA-N 0.000 description 1
YTEOFFUVEKHBLW-UHFFFAOYSA-N N-[5-[2-(aminomethyl)-5-pyridin-4-yl-1H-imidazol-4-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound N1C(CN)=NC(C=2C=C3CCC(C3=CC=2)=NO)=C1C1=CC=NC=C1 YTEOFFUVEKHBLW-UHFFFAOYSA-N 0.000 description 1
DWFBOJKMUCONPK-UHFFFAOYSA-N N-[5-[2-(morpholin-4-ylmethyl)-5-pyridin-4-yl-1H-imidazol-4-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C=1C=C2C(=NO)CCC2=CC=1C(=C(N1)C=2C=CN=CC=2)N=C1CN1CCOCC1 DWFBOJKMUCONPK-UHFFFAOYSA-N 0.000 description 1
YJQQPFBYMUMDGS-UHFFFAOYSA-N N-[5-[2-(piperazin-1-ylmethyl)-5-pyridin-4-yl-1H-imidazol-4-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound ON=C1CCC2=C1C=CC(=C2)C1=C(NC(CN2CCNCC2)=N1)C1=CC=NC=C1 YJQQPFBYMUMDGS-UHFFFAOYSA-N 0.000 description 1
HQZZRVSKPSGKFE-UHFFFAOYSA-N N-[5-[2-(piperidin-1-ylmethyl)-5-pyridin-4-yl-1H-imidazol-4-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C=1C=C2C(=NO)CCC2=CC=1C(=C(N1)C=2C=CN=CC=2)N=C1CN1CCCCC1 HQZZRVSKPSGKFE-UHFFFAOYSA-N 0.000 description 1
FHLPPWQXRSKHLJ-UHFFFAOYSA-N N-[5-[2-[1-(2-methoxyethyl)piperidin-4-yl]-5-pyridin-4-yl-1H-imidazol-4-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C1CN(CCOC)CCC1C1=NC(C=2C=C3CCC(C3=CC=2)=NO)=C(C=2C=CN=CC=2)N1 FHLPPWQXRSKHLJ-UHFFFAOYSA-N 0.000 description 1
YRMBBLQDCUURLF-UHFFFAOYSA-N N-[5-[2-[1-(furan-3-ylmethyl)piperidin-4-yl]-5-pyridin-4-yl-1H-imidazol-4-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1N=C(C2CCN(CC3=COC=C3)CC2)NC=1C1=CC=NC=C1 YRMBBLQDCUURLF-UHFFFAOYSA-N 0.000 description 1
IJXXLTWGLMEGQQ-UHFFFAOYSA-N N-[5-[2-[4-(2-morpholin-4-ylethoxy)phenyl]-5-pyridin-4-yl-1H-imidazol-4-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1N=C(C=2C=CC(OCCN3CCOCC3)=CC=2)NC=1C1=CC=NC=C1 IJXXLTWGLMEGQQ-UHFFFAOYSA-N 0.000 description 1
BPNHLQASGDPOFO-UHFFFAOYSA-N N-[5-[2-pyridin-4-yl-5-(1,2,3,6-tetrahydropyridin-4-yl)furan-3-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C=2CCNCC=2)OC=1C1=CC=NC=C1 BPNHLQASGDPOFO-UHFFFAOYSA-N 0.000 description 1
ULLLBNBPVZKSOP-UHFFFAOYSA-N N-[5-[5-(1-methylpiperidin-3-yl)-2-pyridin-4-ylfuran-3-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C1N(C)CCCC1C1=CC(C=2C=C3CCC(C3=CC=2)=NO)=C(C=2C=CN=CC=2)O1 ULLLBNBPVZKSOP-UHFFFAOYSA-N 0.000 description 1
OEBDODFRQVBWPC-UHFFFAOYSA-N N-[5-[5-(1-methylsulfonylpiperidin-4-yl)-2-pyridin-4-ylfuran-3-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C1CN(S(=O)(=O)C)CCC1C1=CC(C=2C=C3CCC(C3=CC=2)=NO)=C(C=2C=CN=CC=2)O1 OEBDODFRQVBWPC-UHFFFAOYSA-N 0.000 description 1
YXUHCEFKIVTBRQ-UHFFFAOYSA-N N-[5-[5-(morpholin-4-ylmethyl)-2-pyridin-4-ylfuran-3-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C=1C=C2C(=NO)CCC2=CC=1C(=C(O1)C=2C=CN=CC=2)C=C1CN1CCOCC1 YXUHCEFKIVTBRQ-UHFFFAOYSA-N 0.000 description 1
YJFJSGLNANSAJX-UHFFFAOYSA-N N-[5-[5-(piperidin-1-ylmethyl)-2-pyrimidin-4-ylfuran-3-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C=1C=C2C(=NO)CCC2=CC=1C(=C(O1)C=2N=CN=CC=2)C=C1CN1CCCCC1 YJFJSGLNANSAJX-UHFFFAOYSA-N 0.000 description 1
CMQDCGIEGQMNQG-UHFFFAOYSA-N N-[5-[5-[(2-methoxyethylamino)methyl]-2-pyridin-4-ylfuran-3-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound O1C(CNCCOC)=CC(C=2C=C3CCC(C3=CC=2)=NO)=C1C1=CC=NC=C1 CMQDCGIEGQMNQG-UHFFFAOYSA-N 0.000 description 1
XYXUFZYZJLCRBZ-UHFFFAOYSA-N N-[5-[5-[1-(2-methoxyethyl)piperidin-3-yl]-2-pyridin-4-ylfuran-3-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C1N(CCOC)CCCC1C1=CC(C=2C=C3CCC(C3=CC=2)=NO)=C(C=2C=CN=CC=2)O1 XYXUFZYZJLCRBZ-UHFFFAOYSA-N 0.000 description 1
UQGWUXDYJBLBBA-UHFFFAOYSA-N N-[5-[5-[1-(cyclopropylmethyl)piperidin-3-yl]-2-pyridin-4-ylfuran-3-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1C=C(C2CN(CC3CC3)CCC2)OC=1C1=CC=NC=C1 UQGWUXDYJBLBBA-UHFFFAOYSA-N 0.000 description 1
HMJDHFZIVQBUFB-UHFFFAOYSA-N N-[5-[5-[[[1-(2-methoxyethyl)piperidin-4-yl]amino]methyl]-3-pyridin-4-ylfuran-2-yl]-2,3-dihydroinden-1-ylidene]hydroxylamine Chemical compound C1CN(CCOC)CCC1NCC1=CC(C=2C=CN=CC=2)=C(C=2C=C3CCC(C3=CC=2)=NO)O1 HMJDHFZIVQBUFB-UHFFFAOYSA-N 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
DYYZXRCFCVDSKD-UHFFFAOYSA-N N6,N6-dimethyl-N4-[1-(phenylmethyl)-5-indazolyl]pyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 DYYZXRCFCVDSKD-UHFFFAOYSA-N 0.000 description 1
BJLDRONFCLKRLI-UHFFFAOYSA-N N=C(CC1)c(cc2)c1cc2-c1c(-c2ccncc2)[o]c(C2CCN(CCOCl)CC2)c1 Chemical compound N=C(CC1)c(cc2)c1cc2-c1c(-c2ccncc2)[o]c(C2CCN(CCOCl)CC2)c1 BJLDRONFCLKRLI-UHFFFAOYSA-N 0.000 description 1
RJUHOOHZIFTATD-UHFFFAOYSA-N NC1=NC=CC(C2=C(C=C(CN3CCCCC3)O2)C=2C=C3CCC(C3=CC=2)=NO)=N1 Chemical compound NC1=NC=CC(C2=C(C=C(CN3CCCCC3)O2)C=2C=C3CCC(C3=CC=2)=NO)=N1 RJUHOOHZIFTATD-UHFFFAOYSA-N 0.000 description 1
WONWZMZJMAXLKE-UHFFFAOYSA-N NC=1C(=C(C=CC1)S(=O)(=O)N)NC(C1=CC=CC=C1)=O Chemical compound NC=1C(=C(C=CC1)S(=O)(=O)N)NC(C1=CC=CC=C1)=O WONWZMZJMAXLKE-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
208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
SPQIPBMVQUEAAV-UHFFFAOYSA-N O.S(=O)(=O)(O)C1=CC=C(C)C=C1.S(=O)(=O)(O)C1=CC=C(C)C=C1.N1=CN=C(C2=CC=CC=C12)N Chemical compound O.S(=O)(=O)(O)C1=CC=C(C)C=C1.S(=O)(=O)(O)C1=CC=C(C)C=C1.N1=CN=C(C2=CC=CC=C12)N SPQIPBMVQUEAAV-UHFFFAOYSA-N 0.000 description 1
JBKUJAPPYCKHFV-UHFFFAOYSA-N O1C(CN(C)C)=CC(C=2C=C3CCC(C3=CC=2)=NO)=C1C1=CC=NC=C1 Chemical compound O1C(CN(C)C)=CC(C=2C=C3CCC(C3=CC=2)=NO)=C1C1=CC=NC=C1 JBKUJAPPYCKHFV-UHFFFAOYSA-N 0.000 description 1
IEBRQEOMDGMENW-DYTRJAOYSA-N OCc1cc(-c(cc2CC3)ccc2/C3=N/O)c(-c2ccncc2)[o]1 Chemical compound OCc1cc(-c(cc2CC3)ccc2/C3=N/O)c(-c2ccncc2)[o]1 IEBRQEOMDGMENW-DYTRJAOYSA-N 0.000 description 1
REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
108700020796 Oncogene Proteins 0.000 description 1
102000043276 Oncogene Human genes 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
208000002193 Pain Diseases 0.000 description 1
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
229920002230 Pectic acid Chemical class 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
108010039918 Polylysine Proteins 0.000 description 1
229920001710 Polyorthoester Polymers 0.000 description 1
239000004365 Protease Substances 0.000 description 1
102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 description 1
101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 description 1
101150040459 RAS gene Proteins 0.000 description 1
238000002123 RNA extraction Methods 0.000 description 1
102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
230000018199 S phase Effects 0.000 description 1
201000010208 Seminoma Diseases 0.000 description 1
102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
229920001800 Shellac Polymers 0.000 description 1
206010041067 Small cell lung cancer Diseases 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
229920002253 Tannate Polymers 0.000 description 1
YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
108091023040 Transcription factor Proteins 0.000 description 1
102000040945 Transcription factor Human genes 0.000 description 1
102000004357 Transferases Human genes 0.000 description 1
108090000992 Transferases Proteins 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
IEBRQEOMDGMENW-UHFFFAOYSA-N [4-(1-hydroxyimino-2,3-dihydroinden-5-yl)-5-pyridin-4-ylfuran-2-yl]methanol Chemical compound O1C(CO)=CC(C=2C=C3CCC(C3=CC=2)=NO)=C1C1=CC=NC=C1 IEBRQEOMDGMENW-UHFFFAOYSA-N 0.000 description 1
ZBZFQGONULEMKI-UHFFFAOYSA-N [4-[4-(1-hydroxyimino-2,3-dihydroinden-5-yl)-5-pyridin-4-yl-1H-imidazol-2-yl]piperidin-1-yl]-[1-(2-methoxyethyl)piperidin-4-yl]methanone Chemical compound COCCN1CCC(CC1)C(=O)N1CCC(CC1)C1=NC(=C(N1)C1=CC=NC=C1)C1=CC2=C(C=C1)C(CC2)=NO ZBZFQGONULEMKI-UHFFFAOYSA-N 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
239000002250 absorbent Substances 0.000 description 1
230000002745 absorbent Effects 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
229940072056 alginate Drugs 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
125000000033 alkoxyamino group Chemical group 0.000 description 1
125000004466 alkoxycarbonylamino group Chemical group 0.000 description 1
125000002877 alkyl aryl group Chemical group 0.000 description 1
125000005431 alkyl carboxamide group Chemical group 0.000 description 1
125000005157 alkyl carboxy group Chemical group 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
125000004647 alkyl sulfenyl group Chemical group 0.000 description 1
125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
125000004656 alkyl sulfonylamino group Chemical group 0.000 description 1
IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
230000004075 alteration Effects 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
125000000539 amino acid group Chemical group 0.000 description 1
150000001413 amino acids Chemical group 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
229920000469 amphiphilic block copolymer Polymers 0.000 description 1
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
230000001028 anti-proliverative effect Effects 0.000 description 1
230000000692 anti-sense effect Effects 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
239000000074 antisense oligonucleotide Substances 0.000 description 1
238000012230 antisense oligonucleotides Methods 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
125000001691 aryl alkyl amino group Chemical group 0.000 description 1
125000001769 aryl amino group Chemical group 0.000 description 1
125000005135 aryl sulfinyl group Chemical group 0.000 description 1
125000004657 aryl sulfonyl amino group Chemical group 0.000 description 1
125000004391 aryl sulfonyl group Chemical group 0.000 description 1
125000005110 aryl thio group Chemical group 0.000 description 1
230000035578 autophosphorylation Effects 0.000 description 1
125000004931 azocinyl group Chemical group N1=C(C=CC=CC=C1)* 0.000 description 1
UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
ZDKVOUSBTDHELW-UHFFFAOYSA-N benzyl 4-[3-(1-methoxyimino-2,3-dihydroinden-5-yl)-4-oxo-4-pyridin-4-ylbutanoyl]piperidine-1-carboxylate Chemical compound C=1C=C2C(=NOC)CCC2=CC=1C(C(=O)C=1C=CN=CC=1)CC(=O)C(CC1)CCN1C(=O)OCC1=CC=CC=C1 ZDKVOUSBTDHELW-UHFFFAOYSA-N 0.000 description 1
VOETZCCNDJVWCN-UHFFFAOYSA-N benzyl 4-acetylpiperidine-1-carboxylate Chemical compound C1CC(C(=O)C)CCN1C(=O)OCC1=CC=CC=C1 VOETZCCNDJVWCN-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
229920002988 biodegradable polymer Polymers 0.000 description 1
239000004621 biodegradable polymer Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
239000004327 boric acid Substances 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
239000000872 buffer Substances 0.000 description 1
DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 1
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
KVSLPQXJQYNHIK-UHFFFAOYSA-N c1ccc2ncncc2c1.Cc1ccc(cc1)S(O)(=O)=O.Cc1ccc(cc1)S(O)(=O)=O Chemical compound c1ccc2ncncc2c1.Cc1ccc(cc1)S(O)(=O)=O.Cc1ccc(cc1)S(O)(=O)=O KVSLPQXJQYNHIK-UHFFFAOYSA-N 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 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
235000013539 calcium stearate Nutrition 0.000 description 1
239000008116 calcium stearate Substances 0.000 description 1
238000007816 calorimetric assay Methods 0.000 description 1
208000035269 cancer or benign tumor Diseases 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
150000007942 carboxylates Chemical class 0.000 description 1
229940105329 carboxymethylcellulose Drugs 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
230000024245 cell differentiation Effects 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
210000003855 cell nucleus Anatomy 0.000 description 1
238000001516 cell proliferation assay Methods 0.000 description 1
230000003833 cell viability Effects 0.000 description 1
230000005754 cellular signaling Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
208000026106 cerebrovascular disease Diseases 0.000 description 1
KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
XUFXPPUENFNHAF-UHFFFAOYSA-N chembl1851806 Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1N=C(C2CCNCC2)NC=1C1=CC=NC=C1 XUFXPPUENFNHAF-UHFFFAOYSA-N 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
125000000068 chlorophenyl group Chemical group 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
229940090805 clavulanate Drugs 0.000 description 1
HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
239000008119 colloidal silica Substances 0.000 description 1
208000029742 colonic neoplasm Diseases 0.000 description 1
238000002648 combination therapy Methods 0.000 description 1
238000011284 combination treatment Methods 0.000 description 1
238000011109 contamination Methods 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
229920006037 cross link polymer Polymers 0.000 description 1
239000013078 crystal Substances 0.000 description 1
NLCKLZIHJQEMCU-UHFFFAOYSA-N cyano prop-2-enoate Chemical class C=CC(=O)OC#N NLCKLZIHJQEMCU-UHFFFAOYSA-N 0.000 description 1
125000001352 cyclobutyloxy group Chemical group C1(CCC1)O* 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 description 1
230000006378 damage Effects 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
230000002074 deregulated effect Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
FXORZKOZOQWVMQ-UHFFFAOYSA-L dichloropalladium;triphenylphosphane Chemical compound Cl[Pd]Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 FXORZKOZOQWVMQ-UHFFFAOYSA-L 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
239000001177 diphosphate Substances 0.000 description 1
XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical class [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
235000011180 diphosphates Nutrition 0.000 description 1
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
125000004914 dipropylamino group Chemical group C(CC)N(CCC)* 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
238000007876 drug discovery Methods 0.000 description 1
229940125436 dual inhibitor Drugs 0.000 description 1
239000000428 dust Substances 0.000 description 1
229940009662 edetate Drugs 0.000 description 1
229960001484 edetic acid Drugs 0.000 description 1
239000012636 effector Substances 0.000 description 1
229950005627 embonate Drugs 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000007920 enema Substances 0.000 description 1
229940079360 enema for constipation Drugs 0.000 description 1
239000003623 enhancer Substances 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
210000002615 epidermis Anatomy 0.000 description 1
229950000206 estolate Drugs 0.000 description 1
XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
125000006125 ethylsulfonyl group Chemical group 0.000 description 1
239000003889 eye drop Substances 0.000 description 1
229940012356 eye drops Drugs 0.000 description 1
238000010265 fast atom bombardment Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000010419 fine particle Substances 0.000 description 1
229940047127 fiore Drugs 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
239000012530 fluid Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
238000005187 foaming Methods 0.000 description 1
235000011194 food seasoning agent Nutrition 0.000 description 1
239000012458 free base Substances 0.000 description 1
229940050411 fumarate Drugs 0.000 description 1
238000001502 gel electrophoresis Methods 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
125000002686 geranylgeranyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229960001731 gluceptate Drugs 0.000 description 1
KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
229930195712 glutamate Natural products 0.000 description 1
229940049906 glutamate Drugs 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
125000004439 haloalkylsulfanyl group Chemical group 0.000 description 1
235000015220 hamburgers Nutrition 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
125000001183 hydrocarbyl group Chemical group 0.000 description 1
239000000017 hydrogel Substances 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 1
239000008309 hydrophilic cream Substances 0.000 description 1
125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 1
238000009169 immunotherapy Methods 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
SNWQUNCRDLUDEX-UHFFFAOYSA-N inden-1-one Chemical group C1=CC=C2C(=O)C=CC2=C1 SNWQUNCRDLUDEX-UHFFFAOYSA-N 0.000 description 1
HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
230000000266 injurious effect Effects 0.000 description 1
238000009830 intercalation Methods 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
125000005956 isoquinolyl group Chemical group 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 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
229940001447 lactate Drugs 0.000 description 1
229940099584 lactobionate Drugs 0.000 description 1
JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
229940070765 laurate Drugs 0.000 description 1
239000010410 layer Substances 0.000 description 1
230000003902 lesion Effects 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
201000005249 lung adenocarcinoma Diseases 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
208000020816 lung neoplasm Diseases 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
229940049920 malate Drugs 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
230000036210 malignancy Effects 0.000 description 1
230000003211 malignant effect Effects 0.000 description 1
210000004962 mammalian cell Anatomy 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
239000001525 mentha piperita l. herb oil Substances 0.000 description 1
108020004999 messenger RNA Proteins 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 description 1
229940102396 methyl bromide Drugs 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 1
LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
239000003595 mist Substances 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
238000010172 mouse model Methods 0.000 description 1
239000002324 mouth wash Substances 0.000 description 1
210000003097 mucus Anatomy 0.000 description 1
QNDFCSITSCMNGP-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-chloropyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CN=C2C=NC(Cl)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 QNDFCSITSCMNGP-UHFFFAOYSA-N 0.000 description 1
OKOQGGNYPJNMTO-UHFFFAOYSA-N n-[3-bromo-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Br)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 OKOQGGNYPJNMTO-UHFFFAOYSA-N 0.000 description 1
UQKXRKIJTVYGCY-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[2-[(2-propan-2-ylsulfonylethylamino)methyl]-3h-furan-2-yl]quinazolin-4-amine Chemical compound C=1C=C2N=CN=C(NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=CC=1C1(CNCCS(=O)(=O)C(C)C)CC=CO1 UQKXRKIJTVYGCY-UHFFFAOYSA-N 0.000 description 1
UDUYPYDDRVKYAH-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[2-[2-(2-methylsulfonylethylamino)ethyl]-3h-furan-2-yl]quinazolin-4-amine Chemical compound C=1C=C2N=CN=C(NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=CC=1C1(CCNCCS(=O)(=O)C)CC=CO1 UDUYPYDDRVKYAH-UHFFFAOYSA-N 0.000 description 1
RMPVKBBFQRDYJT-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-(2-methylsulfonylethoxymethyl)furan-2-yl]quinazolin-4-amine Chemical compound O1C(COCCS(=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 RMPVKBBFQRDYJT-UHFFFAOYSA-N 0.000 description 1
WEAQVBUETRVQKL-UHFFFAOYSA-N n-methoxy-5-(5-piperidin-4-yl-2-pyridin-4-ylfuran-3-yl)-2,3-dihydroinden-1-imine Chemical compound C=1C=C2C(=NOC)CCC2=CC=1C=1C=C(C2CCNCC2)OC=1C1=CC=NC=C1 WEAQVBUETRVQKL-UHFFFAOYSA-N 0.000 description 1
YUSMWODGNWPEBC-UHFFFAOYSA-N n-morpholin-4-ylacetamide Chemical group CC(=O)NN1CCOCC1 YUSMWODGNWPEBC-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
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000007923 nasal drop Substances 0.000 description 1
229940100662 nasal drops Drugs 0.000 description 1
229940097496 nasal spray Drugs 0.000 description 1
239000007922 nasal spray Substances 0.000 description 1
235000021096 natural sweeteners Nutrition 0.000 description 1
239000006199 nebulizer Substances 0.000 description 1
208000011851 neurological alteration Diseases 0.000 description 1
150000002829 nitrogen Chemical class 0.000 description 1
238000010606 normalization Methods 0.000 description 1
239000011824 nuclear material Substances 0.000 description 1
210000004940 nucleus Anatomy 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000003883 ointment base Substances 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
229960003552 other antineoplastic agent in atc Drugs 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
125000003585 oxepinyl group Chemical group 0.000 description 1
150000002923 oximes Chemical group 0.000 description 1
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
201000002094 pancreatic adenocarcinoma Diseases 0.000 description 1
229940014662 pantothenate Drugs 0.000 description 1
235000019161 pantothenic acid Nutrition 0.000 description 1
239000011713 pantothenic acid Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
239000011236 particulate material Substances 0.000 description 1
235000010603 pastilles Nutrition 0.000 description 1
235000019477 peppermint oil Nutrition 0.000 description 1
125000005010 perfluoroalkyl group Chemical group 0.000 description 1
229950000688 phenothiazine Drugs 0.000 description 1
125000004344 phenylpropyl group Chemical group 0.000 description 1
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
150000008105 phosphatidylcholines Chemical class 0.000 description 1
150000003905 phosphatidylinositols Chemical class 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 1
DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
235000014786 phosphorus Nutrition 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
125000005936 piperidyl group Chemical group 0.000 description 1
229920000747 poly(lactic acid) Polymers 0.000 description 1
229920002401 polyacrylamide Polymers 0.000 description 1
239000010318 polygalacturonic acid Chemical class 0.000 description 1
239000004626 polylactic acid Substances 0.000 description 1
229920000656 polylysine Polymers 0.000 description 1
229920006324 polyoxymethylene Polymers 0.000 description 1
239000011698 potassium fluoride Substances 0.000 description 1
235000003270 potassium fluoride Nutrition 0.000 description 1
FRMWBRPWYBNAFB-UHFFFAOYSA-M potassium salicylate Chemical compound [K+].OC1=CC=CC=C1C([O-])=O FRMWBRPWYBNAFB-UHFFFAOYSA-M 0.000 description 1
229960003629 potassium salicylate Drugs 0.000 description 1
QPMDWIOUHQWKHV-ODZAUARKSA-M potassium;(z)-4-hydroxy-4-oxobut-2-enoate Chemical compound [K+].OC(=O)\C=C/C([O-])=O QPMDWIOUHQWKHV-ODZAUARKSA-M 0.000 description 1
238000003825 pressing Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000008569 process Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
229940080818 propionamide Drugs 0.000 description 1
125000006308 propyl amino group Chemical group 0.000 description 1
125000004673 propylcarbonyl group Chemical group 0.000 description 1
125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
239000011253 protective coating Substances 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000005495 pyridazyl group Chemical group 0.000 description 1
BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 1
125000005554 pyridyloxy group Chemical group 0.000 description 1
ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
DRYRBWIFRVMRPV-UHFFFAOYSA-N quinazolin-4-amine Chemical compound C1=CC=C2C(N)=NC=NC2=C1 DRYRBWIFRVMRPV-UHFFFAOYSA-N 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
238000001959 radiotherapy Methods 0.000 description 1
102000027426 receptor tyrosine kinases Human genes 0.000 description 1
108091008598 receptor tyrosine kinases Proteins 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000009703 regulation of cell differentiation Effects 0.000 description 1
230000026267 regulation of growth Effects 0.000 description 1
230000007363 regulatory process Effects 0.000 description 1
229920005989 resin Polymers 0.000 description 1
239000011347 resin Substances 0.000 description 1
230000004044 response Effects 0.000 description 1
201000006845 reticulosarcoma Diseases 0.000 description 1
208000029922 reticulum cell sarcoma Diseases 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
108091092562 ribozyme Proteins 0.000 description 1
102200006616 rs104894230 Human genes 0.000 description 1
102200006655 rs104894230 Human genes 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000004208 shellac Substances 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
238000009491 slugging Methods 0.000 description 1
208000000587 small cell lung carcinoma Diseases 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
102000009076 src-Family Kinases Human genes 0.000 description 1
108010087686 src-Family Kinases Proteins 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
125000004646 sulfenyl group Chemical group S(*)* 0.000 description 1
BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
229910052815 sulfur oxide Inorganic materials 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
229950002757 teoclate Drugs 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
SGUQXLLGHZISLF-UHFFFAOYSA-N tert-butyl-dimethyl-(pyridin-4-ylmethoxy)silane Chemical compound CC(C)(C)[Si](C)(C)OCC1=CC=NC=C1 SGUQXLLGHZISLF-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
YMBCJWGVCUEGHA-UHFFFAOYSA-M tetraethylammonium chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC YMBCJWGVCUEGHA-UHFFFAOYSA-M 0.000 description 1
RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000005306 thianaphthenyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
125000003777 thiepinyl group Chemical group 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
229940100611 topical cream Drugs 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
229940100615 topical ointment Drugs 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
230000002103 transcriptional effect Effects 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000004565 tumor cell growth Effects 0.000 description 1
230000004614 tumor growth Effects 0.000 description 1
229940070710 valerate Drugs 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
229930195724 β-lactose Natural products 0.000 description 1
PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1