JP2020532551A5 - - Google Patents
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- JP2020532551A5 JP2020532551A5 JP2020512687A JP2020512687A JP2020532551A5 JP 2020532551 A5 JP2020532551 A5 JP 2020532551A5 JP 2020512687 A JP2020512687 A JP 2020512687A JP 2020512687 A JP2020512687 A JP 2020512687A JP 2020532551 A5 JP2020532551 A5 JP 2020532551A5
- Authority
- JP
- Japan
- Prior art keywords
- vinyl
- isoindoline
- bipyrimidine
- pyridin
- pyrimidine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 150000001875 compounds Chemical class 0.000 claims 37
- -1 heteroaliphatic Chemical group 0.000 claims 25
- 125000000623 heterocyclic group Chemical group 0.000 claims 21
- 125000001072 heteroaryl group Chemical group 0.000 claims 14
- 125000001931 aliphatic group Chemical group 0.000 claims 13
- 125000003118 aryl group Chemical group 0.000 claims 13
- 125000005843 halogen group Chemical group 0.000 claims 13
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 12
- 150000002431 hydrogen Chemical group 0.000 claims 12
- 229910052739 hydrogen Inorganic materials 0.000 claims 12
- 239000001257 hydrogen Substances 0.000 claims 12
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims 10
- 229910052805 deuterium Inorganic materials 0.000 claims 10
- 229910052757 nitrogen Inorganic materials 0.000 claims 10
- 101000669917 Homo sapiens Rho-associated protein kinase 1 Proteins 0.000 claims 9
- 102100039313 Rho-associated protein kinase 1 Human genes 0.000 claims 9
- 125000002723 alicyclic group Chemical group 0.000 claims 9
- 125000001424 substituent group Chemical group 0.000 claims 6
- 101000669921 Homo sapiens Rho-associated protein kinase 2 Proteins 0.000 claims 5
- 102100039314 Rho-associated protein kinase 2 Human genes 0.000 claims 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 5
- 239000000203 mixture Substances 0.000 claims 5
- 229910052760 oxygen Inorganic materials 0.000 claims 5
- 239000008194 pharmaceutical composition Substances 0.000 claims 5
- 125000006413 ring segment Chemical group 0.000 claims 5
- 229910052717 sulfur Inorganic materials 0.000 claims 5
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 4
- 229910052799 carbon Inorganic materials 0.000 claims 4
- 150000002390 heteroarenes Chemical class 0.000 claims 4
- 125000005842 heteroatom Chemical group 0.000 claims 4
- 125000002883 imidazolyl group Chemical group 0.000 claims 4
- 230000000302 ischemic effect Effects 0.000 claims 4
- 210000000056 organ Anatomy 0.000 claims 4
- 239000000126 substance Substances 0.000 claims 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 4
- 229920002554 vinyl polymer Polymers 0.000 claims 4
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims 3
- 206010016654 Fibrosis Diseases 0.000 claims 3
- 125000004432 carbon atom Chemical group C* 0.000 claims 3
- 239000003795 chemical substances by application Substances 0.000 claims 3
- 230000001684 chronic effect Effects 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 230000004761 fibrosis Effects 0.000 claims 3
- 230000002401 inhibitory effect Effects 0.000 claims 3
- 125000002950 monocyclic group Chemical group 0.000 claims 3
- 208000031225 myocardial ischemia Diseases 0.000 claims 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims 3
- 125000000335 thiazolyl group Chemical group 0.000 claims 3
- FCRIDQXDGOGPKD-UHFFFAOYSA-N 2,3-dihydro-1H-isoindol-5-yl trifluoromethanesulfonate Chemical compound C1NCC2=CC(=CC=C12)OS(=O)(=O)C(F)(F)F FCRIDQXDGOGPKD-UHFFFAOYSA-N 0.000 claims 2
- WXNJKYNDOHUHGX-HNQUOIGGSA-N 2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindol-5-ol Chemical compound N1=CC=C(C=C1)/C=C/C1=NC(=NC=C1)C1=NC(=NC=C1)N1CC2=CC=C(C=C2C1)O WXNJKYNDOHUHGX-HNQUOIGGSA-N 0.000 claims 2
- VAHJBPFBQPLUNQ-DUXPYHPUSA-N 2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole-5-carbonitrile Chemical compound N1=CC=C(C=C1)/C=C/C1=NC(=NC=C1)C1=NC(=NC=C1)N1CC2=CC=C(C=C2C1)C#N VAHJBPFBQPLUNQ-DUXPYHPUSA-N 0.000 claims 2
- WGHNLVPDICRTER-DUXPYHPUSA-N 4-[(E)-2-[2-[2-(5-methoxy-1,3-dihydroisoindol-2-yl)pyrimidin-4-yl]pyrimidin-4-yl]ethenyl]-1H-pyrrolo[2,3-b]pyridine Chemical compound COC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)/C=C/C1=C2C(=NC=C1)NC=C2 WGHNLVPDICRTER-DUXPYHPUSA-N 0.000 claims 2
- MUSNMWIVQFISER-SOFGYWHQSA-N 4-[(E)-2-[2-[2-(5-methoxy-1,3-dihydroisoindol-2-yl)pyrimidin-4-yl]pyrimidin-4-yl]ethenyl]-1H-quinolin-2-one Chemical compound COC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)/C=C/C1=CC(NC2=CC=CC=C12)=O MUSNMWIVQFISER-SOFGYWHQSA-N 0.000 claims 2
- PKSPBEFFJGRQIN-DAFODLJHSA-N 5-fluoro-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole Chemical compound FC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 PKSPBEFFJGRQIN-DAFODLJHSA-N 0.000 claims 2
- GVGSJWAWCQNWKP-ONEGZZNKSA-N 5-methoxy-2-[4-[4-[(E)-2-(1H-pyrazol-5-yl)ethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole Chemical compound N1N=C(C=C1)/C=C/C1=NC(=NC=C1)C1=NC(=NC=C1)N1CC2=CC=C(C=C2C1)OC GVGSJWAWCQNWKP-ONEGZZNKSA-N 0.000 claims 2
- ZWMBPCIFTLOGCG-DUXPYHPUSA-N 5-methoxy-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole Chemical compound COC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 ZWMBPCIFTLOGCG-DUXPYHPUSA-N 0.000 claims 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- 206010008609 Cholangitis sclerosing Diseases 0.000 claims 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims 2
- 208000001647 Renal Insufficiency Diseases 0.000 claims 2
- 206010063837 Reperfusion injury Diseases 0.000 claims 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims 2
- 125000002619 bicyclic group Chemical group 0.000 claims 2
- 208000026106 cerebrovascular disease Diseases 0.000 claims 2
- 208000019425 cirrhosis of liver Diseases 0.000 claims 2
- 206010012601 diabetes mellitus Diseases 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 239000007943 implant Substances 0.000 claims 2
- 208000017169 kidney disease Diseases 0.000 claims 2
- 201000006370 kidney failure Diseases 0.000 claims 2
- 208000005069 pulmonary fibrosis Diseases 0.000 claims 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims 2
- 125000005494 pyridonyl group Chemical group 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims 2
- 201000002793 renal fibrosis Diseases 0.000 claims 2
- 208000010157 sclerosing cholangitis Diseases 0.000 claims 2
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 claims 2
- 125000004306 triazinyl group Chemical group 0.000 claims 2
- 125000001425 triazolyl group Chemical group 0.000 claims 2
- AZAXMEYBBSDTRP-DAFODLJHSA-N 2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindol-5-amine Chemical compound NC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 AZAXMEYBBSDTRP-DAFODLJHSA-N 0.000 claims 1
- KAGHHSNVLVQYSI-DAFODLJHSA-N 4-[(E)-2-[2-[2-(5-bromo-1,3-dihydroisoindol-2-yl)pyrimidin-4-yl]pyrimidin-4-yl]ethenyl]pyridin-2-amine Chemical compound BrC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)/C=C/C1=CC(=NC=C1)N KAGHHSNVLVQYSI-DAFODLJHSA-N 0.000 claims 1
- KAGKRBBEAAJZRA-DAFODLJHSA-N 4-[(E)-2-[2-[2-(5-chloro-1,3-dihydroisoindol-2-yl)pyrimidin-4-yl]pyrimidin-4-yl]ethenyl]pyridin-2-amine Chemical compound ClC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)/C=C/C1=CC(=NC=C1)N KAGKRBBEAAJZRA-DAFODLJHSA-N 0.000 claims 1
- REWDPZLUDTUTGP-DAFODLJHSA-N 4-[(E)-2-[2-[2-(5-fluoro-1,3-dihydroisoindol-2-yl)pyrimidin-4-yl]pyrimidin-4-yl]ethenyl]pyridin-2-amine Chemical compound FC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)/C=C/C1=CC(=NC=C1)N REWDPZLUDTUTGP-DAFODLJHSA-N 0.000 claims 1
- CQGQRASJFOVYPM-DUXPYHPUSA-N 4-[(E)-2-[2-[2-(5-methoxy-1,3-dihydroisoindol-2-yl)pyrimidin-4-yl]pyrimidin-4-yl]ethenyl]pyridin-2-amine Chemical compound COC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)/C=C/C1=CC(=NC=C1)N CQGQRASJFOVYPM-DUXPYHPUSA-N 0.000 claims 1
- MTMDQMRISYKFHO-HNQUOIGGSA-N 4-[(E)-2-[2-[2-(5-morpholin-4-yl-1,3-dihydroisoindol-2-yl)pyrimidin-4-yl]pyrimidin-4-yl]ethenyl]pyridin-2-amine Chemical compound O1CCN(CC1)C=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)/C=C/C1=CC(=NC=C1)N MTMDQMRISYKFHO-HNQUOIGGSA-N 0.000 claims 1
- PRSRKMSJMBWCPD-HWKANZROSA-N 4-[(E)-2-[2-[2-[5-[2-(dimethylamino)ethoxy]-1,3-dihydroisoindol-2-yl]pyrimidin-4-yl]pyrimidin-4-yl]ethenyl]pyridin-2-amine Chemical compound CN(CCOC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)/C=C/C1=CC(=NC=C1)N)C PRSRKMSJMBWCPD-HWKANZROSA-N 0.000 claims 1
- UVISFXPTVSIFOE-HNQUOIGGSA-N 4-[2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindol-5-yl]morpholine Chemical compound N1=CC=C(C=C1)/C=C/C1=NC(=NC=C1)C1=NC(=NC=C1)N1CC2=CC=C(C=C2C1)N1CCOCC1 UVISFXPTVSIFOE-HNQUOIGGSA-N 0.000 claims 1
- YFPNYVFZILUOQQ-HNQUOIGGSA-N 4-[2-[[2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindol-5-yl]oxy]ethyl]morpholine Chemical compound N1=CC=C(C=C1)/C=C/C1=NC(=NC=C1)C1=NC(=NC=C1)N1CC2=CC=C(C=C2C1)OCCN1CCOCC1 YFPNYVFZILUOQQ-HNQUOIGGSA-N 0.000 claims 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- BRIWHFILIRNOAB-GORDUTHDSA-N 5-(1-methylpyrazol-4-yl)-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole Chemical compound CN1N=CC(=C1)C=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 BRIWHFILIRNOAB-GORDUTHDSA-N 0.000 claims 1
- BKPQVIQEZKKUMO-DUXPYHPUSA-N 5-(4-methylpiperazin-1-yl)-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole Chemical compound CN1CCN(CC1)C=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 BKPQVIQEZKKUMO-DUXPYHPUSA-N 0.000 claims 1
- RBNYRXLAUWSTQR-DAFODLJHSA-N 5-bromo-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole Chemical compound BrC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 RBNYRXLAUWSTQR-DAFODLJHSA-N 0.000 claims 1
- YTGOGGVVARSMDU-DAFODLJHSA-N 5-chloro-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole Chemical compound ClC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 YTGOGGVVARSMDU-DAFODLJHSA-N 0.000 claims 1
- IXIZBYONXUWDTM-LZCJLJQNSA-N 5-cyclopropyl-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole Chemical compound C1(CC1)C=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 IXIZBYONXUWDTM-LZCJLJQNSA-N 0.000 claims 1
- VFXOHOSNAALCET-HNQUOIGGSA-N 5-cyclopropyloxy-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole Chemical compound C1(CC1)OC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 VFXOHOSNAALCET-HNQUOIGGSA-N 0.000 claims 1
- RKHXGMHOJQJRJB-GQCTYLIASA-N 5-ethenyl-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole Chemical compound C(=C)C=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 RKHXGMHOJQJRJB-GQCTYLIASA-N 0.000 claims 1
- OBAULQLYJJIQIY-HWKANZROSA-N 5-ethoxy-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole Chemical compound C(C)OC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 OBAULQLYJJIQIY-HWKANZROSA-N 0.000 claims 1
- LVCMDYKQZCFJGL-GQCTYLIASA-N 5-ethyl-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole Chemical compound C(C)C=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 LVCMDYKQZCFJGL-GQCTYLIASA-N 0.000 claims 1
- KPRSJOXTTTUTQV-DAFODLJHSA-N 5-iodo-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole Chemical compound IC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 KPRSJOXTTTUTQV-DAFODLJHSA-N 0.000 claims 1
- JIMIXDRCHLRIRZ-HWKANZROSA-N 5-methyl-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole Chemical compound CC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 JIMIXDRCHLRIRZ-HWKANZROSA-N 0.000 claims 1
- VFEXXYDRFFYFFF-RMKNXTFCSA-N 5-phenyl-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole Chemical compound C1(=CC=CC=C1)C=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 VFEXXYDRFFYFFF-RMKNXTFCSA-N 0.000 claims 1
- IZFOYURTISLUCM-FNORWQNLSA-N 5-prop-2-ynyl-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole Chemical compound C(C#C)C=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 IZFOYURTISLUCM-FNORWQNLSA-N 0.000 claims 1
- ZBWJXZRDAVKUIE-HWKANZROSA-N 5-propan-2-yloxy-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindole Chemical compound C(C)(C)OC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 ZBWJXZRDAVKUIE-HWKANZROSA-N 0.000 claims 1
- 208000007848 Alcoholism Diseases 0.000 claims 1
- 206010004637 Bile duct stone Diseases 0.000 claims 1
- 208000015163 Biliary Tract disease Diseases 0.000 claims 1
- 208000018565 Hemochromatosis Diseases 0.000 claims 1
- 208000027761 Hepatic autoimmune disease Diseases 0.000 claims 1
- 208000005176 Hepatitis C Diseases 0.000 claims 1
- 208000005331 Hepatitis D Diseases 0.000 claims 1
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 claims 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims 1
- VFJYCLQXUIJSJB-HWKANZROSA-N N,N-dimethyl-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindol-5-amine Chemical compound CN(C=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1)C VFJYCLQXUIJSJB-HWKANZROSA-N 0.000 claims 1
- TZPASUVCXKQLCE-DUXPYHPUSA-N N-methyl-2-[4-[4-[(E)-2-pyridin-4-ylethenyl]pyrimidin-2-yl]pyrimidin-2-yl]-1,3-dihydroisoindol-5-amine Chemical compound CNC=1C=C2CN(CC2=CC=1)C1=NC=CC(=N1)C1=NC=CC(=N1)\C=C\C1=CC=NC=C1 TZPASUVCXKQLCE-DUXPYHPUSA-N 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 206010053648 Vascular occlusion Diseases 0.000 claims 1
- 208000018839 Wilson disease Diseases 0.000 claims 1
- 206010052428 Wound Diseases 0.000 claims 1
- 208000027418 Wounds and injury Diseases 0.000 claims 1
- 201000007930 alcohol dependence Diseases 0.000 claims 1
- 230000001476 alcoholic effect Effects 0.000 claims 1
- 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 claims 1
- 230000033115 angiogenesis Effects 0.000 claims 1
- 230000003510 anti-fibrotic effect Effects 0.000 claims 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims 1
- 239000012472 biological sample Substances 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 210000004556 brain Anatomy 0.000 claims 1
- 206010008118 cerebral infarction Diseases 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- 208000036449 fibrotic liver disease Diseases 0.000 claims 1
- 210000002216 heart Anatomy 0.000 claims 1
- 230000002440 hepatic effect Effects 0.000 claims 1
- 208000006454 hepatitis Diseases 0.000 claims 1
- 231100000283 hepatitis Toxicity 0.000 claims 1
- 208000002672 hepatitis B Diseases 0.000 claims 1
- 208000029570 hepatitis D virus infection Diseases 0.000 claims 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 208000016245 inborn errors of metabolism Diseases 0.000 claims 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims 1
- 125000001041 indolyl group Chemical group 0.000 claims 1
- 208000014674 injury Diseases 0.000 claims 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims 1
- 208000012947 ischemia reperfusion injury Diseases 0.000 claims 1
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 claims 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims 1
- 210000003734 kidney Anatomy 0.000 claims 1
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| TW202132285A (zh) * | 2019-11-13 | 2021-09-01 | 美商愛彼特生物製藥股份有限公司 | 經取代異吲哚啉基2,2’-聯嘧啶基化合物、其類似物及使用其之方法 |
| CA3189725A1 (en) * | 2020-07-21 | 2022-01-27 | Angion Biomedica Corp. | Inhibitors of rho-associated coiled-coil kinase |
| KR20250004773A (ko) * | 2022-04-20 | 2025-01-08 | 상하이 지멍 바이오파마 아이엔씨 | Rho 관련 단백질 키나아제 억제제 및 이의 제조와 응용 |
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Family Cites Families (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5322756A (en) * | 1992-07-09 | 1994-06-21 | Xerox Corporation | Magnetic fluids and method of preparation |
| MY134008A (en) * | 1999-12-22 | 2007-11-30 | Merck Frosst Canada Inc | Subtituted 8-arylquinoline phospohodiestrase-4 inhibitors |
| EP1490362A2 (en) | 2001-03-08 | 2004-12-29 | Millennium Pharmaceuticals, Inc. | (homo)piperazine substituted quinolines for inhibiting the phosphorylation of kinases |
| DE102004039280A1 (de) | 2004-08-13 | 2006-02-23 | Merck Patent Gmbh | 1,5-Diphenyl-pyrazole |
| CR9465A (es) | 2005-03-25 | 2008-06-19 | Surface Logix Inc | Compuestos mejorados farmacocineticamente |
| JP5252404B2 (ja) * | 2006-08-16 | 2013-07-31 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ピラジン化合物、その使用及び調製方法 |
| BRPI0717097A2 (pt) * | 2006-09-21 | 2013-11-26 | Novartis Ag | Derivados de pirrol úteis para o tratamento de doenças mediadas por citocina |
| US7758972B2 (en) * | 2006-09-26 | 2010-07-20 | Semiconductor Energy Laboratory Co., Ltd. | Stilbene derivative, light emitting element, light emitting device, and electronic appliance |
| WO2008054599A2 (en) | 2006-09-27 | 2008-05-08 | Surface Logix, Inc. | Rho kinase inhibitors |
| EP2116522B1 (en) * | 2007-02-28 | 2013-09-18 | JNC Corporation | Pentacyclic liquid crystal compound having cf<sb>2</sb>o bonding group, liquid crystal composition and liquid crystal display |
| WO2008120810A1 (ja) * | 2007-03-29 | 2008-10-09 | Sumitomo Chemical Company, Limited | 化合物、光電変換素子及び光電気化学電池 |
| US20120202793A1 (en) | 2009-03-09 | 2012-08-09 | Paul Sweetnam | Rho kinase inhibitors |
| US8680116B2 (en) * | 2009-07-22 | 2014-03-25 | Merck Sharp & Dohme Corp. | Quinolinone PDE2 inhibitors |
| EP2542528B1 (en) | 2010-03-02 | 2013-06-19 | Amakem NV | Heterocyclic amides as rock inhibitors |
| WO2012040499A2 (en) | 2010-09-22 | 2012-03-29 | Surface Logix, Inc. | Metabolic inhibitors |
| JP5809954B2 (ja) * | 2011-12-15 | 2015-11-11 | 富士フイルム株式会社 | 光電変換素子及び色素増感太陽電池 |
| CN113620933A (zh) | 2012-10-05 | 2021-11-09 | 卡德门企业有限公司 | Rho激酶抑制剂 |
| WO2014093773A1 (en) | 2012-12-14 | 2014-06-19 | The Brigham And Women's Hospital, Inc. | Methods and assays relating to macrophage differentiation |
| PT2951172T (pt) | 2013-01-29 | 2017-07-12 | Redx Pharma Plc | Derivados de piridina como inibidores de rock leves |
| US11311541B2 (en) | 2014-04-09 | 2022-04-26 | Kadmon Corporation, Llc | Treatment of GVHD |
| WO2015190467A1 (ja) * | 2014-06-11 | 2015-12-17 | 富士フイルム株式会社 | 光電変換素子、色素増感太陽電池、金属錯体色素、色素溶液、およびターピリジン化合物またはそのエステル化物 |
| US9902702B2 (en) * | 2014-07-15 | 2018-02-27 | Bristol-Myers Squibb Company | Spirocycloheptanes as inhibitors of rock |
| US10011600B2 (en) | 2014-09-25 | 2018-07-03 | Araxes Pharma Llc | Methods and compositions for inhibition of Ras |
| WO2016081554A1 (en) | 2014-11-18 | 2016-05-26 | Neostem Oncology, Llc | Immunogenic compositions prepared from tumor cells derived from peripheral blood and originating from a solid tumor and their use |
| JP2018501276A (ja) | 2015-01-09 | 2018-01-18 | ギリアド アポロ， エルエルシー | 非アルコール性脂肪肝疾患の処置のためのａｃｃ阻害剤併用療法 |
| US9687483B2 (en) | 2015-01-26 | 2017-06-27 | BioAxone BioSciences, Inc. | Treatment of cerebral cavernous malformations and cerebral aneurysms with Rho kinase inhibitors |
| US10106525B2 (en) | 2015-01-26 | 2018-10-23 | BioAxone BioSciences, Inc. | Rho kinase inhibitor BA-1049 (R) and active metabolites thereof |
| US10149856B2 (en) | 2015-01-26 | 2018-12-11 | BioAxone BioSciences, Inc. | Treatment of cerebral cavernous malformations and cerebral aneurysms with rho kinase inhibitors |
| ES2730112T3 (es) | 2015-03-09 | 2019-11-08 | Bristol Myers Squibb Co | Lactamas como inhibidores de ROCK |
| KR20180021741A (ko) | 2015-05-29 | 2018-03-05 | 에쥐 세라피틱스, 인코포레이티드 | 시각 손실을 감소시키기 위한 조성물 및 방법 |
| DK3312270T3 (da) | 2015-06-16 | 2020-10-12 | Univ Kyoto | Fremgangsmåde til fremstilling af plader med høj ydeevne |
| AU2017246228B2 (en) | 2016-04-04 | 2021-04-15 | Chemocentryx, Inc. | Soluble C5aR antagonists |
| JP2019112307A (ja) | 2016-04-28 | 2019-07-11 | 宇部興産株式会社 | 置換ジヒドロピロロピラゾール化合物および他の乾癬治療薬が組み合わせて投与される医薬組成物 |
| SG11201810602YA (en) | 2016-06-03 | 2018-12-28 | Chemocentryx Inc | Method of treating liver fibrosis |
| CN107019698A (zh) | 2016-08-04 | 2017-08-08 | 上海市第十人民医院 | Rock2抑制剂在制备炎症性肠病药物中的应用 |
| WO2018052953A1 (en) | 2016-09-13 | 2018-03-22 | President And Fellows Of Harvard College | Methods relating to intestinal organ-on-a-chip |
| KR101892154B1 (ko) | 2017-02-22 | 2018-08-28 | 한국과학기술연구원 | Ｒｈｏ-연관된 단백질 키나제 저해제를 포함하는 면역 반응 증강용 조성물 및 이를 이용한 방법 |
| CN106916145B (zh) | 2017-03-06 | 2019-06-04 | 上海应用技术大学 | SLx-2119的合成方法 |
| KR20190122806A (ko) | 2017-03-13 | 2019-10-30 | 장피트 | 조합 치료요법용 약학 조성물 |
| AU2018234059A1 (en) | 2017-03-16 | 2019-10-31 | Takeda Gmbh | Treatment of idiopathic pulmonary fibrosis |
| CN110536682B (zh) | 2017-04-18 | 2023-01-06 | 基恩菲特公司 | 依拉非诺或其衍生物与抗nash、抗纤维化或抗胆汁淤积药剂的组合 |
| US11541046B2 (en) | 2017-06-30 | 2023-01-03 | Quixgen, Inc. | Spirolactone compounds |
| US11542256B2 (en) | 2017-09-03 | 2023-01-03 | Angion Biomedica Corp. | Vinylheterocycles as Rho-associated coiled-coil kinase (ROCK) inhibitors |
| GB201715930D0 (en) | 2017-09-30 | 2017-11-15 | Upside Biotechnologies Ltd | Cell Culture Medium |
| GB201715928D0 (en) | 2017-09-30 | 2017-11-15 | Auckland Uniservices Ltd | Method |
| KR20200109298A (ko) | 2017-10-30 | 2020-09-22 | 케모센트릭스, 인크. | 면역조절제로서의 중수소화된 화합물 |
| WO2019099457A1 (en) | 2017-11-14 | 2019-05-23 | Quixgen, Inc. | Benzodioxinone compounds |
| HRP20241643T1 (hr) | 2017-12-06 | 2025-02-14 | Basf As | Derivati masnih kiselina za liječenje nealkoholnog steatohepatitisa |
| MX2020006460A (es) | 2017-12-22 | 2020-11-06 | Chemocentryx Inc | Compuestos de anillo 5,5 fusionado sustituido con diarilo como inhibidores de c5ar. |
| ES2980175T3 (es) | 2017-12-22 | 2024-09-30 | Chemocentryx Inc | Compuestos anulares fusionados en 6,5 sustituidos con diarilo como inhibidores de C5aR |
| WO2019195159A1 (en) | 2018-04-02 | 2019-10-10 | Chemocentryx, Inc. | PRODRUGS OF FUSED-BICYCLIC C5aR ANTAGONISTS |
| US20190328721A1 (en) | 2018-04-25 | 2019-10-31 | Korea Institute Of Science And Technology | Method of activating dendritic cells |
| CN110200972A (zh) | 2019-05-10 | 2019-09-06 | 南京市儿童医院 | Kd025在制备防治慢性肾纤维化的药物中的用途 |
| EP4003340A4 (en) | 2019-07-22 | 2023-09-27 | Angion Biomedica Corp. | ETHYNYL HETEROCYCLES AS RHO-ASSOCIATED BISPIRAL KINASE (ROCK) INHIBITORS |
| CA3189725A1 (en) | 2020-07-21 | 2022-01-27 | Angion Biomedica Corp. | Inhibitors of rho-associated coiled-coil kinase |
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