CA2772625A1 - Compounds as tyrosine kinase modulators - Google Patents
Compounds as tyrosine kinase modulators Download PDFInfo
- Publication number
- CA2772625A1 CA2772625A1 CA2772625A CA2772625A CA2772625A1 CA 2772625 A1 CA2772625 A1 CA 2772625A1 CA 2772625 A CA2772625 A CA 2772625A CA 2772625 A CA2772625 A CA 2772625A CA 2772625 A1 CA2772625 A1 CA 2772625A1
- Authority
- CA
- Canada
- Prior art keywords
- cr5r6
- group
- alkyl
- independently selected
- hydrogen
- 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.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 86
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 title abstract description 16
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 title abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 239000001257 hydrogen Substances 0.000 claims description 42
- 229910052739 hydrogen Inorganic materials 0.000 claims description 42
- 239000000203 mixture Substances 0.000 claims description 30
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 28
- 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 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
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 239000000651 prodrug Substances 0.000 claims description 14
- 229940002612 prodrug Drugs 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- -1 hydroxy, amino Chemical group 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 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
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 10
- 150000001408 amides Chemical class 0.000 claims description 10
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 10
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 125000003342 alkenyl 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
- 206010029113 Neovascularisation Diseases 0.000 claims description 8
- 201000011510 cancer Diseases 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical group 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
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 125000002950 monocyclic group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 239000005483 tyrosine kinase inhibitor Substances 0.000 claims description 7
- 102100022631 Glutamate receptor ionotropic, NMDA 2C Human genes 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 201000010099 disease Diseases 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
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 108091008646 testicular receptors Proteins 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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
- OQDXZZHGQBFAKM-UHFFFAOYSA-N 2-fluoropyrrolidine Chemical compound FC1CCCN1 OQDXZZHGQBFAKM-UHFFFAOYSA-N 0.000 claims description 5
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 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
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 5
- 230000000699 topical effect Effects 0.000 claims description 5
- 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
- 206010012688 Diabetic retinal oedema Diseases 0.000 claims description 4
- 206010012689 Diabetic retinopathy 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
- 208000001344 Macular Edema 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
- 230000033115 angiogenesis Effects 0.000 claims description 4
- 206010003246 arthritis Diseases 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
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 201000011190 diabetic macular edema Diseases 0.000 claims description 4
- 208000024519 eye neoplasm Diseases 0.000 claims description 4
- 230000002489 hematologic effect Effects 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
- 201000008106 ocular cancer Diseases 0.000 claims description 4
- 239000002674 ointment Substances 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- 201000011195 retinal edema Diseases 0.000 claims description 4
- 208000032253 retinal ischemia Diseases 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 230000029663 wound healing Effects 0.000 claims description 4
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 3
- 125000001627 3 membered heterocyclic group Chemical group 0.000 claims description 3
- 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
- 125000003282 alkyl amino 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
- 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
- 239000003937 drug carrier Substances 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
- 239000000499 gel Substances 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
- 239000003826 tablet Substances 0.000 claims description 3
- 150000002431 hydrogen Chemical group 0.000 claims 14
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 6
- 125000005843 halogen group Chemical group 0.000 claims 6
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 239000003885 eye ointment Substances 0.000 claims 1
- 239000007921 spray Substances 0.000 claims 1
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 claims 1
- 230000006806 disease prevention Effects 0.000 abstract description 4
- 230000002159 abnormal effect Effects 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
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 34
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 26
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 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
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 18
- 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
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 15
- 108020003175 receptors Proteins 0.000 description 15
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 14
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 11
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 11
- 125000001475 halogen functional group Chemical group 0.000 description 10
- 125000003944 tolyl group Chemical group 0.000 description 10
- 101100441108 Arabidopsis thaliana CRR6 gene Proteins 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 230000019491 signal transduction Effects 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
- 230000005764 inhibitory process Effects 0.000 description 8
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 8
- 239000002953 phosphate buffered saline Substances 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 239000013078 crystal Substances 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 239000003446 ligand Substances 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
- 210000004204 blood vessel Anatomy 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- GKTQKQTXHNUFSP-UHFFFAOYSA-N thieno[3,4-c]pyrrole-4,6-dione Chemical compound S1C=C2C(=O)NC(=O)C2=C1 GKTQKQTXHNUFSP-UHFFFAOYSA-N 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- 206010015866 Extravasation Diseases 0.000 description 4
- 101000878540 Homo sapiens Protein-tyrosine kinase 2-beta Proteins 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
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 102100037787 Protein-tyrosine kinase 2-beta Human genes 0.000 description 4
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 230000036251 extravasation Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 230000026731 phosphorylation Effects 0.000 description 4
- 238000006366 phosphorylation reaction Methods 0.000 description 4
- SIOXPEMLGUPBBT-UHFFFAOYSA-M picolinate Chemical compound [O-]C(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-M 0.000 description 4
- 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 239000012453 solvate Substances 0.000 description 4
- OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 description 3
- GYQUXKQLCNFKQT-UHFFFAOYSA-N 7-chlorothieno[3,2-b]pyridine Chemical compound ClC1=CC=NC2=C1SC=C2 GYQUXKQLCNFKQT-UHFFFAOYSA-N 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
- 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
- 230000010261 cell growth Effects 0.000 description 3
- 239000013626 chemical specie Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 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
- 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
- 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 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000000638 stimulation Effects 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
- IDUWPLJMHJJLFD-UHFFFAOYSA-N 3-[[7-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carbonyl]amino]propanoic acid Chemical compound CC1=CC=C(F)C(NC(=O)NC=2C=CC(OC=3C=4SC(=CC=4N=CC=3)C(=O)NCCC(O)=O)=CC=2)=C1 IDUWPLJMHJJLFD-UHFFFAOYSA-N 0.000 description 2
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 2
- 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 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
- 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 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 101150041968 CDC13 gene Proteins 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
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound 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
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 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
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 102000014400 SH2 domains Human genes 0.000 description 2
- 108050003452 SH2 domains 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
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 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
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 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
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000036755 cellular response 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
- 239000006196 drop Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 230000002500 effect on skin Effects 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
- 239000007850 fluorescent dye Substances 0.000 description 2
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 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
- 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
- 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 2
- 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 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
- 239000002997 ophthalmic solution Substances 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-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
- 230000011664 signaling 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
- 239000000126 substance Substances 0.000 description 2
- 230000009897 systematic 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
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- UXOFPHPAEAVMKW-UHFFFAOYSA-N 1-(2-fluoro-5-methylphenyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea Chemical compound CC1=CC=C(F)C(NC(=O)NC=2C=CC(=CC=2)B2OC(C)(C)C(C)(C)O2)=C1 UXOFPHPAEAVMKW-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 class O=C1NC2=CC=CC=C2C=C1C(C=C1)=CCN1C1CC1 RYCSNJCJOVQGBC-UHFFFAOYSA-N 0.000 description 1
- SWFOYPCYOVWWFV-UHFFFAOYSA-N 3-[[7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carbonyl]amino]propanoic acid Chemical compound CC1=CC=C(F)C(NC(=O)NC=2C(=CC(OC=3C=4SC(=CC=4N=CC=3)C(=O)NCCC(O)=O)=CC=2)F)=C1 SWFOYPCYOVWWFV-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
- AACVULYSNJAKEQ-UHFFFAOYSA-N 4h-thieno[3,2-b]pyridin-7-one Chemical compound OC1=CC=NC2=C1SC=C2 AACVULYSNJAKEQ-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
- COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 1
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 241000700199 Cavia porcellus Species 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
- 101100333619 Danio rerio ephb4a gene Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 238000002965 ELISA Methods 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
- YSWHPLCDIMUKFE-QWRGUYRKSA-N Glu-Tyr Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 YSWHPLCDIMUKFE-QWRGUYRKSA-N 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 229910003556 H2 SO4 Inorganic materials 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
- 101000808011 Homo sapiens Vascular endothelial growth factor A 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
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
- 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 1
- 108020002076 NR2 subfamily Proteins 0.000 description 1
- 102400000058 Neuregulin-1 Human genes 0.000 description 1
- 108090000556 Neuregulin-1 Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 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
- 101100372762 Rattus norvegicus Flt1 gene 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
- 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
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 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
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 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
- 230000005754 cellular signaling Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001427 coherent 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
- 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
- 238000013461 design Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 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
- 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
- 230000008472 epithelial growth Effects 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
- 229960003699 evans blue Drugs 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 108091071773 flk family Proteins 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 208000037824 growth disorder Diseases 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
- 102000058223 human VEGFA Human genes 0.000 description 1
- 230000000521 hyperimmunizing effect Effects 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000031146 intracellular signal transduction 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
- 230000003902 lesion Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000011565 manganese chloride Substances 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
- SJMKELNHAJGCDT-UHFFFAOYSA-N methyl 7-[3-[(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=1)=CC=CC=1NC(=O)NC1=CC(C)=CC=C1F SJMKELNHAJGCDT-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 230000000116 mitigating effect Effects 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
- 210000003733 optic disk Anatomy 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
- 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
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- 125000004076 pyridyl group Chemical class 0.000 description 1
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 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
- 239000011734 sodium Substances 0.000 description 1
- 235000017550 sodium carbonate 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
- 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
- 238000001228 spectrum Methods 0.000 description 1
- 125000005504 styryl group Chemical group 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
- 230000002792 vascular Effects 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)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Ophthalmology & Optometry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Gastroenterology & Hepatology (AREA)
- Reproductive Health (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Orthopedic Medicine & Surgery (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 (1)
Publication Number | Publication Date |
---|---|
CA2772625A1 true CA2772625A1 (en) | 2011-03-10 |
Family
ID=43086186
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2772625A Abandoned CA2772625A1 (en) | 2009-09-03 | 2010-09-03 | Compounds as tyrosine kinase modulators |
CA2772718A Active CA2772718C (en) | 2009-09-03 | 2010-09-03 | Compounds as tyrosine kinase modulators |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2772718A Active CA2772718C (en) | 2009-09-03 | 2010-09-03 | Compounds as tyrosine kinase modulators |
Country Status (19)
Country | Link |
---|---|
US (5) | US8614234B2 (OSRAM) |
EP (2) | EP2473513B1 (OSRAM) |
JP (3) | JP5868855B2 (OSRAM) |
KR (2) | KR20120082890A (OSRAM) |
CN (2) | CN102498114A (OSRAM) |
AU (2) | AU2010289359A1 (OSRAM) |
BR (2) | BR112012004718A2 (OSRAM) |
CA (2) | CA2772625A1 (OSRAM) |
CL (2) | CL2012000592A1 (OSRAM) |
ES (1) | ES2730086T3 (OSRAM) |
IL (2) | IL218332A0 (OSRAM) |
IN (1) | IN2012DN02493A (OSRAM) |
MX (2) | MX2012002591A (OSRAM) |
NZ (2) | NZ598455A (OSRAM) |
PH (1) | PH12014500281A1 (OSRAM) |
RU (2) | RU2012109233A (OSRAM) |
SG (2) | SG178965A1 (OSRAM) |
WO (2) | WO2011029001A1 (OSRAM) |
ZA (2) | ZA201201592B (OSRAM) |
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 |
EP2297133B1 (en) * | 2008-06-25 | 2017-09-13 | Forum Pharmaceuticals Inc. | 1, 2 disubstituted heterocyclic compounds |
BRPI0920261A8 (pt) | 2008-10-14 | 2016-01-19 | Xi Ning | Composto, composição farmacêutica, uso do composto, e, método para inibir ou modular atividade de proteína quinase em uma amostra biológica |
CA2752421C (en) | 2009-03-21 | 2013-08-06 | Ning Xi | Amino ester derivatives, salts thereof and methods of use |
RU2531274C2 (ru) | 2009-05-07 | 2014-10-20 | Энвиво Фармасьютикалз, Инк. | Феноксиметильные гетероциклические соединения |
US10206813B2 (en) | 2009-05-18 | 2019-02-19 | Dose Medical 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 |
US9340555B2 (en) * | 2009-09-03 | 2016-05-17 | Allergan, Inc. | Compounds as tyrosine kinase modulators |
US8906944B2 (en) * | 2009-09-03 | 2014-12-09 | Allergan, Inc. | Compounds as tyrosine kinase modulators |
IN2012DN02493A (OSRAM) | 2009-09-03 | 2015-08-28 | Allergan Inc | |
US9668915B2 (en) | 2010-11-24 | 2017-06-06 | Dose Medical Corporation | Drug eluting ocular implant |
US10245178B1 (en) | 2011-06-07 | 2019-04-02 | Glaukos Corporation | Anterior chamber drug-eluting ocular implant |
PL2812337T3 (pl) * | 2012-02-09 | 2017-01-31 | Merck Patent Gmbh | Pochodne furo[3,2-b]pirydynowe jako inhibitory tbk1 oraz ikk |
WO2015069287A1 (en) * | 2013-11-08 | 2015-05-14 | Allergan, Inc. | Compounds as tyrosine kinase modulators |
WO2015089479A1 (en) * | 2013-12-13 | 2015-06-18 | Dana-Farber Cancer Institute, Inc. | Methods to treat lymphoplasmacytic lymphoma |
JP6878004B2 (ja) | 2013-12-13 | 2021-05-26 | ダナ−ファーバー キャンサー インスティテュート, インコーポレイテッド | リンパ形質細胞性リンパ腫を処置する方法 |
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 |
EP3677229A1 (en) | 2014-05-29 | 2020-07-08 | Glaukos Corporation | Implants with controlled drug delivery features |
BR112017003745A2 (pt) | 2014-08-29 | 2017-12-05 | Tes Pharma S R L | inibidores de semialdeído descarboxilase de ácido alfa-amino-beta-carboximucônico |
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 |
CA2965178C (en) | 2014-10-22 | 2023-09-26 | Dana-Farber Cancer Institute, Inc. | Thiazolyl-containing compounds for treating proliferative diseases |
WO2017040853A1 (en) | 2015-09-02 | 2017-03-09 | 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 |
CN107531679B (zh) * | 2016-03-18 | 2021-07-02 | 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 |
AU2017252294B2 (en) | 2016-04-20 | 2021-12-02 | Glaukos Corporation | Bioresorbable ocular drug delivery device |
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 |
US11161859B2 (en) | 2017-03-21 | 2021-11-02 | The Scripps Research Institute | Cu- and Ni-catalyzed decarboxylative borylation reactions |
SMT202100568T1 (it) | 2017-05-11 | 2021-11-12 | Bristol Myers Squibb Co | Tienopiridine e benzotiofeni utili come inibitori di irak4 |
TW201900604A (zh) * | 2017-05-18 | 2019-01-01 | 印度商Pi工業公司 | 新穎的脒化合物 |
PT3860998T (pt) | 2018-10-05 | 2024-04-02 | Annapurna Bio Inc | Compostos e composições para o tratamento de condições associadas à atividade do recetor apj |
CA3121202A1 (en) | 2018-11-30 | 2020-06-04 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
Family Cites Families (50)
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 |
FI924427A7 (fi) | 1990-04-02 | 1992-10-01 | Pfizer | Bentsyylifosfonihappotyrosiinikinaasi-inhibiittorit |
US5302606A (en) | 1990-04-16 | 1994-04-12 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Styryl-substituted pyridyl compounds which inhibit EGF receptor tyrosine kinase |
US5409930A (en) | 1991-05-10 | 1995-04-25 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
US6194439B1 (en) | 1991-05-29 | 2001-02-27 | 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 |
AU9802198A (en) * | 1997-10-21 | 1999-05-10 | Pharmacia & Upjohn Company | Antiinflammatory thiadiazolyl ureas which act as lfa-1 and mac-1 inhibitors |
ATE419239T1 (de) * | 2000-10-20 | 2009-01-15 | Eisai R&D Man Co Ltd | Verfahren zur herstellung von 4-phenoxy chinolin derivaten |
WO2002090352A2 (de) * | 2001-05-08 | 2002-11-14 | Schering Aktiengesellschaft | Selektive anthranylamidpyridinamide als vegfr-2 und vegfr-3 inhibitoren |
EP1430048A1 (en) * | 2001-09-27 | 2004-06-23 | 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 |
TWI319387B (en) * | 2002-04-05 | 2010-01-11 | Astrazeneca Ab | Benzamide derivatives |
UA77303C2 (en) * | 2002-06-14 | 2006-11-15 | Pfizer | Derivatives of thienopyridines substituted by benzocondensed heteroarylamide useful as therapeutic agents, pharmaceutical compositions and methods for their use |
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 |
CA2516627A1 (en) * | 2003-02-28 | 2004-09-16 | Bayer Pharmaceuticals Corporation | Substituted pyridine derivatives useful in the treatment of cancer and other disorders |
CA2526617C (en) * | 2003-05-20 | 2015-04-28 | Bayer Pharmaceuticals Corporation | Diaryl ureas with kinase inhibiting activity |
DE602004017479D1 (de) * | 2003-08-29 | 2008-12-11 | Pfizer | Als neue antiangiogene mittel geeignete thienopyridinphenylacetamide und derivate davon |
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 |
CA2566158A1 (en) * | 2004-05-14 | 2005-11-24 | Abbott Laboratories | Kinase inhibitors as therapeutic agents |
KR20070091675A (ko) * | 2004-12-22 | 2007-09-11 | 아스트라제네카 아베 | 항암제로서 사용하기 위한 피리딘 카르복사미드 유도체 |
CA2595000C (en) * | 2005-01-25 | 2013-10-15 | Synta Pharmaceuticals Corp. | Thiophene compounds for inflammation and immune-related uses |
AU2006208045B2 (en) * | 2005-01-25 | 2012-08-30 | Synta Pharmaceuticals Corp. | Compounds for inflammation and immune-related uses |
WO2006099379A2 (en) | 2005-03-14 | 2006-09-21 | Transtech Pharma, Inc. | 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 |
MX2007014617A (es) * | 2005-05-20 | 2008-02-11 | Methylgene Inc | Inhibidores de senalizacion de receptor de factor de crecimiento endotelial bascular y receptor de factor de crecimiento de hepatocitos. |
CA2610509A1 (en) | 2005-06-03 | 2006-12-14 | Bayer Healthcare Ag | 1-methyl-1h-pyrazole-4-carboxamides useful as cancer chemotherapeutic agents |
DE102005062742A1 (de) * | 2005-12-22 | 2007-06-28 | Bayer Schering Pharma Ag | Sulfoximin substituierte Pyrimidine, Verfahren zu deren Herstellung und ihre Verwendung als Arzneimittel |
WO2007076474A1 (en) * | 2005-12-23 | 2007-07-05 | Kalypsys, Inc. | Novel substituted pyridinyloxy and pyrimidinyloxy amides useful as inhibitors of protein kinases |
CN101522687A (zh) * | 2006-01-30 | 2009-09-02 | 阿雷生物药品公司 | 用于癌症治疗的杂二环噻吩化合物 |
ATE453635T1 (de) * | 2006-03-22 | 2010-01-15 | Vertex Pharma | C-met-proteinkinasehemmer zur behandlung proliferativer erkrankungen |
WO2007107005A1 (en) * | 2006-03-22 | 2007-09-27 | Methylgene, Inc. | 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 |
JP2010524974A (ja) * | 2007-04-20 | 2010-07-22 | デシファラ ファーマスーティカルズ, エルエルシー | 骨髄増殖性疾患および他の増殖性疾患の治療に有用なキナーゼ阻害剤 |
AU2008245461B2 (en) * | 2007-04-30 | 2012-12-06 | Abbvie Inc. | Inhibitors of diacylglycerol O-acyltransferase type 1 enzyme |
MY156536A (en) * | 2007-08-29 | 2016-02-26 | Methylgene Inc | Inhibitors of protein tyrosine kinase activity |
EP2426108B1 (en) | 2007-08-29 | 2016-08-10 | MethylGene Inc. | Processes and intermediates for preparing fused heterocyclic kinase inhibitors |
US20090118276A1 (en) | 2007-11-02 | 2009-05-07 | Wyeth | Thienopyrimidines, thienopyridines, and pyrrolopyrimidines as b-raf 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 |
BRPI0923670A2 (pt) * | 2008-03-05 | 2013-07-30 | Methylgene Inc | inibidores da atividade de proteÍna tirosina quinase e seu uso, bem como composiÇço compreendendo os mesmos |
EP2331530B8 (en) * | 2008-09-26 | 2013-12-25 | National Health Research Institutes | Fused multicyclic compounds as protein kinase inhibitors |
US8906944B2 (en) * | 2009-09-03 | 2014-12-09 | Allergan, Inc. | Compounds as tyrosine kinase modulators |
IN2012DN02493A (OSRAM) | 2009-09-03 | 2015-08-28 | Allergan Inc |
-
2010
- 2010-09-03 IN IN2493DEN2012 patent/IN2012DN02493A/en unknown
- 2010-09-03 RU RU2012109233/04A patent/RU2012109233A/ru not_active Application Discontinuation
- 2010-09-03 US US12/875,218 patent/US8614234B2/en active Active
- 2010-09-03 BR BR112012004718A patent/BR112012004718A2/pt not_active IP Right Cessation
- 2010-09-03 JP JP2012528084A patent/JP5868855B2/ja not_active Expired - Fee Related
- 2010-09-03 SG SG2012015053A patent/SG178965A1/en unknown
- 2010-09-03 AU AU2010289359A patent/AU2010289359A1/en not_active Abandoned
- 2010-09-03 CA CA2772625A patent/CA2772625A1/en not_active Abandoned
- 2010-09-03 US US12/875,223 patent/US8809534B2/en active Active
- 2010-09-03 CA CA2772718A patent/CA2772718C/en active Active
- 2010-09-03 KR KR1020127008525A patent/KR20120082890A/ko not_active Withdrawn
- 2010-09-03 SG SG2012015038A patent/SG178963A1/en unknown
- 2010-09-03 NZ NZ598455A patent/NZ598455A/en not_active IP Right Cessation
- 2010-09-03 WO PCT/US2010/047816 patent/WO2011029001A1/en active Application Filing
- 2010-09-03 KR KR1020127008527A patent/KR20120047313A/ko not_active Withdrawn
- 2010-09-03 EP EP10752975.2A patent/EP2473513B1/en not_active Not-in-force
- 2010-09-03 WO PCT/US2010/047800 patent/WO2011028995A1/en active Application Filing
- 2010-09-03 RU RU2012112151/04A patent/RU2012112151A/ru not_active Application Discontinuation
- 2010-09-03 NZ NZ598781A patent/NZ598781A/en not_active IP Right Cessation
- 2010-09-03 EP EP10760159.3A patent/EP2473501B1/en active Active
- 2010-09-03 MX MX2012002591A patent/MX2012002591A/es not_active Application Discontinuation
- 2010-09-03 CN CN2010800389522A patent/CN102498114A/zh active Pending
- 2010-09-03 MX MX2012002596A patent/MX2012002596A/es not_active Application Discontinuation
- 2010-09-03 BR BR112012004843A patent/BR112012004843A2/pt not_active IP Right Cessation
- 2010-09-03 CN CN2010800482682A patent/CN102686577A/zh active Pending
- 2010-09-03 ES ES10760159T patent/ES2730086T3/es active Active
- 2010-09-03 JP JP2012528089A patent/JP2013503903A/ja active Pending
- 2010-09-03 AU AU2010289353A patent/AU2010289353B2/en not_active Ceased
-
2012
- 2012-02-27 IL IL218332A patent/IL218332A0/en unknown
- 2012-02-28 IL IL218374A patent/IL218374A0/en unknown
- 2012-03-02 CL CL2012000592A patent/CL2012000592A1/es unknown
- 2012-03-02 CL CL2012000587A patent/CL2012000587A1/es unknown
- 2012-03-02 ZA ZA2012/01592A patent/ZA201201592B/en 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 active Active
- 2016-09-19 US US15/269,612 patent/US9725433B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8809534B2 (en) | Compounds as tyrosine kinase modulators | |
US10221192B2 (en) | Compounds as tyrosine kinase modulators | |
CN103965120B (zh) | 喹啉及喹唑啉衍生物、制备方法、中间体、组合物及应用 | |
US6747025B1 (en) | Kinase inhibitors for the treatment of disease | |
WO2015069287A1 (en) | Compounds as tyrosine kinase modulators | |
US6699863B1 (en) | Kinase inhibitors for the treatment of disease | |
JP2009534458A (ja) | アミノ−エチル−アミノ−アリール(aeaa)化合物およびそれらの使用 | |
US8906944B2 (en) | Compounds as tyrosine kinase modulators | |
WO2004050621A2 (en) | Indol derivatives and their use as kinase inhibitors | |
JP2006512400A (ja) | 疾患の治療のためのキナーゼ阻害剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FZDE | Discontinued |
Effective date: 20150903 |