CA2751517A1 - [1, 2, 4] triazolo [1, 5 -a] pyridines as kinase inhibitors - Google Patents
[1, 2, 4] triazolo [1, 5 -a] pyridines as kinase inhibitors Download PDFInfo
- Publication number
- CA2751517A1 CA2751517A1 CA2751517A CA2751517A CA2751517A1 CA 2751517 A1 CA2751517 A1 CA 2751517A1 CA 2751517 A CA2751517 A CA 2751517A CA 2751517 A CA2751517 A CA 2751517A CA 2751517 A1 CA2751517 A1 CA 2751517A1
- Authority
- CA
- Canada
- Prior art keywords
- triazolo
- pyridin
- chloro
- phenyl
- phenylamino
- 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
- 229940043355 kinase inhibitor Drugs 0.000 title abstract description 11
- 239000003757 phosphotransferase inhibitor Substances 0.000 title abstract description 11
- 150000008527 [1,2,4]triazolo-[1,5-a]pyridines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 143
- -1 4-Chloro-3-{2-[4-(2-dimethylamino-ethoxy)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-phenol 4-Chloro-3-{2-[3-(2-dimethylamino-ethoxy)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-phenol Chemical compound 0.000 claims description 19
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- ROAWFGXZLSXEMC-NRFANRHFSA-N (2s)-1-[2-[4-[[6-(2-chloro-5-hydroxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]phenoxy]acetyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)COC(C=C1)=CC=C1NC1=NN2C=C(C=3C(=CC=C(O)C=3)Cl)C=CC2=N1 ROAWFGXZLSXEMC-NRFANRHFSA-N 0.000 claims description 2
- BARSDANYGJRCIS-UHFFFAOYSA-N 1-[4-[[6-(2-chloro-5-hydroxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]phenyl]-3-(2-pyrrolidin-1-ylethyl)imidazolidin-2-one Chemical compound OC1=CC=C(Cl)C(C2=CN3N=C(NC=4C=CC(=CC=4)N4C(N(CCN5CCCC5)CC4)=O)N=C3C=C2)=C1 BARSDANYGJRCIS-UHFFFAOYSA-N 0.000 claims description 2
- WJEJGIVUBFILHU-UHFFFAOYSA-N 1-[4-[[6-(2-chloro-5-hydroxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]phenyl]-3-(2-pyrrolidin-1-ylethyl)urea Chemical compound OC1=CC=C(Cl)C(C2=CN3N=C(NC=4C=CC(NC(=O)NCCN5CCCC5)=CC=4)N=C3C=C2)=C1 WJEJGIVUBFILHU-UHFFFAOYSA-N 0.000 claims description 2
- RPOSMBFRRGRZOH-UHFFFAOYSA-N 1-[4-[[6-(2-chloro-5-hydroxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]phenyl]-3-methylimidazolidin-2-one Chemical compound O=C1N(C)CCN1C(C=C1)=CC=C1NC1=NN2C=C(C=3C(=CC=C(O)C=3)Cl)C=CC2=N1 RPOSMBFRRGRZOH-UHFFFAOYSA-N 0.000 claims description 2
- DSPDRCOCBFODME-FSRHSHDFSA-N 2-[4-[[6-(2-chloro-5-hydroxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]phenoxy]-1-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]ethanone;hydrochloride Chemical compound Cl.C1[C@H](N(C)C)CCN1C(=O)COC(C=C1)=CC=C1NC1=NN2C=C(C=3C(=CC=C(O)C=3)Cl)C=CC2=N1 DSPDRCOCBFODME-FSRHSHDFSA-N 0.000 claims description 2
- ZQLAXZRJCHQQLN-UHFFFAOYSA-N 4-chloro-3-[2-[4-(2-morpholin-4-ylethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenol hydrochloride Chemical compound ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC2=CC=C(C=C2)OCCN2CCOCC2.Cl ZQLAXZRJCHQQLN-UHFFFAOYSA-N 0.000 claims description 2
- LZWAVRVFEJGPHF-UHFFFAOYSA-N 4-chloro-3-[2-[4-(2-piperazin-1-ylethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenol Chemical compound OC1=CC=C(Cl)C(C2=CN3N=C(NC=4C=CC(OCCN5CCNCC5)=CC=4)N=C3C=C2)=C1 LZWAVRVFEJGPHF-UHFFFAOYSA-N 0.000 claims description 2
- YRNOHRHOJLMBMR-UHFFFAOYSA-N 4-chloro-3-[2-[4-(2-pyrrolidin-1-ylethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenol Chemical compound OC1=CC=C(Cl)C(C2=CN3N=C(NC=4C=CC(OCCN5CCCC5)=CC=4)N=C3C=C2)=C1 YRNOHRHOJLMBMR-UHFFFAOYSA-N 0.000 claims description 2
- CLBQOSXQVQDPBN-UHFFFAOYSA-N 4-chloro-3-[2-[4-(2-pyrrolidin-1-ylethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyridin-7-yl]phenol;hydrochloride Chemical compound Cl.OC1=CC=C(Cl)C(C2=CC3=NC(NC=4C=CC(OCCN5CCCC5)=CC=4)=NN3C=C2)=C1 CLBQOSXQVQDPBN-UHFFFAOYSA-N 0.000 claims description 2
- QSWJEWQNQNGKKP-UHFFFAOYSA-N 5-[[6-(2-chloro-5-hydroxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]-1-benzofuran-2-carboxylic acid Chemical compound C=1C=C2OC(C(=O)O)=CC2=CC=1NC(=NN1C=2)N=C1C=CC=2C1=CC(O)=CC=C1Cl QSWJEWQNQNGKKP-UHFFFAOYSA-N 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- PXLLPAINWRMQQX-UHFFFAOYSA-N ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC2=CC=C(C=C2)OCCO.ClC2=C(C=C(C=C2)O)C=2C=CC=1N(C2)N=C(N1)NC1=CC=C(C=C1)S(=O)(=O)N Chemical compound ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC2=CC=C(C=C2)OCCO.ClC2=C(C=C(C=C2)O)C=2C=CC=1N(C2)N=C(N1)NC1=CC=C(C=C1)S(=O)(=O)N PXLLPAINWRMQQX-UHFFFAOYSA-N 0.000 claims description 2
- PIQLFIDMRVMWDR-UHFFFAOYSA-N ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC=2C=C(C=CC2)S(=O)(=O)N.ClC2=C(C=C(C=C2)O)C=2C=CC=1N(C2)N=C(N1)NC1=CC=C(C=C1)N1C(NCC1)=O Chemical compound ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC=2C=C(C=CC2)S(=O)(=O)N.ClC2=C(C=C(C=C2)O)C=2C=CC=1N(C2)N=C(N1)NC1=CC=C(C=C1)N1C(NCC1)=O PIQLFIDMRVMWDR-UHFFFAOYSA-N 0.000 claims description 2
- IXMVZOGJNYHWOO-UHFFFAOYSA-N ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC=2C=C(OCC(=O)N)C=CC2.ClC2=C(C=C(C=C2)O)C=2C=CC=1N(C2)N=C(N1)NC1=CC=C(OCC(=O)N)C=C1 Chemical compound ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC=2C=C(OCC(=O)N)C=CC2.ClC2=C(C=C(C=C2)O)C=2C=CC=1N(C2)N=C(N1)NC1=CC=C(OCC(=O)N)C=C1 IXMVZOGJNYHWOO-UHFFFAOYSA-N 0.000 claims description 2
- 101100295741 Gallus gallus COR4 gene Proteins 0.000 claims description 2
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 4
- ZBDPZYTWLRKACH-UHFFFAOYSA-N 1-[4-[4-[[6-(2-chloro-5-hydroxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]phenyl]piperazin-1-yl]-2-methoxyethanone Chemical compound C1CN(C(=O)COC)CCN1C(C=C1)=CC=C1NC1=NN2C=C(C=3C(=CC=C(O)C=3)Cl)C=CC2=N1 ZBDPZYTWLRKACH-UHFFFAOYSA-N 0.000 claims 1
- PLJUZHRXSVGDPZ-UHFFFAOYSA-N 1-[4-[[6-(2-chloro-5-hydroxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]phenyl]-3-(2-methoxyethyl)imidazolidin-2-one Chemical compound O=C1N(CCOC)CCN1C(C=C1)=CC=C1NC1=NN2C=C(C=3C(=CC=C(O)C=3)Cl)C=CC2=N1 PLJUZHRXSVGDPZ-UHFFFAOYSA-N 0.000 claims 1
- BYQJOSJZOBTXSI-UHFFFAOYSA-N 1-[4-[[6-(2-chloro-5-hydroxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]phenyl]-3-(2-pyrrolidin-1-ylethyl)imidazolidin-2-one hydrochloride Chemical compound ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC2=CC=C(C=C2)N2C(N(CC2)CCN2CCCC2)=O.Cl BYQJOSJZOBTXSI-UHFFFAOYSA-N 0.000 claims 1
- GMVUWYZCXDMBMZ-UHFFFAOYSA-N 3-(2-anilino-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-chlorophenol Chemical compound ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C=1)N=C(N=2)NC1=CC=CC=C1 GMVUWYZCXDMBMZ-UHFFFAOYSA-N 0.000 claims 1
- LTNGMLIFOYKGOA-UHFFFAOYSA-N 4-chloro-3-[2-(4-phenoxyanilino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenol 4-chloro-3-[2-[4-(trifluoromethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenol Chemical compound ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC2=CC=C(C=C2)OC2=CC=CC=C2.ClC2=C(C=C(C=C2)O)C=2C=CC=1N(C2)N=C(N1)NC1=CC=C(C=C1)OC(F)(F)F LTNGMLIFOYKGOA-UHFFFAOYSA-N 0.000 claims 1
- FWHMELQUPGZDDN-UHFFFAOYSA-N 4-chloro-3-[2-[3-(hydroxymethyl)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenol Chemical compound OCC1=CC=CC(NC2=NN3C=C(C=CC3=N2)C=2C(=CC=C(O)C=2)Cl)=C1 FWHMELQUPGZDDN-UHFFFAOYSA-N 0.000 claims 1
- UFMBQIIYUXUYHH-UHFFFAOYSA-N 4-chloro-3-[8-methyl-2-[4-(2-pyrrolidin-1-ylethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenol Chemical compound N1=C2C(C)=CC(C=3C(=CC=C(O)C=3)Cl)=CN2N=C1NC(C=C1)=CC=C1OCCN1CCCC1 UFMBQIIYUXUYHH-UHFFFAOYSA-N 0.000 claims 1
- JQIVVRPTQJDEGG-UHFFFAOYSA-N C(C1=CC=CC=C1)OC1=CC=C(C=C1)NC1=NN2C(C=CC(=C2)C=2C=C(C=CC2Cl)O)=N1.ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC2=CC=C(C=C2)S(=O)(=O)C Chemical compound C(C1=CC=CC=C1)OC1=CC=C(C=C1)NC1=NN2C(C=CC(=C2)C=2C=C(C=CC2Cl)O)=N1.ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC2=CC=C(C=C2)S(=O)(=O)C JQIVVRPTQJDEGG-UHFFFAOYSA-N 0.000 claims 1
- LJTJITAYZOPUNO-UHFFFAOYSA-N ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC2=CC(=CC=C2)N2N=CC=C2.ClC2=C(C=C(C=C2)O)C=2C=CC=1N(C2)N=C(N1)NC1=CC(=CC=C1)OCCN1CCOCC1 Chemical compound ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC2=CC(=CC=C2)N2N=CC=C2.ClC2=C(C=C(C=C2)O)C=2C=CC=1N(C2)N=C(N1)NC1=CC(=CC=C1)OCCN1CCOCC1 LJTJITAYZOPUNO-UHFFFAOYSA-N 0.000 claims 1
- SPXOSOIFILWYSI-UHFFFAOYSA-N ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC2=CC=C(C=C2)CO.ClC2=C(C=C(C=C2)O)C=2C=CC=1N(C2)N=C(N1)NC1=CC(=CC=C1)OCCN1CCCC1 Chemical compound ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC2=CC=C(C=C2)CO.ClC2=C(C=C(C=C2)O)C=2C=CC=1N(C2)N=C(N1)NC1=CC(=CC=C1)OCCN1CCCC1 SPXOSOIFILWYSI-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- CXQZKNRYQQRGQG-UHFFFAOYSA-N [4-[4-[[6-(2-chloro-5-hydroxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]phenyl]piperazin-1-yl]-pyridin-4-ylmethanone Chemical compound OC1=CC=C(Cl)C(C2=CN3N=C(NC=4C=CC(=CC=4)N4CCN(CC4)C(=O)C=4C=CN=CC=4)N=C3C=C2)=C1 CXQZKNRYQQRGQG-UHFFFAOYSA-N 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 61
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 55
- 208000035475 disorder Diseases 0.000 abstract description 34
- 201000010099 disease Diseases 0.000 abstract description 18
- 206010028980 Neoplasm Diseases 0.000 abstract description 17
- 108091000080 Phosphotransferase Proteins 0.000 abstract description 15
- 201000011510 cancer Diseases 0.000 abstract description 15
- 102000020233 phosphotransferase Human genes 0.000 abstract description 15
- 208000002780 macular degeneration Diseases 0.000 abstract description 9
- 230000001404 mediated effect Effects 0.000 abstract description 8
- 206010038923 Retinopathy Diseases 0.000 abstract description 6
- 208000027866 inflammatory disease Diseases 0.000 abstract description 6
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 4
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 2
- 208000026278 immune system disease Diseases 0.000 abstract description 2
- 150000008523 triazolopyridines Chemical class 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 description 55
- 238000006243 chemical reaction Methods 0.000 description 26
- 210000004027 cell Anatomy 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 230000008728 vascular permeability Effects 0.000 description 18
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 17
- 239000000047 product Substances 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 102000009076 src-Family Kinases Human genes 0.000 description 13
- 108010087686 src-Family Kinases Proteins 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 12
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
- 230000008482 dysregulation Effects 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 9
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 239000005022 packaging material Substances 0.000 description 9
- 206010030113 Oedema Diseases 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 230000002792 vascular Effects 0.000 description 8
- 102000001253 Protein Kinase Human genes 0.000 description 7
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 7
- 239000000499 gel Substances 0.000 description 7
- 108060006633 protein kinase Proteins 0.000 description 7
- 230000011664 signaling Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 6
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 230000033115 angiogenesis Effects 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000012091 fetal bovine serum Substances 0.000 description 6
- 239000012530 fluid Substances 0.000 description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 230000000699 topical effect Effects 0.000 description 6
- 238000012384 transportation and delivery Methods 0.000 description 6
- 206010012689 Diabetic retinopathy Diseases 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 208000017442 Retinal disease Diseases 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 230000002207 retinal effect Effects 0.000 description 5
- JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000011200 topical administration Methods 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 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 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 238000001516 cell proliferation assay Methods 0.000 description 4
- 230000001010 compromised effect Effects 0.000 description 4
- 229960003699 evans blue Drugs 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 229940054534 ophthalmic solution Drugs 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 239000002798 polar solvent Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- 230000035899 viability Effects 0.000 description 4
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 206010012688 Diabetic retinal oedema Diseases 0.000 description 3
- 208000010412 Glaucoma Diseases 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 206010025415 Macular oedema Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000000172 allergic effect Effects 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000002260 anti-inflammatory agent Substances 0.000 description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 239000012736 aqueous medium Substances 0.000 description 3
- 208000010668 atopic eczema Diseases 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 3
- 210000004155 blood-retinal barrier Anatomy 0.000 description 3
- 230000004378 blood-retinal barrier Effects 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000012054 celltiter-glo Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000003349 gelling agent Substances 0.000 description 3
- 238000007429 general method Methods 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000002601 intratumoral effect Effects 0.000 description 3
- 208000028867 ischemia Diseases 0.000 description 3
- 201000010230 macular retinal edema Diseases 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000002997 ophthalmic solution Substances 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- OWQPOVKKUWUEKE-UHFFFAOYSA-N 1,2,3-benzotriazine Chemical compound N1=NN=CC2=CC=CC=C21 OWQPOVKKUWUEKE-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 2
- 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 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
- COVZFFKFXRDMKH-UHFFFAOYSA-N 6-(2-chloro-5-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound COC1=CC=C(Cl)C(C2=CN3N=C(N)N=C3C=C2)=C1 COVZFFKFXRDMKH-UHFFFAOYSA-N 0.000 description 2
- WBYMATKSEUQCTP-UHFFFAOYSA-N 7-(2-chloro-5-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound COC1=CC=C(Cl)C(C2=CC3=NC(N)=NN3C=C2)=C1 WBYMATKSEUQCTP-UHFFFAOYSA-N 0.000 description 2
- DAYYXZOMYRSLBX-UHFFFAOYSA-N 7-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound C1=C(Br)C=CN2N=C(N)N=C21 DAYYXZOMYRSLBX-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 208000036487 Arthropathies Diseases 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 229920002148 Gellan gum Polymers 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 102000003964 Histone deacetylase Human genes 0.000 description 2
- 108090000353 Histone deacetylase Proteins 0.000 description 2
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 208000012659 Joint disease Diseases 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 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
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 2
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- YDWKSSWZGXRQET-UHFFFAOYSA-N Pyrrolidine, 1-[2-(4-bromophenoxy)ethyl]- Chemical compound C1=CC(Br)=CC=C1OCCN1CCCC1 YDWKSSWZGXRQET-UHFFFAOYSA-N 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 206010052779 Transplant rejections Diseases 0.000 description 2
- 108091008605 VEGF receptors Proteins 0.000 description 2
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 238000004115 adherent culture Methods 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 206010064930 age-related macular degeneration Diseases 0.000 description 2
- 239000003732 agents acting on the eye Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 239000001045 blue dye Substances 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 239000000679 carrageenan Substances 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 229940113118 carrageenan Drugs 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- LHWWETDBWVTKJO-UHFFFAOYSA-N et3n triethylamine Chemical compound CCN(CC)CC.CCN(CC)CC LHWWETDBWVTKJO-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- LIYGYAHYXQDGEP-UHFFFAOYSA-N firefly oxyluciferin Natural products Oc1csc(n1)-c1nc2ccc(O)cc2s1 LIYGYAHYXQDGEP-UHFFFAOYSA-N 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 230000002519 immonomodulatory effect Effects 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000006193 liquid solution Substances 0.000 description 2
- 239000006194 liquid suspension Substances 0.000 description 2
- 238000004020 luminiscence type Methods 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 230000006677 mitochondrial metabolism Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 229940023490 ophthalmic product Drugs 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- JJVOROULKOMTKG-UHFFFAOYSA-N oxidized Photinus luciferin Chemical compound S1C2=CC(O)=CC=C2N=C1C1=NC(=O)CS1 JJVOROULKOMTKG-UHFFFAOYSA-N 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 150000003246 quinazolines Chemical class 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 210000001525 retina Anatomy 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000005556 structure-activity relationship Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 229940021747 therapeutic vaccine Drugs 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- 210000003556 vascular endothelial cell Anatomy 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 238000003026 viability measurement method Methods 0.000 description 2
- CKMFWGPXCDIZMU-UHFFFAOYSA-N (2-chloro-5-methoxyphenyl)boron Chemical compound [B]C1=CC(OC)=CC=C1Cl CKMFWGPXCDIZMU-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical group COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- 150000003930 2-aminopyridines Chemical class 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- WWINACYDRQWTQL-UHFFFAOYSA-N 2-pyridin-2-ylquinazoline Chemical class N1=CC=CC=C1C1=NC=C(C=CC=C2)C2=N1 WWINACYDRQWTQL-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- JGUBPSBKWJBCDV-UHFFFAOYSA-N 3-(2-amino-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-chlorophenol Chemical compound C=1N2N=C(N)N=C2C=CC=1C1=CC(O)=CC=C1Cl JGUBPSBKWJBCDV-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- 102100037263 3-phosphoinositide-dependent protein kinase 1 Human genes 0.000 description 1
- VLZZRUWVKKOLCI-UHFFFAOYSA-N 4-chloro-3-[2-(4-phenylmethoxyanilino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenol Chemical compound OC1=CC=C(Cl)C(C2=CN3N=C(NC=4C=CC(OCC=5C=CC=CC=5)=CC=4)N=C3C=C2)=C1 VLZZRUWVKKOLCI-UHFFFAOYSA-N 0.000 description 1
- XHBQNLHFUPSZNL-UHFFFAOYSA-N 6-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound C1=CC(Br)=CN2N=C(N)N=C21 XHBQNLHFUPSZNL-UHFFFAOYSA-N 0.000 description 1
- OAJIRBMITRHGDF-UHFFFAOYSA-N 6-phenyl-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound C=1N2N=C(N)N=C2C=CC=1C1=CC=CC=C1 OAJIRBMITRHGDF-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 102000057234 Acyl transferases Human genes 0.000 description 1
- 108700016155 Acyl transferases Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000004736 B-Cell Leukemia Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 229910015845 BBr3 Inorganic materials 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- 108091007914 CDKs Proteins 0.000 description 1
- 101100005789 Caenorhabditis elegans cdk-4 gene Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- OYZFVUSQHSSPSP-UHFFFAOYSA-N ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC2=CC(=CC=C2)CO.ClC2=C(C=C(C=C2)O)C=2C=CC=1N(C2)N=C(N1)NC1=CC=C(C=C1)CO Chemical compound ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC2=CC(=CC=C2)CO.ClC2=C(C=C(C=C2)O)C=2C=CC=1N(C2)N=C(N1)NC1=CC=C(C=C1)CO OYZFVUSQHSSPSP-UHFFFAOYSA-N 0.000 description 1
- KSZNLUDTDBTTML-UHFFFAOYSA-N ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC2=CC=C(C=C2)S(=O)(=O)C.ClC2=C(C=C(C=C2)O)C=2C=CC=1N(C2)N=C(N1)NC1=CC=C(C=C1)OC1=CC=CC=C1 Chemical compound ClC1=C(C=C(C=C1)O)C=1C=CC=2N(C1)N=C(N2)NC2=CC=C(C=C2)S(=O)(=O)C.ClC2=C(C=C(C=C2)O)C=2C=CC=1N(C2)N=C(N1)NC1=CC=C(C=C1)OC1=CC=CC=C1 KSZNLUDTDBTTML-UHFFFAOYSA-N 0.000 description 1
- 102000003903 Cyclin-dependent kinases Human genes 0.000 description 1
- 108090000266 Cyclin-dependent kinases Proteins 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 229920005682 EO-PO block copolymer Polymers 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical class NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000600756 Homo sapiens 3-phosphoinositide-dependent protein kinase 1 Proteins 0.000 description 1
- 101001117146 Homo sapiens [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
- 206010025421 Macule Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 229910017912 NH2OH Inorganic materials 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 229920000148 Polycarbophil calcium Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 101000808006 Rattus norvegicus Vascular endothelial growth factor A Proteins 0.000 description 1
- 206010038886 Retinal oedema Diseases 0.000 description 1
- 206010038903 Retinal vascular occlusion Diseases 0.000 description 1
- 102000038012 SFKs Human genes 0.000 description 1
- 108091008118 SFKs Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 206010044248 Toxic shock syndrome Diseases 0.000 description 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 208000000208 Wet Macular Degeneration Diseases 0.000 description 1
- ZNOZWUKQPJXOIG-XSBHQQIPSA-L [(2r,3s,4r,5r,6s)-6-[[(1r,3s,4r,5r,8s)-3,4-dihydroxy-2,6-dioxabicyclo[3.2.1]octan-8-yl]oxy]-4-[[(1r,3r,4r,5r,8s)-8-[(2s,3r,4r,5r,6r)-3,4-dihydroxy-6-(hydroxymethyl)-5-sulfonatooxyoxan-2-yl]oxy-4-hydroxy-2,6-dioxabicyclo[3.2.1]octan-3-yl]oxy]-5-hydroxy-2-( Chemical compound O[C@@H]1[C@@H](O)[C@@H](OS([O-])(=O)=O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H]2OC[C@H]1O[C@H](O[C@H]1[C@H]([C@@H](CO)O[C@@H](O[C@@H]3[C@@H]4OC[C@H]3O[C@H](O)[C@@H]4O)[C@@H]1O)OS([O-])(=O)=O)[C@@H]2O ZNOZWUKQPJXOIG-XSBHQQIPSA-L 0.000 description 1
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 108700014220 acyltransferase activity proteins Proteins 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000011948 assay development Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 229940088623 biologically active substance Drugs 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229950005499 carbon tetrachloride Drugs 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 230000017455 cell-cell adhesion Effects 0.000 description 1
- 230000010267 cellular communication Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 230000007073 chemical hydrolysis Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 208000021921 corneal disease Diseases 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- PTXJGGGNGMPMBG-UHFFFAOYSA-N ditert-butyl-[2-(1,3,5-triphenylpyrazol-4-yl)pyrazol-3-yl]phosphane Chemical group CC(C)(C)P(C(C)(C)C)C1=CC=NN1C1=C(C=2C=CC=CC=2)N(C=2C=CC=CC=2)N=C1C1=CC=CC=C1 PTXJGGGNGMPMBG-UHFFFAOYSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000012912 drug discovery process Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 230000004438 eyesight Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 235000010492 gellan gum Nutrition 0.000 description 1
- 239000000216 gellan gum Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229920006158 high molecular weight polymer Polymers 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000006872 improvement Effects 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
- 239000000411 inducer Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 238000001499 laser induced fluorescence spectroscopy Methods 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 238000013332 literature search Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 125000001620 monocyclic carbocycle group Chemical group 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000002826 nitrites Chemical class 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000000771 oncological effect Effects 0.000 description 1
- 229940069265 ophthalmic ointment Drugs 0.000 description 1
- 229940100654 ophthalmic suspension Drugs 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229920001987 poloxamine Polymers 0.000 description 1
- 229950005134 polycarbophil Drugs 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000003909 protein kinase inhibitor Substances 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- CZAAKPFIWJXPQT-UHFFFAOYSA-N quinazolin-2-amine Chemical class C1=CC=CC2=NC(N)=NC=C21 CZAAKPFIWJXPQT-UHFFFAOYSA-N 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 208000004644 retinal vein occlusion Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229920001187 thermosetting polymer Polymers 0.000 description 1
- 239000004634 thermosetting polymer Substances 0.000 description 1
- 230000009974 thixotropic effect Effects 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 150000003918 triazines Chemical class 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000004304 visual acuity Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- 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
- 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
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Ophthalmology & Optometry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09360013.8 | 2009-02-13 | ||
| EP09360013 | 2009-02-13 | ||
| PCT/EP2010/051556 WO2010092041A1 (en) | 2009-02-13 | 2010-02-09 | [1, 2, 4] triazolo [1, 5 -a] pyridines as kinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2751517A1 true CA2751517A1 (en) | 2010-08-19 |
Family
ID=42229029
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2751517A Abandoned CA2751517A1 (en) | 2009-02-13 | 2010-02-09 | [1, 2, 4] triazolo [1, 5 -a] pyridines as kinase inhibitors |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US20120041195A1 (https=) |
| EP (1) | EP2396324A1 (https=) |
| JP (1) | JP2012517971A (https=) |
| KR (1) | KR20110116160A (https=) |
| CN (1) | CN102317288A (https=) |
| AR (1) | AR075411A1 (https=) |
| BR (1) | BRPI1008850A2 (https=) |
| CA (1) | CA2751517A1 (https=) |
| CL (1) | CL2011001947A1 (https=) |
| CO (1) | CO6420343A2 (https=) |
| CR (1) | CR20110386A (https=) |
| DO (1) | DOP2011000248A (https=) |
| EA (1) | EA201101188A1 (https=) |
| EC (1) | ECSP11011250A (https=) |
| HN (1) | HN2011002095A (https=) |
| IL (1) | IL214426A0 (https=) |
| MX (1) | MX2011008549A (https=) |
| NI (1) | NI201100151A (https=) |
| NZ (1) | NZ594508A (https=) |
| PE (1) | PE20120110A1 (https=) |
| SG (1) | SG173610A1 (https=) |
| TN (1) | TN2011000379A1 (https=) |
| WO (1) | WO2010092041A1 (https=) |
| ZA (1) | ZA201105896B (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013118986A1 (en) | 2012-02-08 | 2013-08-15 | Hanmi Pharm Co., Ltd. | Triazolopyridine derivatives as a tyrosine kinase inhibitor |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102459258B (zh) * | 2009-06-05 | 2015-11-25 | 赛福伦公司 | 1,2,4-三唑并[1,5a]吡啶衍生物的制备和用途 |
| EP2343294A1 (en) | 2009-11-30 | 2011-07-13 | Bayer Schering Pharma AG | Substituted triazolopyridines |
| EP2343297A1 (en) * | 2009-11-30 | 2011-07-13 | Bayer Schering Pharma AG | Triazolopyridines |
| EP2343295A1 (en) * | 2009-11-30 | 2011-07-13 | Bayer Schering Pharma AG | Triazolopyridine derivates |
| UY33452A (es) * | 2010-06-16 | 2012-01-31 | Bayer Schering Pharma Ag | Triazolopiridinas sustituidas |
| AR081960A1 (es) * | 2010-06-22 | 2012-10-31 | Fovea Pharmaceuticals Sa | Compuestos heterociclicos, su preparacion y su aplicacion terapeutica |
| HRP20150517T1 (hr) * | 2011-04-21 | 2015-06-19 | Bayer Intellectual Property Gmbh | Triazolopiridini |
| WO2012160029A1 (en) | 2011-05-23 | 2012-11-29 | Bayer Intellectual Property Gmbh | Substituted triazolopyridines |
| UA112096C2 (uk) | 2011-12-12 | 2016-07-25 | Байєр Інтеллектуал Проперті Гмбх | Заміщені триазолопіридини та їх застосування як інгібіторів ttk |
| CN104284896B (zh) | 2012-03-14 | 2016-06-01 | 拜耳知识产权有限责任公司 | 取代的咪唑并哒嗪 |
| CA2878481A1 (en) | 2012-07-10 | 2014-01-16 | Bayer Pharma Aktiengesellschaft | Method for preparing substituted triazolopyridines |
| WO2014020043A1 (en) | 2012-08-02 | 2014-02-06 | Bayer Pharma Aktiengesellschaft | Combinations for the treatment of cancer |
| RS56034B1 (sr) | 2013-06-11 | 2017-09-29 | Bayer Pharma AG | Derivati prolekova supstituisanih triazolopiridina |
| AU2020385513A1 (en) * | 2019-11-22 | 2022-07-14 | Medshine Discovery Inc. | Pyrimidopyrrole spiro compounds and derivatives thereof as DNA-PK inhibitors |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6056684B2 (ja) | 1977-11-07 | 1985-12-11 | 東興薬品工業株式会社 | 点眼剤 |
| US4271143A (en) | 1978-01-25 | 1981-06-02 | Alcon Laboratories, Inc. | Sustained release ophthalmic drug dosage |
| US4407792A (en) | 1979-05-09 | 1983-10-04 | Alcon Laboratories, Inc. | Sustained release ophthalmic drug dosage |
| AU565354B2 (en) | 1983-11-14 | 1987-09-10 | Bio-Mimetics Inc. | Bioadhesive compositions and methods of treatment therewith |
| US5041434A (en) | 1991-08-17 | 1991-08-20 | Virginia Lubkin | Drugs for topical application of sex steroids in the treatment of dry eye syndrome, and methods of preparation and application |
| CA2386955A1 (en) | 1999-11-22 | 2001-05-31 | Warner-Lambert Company | Quinazolines and their use for inhibiting cyclin-dependent kinase enzymes |
| WO2004058769A2 (en) * | 2002-12-18 | 2004-07-15 | Vertex Pharmaceuticals Incorporated | Triazolopyridazines as protein kinases inhibitors |
| EP1590341B1 (en) | 2003-01-17 | 2009-06-17 | Warner-Lambert Company LLC | 2-aminopyridine substituted heterocycles as inhibitors of cellular proliferation |
| CN1897950A (zh) * | 2003-10-14 | 2007-01-17 | 惠氏公司 | 稠合芳基和杂芳基衍生物及其使用方法 |
| CN1882345A (zh) | 2003-10-16 | 2006-12-20 | 希龙公司 | 作为raf激酶抑制剂以治疗癌症的2,6－二取代的喹唑啉、喹喔啉、喹啉和异喹啉 |
| KR20070011458A (ko) | 2004-04-08 | 2007-01-24 | 탈자진 인코포레이티드 | 키나제의 벤조트리아진 억제제 |
| PL382308A1 (pl) | 2004-08-25 | 2007-08-20 | Targegen, Inc. | Związki heterocykliczne i sposoby stosowania |
| US20070054916A1 (en) | 2004-10-01 | 2007-03-08 | Amgen Inc. | Aryl nitrogen-containing bicyclic compounds and methods of use |
| US20060247250A1 (en) | 2005-03-16 | 2006-11-02 | Targegen, Inc. | Pyrimidine inhibitors of kinases |
| JP5079500B2 (ja) | 2005-04-28 | 2012-11-21 | 協和発酵キリン株式会社 | ２−アミノキナゾリン誘導体 |
| NZ563984A (en) | 2005-06-08 | 2011-11-25 | Targegen Inc | Methods and compositions for the treatment of ocular disorders |
| WO2007067537A1 (en) * | 2005-12-07 | 2007-06-14 | Osi Pharmaceuticals, Inc. | Pyrrolopyridine kinase inhibiting compounds |
| PE20070978A1 (es) | 2006-02-14 | 2007-11-15 | Novartis Ag | COMPUESTOS HETEROCICLICOS COMO INHIBIDORES DE FOSFATIDILINOSITOL 3-QUINASAS (PI3Ks) |
| JP5336375B2 (ja) * | 2006-08-30 | 2013-11-06 | セルゾーム リミテッド | キナーゼ阻害剤としてのトリアゾール誘導体 |
| EA200900573A1 (ru) * | 2006-10-20 | 2009-10-30 | АйАрЭм ЭлЭлСи | Композиции и способы для модуляции рецепторов c-kit и pdgfr |
| TW200829566A (en) | 2006-12-08 | 2008-07-16 | Astrazeneca Ab | Chemical compounds |
| CA2673003A1 (en) | 2006-12-22 | 2008-07-03 | Novartis Ag | Quinazolines for pdk1 inhibition |
| GB0719803D0 (en) * | 2007-10-10 | 2007-11-21 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
| EP2288260A4 (en) * | 2008-06-20 | 2013-10-23 | Genentech Inc | TRIAZOLOPYRIDINE-JAK HEMMER COMPOUNDS AND METHOD |
| BRPI0909945A2 (pt) * | 2008-06-20 | 2015-07-28 | Genentech Inc | "composto, composição farmacêutica, método para tratar ou atenuar a gravidade de uma doença ou condição responsiva à inibição da atividade jak2 quinase em um paciente, kit para o tratamento de uma doença ou distúrbio responsivo à inibição da jak quinase" |
| WO2010010188A1 (en) * | 2008-07-25 | 2010-01-28 | Galapagos Nv | Novel compounds useful for the treatment of degenerative and inflammatory diseases. |
| WO2010010189A1 (en) * | 2008-07-25 | 2010-01-28 | Galapagos Nv | Novel compounds useful for the treatment of degenerative and inflammatory diseases |
| WO2010010184A1 (en) * | 2008-07-25 | 2010-01-28 | Galapagos Nv | [1, 2, 4] triazolo [1, 5-a] pyridines as jak inhibitors |
| TW201010977A (en) * | 2008-08-12 | 2010-03-16 | Takeda Pharmaceutical | Amide compound |
| TWI453207B (zh) * | 2008-09-08 | 2014-09-21 | Signal Pharm Llc | 胺基三唑并吡啶，其組合物及使用其之治療方法 |
-
2010
- 2010-02-09 SG SG2011057247A patent/SG173610A1/en unknown
- 2010-02-09 CN CN2010800077376A patent/CN102317288A/zh active Pending
- 2010-02-09 EA EA201101188A patent/EA201101188A1/ru unknown
- 2010-02-09 CA CA2751517A patent/CA2751517A1/en not_active Abandoned
- 2010-02-09 US US13/201,165 patent/US20120041195A1/en not_active Abandoned
- 2010-02-09 KR KR1020117018592A patent/KR20110116160A/ko not_active Withdrawn
- 2010-02-09 NZ NZ594508A patent/NZ594508A/en not_active IP Right Cessation
- 2010-02-09 MX MX2011008549A patent/MX2011008549A/es not_active Application Discontinuation
- 2010-02-09 JP JP2011549537A patent/JP2012517971A/ja active Pending
- 2010-02-09 BR BRPI1008850A patent/BRPI1008850A2/pt not_active IP Right Cessation
- 2010-02-09 WO PCT/EP2010/051556 patent/WO2010092041A1/en not_active Ceased
- 2010-02-09 PE PE2011001470A patent/PE20120110A1/es not_active Application Discontinuation
- 2010-02-09 EP EP10706180A patent/EP2396324A1/en not_active Withdrawn
- 2010-02-12 AR ARP100100400A patent/AR075411A1/es not_active Application Discontinuation
-
2011
- 2011-07-15 CR CR20110386A patent/CR20110386A/es unknown
- 2011-07-28 NI NI201100151A patent/NI201100151A/es unknown
- 2011-07-29 HN HN2011002095A patent/HN2011002095A/es unknown
- 2011-07-29 DO DO2011000248A patent/DOP2011000248A/es unknown
- 2011-08-03 IL IL214426A patent/IL214426A0/en unknown
- 2011-08-03 TN TN2011000379A patent/TN2011000379A1/fr unknown
- 2011-08-09 EC EC2011011250A patent/ECSP11011250A/es unknown
- 2011-08-11 ZA ZA2011/05896A patent/ZA201105896B/en unknown
- 2011-08-11 CO CO11102097A patent/CO6420343A2/es not_active Application Discontinuation
- 2011-08-11 CL CL2011001947A patent/CL2011001947A1/es unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013118986A1 (en) | 2012-02-08 | 2013-08-15 | Hanmi Pharm Co., Ltd. | Triazolopyridine derivatives as a tyrosine kinase inhibitor |
Also Published As
| Publication number | Publication date |
|---|---|
| CO6420343A2 (es) | 2012-04-16 |
| US20120041195A1 (en) | 2012-02-16 |
| NZ594508A (en) | 2013-12-20 |
| CL2011001947A1 (es) | 2012-03-16 |
| DOP2011000248A (es) | 2011-10-31 |
| ZA201105896B (en) | 2012-03-28 |
| WO2010092041A1 (en) | 2010-08-19 |
| MX2011008549A (es) | 2011-12-06 |
| ECSP11011250A (es) | 2011-10-31 |
| BRPI1008850A2 (pt) | 2016-03-15 |
| IL214426A0 (en) | 2011-09-27 |
| SG173610A1 (en) | 2011-09-29 |
| TN2011000379A1 (en) | 2013-03-27 |
| EP2396324A1 (en) | 2011-12-21 |
| CR20110386A (es) | 2011-12-02 |
| EA201101188A1 (ru) | 2012-04-30 |
| NI201100151A (es) | 2012-10-03 |
| HN2011002095A (es) | 2014-01-06 |
| JP2012517971A (ja) | 2012-08-09 |
| AR075411A1 (es) | 2011-03-30 |
| CN102317288A (zh) | 2012-01-11 |
| PE20120110A1 (es) | 2012-02-20 |
| KR20110116160A (ko) | 2011-10-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2751517A1 (en) | [1, 2, 4] triazolo [1, 5 -a] pyridines as kinase inhibitors | |
| US8389530B2 (en) | Substituted quinazoline compounds | |
| CA2803496A1 (en) | Heterocyclic compounds, their preparation and their therapeutic application | |
| AU2006224605B2 (en) | Potassium channel modulating agents and their medical use | |
| TWI385165B (zh) | 經二取代之呔猬狀途徑拮抗劑 | |
| EP1091942B1 (en) | Potassium channel blocking agents | |
| EP2942349A1 (en) | Enzyme modulators and treatments | |
| IL197015A (en) | Benzotriazole Kinase Modulators, Methods for their Preparation, Pharmaceuticals Containing Them, and Their Use in the Preparation of Medicines for the Treatment of Diseases | |
| EP1863796A1 (en) | Pyrazolyl-pyrimidines as potassium channel modulating agents and their medical use | |
| US20090036475A1 (en) | Pyrazolyl-Pyrimidines as Potassium Channel Modulating Agents and Their Medical Use | |
| CN117751117A (zh) | Sarm1酶活性抑制剂及其应用 | |
| AU2011211410B2 (en) | [1,2,4] triazolo [1,5-A] pyridines as kinase inhibitors | |
| OA16290A (en) | Heterocyclic compounds, their preparation and their therapeutic application. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20160209 |