JP2020517698A5 - - Google Patents
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- Publication number
- JP2020517698A5 JP2020517698A5 JP2019558390A JP2019558390A JP2020517698A5 JP 2020517698 A5 JP2020517698 A5 JP 2020517698A5 JP 2019558390 A JP2019558390 A JP 2019558390A JP 2019558390 A JP2019558390 A JP 2019558390A JP 2020517698 A5 JP2020517698 A5 JP 2020517698A5
- Authority
- JP
- Japan
- Prior art keywords
- pyrido
- pyrimidin
- amine
- pyridine
- methyl
- 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.)
- Granted
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- 210000004027 cell Anatomy 0.000 claims description 303
- -1 R 0 Chemical group 0.000 claims description 246
- 150000001875 compounds Chemical class 0.000 claims description 198
- 238000000034 method Methods 0.000 claims description 193
- 125000000217 alkyl group Chemical group 0.000 claims description 173
- 229930186657 Lat Natural products 0.000 claims description 101
- 239000003202 long acting thyroid stimulator Substances 0.000 claims description 101
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 98
- 150000003839 salts Chemical class 0.000 claims description 80
- 125000001424 substituent group Chemical group 0.000 claims description 72
- 229910052736 halogen Inorganic materials 0.000 claims description 69
- 150000002367 halogens Chemical class 0.000 claims description 69
- 208000030533 eye disease Diseases 0.000 claims description 63
- 210000000130 stem cell Anatomy 0.000 claims description 61
- 125000005842 heteroatom Chemical group 0.000 claims description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims description 54
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 52
- 241001430066 Anulocaulis Species 0.000 claims description 52
- 239000001257 hydrogen Substances 0.000 claims description 52
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 50
- 210000000399 corneal endothelial cell Anatomy 0.000 claims description 44
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 43
- 229910052757 nitrogen Inorganic materials 0.000 claims description 42
- MFGKTDNWDCJOLN-UHFFFAOYSA-N pyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC=C2C(N)=NC=NC2=C1 MFGKTDNWDCJOLN-UHFFFAOYSA-N 0.000 claims description 42
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
- 208000035475 disorder Diseases 0.000 claims description 36
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 36
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 35
- 108090000623 proteins and genes Proteins 0.000 claims description 31
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 229910052760 oxygen Inorganic materials 0.000 claims description 28
- 229910052717 sulfur Inorganic materials 0.000 claims description 28
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
- 238000012258 culturing Methods 0.000 claims description 25
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims description 24
- 150000002431 hydrogen Chemical class 0.000 claims description 22
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 20
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 19
- 239000001963 growth medium Substances 0.000 claims description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 101000937544 Homo sapiens Beta-2-microglobulin Proteins 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 14
- 230000028993 immune response Effects 0.000 claims description 14
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 14
- 230000014509 gene expression Effects 0.000 claims description 13
- 230000001737 promoting effect Effects 0.000 claims description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- 230000007812 deficiency Effects 0.000 claims description 12
- 238000012217 deletion Methods 0.000 claims description 12
- 230000037430 deletion Effects 0.000 claims description 12
- 238000003780 insertion Methods 0.000 claims description 12
- 230000037431 insertion Effects 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 102100027314 Beta-2-microglobulin Human genes 0.000 claims description 11
- 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 claims description 11
- 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 0.000 claims description 11
- 102100028971 HLA class I histocompatibility antigen, C alpha chain Human genes 0.000 claims description 11
- 108010075704 HLA-A Antigens Proteins 0.000 claims description 11
- 108010058607 HLA-B Antigens Proteins 0.000 claims description 11
- 108010052199 HLA-C Antigens Proteins 0.000 claims description 11
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 10
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
- 125000002950 monocyclic group Chemical group 0.000 claims description 9
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 claims description 9
- 230000010261 cell growth Effects 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 8
- 235000019260 propionic acid Nutrition 0.000 claims description 8
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 238000012239 gene modification Methods 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
- 150000002829 nitrogen Chemical class 0.000 claims description 7
- 150000007523 nucleic acids Chemical group 0.000 claims description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
- 125000003367 polycyclic group Chemical group 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- AOHJOMMDDJHIJH-UHFFFAOYSA-N propylenediamine Chemical compound CC(N)CN AOHJOMMDDJHIJH-UHFFFAOYSA-N 0.000 claims description 6
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- LISLXKHKNUTYFU-UHFFFAOYSA-N 2,2-dimethyl-N'-(2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine Chemical compound CC(C)(CN)CNc1nc(nc2cnccc12)-c1ccncc1 LISLXKHKNUTYFU-UHFFFAOYSA-N 0.000 claims description 3
- MYPGOQOVEQKGDN-UHFFFAOYSA-N 2,3-dimethyl-3-N-(2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-yl)butane-2,3-diamine Chemical compound CC(C)(N)C(C)(C)Nc1nc(nc2cnccc12)-c1ccncc1 MYPGOQOVEQKGDN-UHFFFAOYSA-N 0.000 claims description 3
- CKGSKEKFMDASMJ-UHFFFAOYSA-N 2-methyl-2-N-(2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-yl)propane-1,2-diamine Chemical compound NCC(C)(C)NC=1C2=C(N=C(N=1)C1=CC=NC=C1)C=NC=C2 CKGSKEKFMDASMJ-UHFFFAOYSA-N 0.000 claims description 3
- ZKLQNSBYPMENKE-UHFFFAOYSA-N 3-N,2,2-trimethyl-1-N-(2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine Chemical compound CC(C(CNC=1C2=C(N=C(N=1)C1=CC=NC=C1)C=NC=C2)(C)C)NC ZKLQNSBYPMENKE-UHFFFAOYSA-N 0.000 claims description 3
- PFJAMBGEYIVHBA-UHFFFAOYSA-N 5-chloro-N-(1-methylcyclopropyl)-2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-amine Chemical compound ClC1=CN=CC=2N=C(N=C(C=21)NC1(CC1)C)C1=CC=NC=C1 PFJAMBGEYIVHBA-UHFFFAOYSA-N 0.000 claims description 3
- RLWYFPYOBNIXQH-UHFFFAOYSA-N 8-chloro-N-(1-methylcyclopropyl)-2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-amine Chemical compound ClC1=NC=CC2=C1N=C(N=C2NC1(CC1)C)C1=CC=NC=C1 RLWYFPYOBNIXQH-UHFFFAOYSA-N 0.000 claims description 3
- NCURZWASYVOQOD-UHFFFAOYSA-N 8-methyl-N-(1-methylcyclopropyl)-2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-amine Chemical compound CC1=NC=CC2=C1N=C(N=C2NC1(CC1)C)C1=CC=NC=C1 NCURZWASYVOQOD-UHFFFAOYSA-N 0.000 claims description 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 3
- CPJACQKXXLMUSC-UHFFFAOYSA-N N-tert-butyl-5-chloro-2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-amine Chemical compound C(C)(C)(C)NC=1C2=C(N=C(N=1)C1=CC=NC=C1)C=NC=C2Cl CPJACQKXXLMUSC-UHFFFAOYSA-N 0.000 claims description 3
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 3
- RGTXVXDNHPWPHH-UHFFFAOYSA-N butane-1,3-diamine Chemical compound CC(N)CCN RGTXVXDNHPWPHH-UHFFFAOYSA-N 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 239000007943 implant Substances 0.000 claims description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- MSMNYSIKXYTNCQ-SJLPKXTDSA-N (1R,2R)-1-N,2-N-dimethyl-2-N-(2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-yl)cyclohexane-1,2-diamine Chemical compound CN([C@H]1[C@@H](CCCC1)NC)C=1C2=C(N=C(N=1)C1=CC=NC=C1)C=NC=C2 MSMNYSIKXYTNCQ-SJLPKXTDSA-N 0.000 claims description 2
- KLRVBQBFDCULDA-DZGCQCFKSA-N (1R,2S)-2-[(2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-yl)amino]cyclopentan-1-ol Chemical compound O[C@@H]1CCC[C@@H]1Nc1nc(nc2cnccc12)-c1ccncc1 KLRVBQBFDCULDA-DZGCQCFKSA-N 0.000 claims description 2
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 2
- ASGAQYCHHHOJMV-UHFFFAOYSA-N 1-[2-[[2-(3-chloropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino]-2-methylpropoxy]-2-methylpropan-2-ol Chemical compound ClC=1C=NC=CC=1C=1N=C(C2=C(N=1)C=NC=C2)NC(COCC(C)(O)C)(C)C ASGAQYCHHHOJMV-UHFFFAOYSA-N 0.000 claims description 2
- RQCQSMAAAMSVHQ-UHFFFAOYSA-N 2,4-dimethyl-4-[(2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-yl)amino]pentan-2-ol Chemical compound CC(C)(CC(C)(NC=1C2=C(N=C(N=1)C1=CC=NC=C1)C=NC=C2)C)O RQCQSMAAAMSVHQ-UHFFFAOYSA-N 0.000 claims description 2
- LCMHVCYOECYAMC-UHFFFAOYSA-N 2,4-dimethyl-4-[[2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino]pentan-2-ol Chemical compound CC(C)(CC(C)(NC=1C2=C(N=C(N=1)C=1C=NNC=1)C=NC=C2)C)O LCMHVCYOECYAMC-UHFFFAOYSA-N 0.000 claims description 2
- XFAFYUWFKMLDGN-UHFFFAOYSA-N 2,4-dimethyl-4-[[2-[5-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-yl]amino]pentan-2-ol Chemical compound CC(C)(CC(C)(NC=1C2=C(N=C(N=1)C=1C(=NNC=1)C(F)(F)F)C=NC=C2)C)O XFAFYUWFKMLDGN-UHFFFAOYSA-N 0.000 claims description 2
- FGUYUDSFYMXCSF-UHFFFAOYSA-N 2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound FC(C(C)(C)C=1N=C(C2=C(N=1)C=NC=C2)N)(F)F FGUYUDSFYMXCSF-UHFFFAOYSA-N 0.000 claims description 2
- AJBBECKCWREWAW-UHFFFAOYSA-N 2-(2-aminopyridin-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound CC1(CC1)NC=1C2=C(N=C(N=1)C1=CC(=NC=C1)N)C=NC=C2 AJBBECKCWREWAW-UHFFFAOYSA-N 0.000 claims description 2
- IJGJWWBUSDGYNE-UHFFFAOYSA-N 2-(2-methylpyrazol-3-yl)-N-(1-pyridin-4-ylethyl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound CN1N=CC=C1C=1N=C(C2=C(N=1)C=NC=C2)NC(C)C1=CC=NC=C1 IJGJWWBUSDGYNE-UHFFFAOYSA-N 0.000 claims description 2
- GPKFECYSQTWZCI-UHFFFAOYSA-N 2-(3-chloropyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound ClC=1C=NC=CC=1C=1N=C(C2=C(N=1)C=NC=C2)NC(C(F)(F)F)(C)C GPKFECYSQTWZCI-UHFFFAOYSA-N 0.000 claims description 2
- OXIMJDPCKQGAMC-UHFFFAOYSA-N 2-(3-chloropyridin-4-yl)-N-(2-methylbutan-2-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound ClC=1C=NC=CC=1C=1N=C(C2=C(N=1)C=NC=C2)NC(C)(CC)C OXIMJDPCKQGAMC-UHFFFAOYSA-N 0.000 claims description 2
- NWTRZYRGCGNAAN-SECBINFHSA-N 2-(3-fluoropyridin-4-yl)-N-methyl-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound FC=1C=NC=CC=1C=1N=C(C2=C(N=1)C=NC=C2)N([C@@H](C(F)(F)F)C)C NWTRZYRGCGNAAN-SECBINFHSA-N 0.000 claims description 2
- VBBQTFSHBKUYOD-UHFFFAOYSA-N 2-(3-fluoropyridin-4-yl)-N-methyl-N-propan-2-ylpyrido[3,4-d]pyrimidin-4-amine Chemical compound FC=1C=NC=CC=1C=1N=C(C2=C(N=1)C=NC=C2)N(C(C)C)C VBBQTFSHBKUYOD-UHFFFAOYSA-N 0.000 claims description 2
- CCJRVCDZHWNBTA-UHFFFAOYSA-N 2-(5-methyl-1H-pyrazol-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound CC1=NNC=C1C=1N=C(C2=C(N=1)C=NC=C2)NC(C(F)(F)F)(C)C CCJRVCDZHWNBTA-UHFFFAOYSA-N 0.000 claims description 2
- ZOBZTNONBIVPBE-UHFFFAOYSA-N 2-(hydroxymethyl)-2-[(2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-yl)amino]propane-1,3-diol Chemical compound OCC(CO)(CO)NC=1C2=C(N=C(N=1)C1=CC=NC=C1)C=NC=C2 ZOBZTNONBIVPBE-UHFFFAOYSA-N 0.000 claims description 2
- JVCDXTHYVYGMQC-UHFFFAOYSA-N 2-[2-methyl-2-[(2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-yl)amino]propoxy]ethanol Chemical compound CC(COCCO)(C)NC=1C2=C(N=C(N=1)C1=CC=NC=C1)C=NC=C2 JVCDXTHYVYGMQC-UHFFFAOYSA-N 0.000 claims description 2
- KTRVKZXQBVEQBL-UHFFFAOYSA-N 2-methyl-2-N-[2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]propane-1,2-diamine Chemical compound NCC(C)(C)NC=1C2=C(N=C(N=1)C=1C=NNC=1)C=NC=C2 KTRVKZXQBVEQBL-UHFFFAOYSA-N 0.000 claims description 2
- DCIPFXLSLUFVQA-UHFFFAOYSA-N 2-methyl-2-[(2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-yl)amino]propan-1-ol Chemical compound CC(CO)(C)NC=1C2=C(N=C(N=1)C1=CC=NC=C1)C=NC=C2 DCIPFXLSLUFVQA-UHFFFAOYSA-N 0.000 claims description 2
- GASZFPAPBAGRFK-UHFFFAOYSA-N 2-methyl-2-[(2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-yl)amino]propane-1,3-diol Chemical compound CC(CO)(CO)NC=1C2=C(N=C(N=1)C1=CC=NC=C1)C=NC=C2 GASZFPAPBAGRFK-UHFFFAOYSA-N 0.000 claims description 2
- YSXUPBSDPJABHI-UHFFFAOYSA-N 2-methyl-4-N-(2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-yl)pentane-2,4-diamine Chemical compound CC(CC(C)(N)C)NC=1C2=C(N=C(N=1)C1=CC=NC=C1)C=NC=C2 YSXUPBSDPJABHI-UHFFFAOYSA-N 0.000 claims description 2
- JYVLIDXNZAXMDK-UHFFFAOYSA-N 2-pentanol Substances CCCC(C)O JYVLIDXNZAXMDK-UHFFFAOYSA-N 0.000 claims description 2
- NCWUWMQIMGPXQR-AWEZNQCLSA-N 2-pyridin-4-yl-4-[(3S)-3-(trifluoromethyl)piperazin-1-yl]pyrido[3,4-d]pyrimidine Chemical compound N1=CC=C(C=C1)C=1N=C(C2=C(N=1)C=NC=C2)N1C[C@H](NCC1)C(F)(F)F NCWUWMQIMGPXQR-AWEZNQCLSA-N 0.000 claims description 2
- PTTKHXBEPPAXSE-UHFFFAOYSA-N 2-pyridin-4-yl-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC=C(C=C1)C=1N=C(C2=C(N=1)C=NC=C2)NC(C(F)(F)F)C PTTKHXBEPPAXSE-UHFFFAOYSA-N 0.000 claims description 2
- RGIKJUZEMMTILQ-UHFFFAOYSA-N 2-pyridin-4-yl-N-[1-(trifluoromethyl)cyclobutyl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC=C(C=C1)C=1N=C(C2=C(N=1)C=NC=C2)NC1(CCC1)C(F)(F)F RGIKJUZEMMTILQ-UHFFFAOYSA-N 0.000 claims description 2
- ACTDLFQRJKPKFQ-UHFFFAOYSA-N 2-pyridin-4-yl-N-[1-(trifluoromethyl)cyclopropyl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC=C(C=C1)C=1N=C(C2=C(N=1)C=NC=C2)NC1(CC1)C(F)(F)F ACTDLFQRJKPKFQ-UHFFFAOYSA-N 0.000 claims description 2
- GSYJHCKYYPELPH-UHFFFAOYSA-N 2-pyridin-4-yl-N-[3-(2H-tetrazol-5-yl)propyl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC=C(C=C1)C=1N=C(C2=C(N=1)C=NC=C2)NCCCC1=NN=NN1 GSYJHCKYYPELPH-UHFFFAOYSA-N 0.000 claims description 2
- PEYNBYLLSKMKNU-UHFFFAOYSA-N 2-pyridin-4-ylpyrido[3,4-d]pyrimidin-4-amine Chemical compound N=1C2=CN=CC=C2C(N)=NC=1C1=CC=NC=C1 PEYNBYLLSKMKNU-UHFFFAOYSA-N 0.000 claims description 2
- STAZQQYFJAXCJL-UHFFFAOYSA-N 2-pyridin-4-ylpyrido[3,4-d]pyrimidine Chemical compound C1=NC=CC(C=2N=C3C=NC=CC3=CN=2)=C1 STAZQQYFJAXCJL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
- KSQYPFHEXAQSRA-UHFFFAOYSA-N 4-N,2-dimethyl-2-N-[2-[5-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-yl]pentane-2,4-diamine Chemical compound CC(CC(C)(NC=1C2=C(N=C(N=1)C=1C(=NNC=1)C(F)(F)F)C=NC=C2)C)NC KSQYPFHEXAQSRA-UHFFFAOYSA-N 0.000 claims description 2
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| JP2018536436A (ja) | 2015-12-04 | 2018-12-13 | ノバルティス アーゲー | 免疫腫瘍学のための組成物および方法 |
| WO2017172596A1 (en) | 2016-03-28 | 2017-10-05 | Incyte Corporation | Pyrrolotriazine compounds as tam inhibitors |
| MX2019011272A (es) | 2017-03-22 | 2019-10-24 | Novartis Ag | Composiciones y metodos para inmunooncologia. |
| JOP20190257A1 (ar) | 2017-04-28 | 2019-10-28 | Novartis Ag | مركبات أريل غير متجانسة ثنائية الحلقة مندمجة 6-6 واستخدامها كمثبطات lats |
| CA3077308A1 (en) | 2017-09-27 | 2019-04-04 | Incyte Corporation | Salts of pyrrolotriazine derivatives useful as tam inhibitors |
| US20210253518A1 (en) | 2018-06-08 | 2021-08-19 | Nissan Chemical Corporation | Kinase inhibitor |
| PL3813800T3 (pl) | 2018-06-29 | 2025-08-18 | Incyte Corporation | Formulacje inhibitora axl/mer |
| US20220001074A1 (en) * | 2018-10-16 | 2022-01-06 | The Schepens Eye Research Institute, Inc. | Bioadhesive for Soft Tissue Repair |
| UY38427A (es) * | 2018-10-26 | 2020-05-29 | Novartis Ag | Métodos y composiciones para terapia con células oculares |
| EP3896158A4 (en) * | 2018-12-11 | 2022-11-02 | Kyoto University | METHODS OF INDUCING A DELETION IN GENOMIC DNA |
| WO2020158841A1 (ja) | 2019-01-30 | 2020-08-06 | 日産化学株式会社 | ヒドラジド化合物及びキナーゼ阻害剤 |
| CN112707905B (zh) * | 2019-10-25 | 2024-07-02 | 武汉誉祥医药科技有限公司 | 一种三并杂环化合物及其制备方法和用途 |
| GB201915829D0 (en) * | 2019-10-31 | 2019-12-18 | Cancer Research Tech Ltd | Compounds, compositions and therapeutic uses thereof |
| GB201915831D0 (en) * | 2019-10-31 | 2019-12-18 | Cancer Research Tech Ltd | Compounds, compositions and therapeutic uses thereof |
| JP7759877B2 (ja) * | 2019-11-27 | 2025-10-24 | ジェネンテック， インコーポレイテッド | 治療用化合物 |
| CN115515579B (zh) * | 2020-02-05 | 2025-09-30 | 洛克菲勒大学 | 吡咯并[2,3-b]吡啶-3-甲酰胺组合物和改善听力损失的方法 |
| AU2021230385A1 (en) | 2020-03-06 | 2022-09-22 | Incyte Corporation | Combination therapy comprising AXL/MER and PD-1/PD-L1 inhibitors |
| CN111443068B (zh) * | 2020-03-06 | 2023-06-27 | 天津大学 | 具有多重刺激响应特性的纯有机室温磷光材料及筛选方法和应用 |
| US20230348852A1 (en) | 2020-04-27 | 2023-11-02 | Novartis Ag | Methods and compositions for ocular cell therapy |
| MX2022013518A (es) * | 2020-04-28 | 2023-02-01 | Global Blood Therapeutics Inc | Pirimidinas cicloalquiladas como inhibidores de la ferroportina. |
| CN112305126A (zh) * | 2020-11-02 | 2021-02-02 | 宁夏贝利特生物科技有限公司 | 一种硝酸胍含量的测定方法 |
| JP7738165B2 (ja) * | 2021-08-23 | 2025-09-11 | イー・エム・デイー・ミリポア・コーポレイシヨン | 電気泳動ゲルの光重合システム及び方法 |
| CN115974868B (zh) * | 2022-11-07 | 2024-04-12 | 安徽理工大学 | 一种尿嘧啶衍生物的合成方法及其抗肺纤维化方面的潜在应用 |
| WO2024211621A1 (en) * | 2023-04-04 | 2024-10-10 | Children's Hospital Los Angeles | Lats kinase inhibitor to treat retinal degeneration |
| CN119462609A (zh) * | 2024-10-25 | 2025-02-18 | 烟台皓元生物医药科技有限公司 | 一种lats抑制剂vt02956的制备方法 |
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| WO2004065392A1 (en) | 2003-01-24 | 2004-08-05 | Smithkline Beecham Corporation | Condensed pyridines and pyrimidines and their use as alk-5 receptor ligands |
| KR20070113252A (ko) * | 2005-02-25 | 2007-11-28 | 쿠도스 파마슈티칼스 리미티드 | 2,4-디아미노-피리도피리미딘 유도체 및 이의 ｍＴＯＲ억제제로서의 용도 |
| MX2009010696A (es) * | 2007-04-06 | 2009-10-20 | Novartis Ag | Derivados de 2,6-naftiridina como moduladores de cinasa de proteina. |
| KR20110046514A (ko) | 2008-07-31 | 2011-05-04 | 제넨테크, 인크. | 피리미딘 화합물, 조성물 및 사용 방법 |
| US20110319409A1 (en) * | 2010-06-23 | 2011-12-29 | Cox Christopher D | 7-aza-quinazoline pde10 inhibitors |
| WO2013012087A1 (ja) * | 2011-07-15 | 2013-01-24 | 国立大学法人大阪大学 | 角膜内皮細胞の調製方法 |
| KR20140074964A (ko) | 2011-09-27 | 2014-06-18 | 에프. 호프만-라 로슈 아게 | 피라졸-4-일-헤테로사이클릴-카복사마이드 화합물 및 사용 방법 |
| NZ706857A (en) * | 2012-09-28 | 2018-05-25 | Ignyta Inc | Azaquinazoline inhibitors of atypical protein kinase c |
| BR112016013201B1 (pt) * | 2013-12-12 | 2023-01-31 | The Broad Institute, Inc. | Uso de uma composição compreendendo um sistema crispr-cas no tratamento de uma doença genética ocular |
| TWI675836B (zh) * | 2014-03-25 | 2019-11-01 | 美商伊格尼塔公司 | 非典型蛋白質激酶ｃ之氮雜喹唑啉抑制劑 |
| EP3197557A1 (en) | 2014-09-24 | 2017-08-02 | Friedrich Miescher Institute for Biomedical Research | Lats and breast cancer |
| MA43512A (fr) * | 2015-08-03 | 2018-11-07 | Bristol Myers Squibb Co | Composés hétérocycliques utiles en tant que modulateurs du tnf alpha |
| CA2996513A1 (en) | 2015-08-25 | 2018-03-02 | President And Fellows Of Harvard College | Methods and compositions relating to the diagnosis and treatment of cancer |
| JOP20190257A1 (ar) | 2017-04-28 | 2019-10-28 | Novartis Ag | مركبات أريل غير متجانسة ثنائية الحلقة مندمجة 6-6 واستخدامها كمثبطات lats |
| UY38427A (es) * | 2018-10-26 | 2020-05-29 | Novartis Ag | Métodos y composiciones para terapia con células oculares |
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