JP2013503903A - チロシンキナーゼモジュレーターとしての化合物 - Google Patents
チロシンキナーゼモジュレーターとしての化合物 Download PDFInfo
- Publication number
- JP2013503903A JP2013503903A JP2012528089A JP2012528089A JP2013503903A JP 2013503903 A JP2013503903 A JP 2013503903A JP 2012528089 A JP2012528089 A JP 2012528089A JP 2012528089 A JP2012528089 A JP 2012528089A JP 2013503903 A JP2013503903 A JP 2013503903A
- Authority
- JP
- Japan
- Prior art keywords
- group
- alkyl
- independently selected
- hydrogen
- alkoxycarbonyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 83
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 title abstract description 18
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 title abstract description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 18
- 201000010099 disease Diseases 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims description 42
- 239000001257 hydrogen Substances 0.000 claims description 42
- 239000000203 mixture Substances 0.000 claims description 30
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 29
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 27
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 21
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- -1 C 1 -C 5 alkoxy Chemical group 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 16
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 239000000651 prodrug Substances 0.000 claims description 14
- 229940002612 prodrug Drugs 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 12
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 12
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 238000002347 injection Methods 0.000 claims description 12
- 239000007924 injection Substances 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 9
- 125000001188 haloalkyl group Chemical group 0.000 claims description 9
- 208000005590 Choroidal Neovascularization Diseases 0.000 claims description 8
- 206010060823 Choroidal neovascularisation Diseases 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 208000002780 macular degeneration Diseases 0.000 claims description 8
- 230000004770 neurodegeneration Effects 0.000 claims description 8
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 208000004644 retinal vein occlusion Diseases 0.000 claims description 8
- 125000003368 amide group Chemical group 0.000 claims description 7
- 230000033115 angiogenesis Effects 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 125000002837 carbocyclic group Chemical group 0.000 claims description 7
- 125000002950 monocyclic group Chemical group 0.000 claims description 7
- 230000000699 topical effect Effects 0.000 claims description 7
- 239000005483 tyrosine kinase inhibitor Substances 0.000 claims description 7
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 6
- 208000026278 immune system disease Diseases 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 6
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims description 6
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 5
- HNVIQLPOGUDBSU-UHFFFAOYSA-N 2,6-dimethylmorpholine Chemical compound CC1CNCC(C)O1 HNVIQLPOGUDBSU-UHFFFAOYSA-N 0.000 claims description 5
- UYGRGONQGJGYDY-UHFFFAOYSA-N 2-fluoropiperidine Chemical compound FC1CCCCN1 UYGRGONQGJGYDY-UHFFFAOYSA-N 0.000 claims description 5
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 5
- 208000001344 Macular Edema Diseases 0.000 claims description 5
- 206010029113 Neovascularisation Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 5
- OQDXZZHGQBFAKM-UHFFFAOYSA-N 2-fluoropyrrolidine Chemical compound FC1CCCN1 OQDXZZHGQBFAKM-UHFFFAOYSA-N 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 4
- 206010058202 Cystoid macular oedema Diseases 0.000 claims description 4
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 4
- 206010016654 Fibrosis Diseases 0.000 claims description 4
- 208000010412 Glaucoma Diseases 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- 201000010183 Papilledema Diseases 0.000 claims description 4
- 206010038389 Renal cancer Diseases 0.000 claims description 4
- 206010038886 Retinal oedema Diseases 0.000 claims description 4
- 206010038933 Retinopathy of prematurity Diseases 0.000 claims description 4
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 229910052786 argon Inorganic materials 0.000 claims description 4
- 206010003246 arthritis Diseases 0.000 claims description 4
- 230000007882 cirrhosis Effects 0.000 claims description 4
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 201000010206 cystoid macular edema Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 201000005787 hematologic cancer Diseases 0.000 claims description 4
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 201000010982 kidney cancer Diseases 0.000 claims description 4
- 201000007270 liver cancer Diseases 0.000 claims description 4
- 208000014018 liver neoplasm Diseases 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 239000002674 ointment Substances 0.000 claims description 4
- 201000011195 retinal edema Diseases 0.000 claims description 4
- 208000032253 retinal ischemia Diseases 0.000 claims description 4
- 150000003871 sulfonates Chemical class 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- 238000002054 transplantation Methods 0.000 claims description 4
- 230000029663 wound healing Effects 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 3
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000005243 carbonyl alkyl group Chemical group 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 239000006071 cream Substances 0.000 claims description 3
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
- 239000000839 emulsion Substances 0.000 claims description 3
- 239000003889 eye drop Substances 0.000 claims description 3
- 229940012356 eye drops Drugs 0.000 claims description 3
- 208000024519 eye neoplasm Diseases 0.000 claims description 3
- 239000000499 gel Substances 0.000 claims description 3
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 3
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 3
- 239000007943 implant Substances 0.000 claims description 3
- 239000007927 intramuscular injection Substances 0.000 claims description 3
- 238000010255 intramuscular injection Methods 0.000 claims description 3
- 238000010253 intravenous injection Methods 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims 14
- 125000005843 halogen group Chemical group 0.000 claims 6
- OTWVFHZMWFGHSJ-UHFFFAOYSA-N 1-fluoropyrrolidine Chemical compound FN1CCCC1 OTWVFHZMWFGHSJ-UHFFFAOYSA-N 0.000 claims 1
- 206010025415 Macular oedema Diseases 0.000 claims 1
- 208000034189 Sclerosis Diseases 0.000 claims 1
- 239000003885 eye ointment Substances 0.000 claims 1
- 201000010230 macular retinal edema Diseases 0.000 claims 1
- 239000007921 spray Substances 0.000 claims 1
- 230000002159 abnormal effect Effects 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 abstract description 2
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 abstract description 2
- 230000003389 potentiating effect Effects 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000007787 solid Substances 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 16
- 102000005962 receptors Human genes 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000003814 drug Substances 0.000 description 15
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 15
- 108020003175 receptors Proteins 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 10
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 10
- 125000001475 halogen functional group Chemical group 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 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 8
- 229940079593 drug Drugs 0.000 description 8
- 239000002953 phosphate buffered saline Substances 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 230000011664 signaling Effects 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 6
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 230000026731 phosphorylation Effects 0.000 description 5
- 238000006366 phosphorylation reaction Methods 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 230000002792 vascular Effects 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- 206010015866 Extravasation Diseases 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
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 230000036251 extravasation Effects 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 239000012453 solvate Substances 0.000 description 4
- 206010012688 Diabetic retinal oedema Diseases 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 3
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000005252 bulbus oculi Anatomy 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000013626 chemical specie Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 201000011190 diabetic macular edema Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 210000001508 eye Anatomy 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- WOXQCRSGRDIOMP-UHFFFAOYSA-N methyl 7-(4-amino-3-fluorophenoxy)thieno[3,2-b]pyridine-2-carboxylate Chemical compound C=12SC(C(=O)OC)=CC2=NC=CC=1OC1=CC=C(N)C(F)=C1 WOXQCRSGRDIOMP-UHFFFAOYSA-N 0.000 description 3
- ZXRHGKRJKKAITR-UHFFFAOYSA-N methyl 7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carboxylate Chemical compound C=12SC(C(=O)OC)=CC2=NC=CC=1OC(C=C1F)=CC=C1NC(=O)NC1=CC(C)=CC=C1F ZXRHGKRJKKAITR-UHFFFAOYSA-N 0.000 description 3
- SBDWNJUPCVOJLH-UHFFFAOYSA-N methyl 7-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carboxylate Chemical compound C=12SC(C(=O)OC)=CC2=NC=CC=1OC(C=C1)=CC=C1NC(=O)NC1=CC(C)=CC=C1F SBDWNJUPCVOJLH-UHFFFAOYSA-N 0.000 description 3
- TVCVLFYBAYEPTE-UHFFFAOYSA-N methyl 7-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenyl]thieno[3,2-b]pyridine-2-carboxylate Chemical compound C=12SC(C(=O)OC)=CC2=NC=CC=1C(C=C1)=CC=C1NC(=O)NC1=CC(C)=CC=C1F TVCVLFYBAYEPTE-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
- 102000020233 phosphotransferase Human genes 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- GLSUJZPVKMKUPJ-UHFFFAOYSA-N 1-fluoro-2-isocyanato-4-methylbenzene Chemical compound CC1=CC=C(F)C(N=C=O)=C1 GLSUJZPVKMKUPJ-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 2
- QLVYHQCCXVCBRH-UHFFFAOYSA-N 7-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carboxylic acid Chemical compound CC1=CC=C(F)C(NC(=O)NC=2C=CC(OC=3C=4SC(=CC=4N=CC=3)C(O)=O)=CC=2)=C1 QLVYHQCCXVCBRH-UHFFFAOYSA-N 0.000 description 2
- GYQUXKQLCNFKQT-UHFFFAOYSA-N 7-chlorothieno[3,2-b]pyridine Chemical compound ClC1=CC=NC2=C1SC=C2 GYQUXKQLCNFKQT-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102100037362 Fibronectin Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- OUVXYXNWSVIOSJ-UHFFFAOYSA-N Fluo-4 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(F)C(=O)C=C3OC3=CC(O)=C(F)C=C32)N(CC(O)=O)CC(O)=O)=C1 OUVXYXNWSVIOSJ-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 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
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 102000014400 SH2 domains Human genes 0.000 description 2
- 108050003452 SH2 domains Proteins 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 208000035269 cancer or benign tumor Diseases 0.000 description 2
- 108020001778 catalytic domains Proteins 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- FGSGHBPKHFDJOP-UHFFFAOYSA-N ethyl 2-oxocyclohexane-1-carboxylate Chemical compound CCOC(=O)C1CCCCC1=O FGSGHBPKHFDJOP-UHFFFAOYSA-N 0.000 description 2
- 230000003176 fibrotic effect Effects 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 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 2
- 150000002500 ions Chemical class 0.000 description 2
- 238000000021 kinase assay Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 208000030159 metabolic disease Diseases 0.000 description 2
- BRNXSVBUFXHKKJ-UHFFFAOYSA-N methyl 3-[[7-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carbonyl]amino]propanoate Chemical compound C=12SC(C(=O)NCCC(=O)OC)=CC2=NC=CC=1OC(C=C1)=CC=C1NC(=O)NC1=CC(C)=CC=C1F BRNXSVBUFXHKKJ-UHFFFAOYSA-N 0.000 description 2
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000002997 ophthalmic solution Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 125000005504 styryl group Chemical group 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 238000012546 transfer Methods 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
- JHHZLHWJQPUNKB-SCSAIBSYSA-N (3r)-pyrrolidin-3-ol Chemical compound O[C@@H]1CCNC1 JHHZLHWJQPUNKB-SCSAIBSYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
- RYCSNJCJOVQGBC-UHFFFAOYSA-N 3-(1-cyclopropyl-2h-pyridin-4-yl)-1h-quinolin-2-one Chemical compound O=C1NC2=CC=CC=C2C=C1C(C=C1)=CCN1C1CC1 RYCSNJCJOVQGBC-UHFFFAOYSA-N 0.000 description 1
- MYDSAMPAYOLUMG-UHFFFAOYSA-N 3-aminothieno[3,2-b]pyridine-2-carboxylic acid Chemical compound C1=CN=C2C(N)=C(C(O)=O)SC2=C1 MYDSAMPAYOLUMG-UHFFFAOYSA-N 0.000 description 1
- MNPLTKHJEAFOCA-UHFFFAOYSA-N 4-amino-3-fluorophenol Chemical compound NC1=CC=C(O)C=C1F MNPLTKHJEAFOCA-UHFFFAOYSA-N 0.000 description 1
- SPGOVUHEKLSWMN-UHFFFAOYSA-N 7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carboxylic acid Chemical compound CC1=CC=C(F)C(NC(=O)NC=2C(=CC(OC=3C=4SC(=CC=4N=CC=3)C(O)=O)=CC=2)F)=C1 SPGOVUHEKLSWMN-UHFFFAOYSA-N 0.000 description 1
- RURFZMWFAJCNHV-UHFFFAOYSA-N 7-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenyl]thieno[3,2-b]pyridine-2-carboxylic acid Chemical compound CC1=CC=C(F)C(NC(=O)NC=2C=CC(=CC=2)C=2C=3SC(=CC=3N=CC=2)C(O)=O)=C1 RURFZMWFAJCNHV-UHFFFAOYSA-N 0.000 description 1
- 102000007299 Amphiregulin Human genes 0.000 description 1
- 108010033760 Amphiregulin Proteins 0.000 description 1
- OGBVRMYSNSKIEF-UHFFFAOYSA-N Benzylphosphonic acid Chemical class OP(O)(=O)CC1=CC=CC=C1 OGBVRMYSNSKIEF-UHFFFAOYSA-N 0.000 description 1
- 102000056058 Betacellulin Human genes 0.000 description 1
- 101800001382 Betacellulin Proteins 0.000 description 1
- 0 CC(N=S(*)=O)=O Chemical compound CC(N=S(*)=O)=O 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- MKSHKYWKNLBVDL-UHFFFAOYSA-O Cc(cc1)cc(NC(Nc2cc([ClH]C3=C4[NH2+]C(C(OC)=O)=CC4=NCC3)ccc2)=[U])c1F Chemical compound Cc(cc1)cc(NC(Nc2cc([ClH]C3=C4[NH2+]C(C(OC)=O)=CC4=NCC3)ccc2)=[U])c1F MKSHKYWKNLBVDL-UHFFFAOYSA-O 0.000 description 1
- ZEOWTGPWHLSLOG-UHFFFAOYSA-N Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F Chemical compound Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F ZEOWTGPWHLSLOG-UHFFFAOYSA-N 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- YCAGGFXSFQFVQL-UHFFFAOYSA-N Endothion Chemical compound COC1=COC(CSP(=O)(OC)OC)=CC1=O YCAGGFXSFQFVQL-UHFFFAOYSA-N 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 108091008794 FGF receptors Proteins 0.000 description 1
- 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 description 1
- 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 description 1
- 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 1
- 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 description 1
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 1
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 1
- 102100027844 Fibroblast growth factor receptor 4 Human genes 0.000 description 1
- XBGGUPMXALFZOT-VIFPVBQESA-N Gly-Tyr Chemical compound NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-VIFPVBQESA-N 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 102000018710 Heparin-binding EGF-like Growth Factor Human genes 0.000 description 1
- 101800001649 Heparin-binding EGF-like growth factor Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000917134 Homo sapiens Fibroblast growth factor receptor 4 Proteins 0.000 description 1
- 101001005128 Homo sapiens LIM domain kinase 1 Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- 102100026023 LIM domain kinase 1 Human genes 0.000 description 1
- 244000178870 Lavandula angustifolia Species 0.000 description 1
- 235000010663 Lavandula angustifolia Nutrition 0.000 description 1
- 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 1
- 102400000058 Neuregulin-1 Human genes 0.000 description 1
- 108090000556 Neuregulin-1 Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- SIOXPEMLGUPBBT-UHFFFAOYSA-N Picolinic acid Natural products OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 1
- 102000001393 Platelet-Derived Growth Factor alpha Receptor Human genes 0.000 description 1
- 108010068588 Platelet-Derived Growth Factor alpha Receptor Proteins 0.000 description 1
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
- 101000852966 Rattus norvegicus Interleukin-1 receptor-like 1 Proteins 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
- 102000006747 Transforming Growth Factor alpha Human genes 0.000 description 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
- BGDKAVGWHJFAGW-UHFFFAOYSA-N Tropicamide Chemical compound C=1C=CC=CC=1C(CO)C(=O)N(CC)CC1=CC=NC=C1 BGDKAVGWHJFAGW-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
- 125000005197 alkyl carbonyloxy alkyl group Chemical group 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- RIIWUGSYXOBDMC-UHFFFAOYSA-N benzene-1,2-diamine;hydron;dichloride Chemical compound Cl.Cl.NC1=CC=CC=C1N RIIWUGSYXOBDMC-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000001045 blue dye Substances 0.000 description 1
- 238000011685 brown norway rat Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 230000001427 coherent effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 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 1
- 230000006378 damage Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 108091071773 flk family Proteins 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 238000011597 hartley guinea pig Methods 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000000521 hyperimmunizing effect Effects 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 150000003949 imides Chemical group 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical group CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical group C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 239000001102 lavandula vera Substances 0.000 description 1
- 235000018219 lavender Nutrition 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- AJKZXGXUEIMAPP-UHFFFAOYSA-N methyl 7-bromothieno[3,2-b]pyridine-2-carboxylate Chemical compound C1=CC(Br)=C2SC(C(=O)OC)=CC2=N1 AJKZXGXUEIMAPP-UHFFFAOYSA-N 0.000 description 1
- WYMRMHKAXXQOMO-UHFFFAOYSA-N methyl 7-chlorothieno[3,2-b]pyridine-2-carboxylate Chemical compound C1=CC(Cl)=C2SC(C(=O)OC)=CC2=N1 WYMRMHKAXXQOMO-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 201000008106 ocular cancer Diseases 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000007981 phosphate-citrate buffer Substances 0.000 description 1
- DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical group OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 210000001210 retinal vessel Anatomy 0.000 description 1
- 150000003346 selenoethers Chemical class 0.000 description 1
- 210000001626 skin fibroblast Anatomy 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-N sodium;5-ethyl-5-pentan-2-yl-1,3-diazinane-2,4,6-trione Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)NC1=O QGMRQYFBGABWDR-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- WVWCTPQHJWMLKI-UHFFFAOYSA-N thieno[3,2-b]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(C(=O)O)=CC2=N1 WVWCTPQHJWMLKI-UHFFFAOYSA-N 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 229960004791 tropicamide Drugs 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Ophthalmology & Optometry (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Endocrinology (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Gastroenterology & Hepatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Vascular Medicine (AREA)
- Reproductive Health (AREA)
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23960309P | 2009-09-03 | 2009-09-03 | |
| US61/239,603 | 2009-09-03 | ||
| US30661610P | 2010-02-22 | 2010-02-22 | |
| US61/306,616 | 2010-02-22 | ||
| US35669910P | 2010-06-21 | 2010-06-21 | |
| US61/356,699 | 2010-06-21 | ||
| US36053110P | 2010-07-01 | 2010-07-01 | |
| US61/360,531 | 2010-07-01 | ||
| PCT/US2010/047816 WO2011029001A1 (en) | 2009-09-03 | 2010-09-03 | Compounds as tyrosine kinase modulators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2013503903A true JP2013503903A (ja) | 2013-02-04 |
| JP2013503903A5 JP2013503903A5 (OSRAM) | 2013-10-24 |
Family
ID=43086186
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012528089A Pending JP2013503903A (ja) | 2009-09-03 | 2010-09-03 | チロシンキナーゼモジュレーターとしての化合物 |
| JP2012528084A Expired - Fee Related JP5868855B2 (ja) | 2009-09-03 | 2010-09-03 | チロシンキナーゼ調節剤としての化合物 |
| JP2016001387A Expired - Fee Related JP6109974B2 (ja) | 2009-09-03 | 2016-01-06 | チロシンキナーゼ調節剤としての化合物 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012528084A Expired - Fee Related JP5868855B2 (ja) | 2009-09-03 | 2010-09-03 | チロシンキナーゼ調節剤としての化合物 |
| JP2016001387A Expired - Fee Related JP6109974B2 (ja) | 2009-09-03 | 2016-01-06 | チロシンキナーゼ調節剤としての化合物 |
Country Status (19)
| Country | Link |
|---|---|
| US (5) | US8809534B2 (OSRAM) |
| EP (2) | EP2473501B1 (OSRAM) |
| JP (3) | JP2013503903A (OSRAM) |
| KR (2) | KR20120082890A (OSRAM) |
| CN (2) | CN102498114A (OSRAM) |
| AU (2) | AU2010289359A1 (OSRAM) |
| BR (2) | BR112012004843A2 (OSRAM) |
| CA (2) | CA2772625A1 (OSRAM) |
| CL (2) | CL2012000587A1 (OSRAM) |
| ES (1) | ES2730086T3 (OSRAM) |
| IL (2) | IL218332A0 (OSRAM) |
| IN (1) | IN2012DN02493A (OSRAM) |
| MX (2) | MX2012002596A (OSRAM) |
| NZ (2) | NZ598455A (OSRAM) |
| PH (1) | PH12014500281A1 (OSRAM) |
| RU (2) | RU2012109233A (OSRAM) |
| SG (2) | SG178965A1 (OSRAM) |
| WO (2) | WO2011028995A1 (OSRAM) |
| ZA (2) | ZA201201592B (OSRAM) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020520373A (ja) * | 2017-05-18 | 2020-07-09 | ピーアイ インダストリーズ リミテッドＰｉ Ｉｎｄｕｓｔｒｉｅｓ Ｌｔｄ | 植物病原性微生物に対して有用なホルムイミドアミジン化合物 |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7431710B2 (en) | 2002-04-08 | 2008-10-07 | Glaukos Corporation | Ocular implants with anchors and methods thereof |
| MX2011000175A (es) * | 2008-06-25 | 2011-06-27 | Envivo Pharmaceuticals Inc | Compuestos heterociclicos 1,2-di-substituidos. |
| WO2010045095A1 (en) | 2008-10-14 | 2010-04-22 | Ning Xi | Compounds and methods of use |
| WO2010111063A1 (en) | 2009-03-21 | 2010-09-30 | Ning Xi | Amino ester derivatives, salts thereof and methods of use |
| PE20120900A1 (es) | 2009-05-07 | 2012-08-14 | Envivo Pharmaceuticals Inc | Compuestos heterociclicos de fenoximetilo |
| US10206813B2 (en) | 2009-05-18 | 2019-02-19 | Dose Medical Corporation | Implants with controlled drug delivery features and methods of using same |
| US12478503B2 (en) | 2009-05-18 | 2025-11-25 | Glaukos Corporation | Implants with controlled drug delivery features and methods of using same |
| EP3412260B1 (en) | 2009-05-18 | 2020-08-26 | Dose Medical Corporation | Drug eluting ocular implant |
| RU2012109233A (ru) | 2009-09-03 | 2013-10-10 | Аллерган, Инк. | Соединения как модуляторы тирозинкиназы |
| US8906944B2 (en) * | 2009-09-03 | 2014-12-09 | Allergan, Inc. | Compounds as tyrosine kinase modulators |
| US9340555B2 (en) * | 2009-09-03 | 2016-05-17 | Allergan, Inc. | Compounds as tyrosine kinase modulators |
| EP2654715B1 (en) | 2010-11-24 | 2017-01-25 | Dose Medical Corporation | Drug eluting ocular implant |
| US10245178B1 (en) | 2011-06-07 | 2019-04-02 | Glaukos Corporation | Anterior chamber drug-eluting ocular implant |
| HRP20161578T1 (hr) * | 2012-02-09 | 2016-12-30 | Merck Patent Gmbh | Derivati furo[3, 2-b]piridina kao inhibitori tbk1 i ikk |
| WO2015069287A1 (en) * | 2013-11-08 | 2015-05-14 | Allergan, Inc. | Compounds as tyrosine kinase modulators |
| AU2014361800B2 (en) | 2013-12-13 | 2020-05-07 | Dana-Farber Cancer Institute, Inc. | Methods to treat lymphoplasmacytic lymphoma |
| AU2014361798B2 (en) * | 2013-12-13 | 2020-06-11 | Dana-Farber Cancer Institute, Inc. | Methods to treat lymphoplasmacytic lymphoma |
| CN104974132B (zh) * | 2014-04-08 | 2017-05-17 | 北大方正集团有限公司 | 多取代的吡啶化合物、制备方法、用途及药物组合物 |
| US20150342875A1 (en) | 2014-05-29 | 2015-12-03 | Dose Medical Corporation | Implants with controlled drug delivery features and methods of using same |
| RU2021109549A (ru) | 2014-08-29 | 2021-05-13 | Тес Фарма С.Р.Л. | ИНГИБИТОРЫ α-АМИНО-β-КАРБОКСИМУКОНАТ ε-СЕМИАЛЬДЕГИД-ДЕКАРБОКСИЛАЗЫ |
| CN104326985A (zh) * | 2014-09-24 | 2015-02-04 | 安润医药科技（苏州）有限公司 | 利你法尼的制备方法 |
| EP3209648B1 (en) | 2014-10-22 | 2020-03-11 | Dana-Farber Cancer Institute, Inc. | Thiazolyl-containing compounds for treating proliferative diseases |
| US11925578B2 (en) | 2015-09-02 | 2024-03-12 | Glaukos Corporation | Drug delivery implants with bi-directional delivery capacity |
| WO2017053885A1 (en) | 2015-09-25 | 2017-03-30 | Glaukos Corporation | Punctal implants with controlled drug delivery features and methods of using same |
| WO2017157332A1 (zh) * | 2016-03-18 | 2017-09-21 | 江苏恒瑞医药股份有限公司 | 芳香酰胺类衍生物、其制备方法及其在医药上的应用 |
| JP7003110B2 (ja) | 2016-04-20 | 2022-01-20 | ドーズ メディカル コーポレーション | 生体吸収性眼球薬物送達デバイス |
| CN107663202B (zh) * | 2016-07-29 | 2020-09-04 | 西华大学 | 3-(脲基-甲基)-4-芳基-吡啶衍生物及其制备方法和作为抗肝癌药物的应用 |
| WO2018175173A1 (en) * | 2017-03-21 | 2018-09-27 | The Scripps Research Institute | Cu-and ni-catalyzed decarboxylative borylation reactions |
| JP7154229B2 (ja) | 2017-05-11 | 2022-10-17 | ブリストル－マイヤーズ スクイブ カンパニー | Ｉｒａｋ－４阻害剤として有用なチエノピリジンおよびベンゾチオフェン |
| TWI833819B (zh) | 2018-10-05 | 2024-03-01 | 美商安尼波那生物公司 | 用於治療與apj受體活性相關的病狀的化合物及組成物 |
| US11034669B2 (en) | 2018-11-30 | 2021-06-15 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005533011A (ja) * | 2002-04-05 | 2005-11-04 | アストラゼネカ アクチボラグ | ヒストンデアセチラーゼ阻害剤として有用なベンズアミド誘導体 |
| JP2005534669A (ja) * | 2002-06-14 | 2005-11-17 | ファイザー・インク | 治療剤として有用なチエノピリジンのベンゾ縮合ヘテロアリールアミド誘導体、それが含まれる医薬組成物、並びにその使用の方法 |
| JP2007504121A (ja) * | 2003-08-29 | 2007-03-01 | ファイザー・インク | 新たな抗血管形成剤として有用なナフタレン・カルボキサミド及びその誘導体 |
| JP2007504122A (ja) * | 2003-08-29 | 2007-03-01 | ファイザー・インク | 新規抗血管形成剤として有用なチエノピリジン−フェニルアセトアミドおよびその誘導体 |
| JP2007537296A (ja) * | 2004-05-14 | 2007-12-20 | アボット・ラボラトリーズ | 治療薬としてのキナーゼ阻害薬 |
| US20090118276A1 (en) * | 2007-11-02 | 2009-05-07 | Wyeth | Thienopyrimidines, thienopyridines, and pyrrolopyrimidines as b-raf inhibitors |
| JP2009526761A (ja) * | 2006-01-30 | 2009-07-23 | アレイ バイオファーマ、インコーポレイテッド | ヘテロ二環式チオフェン化合物および使用の方法 |
| WO2009109035A1 (en) * | 2008-03-05 | 2009-09-11 | Methylgene Inc. | Inhibitors of protein tyrosine kinase activity |
| US20100081675A1 (en) * | 2008-09-26 | 2010-04-01 | National Health Research Institutes | Fused multicyclic compounds as protein kinase inhibitors |
| JP2010536887A (ja) * | 2007-08-29 | 2010-12-02 | メチルジーン インコーポレイテッド | タンパク質チロシンキナーゼ活性の阻害剤 |
Family Cites Families (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT72878B (en) | 1980-04-24 | 1983-03-29 | Merck & Co Inc | Process for preparing mannich-base hydroxamic acid pro-drugs for the improved delivery of non-steroidal anti-inflammatory agents |
| US4966849A (en) | 1985-09-20 | 1990-10-30 | President And Fellows Of Harvard College | CDNA and genes for human angiogenin (angiogenesis factor) and methods of expression |
| US5217999A (en) | 1987-12-24 | 1993-06-08 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Styryl compounds which inhibit EGF receptor protein tyrosine kinase |
| JPH0662650B2 (ja) | 1990-04-02 | 1994-08-17 | ファイザー・インコーポレーテッド | チロシンキナーゼ阻害剤としてのベンジルホスホン酸 |
| US5302606A (en) | 1990-04-16 | 1994-04-12 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Styryl-substituted pyridyl compounds which inhibit EGF receptor tyrosine kinase |
| ES2108120T3 (es) | 1991-05-10 | 1997-12-16 | Rhone Poulenc Rorer Int | Compuestos bis arilicos y heteroarilicos mono- y biciclicos que inhiben tirosina quinasa receptora de egf y/o pdgf. |
| EP0586608A1 (en) | 1991-05-29 | 1994-03-16 | Pfizer Inc. | Tricyclic polyhydroxylic tyrosine kinase inhibitors |
| CZ283965B6 (cs) | 1992-08-06 | 1998-07-15 | Warner-Lambert Company | 2-thioindolové, 2-indolinthionové a polysulfidové sloučeniny, 2-selenoindolové, 2-indolinselenonové a selenidové sloučeniny a farmaceutické prostředky na jejich bázi |
| US5330992A (en) | 1992-10-23 | 1994-07-19 | Sterling Winthrop Inc. | 1-cyclopropyl-4-pyridyl-quinolinones |
| GB9226855D0 (en) | 1992-12-23 | 1993-02-17 | Erba Carlo Spa | Vinylene-azaindole derivatives and process for their preparation |
| US5880141A (en) * | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
| WO1999020617A1 (en) * | 1997-10-21 | 1999-04-29 | Active Biotech Ab | Antiinflammatory thiadiazolyl ureas which act as lfa-1 and mac-1 inhibitors |
| HU230302B1 (hu) * | 2000-10-20 | 2015-12-28 | Eisai R&D Management Co., Ltd. | Nitrogéntartalmú aromás származékok és ezeket tartalmazó gyógyászati készítmények |
| JP2004528379A (ja) | 2001-05-08 | 2004-09-16 | シエーリング アクチエンゲゼルシャフト | Ｖｅｇｆｒ−２およびｖｅｇｆｒ−３インヒビターとしての選択的アントラニルアミドピリジンアミド |
| CA2461812C (en) | 2001-09-27 | 2011-09-20 | Allergan, Inc. | 3-(arylamino)methylene-1,3-dihydro-2h-indol-2-ones as kinase inhibitors |
| US6541504B1 (en) | 2002-04-03 | 2003-04-01 | Allergan Sales, Llc | (3Z)-3-(2,3-dihydro-1H-inden-1-ylidene)-1,3-dihydro-2H-indol-2-ones as kinase inhibitors |
| US20050058689A1 (en) | 2003-07-03 | 2005-03-17 | Reactive Surfaces, Ltd. | Antifungal paints and coatings |
| US6747025B1 (en) | 2002-11-27 | 2004-06-08 | Allergan, Inc. | Kinase inhibitors for the treatment of disease |
| GB0229022D0 (en) * | 2002-12-12 | 2003-01-15 | Novartis Ag | Organic Compounds |
| MXPA05009102A (es) * | 2003-02-28 | 2006-05-31 | Bayer Pharmaceuticals Corp | Derivados de piridina sustituida utiles en el tratamiento del cancer y otros trastornos. |
| PT1636585E (pt) * | 2003-05-20 | 2008-03-27 | Bayer Pharmaceuticals Corp | Diarilureias com actividade inibidora de cinase |
| CA2589773A1 (en) * | 2004-12-22 | 2006-06-29 | Astrazeneca Ab | Pyridine carboxamide derivatives for use as anticancer agents |
| TWI444187B (zh) * | 2005-01-25 | 2014-07-11 | Synta Pharmaceuticals Corp | 用於炎症及免疫相關用途之噻吩化合物 |
| CN101163478B (zh) * | 2005-01-25 | 2013-11-27 | 幸讬制药公司 | 用于炎症及免疫相关用途之化合物 |
| AU2006223070B2 (en) * | 2005-03-14 | 2012-02-09 | High Point Pharmaceuticals, Llc | Benzazole derivatives, compositions, and methods of use as B-secretase inhibitors |
| JO2787B1 (en) | 2005-04-27 | 2014-03-15 | امجين إنك, | Alternative amide derivatives and methods of use |
| CA2608726C (en) * | 2005-05-20 | 2013-07-09 | Methylgene Inc. | Inhibitors of vegf receptor and hgf receptor signaling |
| EP1891047A4 (en) | 2005-06-03 | 2008-07-09 | Bayer Healthcare Ag | A 1-METHYL-1H-PYRAZOLE-4-CARBOXYLIC ACID SUITABLE FOR THE CHEMOTHERAPY OF CANCER |
| DE102005062742A1 (de) * | 2005-12-22 | 2007-06-28 | Bayer Schering Pharma Ag | Sulfoximin substituierte Pyrimidine, Verfahren zu deren Herstellung und ihre Verwendung als Arzneimittel |
| US20070155746A1 (en) * | 2005-12-23 | 2007-07-05 | Kalypsys, Inc. | Novel substituted pyridinyloxy and pyrimidinyloxy amides useful as inhibitors of protein kinases |
| JP2009533327A (ja) * | 2006-03-22 | 2009-09-17 | バーテックス ファーマシューティカルズ インコーポレイテッド | 増殖性疾患を処置するためのｃ−ＭＥＴキナーゼ阻害剤 |
| US20080064718A1 (en) | 2006-03-22 | 2008-03-13 | Saavedra Oscar M | Inhibitors of protein tyrosine kinase activity |
| US7790756B2 (en) * | 2006-10-11 | 2010-09-07 | Deciphera Pharmaceuticals, Llc | Kinase inhibitors useful for the treatment of myleoproliferative diseases and other proliferative diseases |
| CA2684950A1 (en) * | 2007-04-20 | 2008-10-30 | Deciphera Pharmaceuticals, Llc | Kinase inhibitors useful for the treatment of myleoproliferative diseases and other proliferative diseases |
| JP2010526781A (ja) * | 2007-04-30 | 2010-08-05 | アボット・ラボラトリーズ | ジアシルグリセロールｏ−アシル転移酵素１型酵素の阻害剤 |
| WO2009026720A1 (en) * | 2007-08-29 | 2009-03-05 | Methylgene Inc. | Processes and intermediates for preparing fused heterocyclic kinase inhibitors |
| WO2009070328A1 (en) | 2007-11-26 | 2009-06-04 | The Regents Of The University Of California | Modulators of the epidermal growth factor receptor (egfr) pathway for use in the treatment or prevention of substance abuse |
| US20100324086A1 (en) * | 2008-02-19 | 2010-12-23 | Novasaid Ab | Compounds and methods |
| RU2012109233A (ru) * | 2009-09-03 | 2013-10-10 | Аллерган, Инк. | Соединения как модуляторы тирозинкиназы |
| US8906944B2 (en) * | 2009-09-03 | 2014-12-09 | Allergan, Inc. | Compounds as tyrosine kinase modulators |
-
2010
- 2010-09-03 RU RU2012109233/04A patent/RU2012109233A/ru not_active Application Discontinuation
- 2010-09-03 CA CA2772625A patent/CA2772625A1/en not_active Abandoned
- 2010-09-03 EP EP10760159.3A patent/EP2473501B1/en not_active Not-in-force
- 2010-09-03 WO PCT/US2010/047800 patent/WO2011028995A1/en not_active Ceased
- 2010-09-03 KR KR1020127008525A patent/KR20120082890A/ko not_active Withdrawn
- 2010-09-03 EP EP10752975.2A patent/EP2473513B1/en not_active Not-in-force
- 2010-09-03 US US12/875,223 patent/US8809534B2/en active Active
- 2010-09-03 MX MX2012002596A patent/MX2012002596A/es not_active Application Discontinuation
- 2010-09-03 ES ES10760159T patent/ES2730086T3/es active Active
- 2010-09-03 RU RU2012112151/04A patent/RU2012112151A/ru not_active Application Discontinuation
- 2010-09-03 BR BR112012004843A patent/BR112012004843A2/pt not_active IP Right Cessation
- 2010-09-03 SG SG2012015053A patent/SG178965A1/en unknown
- 2010-09-03 KR KR1020127008527A patent/KR20120047313A/ko not_active Withdrawn
- 2010-09-03 MX MX2012002591A patent/MX2012002591A/es not_active Application Discontinuation
- 2010-09-03 NZ NZ598455A patent/NZ598455A/en not_active IP Right Cessation
- 2010-09-03 CN CN2010800389522A patent/CN102498114A/zh active Pending
- 2010-09-03 JP JP2012528089A patent/JP2013503903A/ja active Pending
- 2010-09-03 CA CA2772718A patent/CA2772718C/en active Active
- 2010-09-03 US US12/875,218 patent/US8614234B2/en active Active
- 2010-09-03 NZ NZ598781A patent/NZ598781A/en not_active IP Right Cessation
- 2010-09-03 AU AU2010289359A patent/AU2010289359A1/en not_active Abandoned
- 2010-09-03 JP JP2012528084A patent/JP5868855B2/ja not_active Expired - Fee Related
- 2010-09-03 AU AU2010289353A patent/AU2010289353B2/en not_active Ceased
- 2010-09-03 WO PCT/US2010/047816 patent/WO2011029001A1/en not_active Ceased
- 2010-09-03 CN CN2010800482682A patent/CN102686577A/zh active Pending
- 2010-09-03 BR BR112012004718A patent/BR112012004718A2/pt not_active IP Right Cessation
- 2010-09-03 IN IN2493DEN2012 patent/IN2012DN02493A/en unknown
- 2010-09-03 SG SG2012015038A patent/SG178963A1/en unknown
-
2012
- 2012-02-27 IL IL218332A patent/IL218332A0/en unknown
- 2012-02-28 IL IL218374A patent/IL218374A0/en unknown
- 2012-03-02 CL CL2012000587A patent/CL2012000587A1/es unknown
- 2012-03-02 ZA ZA2012/01592A patent/ZA201201592B/en unknown
- 2012-03-02 CL CL2012000592A patent/CL2012000592A1/es unknown
- 2012-03-05 ZA ZA2012/01627A patent/ZA201201627B/en unknown
-
2013
- 2013-10-15 US US14/054,444 patent/US9328103B2/en active Active
-
2014
- 2014-02-03 PH PH12014500281A patent/PH12014500281A1/en unknown
-
2015
- 2015-07-08 US US14/793,913 patent/US9475801B2/en active Active
-
2016
- 2016-01-06 JP JP2016001387A patent/JP6109974B2/ja not_active Expired - Fee Related
- 2016-09-19 US US15/269,612 patent/US9725433B2/en not_active Expired - Fee Related
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005533011A (ja) * | 2002-04-05 | 2005-11-04 | アストラゼネカ アクチボラグ | ヒストンデアセチラーゼ阻害剤として有用なベンズアミド誘導体 |
| JP2005534669A (ja) * | 2002-06-14 | 2005-11-17 | ファイザー・インク | 治療剤として有用なチエノピリジンのベンゾ縮合ヘテロアリールアミド誘導体、それが含まれる医薬組成物、並びにその使用の方法 |
| JP2007504121A (ja) * | 2003-08-29 | 2007-03-01 | ファイザー・インク | 新たな抗血管形成剤として有用なナフタレン・カルボキサミド及びその誘導体 |
| JP2007504122A (ja) * | 2003-08-29 | 2007-03-01 | ファイザー・インク | 新規抗血管形成剤として有用なチエノピリジン−フェニルアセトアミドおよびその誘導体 |
| JP2007537296A (ja) * | 2004-05-14 | 2007-12-20 | アボット・ラボラトリーズ | 治療薬としてのキナーゼ阻害薬 |
| JP2009526761A (ja) * | 2006-01-30 | 2009-07-23 | アレイ バイオファーマ、インコーポレイテッド | ヘテロ二環式チオフェン化合物および使用の方法 |
| JP2010536887A (ja) * | 2007-08-29 | 2010-12-02 | メチルジーン インコーポレイテッド | タンパク質チロシンキナーゼ活性の阻害剤 |
| US20090118276A1 (en) * | 2007-11-02 | 2009-05-07 | Wyeth | Thienopyrimidines, thienopyridines, and pyrrolopyrimidines as b-raf inhibitors |
| WO2009109035A1 (en) * | 2008-03-05 | 2009-09-11 | Methylgene Inc. | Inhibitors of protein tyrosine kinase activity |
| US20100081675A1 (en) * | 2008-09-26 | 2010-04-01 | National Health Research Institutes | Fused multicyclic compounds as protein kinase inhibitors |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020520373A (ja) * | 2017-05-18 | 2020-07-09 | ピーアイ インダストリーズ リミテッドＰｉ Ｉｎｄｕｓｔｒｉｅｓ Ｌｔｄ | 植物病原性微生物に対して有用なホルムイミドアミジン化合物 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8809534B2 (en) | Compounds as tyrosine kinase modulators | |
| US6747025B1 (en) | Kinase inhibitors for the treatment of disease | |
| US10221192B2 (en) | Compounds as tyrosine kinase modulators | |
| JP7034512B2 (ja) | キナーゼ阻害剤としてのヘテロアリール化合物 | |
| US6699863B1 (en) | Kinase inhibitors for the treatment of disease | |
| JP6239149B2 (ja) | 複素芳香族化合物およびそのドーパミンｄ１リガンドとしての使用 | |
| US20130065880A1 (en) | Compounds as tyrosine kinase modulators | |
| JP6564394B2 (ja) | 複素環式化合物およびそのドーパミンｄ１リガンドとしての使用 | |
| TWI565698B (zh) | 喹啉化合物，其製造方法及用途 | |
| JP2017534588A (ja) | グループｉｉの代謝型グルタミン酸受容体のアロステリックモジュレーターとしての置換ピラゾロキナゾリノンおよびピロロキナゾリノン | |
| JP2011225582A (ja) | 疾患の治療のためのキナーゼ阻害剤 | |
| WO2004050621A2 (en) | Indol derivatives and their use as kinase inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130903 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130903 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20140731 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140804 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150126 |