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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| CN114502163A (zh) * | 2019-07-22 | 2022-05-13 | 安吉昂生物医药公司 | 作为rho相关卷曲螺旋激酶(rock)抑制剂的乙炔基杂环 |
| 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 |
| EP4185579A1 (en) * | 2020-07-21 | 2023-05-31 | Angion Biomedica Corp. | Inhibitors of rho-associated coiled-coil kinase |
| WO2023202642A1 (zh) * | 2022-04-20 | 2023-10-26 | 上海挚盟医药科技有限公司 | Rho相关蛋白激酶抑制剂及其制备和应用 |
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