WO2022033548A1 - 免疫调节化合物及其抗肿瘤应用 - Google Patents
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- ICCUKWUFVQPBFR-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-(pyridin-2-ylmethylamino)quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(NCC3=NC=CC=C3)=C2C1=O ICCUKWUFVQPBFR-UHFFFAOYSA-N 0.000 claims 1
- IYJOWFIVKYWDQW-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-(pyridin-2-ylmethylsulfanyl)quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(SCC3=NC=CC=C3)=C2C1=O IYJOWFIVKYWDQW-UHFFFAOYSA-N 0.000 claims 1
- GPPFWRCFHUONKE-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[2-[4-(2-piperidin-1-ylethyl)phenyl]ethyl]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC(C=CC=C2CCC3=CC=C(CCN4CCCCC4)C=C3)=C2C1=O GPPFWRCFHUONKE-UHFFFAOYSA-N 0.000 claims 1
- LSBNGPMOOJUJPQ-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[2-[4-(2-piperidin-1-ylethyl)phenyl]ethynyl]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(C#CC3=CC=C(CCN4CCCCC4)C=C3)=C2C1=O LSBNGPMOOJUJPQ-UHFFFAOYSA-N 0.000 claims 1
- VQZYLFGIEAYQKD-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[2-[4-(piperidin-1-ylmethyl)phenyl]ethylamino]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(NCCC3=CC=C(CN4CCCCC4)C=C3)=C2C1=O VQZYLFGIEAYQKD-UHFFFAOYSA-N 0.000 claims 1
- MWPLUPXCAQQILO-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[2-[4-(piperidin-1-ylmethyl)phenyl]ethylsulfanyl]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(SCCC3=CC=C(CN4CCCCC4)C=C3)=C2C1=O MWPLUPXCAQQILO-UHFFFAOYSA-N 0.000 claims 1
- RJKPJWXPFWOLBT-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[2-[4-(piperidin-1-ylmethyl)phenyl]ethynyl]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC(C=CC=C2C#CC3=CC=C(CN4CCCCC4)C=C3)=C2C1=O RJKPJWXPFWOLBT-UHFFFAOYSA-N 0.000 claims 1
- LMWOYIWTEIDCKQ-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[2-[5-(piperidin-1-ylmethyl)-1,3-thiazol-2-yl]ethyl]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(CCC3=NC=C(CN4CCCCC4)S3)=C2C1=O LMWOYIWTEIDCKQ-UHFFFAOYSA-N 0.000 claims 1
- WLUSAYPSUYACJL-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[2-[5-(piperidin-1-ylmethyl)pyridin-2-yl]ethyl]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(CCC3=CC=C(CN4CCCCC4)C=N3)=C2C1=O WLUSAYPSUYACJL-UHFFFAOYSA-N 0.000 claims 1
- DHHGQGIXWJEZNT-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[3-[4-(piperidin-1-ylmethyl)phenyl]prop-1-ynyl]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(C#CCC3=CC=C(CN4CCCCC4)C=C3)=C2C1=O DHHGQGIXWJEZNT-UHFFFAOYSA-N 0.000 claims 1
- GYKYAUGKDSISGT-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[3-[4-(piperidin-1-ylmethyl)phenyl]propyl]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(CCCC3=CC=C(CN4CCCCC4)C=C3)=C2C1=O GYKYAUGKDSISGT-UHFFFAOYSA-N 0.000 claims 1
- YCWVERRPEUFLCL-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[[4-(2-piperidin-1-ylethyl)phenyl]methoxy]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(OCC3=CC=C(CCN4CCCCC4)C=C3)=C2C1=O YCWVERRPEUFLCL-UHFFFAOYSA-N 0.000 claims 1
- QVFCMBKVCRKZSA-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[[4-(2-piperidin-1-ylethyl)phenyl]methylsulfanyl]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(SCC3=CC=C(CCN4CCCCC4)C=C3)=C2C1=O QVFCMBKVCRKZSA-UHFFFAOYSA-N 0.000 claims 1
- PFFBXBBIZYHUKB-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[[4-(3-piperidin-1-ylpropyl)phenyl]methylsulfanyl]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(SCC3=CC=C(CCCN4CCCCC4)C=C3)=C2C1=O PFFBXBBIZYHUKB-UHFFFAOYSA-N 0.000 claims 1
- GAFDABLAFNURDJ-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[[4-(piperidin-1-ylmethyl)phenyl]methoxy]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(OCC3=CC=C(CN4CCCCC4)C=C3)=C2C1=O GAFDABLAFNURDJ-UHFFFAOYSA-N 0.000 claims 1
- ADUDYWANWFWQMY-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[[4-(piperidin-1-ylmethyl)phenyl]methylsulfanyl]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(SCC3=CC=C(CN4CCCCC4)C=C3)=C2C1=O ADUDYWANWFWQMY-UHFFFAOYSA-N 0.000 claims 1
- LVPMHZUHUJLQPN-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[[5-(piperidin-1-ylmethyl)-1,3-thiazol-2-yl]methoxy]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(OCC3=NC=C(CN4CCCCC4)S3)=C2C1=O LVPMHZUHUJLQPN-UHFFFAOYSA-N 0.000 claims 1
- ZTCISKDAYUCPSF-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[[5-(piperidin-1-ylmethyl)-1,3-thiazol-2-yl]methylsulfanyl]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(SCC3=NC=C(CN4CCCCC4)S3)=C2C1=O ZTCISKDAYUCPSF-UHFFFAOYSA-N 0.000 claims 1
- LPRQCRBHEBDRIA-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[[5-(piperidin-1-ylmethyl)pyridin-2-yl]methoxy]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(OCC3=NC=C(CN4CCCCC4)C=C3)=C2C1=O LPRQCRBHEBDRIA-UHFFFAOYSA-N 0.000 claims 1
- WXSCNNWNIISKAH-UHFFFAOYSA-N 3-[2-methyl-4-oxo-5-[[5-(piperidin-1-ylmethyl)pyridin-2-yl]methylsulfanyl]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(SCC3=NC=C(CN4CCCCC4)C=C3)=C2C1=O WXSCNNWNIISKAH-UHFFFAOYSA-N 0.000 claims 1
- OCMGYWHLSCEJNA-UHFFFAOYSA-N 3-[2-methyl-4-oxo-6-[2-[4-(piperidin-1-ylmethyl)phenyl]ethynyl]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N(C(CCC(N1)=O)C1=O)C(C1=C2)=O)=NC1=CC=C2C#CC1=CC=C(CN2CCCCC2)C=C1 OCMGYWHLSCEJNA-UHFFFAOYSA-N 0.000 claims 1
- DWBKXQKAVNTLHH-UHFFFAOYSA-N 3-[2-methyl-4-oxo-6-[[4-(piperidin-1-ylmethyl)phenyl]methoxy]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC(C=CC(OCC2=CC=C(CN3CCCCC3)C=C2)=C2)=C2C1=O DWBKXQKAVNTLHH-UHFFFAOYSA-N 0.000 claims 1
- NGLPYHBBULLTCX-UHFFFAOYSA-N 3-[2-methyl-4-oxo-8-[2-[4-(piperidin-1-ylmethyl)phenyl]ethynyl]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N(C(CCC(N1)=O)C1=O)C(C1=CC=C2)=O)=NC1=C2C#CC1=CC=C(CN2CCCCC2)C=C1 NGLPYHBBULLTCX-UHFFFAOYSA-N 0.000 claims 1
- KMHIPWQBPPASOY-UHFFFAOYSA-N 3-[2-methyl-4-oxo-8-[[4-(piperidin-1-ylmethyl)phenyl]methoxy]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC(C(OCC2=CC=C(CN3CCCCC3)C=C2)=CC=C2)=C2C1=O KMHIPWQBPPASOY-UHFFFAOYSA-N 0.000 claims 1
- HRFBDUPKLWJWTR-UHFFFAOYSA-N 3-[2-methyl-4-oxo-8-[[4-(piperidin-1-ylmethyl)phenyl]methylsulfanyl]quinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC(C(SCC2=CC=C(CN3CCCCC3)C=C2)=CC=C2)=C2C1=O HRFBDUPKLWJWTR-UHFFFAOYSA-N 0.000 claims 1
- WXOBUXQBAUTFGT-UHFFFAOYSA-N 3-[2-methyl-5-(oxan-4-ylmethylamino)-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(NCC3CCOCC3)=C2C1=O WXOBUXQBAUTFGT-UHFFFAOYSA-N 0.000 claims 1
- UFLQMPNVTXXBIK-UHFFFAOYSA-N 3-[2-methyl-5-[[4-(morpholine-4-carbonyl)cyclohexyl]methylamino]-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(NCC(CC3)CCC3C(N3CCOCC3)=O)=C2C1=O UFLQMPNVTXXBIK-UHFFFAOYSA-N 0.000 claims 1
- RQVFNKVUUDUXQG-UHFFFAOYSA-N 3-[5-(1,3-benzodioxol-5-ylmethylamino)-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(NCC(C=C3)=CC4=C3OCO4)=C2C1=O RQVFNKVUUDUXQG-UHFFFAOYSA-N 0.000 claims 1
- HAKLEJCZDFFQJG-UHFFFAOYSA-N 3-[5-(2-anilinoethylamino)-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(NCCNC3=CC=CC=C3)=C2C1=O HAKLEJCZDFFQJG-UHFFFAOYSA-N 0.000 claims 1
- IGURWDOFFTXIEY-UHFFFAOYSA-N 3-[5-[(2-fluorophenyl)methoxy]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(OCC(C=CC=C3)=C3F)=C2C1=O IGURWDOFFTXIEY-UHFFFAOYSA-N 0.000 claims 1
- WSIOKENUOAERGD-UHFFFAOYSA-N 3-[5-[(2-fluorophenyl)methylsulfanyl]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(SCC(C=CC=C3)=C3F)=C2C1=O WSIOKENUOAERGD-UHFFFAOYSA-N 0.000 claims 1
- NLWSCOBUWBJIIU-UHFFFAOYSA-N 3-[5-[2-[4-(azepan-1-ylmethyl)-2-bromophenyl]ethyl]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(CCC3=CC=C(CN4CCCCCC4)C=C3Br)=C2C1=O NLWSCOBUWBJIIU-UHFFFAOYSA-N 0.000 claims 1
- NZMLZMUHGKJZSP-UHFFFAOYSA-N 3-[5-[2-[4-(azepan-1-ylmethyl)-2-fluorophenyl]ethyl]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(CCC3=CC=C(CN4CCCCCC4)C=C3F)=C2C1=O NZMLZMUHGKJZSP-UHFFFAOYSA-N 0.000 claims 1
- YVVKOTYMOQUWCU-UHFFFAOYSA-N 3-[5-[2-[4-(azepan-1-ylmethyl)phenyl]ethyl]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(CCC3=CC=C(CN4CCCCCC4)C=C3)=C2C1=O YVVKOTYMOQUWCU-UHFFFAOYSA-N 0.000 claims 1
- GQDQCEHSTMUSPU-UHFFFAOYSA-N 3-[5-[2-[4-(hydroxymethyl)phenyl]ethynyl]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(C#CC3=CC=C(CO)C=C3)=C2C1=O GQDQCEHSTMUSPU-UHFFFAOYSA-N 0.000 claims 1
- RLNPXRBHUHAWCM-UHFFFAOYSA-N 3-[5-[2-[4-[(1-adamantylamino)methyl]phenyl]ethyl]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(CCC3=CC=C(CNC4(CC(C5)C6)CC6CC5C4)C=C3)=C2C1=O RLNPXRBHUHAWCM-UHFFFAOYSA-N 0.000 claims 1
- JSGOWSBTGBUWER-UHFFFAOYSA-N 3-[5-[2-[5-(azepan-1-ylmethyl)-1,3-thiazol-2-yl]ethyl]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(CCC3=NC=C(CN4CCCCCC4)S3)=C2C1=O JSGOWSBTGBUWER-UHFFFAOYSA-N 0.000 claims 1
- OERHCECSVORONH-UHFFFAOYSA-N 3-[5-[2-[5-(azepan-1-ylmethyl)pyridin-2-yl]ethyl]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(CCC3=CC=C(CN4CCCCCC4)C=N3)=C2C1=O OERHCECSVORONH-UHFFFAOYSA-N 0.000 claims 1
- GFOUFKUTHJXYBN-UHFFFAOYSA-N 3-[5-[2-[5-[(3,5-dimethylpiperidin-1-yl)methyl]pyridin-2-yl]ethynyl]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC1CN(CC(C=C2)=CN=C2C#CC(C=CC=C2N=C(C)N3C(CCC(N4)=O)C4=O)=C2C3=O)CC(C)C1 GFOUFKUTHJXYBN-UHFFFAOYSA-N 0.000 claims 1
- ZYELDUVNYCXEFZ-UHFFFAOYSA-N 3-[5-[3-[4-(azepan-1-ylmethyl)-2-fluorophenyl]prop-1-ynyl]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(C#CCC3=CC=C(CN4CCCCCC4)C=C3F)=C2C1=O ZYELDUVNYCXEFZ-UHFFFAOYSA-N 0.000 claims 1
- DNSWZUBXVUXNJO-UHFFFAOYSA-N 3-[5-[3-[4-(azepan-1-ylmethyl)phenyl]prop-1-ynyl]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(C#CCC3=CC=C(CN4CCCCCC4)C=C3)=C2C1=O DNSWZUBXVUXNJO-UHFFFAOYSA-N 0.000 claims 1
- NIBVRMJBGHLKEI-UHFFFAOYSA-N 3-[5-[4-[4-(azepan-1-ylmethyl)phenyl]but-1-ynyl]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(C#CCCC3=CC=C(CN4CCCCCC4)C=C3)=C2C1=O NIBVRMJBGHLKEI-UHFFFAOYSA-N 0.000 claims 1
- XMPATOUGSOVVRL-UHFFFAOYSA-N 3-[5-[[2-fluoro-4-(piperidin-1-ylmethyl)phenyl]methylsulfanyl]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(SCC(C=CC(CN3CCCCC3)=C3)=C3F)=C2C1=O XMPATOUGSOVVRL-UHFFFAOYSA-N 0.000 claims 1
- AYMDANPHVSDKME-UHFFFAOYSA-N 3-[5-[[4-(azepan-1-ylmethyl)-2-fluorophenyl]methoxy]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(OCC(C=CC(CN3CCCCCC3)=C3)=C3F)=C2C1=O AYMDANPHVSDKME-UHFFFAOYSA-N 0.000 claims 1
- RTCQCTFUDOPTEB-UHFFFAOYSA-N 3-[5-[[4-(azepan-1-ylmethyl)-2-fluorophenyl]methylsulfanyl]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(SCC(C=CC(CN3CCCCCC3)=C3)=C3F)=C2C1=O RTCQCTFUDOPTEB-UHFFFAOYSA-N 0.000 claims 1
- CLNHVUFOSXOJAU-UHFFFAOYSA-N 3-[5-[[4-(azepan-1-ylmethyl)phenyl]methylamino]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(NCC3=CC=C(CN4CCCCCC4)C=C3)=C2C1=O CLNHVUFOSXOJAU-UHFFFAOYSA-N 0.000 claims 1
- UDWLXKIRYLEXMN-UHFFFAOYSA-N 3-[5-[[4-(hydroxymethyl)phenyl]methoxy]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(OCC3=CC=C(CO)C=C3)=C2C1=O UDWLXKIRYLEXMN-UHFFFAOYSA-N 0.000 claims 1
- HOFGPPXGEAIQBV-UHFFFAOYSA-N 3-[5-[[4-(hydroxymethyl)phenyl]methylsulfanyl]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(SCC3=CC=C(CO)C=C3)=C2C1=O HOFGPPXGEAIQBV-UHFFFAOYSA-N 0.000 claims 1
- IZACBNPPMVYKKV-UHFFFAOYSA-N 3-[5-[[4-[(3,5-dimethylpiperidin-1-yl)methyl]-2-fluorophenyl]methylamino]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC1CN(CC2=CC(F)=C(CNC(C=CC=C3N=C(C)N4C(CCC(N5)=O)C5=O)=C3C4=O)C=C2)CC(C)C1 IZACBNPPMVYKKV-UHFFFAOYSA-N 0.000 claims 1
- DPNUVBRFTZGVIV-UHFFFAOYSA-N 3-[5-[[4-[(3,5-dimethylpiperidin-1-yl)methyl]phenyl]methylamino]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC1CN(CC2=CC=C(CNC(C=CC=C3N=C(C)N4C(CCC(N5)=O)C5=O)=C3C4=O)C=C2)CC(C)C1 DPNUVBRFTZGVIV-UHFFFAOYSA-N 0.000 claims 1
- QOBLGAWGECLVMJ-UHFFFAOYSA-N 3-[5-[[4-[[4-(2-hydroxyethyl)piperazin-1-yl]methyl]phenyl]methylamino]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(NCC3=CC=C(CN4CCN(CCO)CC4)C=C3)=C2C1=O QOBLGAWGECLVMJ-UHFFFAOYSA-N 0.000 claims 1
- FOGRMKDWENCBBH-UHFFFAOYSA-N 3-[5-[[5-(azepan-1-ylmethyl)-1,3-thiazol-2-yl]methoxy]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(OCC3=NC=C(CN4CCCCCC4)S3)=C2C1=O FOGRMKDWENCBBH-UHFFFAOYSA-N 0.000 claims 1
- AKJZMSYQWSMZKB-UHFFFAOYSA-N 3-[5-[[5-(azepan-1-ylmethyl)-1,3-thiazol-2-yl]methylamino]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(NCC3=NC=C(CN4CCCCCC4)S3)=C2C1=O AKJZMSYQWSMZKB-UHFFFAOYSA-N 0.000 claims 1
- NDTHQPPPBPBJJW-UHFFFAOYSA-N 3-[5-[[5-(azepan-1-ylmethyl)-1,3-thiazol-2-yl]methylsulfanyl]-2-methyl-4-oxoquinazolin-3-yl]piperidine-2,6-dione Chemical compound CC(N1C(CCC(N2)=O)C2=O)=NC2=CC=CC(SCC3=NC=C(CN4CCCCCC4)S3)=C2C1=O NDTHQPPPBPBJJW-UHFFFAOYSA-N 0.000 claims 1
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Abstract
Description
Claims (53)
- 式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中X表示N(R a1)、O或S,其中R a1表示H或C 1-3烷基;且L表示可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代的直链或支链C 1-3亚烷基;且R表示:NR a7R a8,其中R a7为H或C 1-3烷基,R a8为可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的取代基取代的苯基;或苯并[d][1,3]二氧杂环戊烯基、四氢吡喃基、吡啶基或苯基,所述苯并[d][1,3]二氧杂环戊烯基、四氢吡喃基、吡啶基和苯基各自独立地可选地被选自由卤素、羟基、巯基、氰基、C 1-3烷基、卤代C 1-3烷基、羟基取代的C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的取代基取代;或者L表示式-L a2-L a1-*,其中L a1表示可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代的直链或支链C 1-40亚烷基,L a2表示可选地经取代的C 3-15亚环烷基或可选地经取代的C 5-15亚芳基,其中所述C 3-15亚环烷基可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、氨基取代的C 1-3烷基、C 1-3烷基氨基、氧代基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的取代基取代,以及所述C 5-15亚芳基可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的取代基取代,以及*表示与基团X的连接点,且R表示C(O)NR a9R a10、N(R a11)C(O)R a12、OR a16、SR a17、C(O)R a18、OC(O)R a19、C(O)OR a20、S(O) 2NR a21R a22、N(R a23)S(O) 2R a24、S(O)R a25、S(O) 2R a26、S(O) 2OR a27、或OS(O) 2R a28,其中R a16和R a17各自独立地表示H、可选地经取代的环烷基或可选地经取代的杂环基;R a9、R a11、R a21和R a23各自独立地表示H或C 1-3烷基;以及R a10、R a12、R a18、R a19、R a20、R a22、R a24、R a25、R a26、R a27和R a28各自独立地表 示可选地经取代的环烷基或可选地经取代的杂环基;或者L表示被一或多个选自由可选地经取代的亚芳基、可选地经取代的亚杂芳基或它们的任意组合组成的群组的基团中断一或多次的直链或支链亚烷基,其中所述直链或支链的亚烷基可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代;R表示NR a7R a8、C(O)NR a9R a10、N(R a11)C(O)R a12、OR a16、SR a17、C(O)R a18、OC(O)R a19、C(O)OR a20、S(O) 2NR a21R a22、N(R a23)S(O) 2R a24、S(O)R a25、S(O) 2R a26、S(O) 2OR a27、OS(O) 2R a28、可选地经取代的环烷基或可选地经取代的杂环基,其中R a7、R a8、R a9、R a10、R a16、R a17、R a21和R a22各自独立地表示H、可选地经取代的直链或支链烷基、可选地经取代的环烷基或可选地经取代的杂环基;R a11和R a23各自独立地表示H或C 1-3烷基;以及R a12、R a18、R a19、R a20、R a24、R a25、R a26、R a27和R a28各自独立地表示可选地经取代的直链或支链烷基、可选地经取代的环烷基或可选地经取代的杂环基;或者X表示亚炔基或亚烯基;且L表示被一或多个选自由可选地经取代的亚芳基、可选地经取代的亚杂芳基或它们的任意组合组成的群组的基团中断一或多次的直链或支链亚烷基,其中所述直链或支链的亚烷基可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代;或者式-L b2-L b1-#,其中L b1表示可选地经取代的C 5-15亚芳基或C 5-15亚杂芳基,其中所述C 5-15亚芳基和所述C 5-15亚杂芳基各自独立地可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,L b2表示可选地经取代的直链或支链C 1-40亚烷基,以及#表示与基团X的连接点;且R表示NR b7R b8、C(O)NR b9R b10、N(R b11)C(O)R b12、OR b16、SR b17、C(O)R b18、OC(O)R b19、C(O)OR b20、S(O) 2NR b21R b22、N(R b23)S(O) 2R b24、S(O)R b25、S(O) 2R b26、S(O) 2OR b27、OS(O) 2R b28、可选地经取代的环烷基或可选地经取代的杂环基,其中R b7、R b8、R b9、R b10、R b16、R b17、R b21和R b22各自独立地表示H、可选地经取代的直链或支链烷基、可选地经取代的环烷基或可选地经取代的杂环基;R b11和R b23各自独立地表示H或C 1-3烷基;以及R b12、R b18、R b19、R b20、R b24、R b25、R b26、R b27和R b28各自独立地表示可选地经取代的直链或支链烷基、可选地经取代的环烷基或可选地经取代的杂环基;或者X表示键;且L表示被一或多个选自由可选地经取代的亚芳基、可选地经取代的亚杂芳基或它们的任意组合组成的群组的基团中断一或多次的直链或支链亚烷基,其中所述直链或支链的亚烷基可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代;且R表示NR c4R c5、C(O)NR c6R c7、N(R c8)C(O)R c9、OR c13、SR c14、C(O)R c15、OC(O)R c16、C(O)OR c17、S(O) 2NR c18R c19、N(R c20)S(O) 2R c21、S(O)R c22、S(O) 2R c23、S(O) 2OR c24、OS(O) 2R c25、可选地经取代的C 5-20环烷基或可选地经取代的C 5-20杂环基,其中R c8和R c20各自独立地表示H或C 1-3烷基;R c4、R c6和R c18各自独立地表示H、可选地经取代的直链或支链C 1-10烷基、可选地经取代的环烷基、可选地经取代的芳基、可选地经取代的杂环基或可选地经取代的杂芳基;和R c5、R c7、R c9、R c13、R c14、R c15、R c16、R c17、R c19、R c21、R c22、R c23、R c24和R c25各自独立地表示可选地经取代的C 5-20环烷基或可选地经取代的C 5-20杂环基。
- 如权利要求1或2所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中X表示N(R a1)、O或S,其中R a1表示H或C 1-3烷基;且L表示可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代的直链或支链C 1-3亚烷基,且R表示:NR a7R a8,其中R a7为H或C 1-3烷基,R a8为可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的取代基取代的苯基;或苯并[d][1,3]二氧杂环戊烯基、四氢吡喃基、吡啶基或苯基,所述苯并[d][1,3]二氧杂环戊烯基、四氢吡喃基、吡啶基和苯基各自独立地可选地被选自由卤素、羟基、巯基、氰基、C 1-3烷基、卤代C 1-3烷基、羟基取代的C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的取代基取代;或者L表示式-L a2-L a1-*,其中L a1表示可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代的直链或支链C 1-40亚烷基,L a2表示可选地经取代的C 3-15亚环烷基或可选地经取代的C 5-15亚芳基,其中所述C 3-15亚环烷基可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、氨基取代的C 1-3烷基、C 1-3烷基氨基、氧代基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的取代基取代,以及所述C 5-15亚芳基可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的取代基取代,以及*表示与基团X的连接点,且R表示C(O)NR a9R a10、N(R a11)C(O)R a12、OR a16、SR a17、C(O)R a18、OC(O)R a19、C(O)OR a20、S(O) 2NR a21R a22、N(R a23)S(O) 2R a24、S(O)R a25、S(O) 2R a26、S(O) 2OR a27、或OS(O) 2R a28,其中R a16和R a17各自独立地表示H、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基;R a9、R a11、R a21和R a23各自独立地表示H或C 1-3烷基;以及R a10、R a12、R a18、R a19、R a20、R a22、R a24、R a25、R a26、R a27和R a28各自独立地表示可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基;或者L表示被一或多个选自由可选地经取代的C 5-15亚芳基、可选地经取代的C 5-15亚杂芳基或它们的任意组合组成的群组的基团中断一或多次的直链或支链C 2-40亚烷基,其中所述直链或支链的C 2-40亚烷基可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代;R表示NR a7R a8、C(O)NR a9R a10、N(R a11)C(O)R a12、OR a16、SR a17、C(O)R a18、OC(O)R a19、C(O)OR a20、S(O) 2NR a21R a22、N(R a23)S(O) 2R a24、S(O)R a25、S(O) 2R a26、S(O) 2OR a27、OS(O) 2R a28、可选地经取代的环烷基或可选地经取代的杂环基,其中R a7、R a8、R a9、R a10、R a16、R a17、R a21和R a22各自独立地表示H、可选地经取代的直链或支链C 1-10烷基、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基;R a11和R a23各自独立地表示H或C 1-3烷基;以及R a12、R a18、R a19、R a20、R a24、R a25、R a26、R a27和R a28各自独立地表示可选地经取代的直链或支链C 1-10烷基、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基;或者X表示C 2-6亚炔基或C 2-6亚烯基;且L表示被一或多个选自由可选地经取代的C 5-20亚芳基、可选地经取代的C 5-20亚杂芳基或它们的任意组合组成的群组的基团中断一或多次的直链或支链C 2-40亚烷基,其中所述直链或支链的C 2-40亚烷基可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代;或者式-L b2-L b1-#,其中L b1表示可选地经取代的C 5-15亚芳基或C 5-15亚杂芳基,其中所述C 5-15亚芳基和所述C 5-15亚杂芳基各自独立地可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的1-3个取代基取代,L b2表示可选地经取代的直链或支链C 1-40亚烷基,以及#表示与基团X的连接点;且R表示NR b7R b8、C(O)NR b9R b10、N(R b11)C(O)R b12、OR b16、SR b17、C(O)R b18、OC(O)R b19、C(O)OR b20、S(O) 2NR b21R b22、N(R b23)S(O) 2R b24、S(O)R b25、S(O) 2R b26、S(O) 2OR b27、OS(O) 2R b28、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基,其中R b7、R b8、R b9、R b10、R b16、R b17、R b21和R b22各自独立地表示H、可选地经取代的直链或支链C 1-10烷基、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环 基;R b11和R b23各自独立地表示H或C 1-3烷基;以及R b12、R b18、R b19、R b20、R b24、R b25、R b26、R b27和R b28各自独立地表示可选地经取代的直链或支链C 1-10烷基、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基;或者X表示键;且L表示被一或多个选自由可选地经取代的C 5-15亚芳基、可选地经取代的C 5-15亚杂芳基或它们的任意组合组成的群组的基团中断一或多次的直链或支链C 2-40亚烷基,其中所述直链或支链的C 2-40亚烷基可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代;且R表示NR c4R c5、C(O)NR c6R c7、N(R c8)C(O)R c9、OR c13、SR c14、C(O)R c15、OC(O)R c16、C(O)OR c17、S(O) 2NR c18R c19、N(R c20)S(O) 2R c21、S(O)R c22、S(O) 2R c23、S(O) 2OR c24、OS(O) 2R c25、可选地经取代的C 5-20环烷基、或可选地经取代的C 5-20杂环基,其中R c8和R c20各自独立地表示H或C 1-3烷基;R c4、R c6和R c18各自独立地表示H、可选地经取代的直链或支链C 1-10烷基、可选地经取代的C 3-20环烷基、可选地经取代的C 5-20芳基、可选地经取代的C 3-20杂环基或可选地经取代的C 5-20杂芳基;和R c5、R c7、R c9、R c13、R c14、R c15、R c16、R c17、R c19、R c21、R c22、R c23、R c24和R c25各自独立地表示可选地经取代的C 5-20环烷基、或可选地经取代的C 5-20杂环基。
- 如权利要求1或2所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中X表示N(R a1)、O或S,其中R a1表示H或C 1-3烷基;且L表示可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代的直链或支链C 1-3亚烷基;且R表示:NR a7R a8,其中R a7为H或C 1-3烷基,R a8为可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的取代基取代的苯基;或苯并[d][1,3]二氧杂环戊烯基、四氢吡喃基、吡啶基或苯基,所述苯并[d][1,3]二氧杂环戊烯基、四氢吡喃基、吡啶基和苯基各自独立地可选地被选自由卤素、羟基、巯基、氰基、C 1-3烷基、卤代C 1-3烷基、羟基取代的C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的取代基取代。
- 如权利要求1或2所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂 化物、多晶型物,其中X表示N(R a1)、O或S,其中R a1表示H或C 1-3烷基;且L表示式-L a2-L a1-*,其中L a1表示可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代的直链或支链C 1-40亚烷基,L a2表示可选地经取代的C 3-15亚环烷基或可选地经取代的C 5-15亚芳基,其中所述C 3-15亚环烷基可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、氨基取代的C 1-3烷基、C 1-3烷基氨基、氧代基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的1至3个取代基取代,以及所述C 5-15亚芳基可选地被1至3个选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的取代基取代,以及*表示与基团X的连接点,且R表示C(O)NR a9R a10、N(R a11)C(O)R a12、OR a16、SR a17、C(O)R a18、OC(O)R a19、C(O)OR a20、S(O) 2NR a21R a22、N(R a23)S(O) 2R a24、S(O)R a25、S(O) 2R a26、S(O) 2OR a27、或OS(O) 2R a28,其中R a16和R a17各自独立地表示H、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基;R a9、R a11、R a21和R a23各自独立地表示H或C 1-3烷基;以及R a10、R a12、R a18、R a19、R a20、R a22、R a24、R a25、R a26、R a27和R a28各自独立地表示可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基。
- 如权利要求1或2所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中X表示N(R a1)、O或S,其中R a1表示H或C 1-3烷基;且L表示被一或多个选自由可选地经取代的C 5-15亚芳基、可选地经取代的C 5-15亚杂芳基或它们的任意组合组成的群组的基团中断一或多次的直链或支链C 2-40亚烷基,其中所述直链或支链的C 2-40亚烷基可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代,以及各个所述C 5-15亚芳基和各个所述C 5-15亚杂芳基分别可选地被1至3个选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、氨基取代的C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的取代基取代;且R表示NR a7R a8、C(O)NR a9R a10、N(R a11)C(O)R a12、OR a16、SR a17、C(O)R a18、OC(O)R a19、C(O)OR a20、S(O) 2NR a21R a22、N(R a23)S(O) 2R a24、S(O)R a25、S(O) 2R a26、S(O) 2OR a27、OS(O) 2R a28、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基,其中R a7、R a8、R a9、R a10、R a16、R a17、R a21和R a22相同或不同且各自独立地表示H、可选地经取代的直链或支链C 1-10烷基、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基;R a11和R a23各自独立地表示H或C 1-3烷基;以及R a12、R a18、R a19、R a20、R a24、R a25、R a26、R a27和R a28各自独立地表示可选地经取代的直链或支链C 1-10烷基、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基;其中,所述直链或支链C 1-10烷基可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代;和各个所述C 3-20环烷基和各个所述C 3-20杂环基分别独立地可选地被选自由卤素、羟基、巯基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、氨基取代的C 1-3烷基、C 1-3烷基氨基、氧代基、C 1-3烷基-NHC(O)-、可选地经取代的C 6-20芳基或其任意组合组成的群组的一或多个取代基取代,其中所述C 6-20芳基可选地经被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基或其任意组合组成的群组的一或多个取代基取代。
- 如权利要求1或2所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中X表示C 2-6亚炔基或C 2-6亚烯基;且L表示被一或多个选自由可选地经取代的C 5-15亚芳基、可选地经取代的C 5-15亚杂芳基或它们的任意组合组成的群组的基团中断一或多次的直链或支链C 2-40亚烷基,其中所述直链或支链的C 2-40亚烷基可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代,其中所述C 5-15亚芳基和所述C 5-15亚杂芳基各自独立地可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代;或式-L b2-L b1-#,其中L b1表示可选地经取代的C 5-15亚芳基或C 5-15亚杂芳基,其中所述C 5-15亚芳基和所述C 5-15亚杂芳基各自独立地可选地被1-3个选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的取代基取代,L b2表示可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代的直链或支链C 1-40亚烷基,以及#表示与基团X的连接点;且R表示NR b7R b8、C(O)NR b9R b10、N(R b11)C(O)R b12、OR b16、SR b17、C(O)R b18、OC(O)R b19、C(O)OR b20、S(O) 2NR b21R b22、N(R b23)S(O) 2R b24、S(O)R b25、S(O) 2R b26、S(O) 2OR b27、OS(O) 2R b28、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基,其中R b7、R b8、R b9、R b10、R a21和R a22相同或不同且各自独立地表示H、可选地经取代的直链或支链C 1-10烷基、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基;R b16和R b17各自独立地表示H、可选地经取代的直链或支链C 1-10烷基、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基;R b11和R b23各自独立地表示H或C 1-3烷基;R b12、R b18、R b19、R b20、R b24、R b25、R b26、R b27和R b28各自独立地表示可选地经取代的直链或支链C 1-10烷基、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基;以及其中,所述直链或支链C 1-10烷基可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代;各个所述C 3-20环烷基和各个所述C 3-20杂环基分别独立地可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、氨基取代的C 1-3烷基、C 1-3烷基氨基、氧代基、C 1-3烷基-NHC(O)-、可选地经取代的C 6-20芳基或其任意组合组成的群组的一或多个取代基取代,其中所述C 6-20芳基可选地经被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基或其任意组合组成的群组的一或多个取代基取代。
- 如权利要求1或2所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中X表示键;且L表示被一或多个选自由可选地经取代的C 5-15亚芳基、可选地经取代的C 5-15亚杂芳基或它们的任意组合组成的群组的基团中断一或多次的直链或支链C 2-40亚烷基,其中所述直链或支链的C 2-40亚烷基可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代,以及所述C 5-15亚芳基和所述C 5-15亚杂芳基各自独立地可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代;且R表示NR c4R c5、C(O)NR c6R c7、N(R c8)C(O)R c9、OR c13、SR c14、C(O)R c15、OC(O)R c16、C(O)OR c17、S(O) 2NR c18R c19、N(R c20)S(O) 2R c21、S(O)R c22、S(O) 2R c23、S(O) 2OR c24、OS(O) 2R c25、可选地经取代的C 5-20环烷基、或可选地经取代的C 5-20杂环基,其中R c8和R c20各自独立地表示H或C 1-3烷基;R c4、R c6和R c18各自独立地表示H、可选地经取代的直链或支链C 1-10烷基、可选地经取代的C 3-20环烷基、可选地经取代的C 5-20芳基、可选地经取代的C 3-20杂环 基或可选地经取代的C 5-20杂芳基;R c5、R c7、R c9、R c13、R c14、R c15、R c16、R c17、R c19、R c21、R c22、R c23、R c24和R c25各自独立地表示可选地经取代的C 5-20环烷基、或可选地经取代的C 5-20杂环基;其中,所述直链或支链C 1-10烷基可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代;各个所述C 3-20环烷基和各个所述C 3-20杂环基分别独立地可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、氨基取代的C 1-3烷基、C 1-3烷基氨基、氧代基、C 1-3烷基-NHC(O)-、可选地经取代的C 6-20芳基或其任意组合组成的群组的一或多个取代基取代,其中所述C 6-20芳基可选地经被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基或其任意组合组成的群组的一或多个取代基取代;和各个所述C 5-20芳基和各个所述C 5-20杂芳基分别独立地可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、氨基取代的C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-、可选地经取代的C 6-20芳基或其任意组合组成的群组的一或多个取代基取代,其中所述C 6-20芳基可选地经被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、氨基取代的C 1-3烷基、C 1-3烷基氨基或其任意组合组成的群组的一或多个取代基取代。
- 如权利要求1或2所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中X表示N(R a1)、O或S,其中R a1表示H或C 1-3烷基;且L表示可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代的以下基团:-CH 2-;-(CH 2) 2-;-CH 2-CH(CH 3)-;或-(CH 2) 3-;R表示:NR a7R a8,其中R a7为H或C 1-3烷基,R a8为可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的取代基取代的苯基;或苯并[d][1,3]二氧杂环戊烯基、四氢吡喃基、吡啶基或苯基,所述苯并[d][1,3]二氧杂环戊烯基、四氢吡喃基、吡啶基和苯基各自独立地可选地被选自由卤素、羟基、巯基、氰基、C 1-3烷基、卤代C 1-3烷基、羟基取代的C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的取代基取代。
- 如权利要求1或2所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中X表示N(R a1)、O或S,其中R a1表示H或C 1-3烷基;且L表示以下式表示的基团:-(CH 2) n1-C 5-15亚芳基-(CH 2) n2-**,或-(CH 2) n1-C 5-15亚杂芳基-(CH 2) n2-**,其中**表示与基团X的连接点;其中n1、n2分别独立地表示整数1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19或20;所述C 5-15亚芳基和所述C 5-15亚杂芳基各自独立地可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代;R表示NR a7R a8、C(O)NR a9R a10、N(R a11)C(O)R a12、OR a16、SR a17、C(O)R a18、OC(O)R a19、C(O)OR a20、S(O) 2NR a21R a22、N(R a23)S(O) 2R a24、S(O)R a25、S(O) 2R a26、S(O) 2OR a27、OS(O) 2R a28、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基,其中R a7、R a8、R a9、R a10、R a16、R a17、R a21和R a22相同或不同且各自独立地表示H、可选地经取代的直链或支链C 1-10烷基、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基;R a11和R a23各自独立地表示H或C 1-3烷基;以及R a12、R a18、R a19、R a20、R a24、R a25、R a26、R a27和R a28各自独立地表示可选地经取代的直链或支链C 1-10烷基、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基;其中,所述直链或支链C 1-10烷基可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代;和各个所述C 3-20环烷基和各个所述C 3-20杂环基分别独立地可选地被选自由卤素、羟基、巯基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、氨基取代的C 1-3烷基、C 1-3烷基氨基、氧代基、C 1-3烷基-NHC(O)-、可选地经取代的C 6-20芳基或其任意组合组成的群组的一或多个取代基取代,其中所述C 6-20芳基可选地经被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基或其任意组合组成的群组的一或多个取代基取代。
- 如权利要求1或2所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中X表示N(R a1)、O或S,其中R a1表示H或C 1-3烷基;且L表示以下式表示的基团:-C 3-15亚环烷基-(CH 2) 1-40-*,或-C 5-15亚芳基-(CH 2) 1-40-*,其中*表示与基团X的连接点;以及其中所述C 3-15亚环烷基可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、氨基取代的C 1-3烷基、C 1-3烷基氨基、氧代基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,以及所述C 5-15亚芳基可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代;R表示C(O)NR a9R a10、N(R a11)C(O)R a12、OR a16、SR a17、C(O)R a18、OC(O)R a19、C(O)OR a20、S(O) 2NR a21R a22、N(R a23)S(O) 2R a24、S(O)R a25、S(O) 2R a26、S(O) 2OR a27、或OS(O) 2R a28,其中R a16和R a17各自独立地表示H、可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基;R a9、R a11、R a21和R a23各自独立地表示H或C 1-3烷基;以及R a10、R a12、R a18、R a19、R a20、R a22、R a24、R a25、R a26、R a27和R a28各自独立地表示可选地经取代的C 3-20环烷基或可选地经取代的C 3-20杂环基。
- 如权利要求1或2所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中X表示C 2-6亚炔基或C 2-6亚烯基;且L表示以下式表示的基团:-(CH 2) n1-C 5-15亚芳基-(CH 2) n2-**,或-(CH 2) n1-C 5-15亚杂芳基-(CH 2) n2-**,其中**表示与基团X的连接点;其中n1、n2分别独立地表示整数1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19或20;所述C 5-15亚芳基和所述C 5-15亚杂芳基各自独立地可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代。
- 如权利要求1或2所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中X表示C 2-6亚炔基或C 2-6亚烯基;且L表示以下式表示的基团:-(CH 2) 1-40-C 5-15亚芳基-#,或-(CH 2) 1-40-C 5-15亚杂芳基-#,其中所述C 5-15亚芳基和所述C 5-15亚杂芳基各自独立地可选地被选自由卤素、羟基、 氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,以及#表示与基团X的连接点。
- 如权利要求1所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中X表示键;且L表示-(CH 2) n1-C 5-15亚芳基-(CH 2) n2-**,或-(CH 2) n1-C 5-15亚杂芳基-(CH 2) n2-**,其中**表示与基团X的连接点;其中n1、n2分别独立地表示整数1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19或20;所述C 5-15亚芳基和所述C 5-15亚杂芳基各自独立地可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代。
- 如权利要求14至18中任一项所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中在L表示的通式中,所述C 5-15亚杂芳基包括:亚呋喃基、亚噁唑基、亚异噁唑基、亚噁二唑基、亚噻吩基、亚噻唑基、亚异噻唑基、亚噻二唑基、亚吡咯基、亚咪唑基、亚吡唑基、亚三唑基、亚吡啶基、亚嘧啶基、亚哒嗪基、亚吡嗪基、亚吲哚基、亚异吲哚基、亚苯并呋喃基、亚异苯并呋喃基、亚苯并噻吩基、亚吲唑基、亚苯并[d][1,3]二氧杂环戊烯基、亚苯并咪唑基、亚苯并噁唑基、亚苯并异噁唑基、亚苯并噻唑基、亚苯并异噻唑基、亚苯并三唑基、亚苯并[2,1,3]噁二唑基、亚苯并[2,1,3]噻二唑基、亚苯并[1,2,3]噻二唑基、亚喹啉基、亚异喹啉基、亚萘啶基、亚噌啉基、亚喹唑啉基、亚喹喔啉基、亚酞嗪基、吡唑并[1,5-a]吡啶亚基、吡唑并[1,5-a]嘧啶亚基、咪唑并[1,2-a]吡啶亚基、1H-吡咯并[3,2-b]吡啶亚基、1H-吡咯并[2,3-b]吡啶亚基、4H-氟[3,2-b]吡咯亚基、吡咯并[2,1-b]噻唑亚基、和咪唑并[2,1-b]噻唑亚基;所述C 5-15亚芳基包括:亚苯基和亚萘基;以及所述C 3-15亚环烷基包括:亚环丙基、亚环丁基、亚环戊基、亚环戊烯基、亚环己基、亚环己烯基、亚环庚基、亚环辛基、亚十氢萘基、八氢并环戊二烯亚基、八氢-1H-茚亚基、C 5-15亚螺环基、亚金刚烷基、亚降金刚烷基、亚冰片基、二环[2.2.1]庚烷亚基、和二环[2.2.1]庚烯亚基;其中,所述C 3-15亚环烷基可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、氨基取代的C 1-3烷基、C 1-3烷基氨基、氧代基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,以及所述C 5-15亚芳基和所述C 5-15亚杂芳基各自独立地可选地被选自由卤素、羟基、氰基、氨 基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代。
- 如权利要求14、16或18所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中L表示-CH 2-亚苯基-CH 2-**、-CH 2-亚苯基-(CH 2) 2-**、-CH 2-亚苯基-(CH 2) 3-**、-CH 2-亚苯基-(CH 2) 4-**、-CH 2-亚苯基-(CH 2) 5-**、-CH 2-亚苯基-(CH 2) 6-**、-CH 2-亚苯基-(CH 2) 7-**、-CH 2-亚苯基-(CH 2) 8-**、-(CH 2) 2-亚苯基-CH 2-**、-(CH 2) 2-亚苯基-(CH 2) 2-**、-(CH 2) 2-亚苯基-(CH 2) 3-**、-(CH 2) 2-亚苯基-(CH 2) 4-**、-(CH 2) 2-亚苯基-(CH 2) 5-**、-(CH 2) 2-亚苯基-(CH 2) 6-**、-(CH 2) 2-亚苯基-(CH 2) 7-**、-(CH 2) 2-亚苯基-(CH 2) 8-**、-(CH 2) 3-亚苯基-CH 2-**、-(CH 2) 3-亚苯基-(CH 2) 2-**、-(CH 2) 3-亚苯基-(CH 2) 3-**、-(CH 2) 3-亚苯基-(CH 2) 4-**、-(CH 2) 3-亚苯基-(CH 2) 5-**、-(CH 2) 3-亚苯基-(CH 2) 6-**、-(CH 2) 3-亚苯基-(CH 2) 7-**、-(CH 2) 3-亚苯基-(CH 2) 8-**、-(CH 2) 4-亚苯基-CH 2-**、-(CH 2) 4-亚苯基-(CH 2) 2-**、-(CH 2) 4-亚苯基-(CH 2) 3-**、-(CH 2) 4-亚苯基-(CH 2) 4-**、-(CH 2) 4-亚苯基-(CH 2) 5-**、-(CH 2) 4-亚苯基-(CH 2) 6-**、-(CH 2) 4-亚苯基-(CH 2) 7-**、-(CH 2) 4-亚苯基-(CH 2) 8-**、-(CH 2) 5-亚苯基-CH 2-**、-(CH 2) 5-亚苯基-(CH 2) 2-**、-(CH 2) 5-亚苯基-(CH 2) 3-**、-(CH 2) 5-亚苯基-(CH 2) 4-**、-(CH 2) 5-亚苯基-(CH 2) 5-**、-(CH 2) 6-亚苯基-CH 2-**、-(CH 2) 6-亚苯基-(CH 2) 2-**、-(CH 2) 6-亚苯基-(CH 2) 3-**、-(CH 2) 6-亚苯基-(CH 2) 4-**、-(CH 2) 6-亚苯基-(CH 2) 5-**、-(CH 2) 6-亚苯基-(CH 2) 6-**、-(CH 2) 7-亚苯基-CH 2-**、-(CH 2) 7-亚苯基-(CH 2) 2-**、-(CH 2) 7-亚苯基-(CH 2) 3-**、-(CH 2) 7-亚苯基-(CH 2) 4-**、-(CH 2) 7-亚苯基-(CH 2) 5-**、-(CH 2) 7-亚苯基-(CH 2) 6-**、-(CH 2) 8-亚苯基-CH 2-**、-(CH 2) 8-亚苯基-(CH 2) 2-**、-(CH 2) 8-亚苯基-(CH 2) 3-**、-(CH 2) 8-亚苯基-(CH 2) 4-**、-(CH 2) 8-亚苯基-(CH 2) 5-**、-(CH 2) 8-亚苯基-(CH 2) 6-**、-(CH 2) 8-亚苯基-(CH 2) 7-**、-(CH 2) 8-亚苯基-(CH 2) 8-**、-CH 2-亚吡啶基-CH 2-**、-CH 2-亚吡啶基-(CH 2) 2-**、-CH 2-亚吡啶基-(CH 2) 3-**、-CH 2-亚吡啶基-(CH 2) 4-**、-CH 2-亚吡啶基-(CH 2) 5-**、-CH 2-亚吡啶基-(CH 2) 6-**、-CH 2-亚吡啶基-(CH 2) 7-**、-CH 2-亚吡啶基-(CH 2) 8-**、-(CH 2) 2-亚吡啶基-CH 2-**、-(CH 2) 2-亚吡啶基-(CH 2) 2-**、-(CH 2) 2-亚吡啶基-(CH 2) 3-**、-(CH 2) 2-亚吡啶基-(CH 2) 4-**、-(CH 2) 2-亚吡啶基-(CH 2) 5-**、-(CH 2) 2-亚吡啶基-(CH 2) 6-**、-(CH 2) 2-亚吡啶基-(CH 2) 7-**、-(CH 2) 2-亚吡啶基-(CH 2) 8-**、-(CH 2) 3-亚吡啶基-CH 2-**、-(CH 2) 3-亚吡啶基-(CH 2) 2-**、-(CH 2) 3-亚吡啶基-(CH 2) 3-**、-(CH 2) 3-亚吡啶基-(CH 2) 4-**、-(CH 2) 3-亚吡啶基-(CH 2) 5-**、-(CH 2) 3-亚吡啶基-(CH 2) 6-**、-(CH 2) 3-亚吡啶基-(CH 2) 7-**、-(CH 2) 3-亚吡啶基-(CH 2) 8-**、-(CH 2) 4-亚吡啶基-CH 2-**、-(CH 2) 4-亚吡啶基-(CH 2) 2-**、-(CH 2) 4-亚吡啶基-(CH 2) 3-**、-(CH 2) 4-亚吡啶基-(CH 2) 4-**、-(CH 2) 4-亚吡啶基-(CH 2) 5-**、-(CH 2) 4-亚吡啶基-(CH 2) 6-**、-(CH 2) 4-亚吡啶基-(CH 2) 7-**、-(CH 2) 4-亚吡啶基-(CH 2) 8-**、-(CH 2) 5-亚吡啶基-CH 2-**、-(CH 2) 5-亚吡啶基-(CH 2) 2-**、-(CH 2) 5-亚吡啶基-(CH 2) 3-**、-(CH 2) 5-亚吡啶基-(CH 2) 4-**、-(CH 2) 5-亚吡啶基-(CH 2) 5-**、-(CH 2) 6-亚吡啶基-CH 2-**、-(CH 2) 6-亚吡啶基-(CH 2) 2-**、-(CH 2) 6-亚吡啶基-(CH 2) 3-**、-(CH 2) 6-亚吡啶基-(CH 2) 4-**、-(CH 2) 6-亚吡啶基- (CH 2) 5-**、-(CH 2) 6-亚吡啶基-(CH 2) 6-**、-(CH 2) 7-亚吡啶基-CH 2-**、-(CH 2) 7-亚吡啶基-(CH 2) 2-**、-(CH 2) 7-亚吡啶基-(CH 2) 3-**、-(CH 2) 7-亚吡啶基-(CH 2) 4-**、-(CH 2) 7-亚吡啶基-(CH 2) 5-**、-(CH 2) 7-亚吡啶基-(CH 2) 6-**、-(CH 2) 8-亚吡啶基-CH 2-**、-(CH 2) 8-亚吡啶基-(CH 2) 2-**、-(CH 2) 8-亚吡啶基-(CH 2) 3-**、-(CH 2) 8-亚吡啶基-(CH 2) 4-**、-(CH 2) 8-亚吡啶基-(CH 2) 5-**、-(CH 2) 8-亚吡啶基-(CH 2) 6-**、-(CH 2) 8-亚吡啶基-(CH 2) 7-**、-(CH 2) 8-亚吡啶基-(CH 2) 8-**、-CH 2-亚噻唑基-CH 2-**、-CH 2-亚噻唑基-(CH 2) 2-**、-CH 2-亚噻唑基-(CH 2) 3-**、-CH 2-亚噻唑基-(CH 2) 4-**、-CH 2-亚噻唑基-(CH 2) 5-**、-CH 2-亚噻唑基-(CH 2) 6-**、-CH 2-亚噻唑基-(CH 2) 7-**、-CH 2-亚噻唑基-(CH 2) 8-**、-(CH 2) 2-亚噻唑基-CH 2-**、-(CH 2) 2-亚噻唑基-(CH 2) 2-**、-(CH 2) 2-亚噻唑基-(CH 2) 3-**、-(CH 2) 2-亚噻唑基-(CH 2) 4-**、-(CH 2) 2-亚噻唑基-(CH 2) 5-**、-(CH 2) 2-亚噻唑基-(CH 2) 6-**、-(CH 2) 2-亚噻唑基-(CH 2) 7-**、-(CH 2) 2-亚噻唑基-(CH 2) 8-**、-(CH 2) 3-亚噻唑基-CH 2-**、-(CH 2) 3-亚噻唑基-(CH 2) 2-**、-(CH 2) 3-亚噻唑基-(CH 2) 3-**、-(CH 2) 3-亚噻唑基-(CH 2) 4-**、-(CH 2) 3-亚噻唑基-(CH 2) 5-**、-(CH 2) 3-亚噻唑基-(CH 2) 6-**、-(CH 2) 3-亚噻唑基-(CH 2) 7-**、-(CH 2) 3-亚噻唑基-(CH 2) 8-**、-(CH 2) 4-亚噻唑基-CH 2-**、-(CH 2) 4-亚噻唑基-(CH 2) 2-**、-(CH 2) 4-亚噻唑基-(CH 2) 3-**、-(CH 2) 4-亚噻唑基-(CH 2) 4-**、-(CH 2) 4-亚噻唑基-(CH 2) 5-**、-(CH 2) 4-亚噻唑基-(CH 2) 6-**、-(CH 2) 4-亚噻唑基-(CH 2) 7-**、-(CH 2) 4-亚噻唑基-(CH 2) 8-**、-(CH 2) 5-亚噻唑基-CH 2-**、-(CH 2) 5-亚噻唑基-(CH 2) 2-**、-(CH 2) 5-亚噻唑基-(CH 2) 3-**、-(CH 2) 5-亚噻唑基-(CH 2) 4-**、-(CH 2) 5-亚噻唑基-(CH 2) 5-**、-(CH 2) 6-亚噻唑基-CH 2-**、-(CH 2) 6-亚噻唑基-(CH 2) 2-**、-(CH 2) 6-亚噻唑基-(CH 2) 3-**、-(CH 2) 6-亚噻唑基-(CH 2) 4-**、-(CH 2) 6-亚噻唑基-(CH 2) 5-**、-(CH 2) 6-亚噻唑基-(CH 2) 6-**、-(CH 2) 7-亚噻唑基-CH 2-**、-(CH 2) 7-亚噻唑基-(CH 2) 2-**、-(CH 2) 7-亚噻唑基-(CH 2) 3-**、-(CH 2) 7-亚噻唑基-(CH 2) 4-**、-(CH 2) 7-亚噻唑基-(CH 2) 5-**、-(CH 2) 7-亚噻唑基-(CH 2) 6-**、-(CH 2) 8-亚噻唑基-CH 2-**、-(CH 2) 8-亚噻唑基-(CH 2) 2-**、-(CH 2) 8-亚噻唑基-(CH 2) 3-**、-(CH 2) 8-亚噻唑基-(CH 2) 4-**、-(CH 2) 8-亚噻唑基-(CH 2) 5-**、-(CH 2) 8-亚噻唑基-(CH 2) 6-**、-(CH 2) 8-亚噻唑基-(CH 2) 7-**、或-(CH 2) 8-亚噻唑基-(CH 2) 8-**,其中**表示与基团X的连接点;其中,所述亚苯基、所述亚吡啶基和所述亚噻唑基各自独立地可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代。
- 如权利要求15所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中L表示:-亚环己基-CH 2-*、-亚环己基-(CH 2) 2-*、-亚环己基-(CH 2) 3-*、-亚环己基-(CH 2) 4-*、-亚环己基-(CH 2) 5-*、-亚环己基-(CH 2) 6-*、-亚环己基-(CH 2) 7-*、-亚环己基-(CH 2) 8-*、-亚环己基-(CH 2) 9-*、-亚环己基-(CH 2) 10-*、-亚环己基-(CH 2) 11-*、-亚环己基-(CH 2) 12-*、-亚苯基-CH 2-*、-亚苯基-(CH 2) 2-*、-亚苯基-(CH 2) 3-*、-亚苯基-(CH 2) 4-*、-亚苯基-(CH 2) 5-*、-亚苯基-(CH 2) 6-*、-亚苯基-(CH 2) 7-*、-亚苯基-(CH 2) 8-*、-亚苯基-(CH 2) 9-*、-亚苯基-(CH 2) 10-*、-亚苯基-(CH 2) 11-*、或-亚苯基-(CH 2) 12-*,其中*表示与基团X的连接点;以及其中所述亚环己基可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、氨基取代的C 1-3烷基、C 1-3烷基氨基、氧代基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,以及所述亚苯基可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代。
- 如权利要求17所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中L表示:-CH 2-亚苯基-#、-(CH 2) 2-亚苯基-#、-(CH 2) 3-亚苯基-#、-(CH 2) 4-亚苯基-#、-(CH 2) 5-亚苯基-#、-(CH 2) 6-亚苯基-#、-(CH 2) 7-亚苯基-#、-(CH 2) 8-亚苯基-#、-(CH 2) 9-亚苯基-#、-(CH 2) 10-亚苯基-#、-(CH 2) 11-亚苯基-#、-(CH 2) 12-亚苯基-#、-CH 2-亚吡啶基-#、-(CH 2) 2-亚吡啶基-#、-(CH 2) 3-亚吡啶基-#、-(CH 2) 4-亚吡啶基-#、-(CH 2) 5-亚吡啶基-#、-(CH 2) 6-亚吡啶基-#、-(CH 2) 7-亚吡啶基-#、-(CH 2) 8-亚吡啶基-#、-(CH 2) 9-亚吡啶基-#、-(CH 2) 10-亚吡啶基-#、-(CH 2) 11-亚吡啶基-#、-(CH 2) 12-亚吡啶基-#、-CH 2-亚噻唑基-#、-(CH 2) 2-亚噻唑基-#、-(CH 2) 3-亚噻唑基-#、-(CH 2) 4-亚噻唑基-#、-(CH 2) 5-亚噻唑基-#、-(CH 2) 6-亚噻唑基-#、-(CH 2) 7-亚噻唑基-#、-(CH 2) 8-亚噻唑基-#、-(CH 2) 9-亚噻唑基-#、-(CH 2) 10-亚噻唑基-#、-(CH 2) 11-亚噻唑基-#、或-(CH 2) 12-亚噻唑基-#,其中#表示与基团X的连接点;以及其中所述亚苯基、亚吡啶基和亚噻唑基各自独立地可选地被选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代。
- 如权利要求10所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中L表示被一或多个选自由可选地经取代的C 5-15亚芳基、可选地经取代的C 5-15亚杂芳基或它们的任意组合组成的群组的基团中断一或多次的直链或支链C 2-40亚烷基,其中所述直链或支链的C 2-40亚烷基可选地经选自由卤素、羟基、氨基或其任意组合组成的群组的取代基取代,以及各个所述C 5-15亚芳基和各个所述C 5-15亚杂芳基分别可选地被1至3个选自由卤素、羟基、氰基、氨基、C 1-3烷基、C 1-3烷氧基、卤代C 1-3烷基、羟基取代的C 1-3烷基、氨基取代的C 1-3烷基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的取代基取代;R表示NR a7R a8,其中R a7和R a8各自独立地表示H,或甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、戊基、异戊基、新戊基、特戊基、己基、庚基、辛基、壬基或癸基,其可选地被选自由卤素、羟基、氰基、氨基、巯基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或金刚烷-1-基、金刚烷-2-基、金刚烷-3-基、金刚烷-4-基、金刚烷-5-基、金刚烷-6-基、金刚烷-7-基、金刚烷-8-基、金刚烷-9-基或金刚烷-10-基,其可选地被选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或降金刚烷-1-基、降金刚烷-2-基、降金刚烷-3-基、降金刚烷-4-基、降金刚烷-5-基、降金刚烷-6-基、降金刚烷-7-基、降金刚烷-8-基或降金刚烷-9-基,其可选地被选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或环丙基、环丁基、环戊基、环戊烯基、环己基、环己烯基、环庚基或环辛基,其可选地经选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或对薄荷烷基、间薄荷烷基、奎宁环基、二环[2.2.1]庚烷-2-基、二环[2.2.1]庚烷-3-基、二环[2.2.1]庚烷-4-基、二环[2.2.1]庚烷-5-基、二环[2.2.1]庚烷-6-基、1,7,7-三甲基二环[2.2.1]庚烷-2-基、1,7,7-三甲基二环[2.2.1]庚烷-3-基、1,7,7-三甲基二环[2.2.1] 庚烷-4-基、1,7,7-三甲基二环[2.2.1]庚烷-5-基、1,7,7-三甲基二环[2.2.1]庚烷-6-基、 7,7-二甲基-2-氧代二环[2.2.1]庚烷-1-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-3-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-4-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-5-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-6-基、二环[2.2.1]庚-5-烯-2-基、二环[2.2.1]庚-5-烯-3-基或二环[2.2.1]庚-5-烯-7-基。
- 如权利要求9或10所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中R表示OR a16,其中R a16表示H,或金刚烷-1-基、金刚烷-2-基、金刚烷-3-基、金刚烷-4-基、金刚烷-5-基、金刚烷-6-基、金刚烷-7-基、金刚烷-8-基、金刚烷-9-基或金刚烷-10-基,其可选地被选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或降金刚烷-1-基、降金刚烷-2-基、降金刚烷-3-基、降金刚烷-4-基、降金刚烷-5-基、降金刚烷-6-基、降金刚烷-7-基、降金刚烷-8-基或降金刚烷-9-基,其可选地被选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或环丙基、环丁基、环戊基、环戊烯基、环己基、环己烯基、环庚基或环辛基,其可选地经选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或对薄荷烷基、间薄荷烷基、奎宁环基、二环[2.2.1]庚烷-2-基、二环[2.2.1]庚烷-3-基、二环[2.2.1]庚烷-4-基、二环[2.2.1]庚烷-5-基、二环[2.2.1]庚烷-6-基、1,7,7-三甲基二环[2.2.1]庚烷-2-基、1,7,7-三甲基二环[2.2.1]庚烷-3-基、1,7,7-三甲基二环[2.2.1]庚烷-4-基、1,7,7-三甲基二环[2.2.1]庚烷-5-基、1,7,7-三甲基二环[2.2.1]庚烷-6-基、 7,7-二甲基-2-氧代二环[2.2.1]庚烷-1-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-3-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-4-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-5-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-6-基、二环[2.2.1]庚-5-烯-2-基、二环[2.2.1]庚-5-烯-3-基或二环[2.2.1]庚-5-烯-7-基。
- 如权利要求10所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中R表示氮杂环丁基、氧杂环丁基、吡咯烷基、咪唑烷基、吡唑烷基、四氢呋喃基、四氢吡喃基、四氢噻吩基、四氢噻喃基、噁唑烷基、噻唑烷基、哌啶基、哌嗪基、吗啉基、硫代吗啉基、二氧杂环己基、氮杂环庚烷基、1,4-二氮杂环庚烷-1-基、3,8-二氮杂双环[3.2.1]辛烷-3-基、2,5-二氮杂双环[2.2.2]辛烷-2-基或C 7-11氮杂螺环基,其独立地可选地经选自由以下组成的群组的一或多个取代基取代:卤素、羟基、巯基、氧代基、氰基、氨基、C 1-3烷基、卤代C 1-3烷基、羟基取代的C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-、可选经取代的苯基或其任意组合,其中所述可选经取代的苯基可选地经选自由卤素、羟基、氨基、氰基、巯基、C 1-3烷基或其任意组合组成的群组的取代基取代。
- 如权利要求9或10所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中R表示C(O)NR a9R a10、N(R a11)C(O)R a12、C(O)R a18、OC(O)R a19、C(O)OR a20、S(O) 2NR a21R a22或N(R a23)S(O) 2R a24,其中,R a9、R a11、R a21和R a23各自独立地表示H或C 1-3烷基;且R a10、R a12、R a18、R a19、R a20、R a22和R a24各自独立地表示以下基团:金刚烷-1-基、金刚烷-2-基、金刚烷-3-基、金刚烷-4-基、金刚烷-5-基、金刚烷-6-基、金刚烷-7-基、金刚烷-8-基、金刚烷-9-基、金刚烷-10-基、降金刚烷-1-基、降金刚烷-2-基、降金刚烷-3-基、降金刚烷-4-基、降金刚烷-5-基、降金刚烷-6-基、降金刚烷-7-基、降金刚烷-8-基、降金刚烷-9-基、环丙基、环丁基、环戊基、环戊烯基、环己基、环己烯基、环庚基、环辛基、氮杂环丁基、氧杂环丁基、吡咯烷基、咪唑烷基、吡唑烷基、四氢呋喃基、四氢吡喃基、四氢噻吩基、四氢噻喃基、噁唑烷基、噻唑烷基、哌啶基、哌嗪基、吗啉基、硫代吗啉基、二氧杂环己基、氮杂环庚烷基、1,4-二氮杂环庚烷-1-基、3,8-二氮杂双环[3.2.1]辛烷-3-基、2,5-二氮杂双环[2.2.2]辛烷-2-基、C 7-11氮杂螺环基、对薄荷烷基、间薄荷烷基、奎宁环基、二环[2.2.1]庚烷-2-基、二环[2.2.1]庚烷-3-基、二环[2.2.1]庚烷-4-基、二环[2.2.1]庚烷-5-基、二环[2.2.1]庚烷-6-基、1,7,7-三甲基二环[2.2.1]庚烷-2-基、1,7,7-三甲基二环[2.2.1]庚烷-3-基、1,7,7-三甲基二环[2.2.1]庚烷-4-基、1,7,7-三甲基二环[2.2.1]庚烷-5-基、1,7,7-三甲基二环[2.2.1]庚烷-6-基、 7,7-二甲基-2-氧代二环[2.2.1]庚烷-1-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-3-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-4-基、7,7-二甲基-2-氧代二环[2.2.1] 庚烷-5-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-6-基、二环[2.2.1]庚-5-烯-2-基、二环[2.2.1]庚-5-烯-3-基或二环[2.2.1]庚-5-烯-7-基,其中所述基团可选地经选自由卤素、羟基、巯基、氧代基、氰基、氨基、C 1-3烷基、卤代C 1-3烷基、羟基取代的C 1-3烷基、氨基取代的C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代。
- 如权利要求11所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中R表示NR b7R b8,其中R b7和R b8各自独立地表示H,或甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、戊基、异戊基、新戊基、特戊基、己基、庚基、辛基、壬基或癸基,其可选地被选自由卤素、羟基、氰基、氨基、巯基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或金刚烷-1-基、金刚烷-2-基、金刚烷-3-基、金刚烷-4-基、金刚烷-5-基、金刚烷-6-基、金刚烷-7-基、金刚烷-8-基、金刚烷-9-基或金刚烷-10-基,其可选地被选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或降金刚烷-1-基、降金刚烷-2-基、降金刚烷-3-基、降金刚烷-4-基、降金刚烷-5-基、降金刚烷-6-基、降金刚烷-7-基、降金刚烷-8-基或降金刚烷-9-基,其可选地被选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或环丙基、环丁基、环戊基、环戊烯基、环己基、环己烯基、环庚基或环辛基,其可选地经选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或对薄荷烷基、间薄荷烷基、奎宁环基、二环[2.2.1]庚烷-2-基、二环[2.2.1]庚烷-3-基、二环[2.2.1]庚烷-4-基、二环[2.2.1]庚烷-5-基、二环[2.2.1]庚烷-6-基、1,7,7-三甲基二环[2.2.1]庚烷-2-基、1,7,7-三甲基二环[2.2.1]庚烷-3-基、1,7,7-三甲基二环[2.2.1]庚烷-4-基、1,7,7-三甲基二环[2.2.1]庚烷-5-基、1,7,7-三甲基二环[2.2.1]庚烷-6-基、 7,7-二甲基-2-氧代二环[2.2.1]庚烷-1-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-3-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-4-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-5-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-6-基、二环[2.2.1]庚 -5-烯-2-基、二环[2.2.1]庚-5-烯-3-基或二环[2.2.1]庚-5-烯-7-基。
- 如权利要求11所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中R表示OR b16,其中R b16表示H,或甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、戊基、异戊基、新戊基、特戊基、己基、庚基、辛基、壬基或癸基,其可选地被选自由卤素、羟基、氰基、氨基、巯基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或金刚烷-1-基、金刚烷-2-基、金刚烷-3-基、金刚烷-4-基、金刚烷-5-基、金刚烷-6-基、金刚烷-7-基、金刚烷-8-基、金刚烷-9-基或金刚烷-10-基,其可选地被选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或降金刚烷-1-基、降金刚烷-2-基、降金刚烷-3-基、降金刚烷-4-基、降金刚烷-5-基、降金刚烷-6-基、降金刚烷-7-基、降金刚烷-8-基或降金刚烷-9-基,其可选地被选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或环丙基、环丁基、环戊基、环戊烯基、环己基、环己烯基、环庚基或环辛基,其可选地经选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或对薄荷烷基、间薄荷烷基、奎宁环基、二环[2.2.1]庚烷-2-基、二环[2.2.1]庚烷-3-基、二环[2.2.1]庚烷-4-基、二环[2.2.1]庚烷-5-基、二环[2.2.1]庚烷-6-基、1,7,7-三甲基二环[2.2.1]庚烷-2-基、1,7,7-三甲基二环[2.2.1]庚烷-3-基、1,7,7-三甲基二环[2.2.1]庚烷-4-基、1,7,7-三甲基二环[2.2.1]庚烷-5-基、1,7,7-三甲基二环[2.2.1]庚烷-6-基、 7,7-二甲基-2-氧代二环[2.2.1]庚烷-1-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-3-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-4-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-5-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-6-基、二环[2.2.1]庚-5-烯-2-基、二环[2.2.1]庚-5-烯-3-基或二环[2.2.1]庚-5-烯-7-基。
- 如权利要求11所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中R表示氮杂环丁基、氧杂环丁基、吡咯烷基、咪唑烷基、吡唑烷基、四氢呋喃基、四氢吡喃基、 四氢噻吩基、四氢噻喃基、噁唑烷基、噻唑烷基、哌啶基、哌嗪基、吗啉基、硫代吗啉基、二氧杂环己基、氮杂环庚烷基、1,4-二氮杂环庚烷-1-基、3,8-二氮杂双环[3.2.1]辛烷-3-基、2,5-二氮杂双环[2.2.2]辛烷-2-基或C 7-11氮杂螺环基,其独立地可选地经选自由以下组成的群组的一或多个取代基取代:卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、羟基取代的C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-、可选经取代的苯基或其任意组合,其中所述可选经取代的苯基可选地经选自由卤素、羟基、氨基、氰基、巯基、C 1-3烷基或其任意组合组成的群组的取代基取代。
- 如权利要求11所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中R表示C(O)NR b9R b10、N(R b11)C(O)R b12、C(O)R b18、OC(O)R b19、C(O)OR b20、S(O) 2NR b21R b22或N(R b23)S(O) 2R b24,其中,R b9、R b11、R b21和R b23各自独立地表示H或C 1-3烷基;且R b10、R b12、R b18、R b19、R b20、R b22和R b24各自独立地表示以下基团:金刚烷-1-基、金刚烷-2-基、金刚烷-3-基、金刚烷-4-基、金刚烷-5-基、金刚烷-6-基、金刚烷-7-基、金刚烷-8-基、金刚烷-9-基、金刚烷-10-基、降金刚烷-1-基、降金刚烷-2-基、降金刚烷-3-基、降金刚烷-4-基、降金刚烷-5-基、降金刚烷-6-基、降金刚烷-7-基、降金刚烷-8-基、降金刚烷-9-基、环丙基、环丁基、环戊基、环戊烯基、环己基、环己烯基、环庚基、环辛基、氮杂环丁基、氧杂环丁基、吡咯烷基、咪唑烷基、吡唑烷基、四氢呋喃基、四氢吡喃基、四氢噻吩基、四氢噻喃基、噁唑烷基、噻唑烷基、哌啶基、哌嗪基、吗啉基、硫代吗啉基、二氧杂环己基、氮杂环庚烷基、1,4-二氮杂环庚烷-1-基、3,8-二氮杂双环[3.2.1]辛烷-3-基、2,5-二氮杂双环[2.2.2]辛烷-2-基、C 7-11氮杂螺环基、对薄荷烷基、间薄荷烷基、奎宁环基、二环[2.2.1]庚烷-2-基、二环[2.2.1]庚烷-3-基、二环[2.2.1]庚烷-4-基、二环[2.2.1]庚烷-5-基、二环[2.2.1]庚烷-6-基、1,7,7-三甲基二环[2.2.1]庚烷-2-基、1,7,7-三甲基二环[2.2.1]庚烷-3-基、1,7,7-三甲基二环[2.2.1]庚烷-4-基、1,7,7-三甲基二环[2.2.1]庚烷-5-基、1,7,7-三甲基二环[2.2.1]庚烷-6-基、 7,7-二甲基-2-氧代二环[2.2.1]庚烷-1-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-3-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-4-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-5-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-6-基、二环[2.2.1]庚-5-烯-2- 基、二环[2.2.1]庚-5-烯-3-基或二环[2.2.1]庚-5-烯-7-基,其中所述基团可选地经选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代。
- 如权利要求12所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中R表示NR c4R c5,其中R c4表示H或C 1-3烷基;R c5表示:金刚烷-1-基、金刚烷-2-基、金刚烷-3-基、金刚烷-4-基、金刚烷-5-基、金刚烷-6-基、金刚烷-7-基、金刚烷-8-基、金刚烷-9-基或金刚烷-10-基,其可选地被选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或降金刚烷-1-基、降金刚烷-2-基、降金刚烷-3-基、降金刚烷-4-基、降金刚烷-5-基、降金刚烷-6-基、降金刚烷-7-基、降金刚烷-8-基或降金刚烷-9-基,其可选地被选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取 代基取代,或环丙基、环丁基、环戊基、环戊烯基、环己基、环己烯基、环庚基或环辛基,其可选地经选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或对薄荷烷基、间薄荷烷基、奎宁环基、二环[2.2.1]庚烷-2-基、二环[2.2.1]庚烷-3-基、二环[2.2.1]庚烷-4-基、二环[2.2.1]庚烷-5-基、二环[2.2.1]庚烷-6-基、1,7,7-三甲基二环[2.2.1]庚烷-2-基、1,7,7-三甲基二环[2.2.1]庚烷-3-基、1,7,7-三甲基二环[2.2.1]庚烷-4-基、1,7,7-三甲基二环[2.2.1]庚烷-5-基、1,7,7-三甲基二环[2.2.1]庚烷-6-基、 7,7-二甲基-2-氧代二环[2.2.1]庚烷-1-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-3-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-4-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-5-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-6-基、二环[2.2.1]庚-5-烯-2-基、二环[2.2.1]庚-5-烯-3-基或二环[2.2.1]庚-5-烯-7-基。
- 如权利要求12所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中R表示OR c13,其中R c13表示金刚烷-1-基、金刚烷-2-基、金刚烷-3-基、金刚烷-4-基、金刚烷-5-基、金刚烷-6-基、金刚烷-7-基、金刚烷-8-基、金刚烷-9-基或金刚烷-10-基,其可选地被选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或降金刚烷-1-基、降金刚烷-2-基、降金刚烷-3-基、降金刚烷-4-基、降金刚烷-5-基、降金刚烷-6-基、降金刚烷-7-基、降金刚烷-8-基或降金刚烷-9-基,其可选地被选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或环丙基、环丁基、环戊基、环戊烯基、环己基、环己烯基、环庚基或环辛基,其可选地经选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代,或对薄荷烷基、间薄荷烷基、奎宁环基、二环[2.2.1]庚烷-2-基、二环[2.2.1]庚烷-3-基、二环[2.2.1]庚烷-4-基、二环[2.2.1]庚烷-5-基、二环[2.2.1]庚烷-6-基、1,7,7-三甲基二环[2.2.1]庚烷-2-基、1,7,7-三甲基二环[2.2.1]庚烷-3-基、1,7,7-三甲基二环[2.2.1]庚烷-4-基、1,7,7-三甲基二环[2.2.1]庚烷-5-基、1,7,7-三甲基二环[2.2.1]庚烷-6-基、 7,7-二甲基-2-氧代二环[2.2.1]庚烷-1-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-3-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-4-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-5-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-6-基、二环[2.2.1]庚-5-烯-2-基、二环[2.2.1]庚-5-烯-3-基或二环[2.2.1]庚-5-烯-7-基。
- 如权利要求12所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中R表示氮杂环丁基、氧杂环丁基、吡咯烷基、咪唑烷基、吡唑烷基、四氢呋喃基、四氢吡喃基、四氢噻吩基、四氢噻喃基、噁唑烷基、噻唑烷基、哌啶基、哌嗪基、吗啉基、硫代吗啉基、二氧杂环己基、氮杂环庚烷基、1,4-二氮杂环庚烷-1-基、3,8-二氮杂双环[3.2.1]辛烷-3-基、2,5-二氮杂双环[2.2.2]辛烷-2-基或C 7-11氮杂螺环基,其独立地可选地经选自由以下组成的群组的一或多个取代基取代:卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、羟基取代的C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合。
- 如权利要求12所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其中R表示C(O)NR c6R c7、N(R c8)C(O)R c9、C(O)R c15、OC(O)R c16、C(O)OR c17、S(O) 2NR c18R c19或N(R c20)S(O) 2R c21,其中,R c6、R c8、R c18和R c20各自独立地表示H或C 1-3烷基;且R c7、R c9、R c15、R c16、R c17、R c19和R c21各自独立地表示以下基团:金刚烷-1-基、金刚烷-2-基、金刚烷-3-基、金刚烷-4-基、金刚烷-5-基、金刚烷-6-基、金刚烷-7-基、金刚烷-8-基、金刚烷-9-基、金刚烷-10-基、降金刚烷-1-基、降金刚烷-2-基、降金刚烷-3-基、降金刚烷-4-基、降金刚烷-5-基、降金刚烷-6-基、降金刚烷-7-基、降金刚烷-8-基、降金刚烷-9-基、环丙基、环丁基、环戊基、环戊烯基、环己基、环己烯基、环庚基、环辛基、氮杂环丁基、氧杂环丁基、吡咯烷基、咪唑烷基、吡唑烷基、四氢呋喃基、四氢吡喃基、四氢噻吩基、四氢噻喃基、噁唑烷基、噻唑烷基、哌啶基、哌嗪基、吗啉基、硫代吗啉基、二氧杂环己基、氮杂环庚烷基、1,4-二氮杂环庚烷-1-基、3,8-二氮杂双环[3.2.1]辛烷-3-基、2,5-二氮杂双环[2.2.2]辛烷-2-基、C 7-11氮杂螺环基、对薄荷烷基、间薄荷烷基、奎宁环基、二环[2.2.1]庚烷-2-基、二环[2.2.1]庚烷-3-基、二环[2.2.1]庚烷-4-基、二环[2.2.1]庚烷-5-基、二环[2.2.1]庚烷-6-基、1,7,7-三甲基二环[2.2.1]庚烷-2-基、1,7,7-三甲基 二环[2.2.1]庚烷-3-基、1,7,7-三甲基二环[2.2.1]庚烷-4-基、1,7,7-三甲基二环[2.2.1]庚烷-5-基、1,7,7-三甲基二环[2.2.1]庚烷-6-基、 7,7-二甲基-2-氧代二环[2.2.1]庚烷-1-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-3-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-4-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-5-基、7,7-二甲基-2-氧代二环[2.2.1]庚烷-6-基、二环[2.2.1]庚-5-烯-2-基、二环[2.2.1]庚-5-烯-3-基或二环[2.2.1]庚-5-烯-7-基,其中所述基团可选地经选自由卤素、羟基、巯基、氧代基、氰基、C 1-3烷基、卤代C 1-3烷基、C 1-3烷氧基、C 1-3烷基氨基、C 1-3烷基-NHC(O)-或其任意组合组成的群组的一或多个取代基取代。
- 如权利要求1所述的式(I)化合物或其盐、对映异构体、立体异构体、溶剂化物、多晶型物,其选自:3-(5-((苯并[d][1,3]二氧杂环戊烯-5-基甲基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-(((四氢-2H-吡喃-4-基)甲基)氨基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((吡啶-2-基甲基)氨基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((2-氟苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-(((1R,3R,5S)-金刚烷-1-基氨基)甲基)苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-(((1R,2s,3S,5r)-金刚烷-2-基氨基)甲基)苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-((金刚烷-2-基氧基)甲基)苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-(羟基甲基)苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((4-(哌啶-1-基甲基)苄基)氨基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-((二甲基氨基)甲基)苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-((二乙基氨基)甲基)苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-((3,5-二甲基哌啶-1-基)甲基)苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶- 2,6-二酮;3-(2-甲基-4-氧代-5-((4-(硫代吗啉代基甲基)苄基)氨基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-(氮杂环庚烷-1-基甲基)苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-5-((4-(吗啉代基甲基)苄基)氨基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;4-(4-(4-(((3-(2,6-二氧代哌啶-3-基)-2-甲基-4-氧代-3,4-二氢喹唑啉-5-基)氨基)甲基)苄基)哌嗪-1-基)-3-氟苯甲腈;3-(2-甲基-4-氧代-5-((2-(苯基氨基)乙基)氨基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-(苯乙基氨基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-((金刚烷-1-基氨基)甲基)-2-氟苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((2-氟-4-(哌啶-1-基甲基)苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-((3,5-二甲基哌啶-1-基)甲基)-2-氟苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((2-氟-4-(硫代吗啉代基甲基)苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-(氮杂环庚烷-1-基甲基)-2-氟苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((2-氟-4-(吗啉代基甲基)苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;4-(4-(4-(((3-(2,6-二氧代哌啶-3-基)-2-甲基-4-氧代-3,4-二氢喹唑啉-5-基)氨基)甲基)-3-氟苄基)哌嗪-1-基)-3-氟苯甲腈;3-(2-甲基-4-氧代-5-(((5-(哌啶-1-基甲基)吡啶-2-基)甲基)氨基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(((5-((3,5-二甲基哌啶-1-基)甲基)吡啶-2-基)甲基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-(((5-(硫代吗啉代基甲基)吡啶-2-基)甲基)氨基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(((5-(氮杂环庚烷-1-基甲基)吡啶-2-基)甲基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(((5-(((金刚烷-1-基)氨基)甲基)吡啶-2-基)甲基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-5-(((5-(吗啉代基甲基)吡啶-2-基)甲基)氨基)-4-氧代喹唑啉-3(4H)-基)哌啶- 2,6-二酮;3-(5-(((5-((金刚烷-1-基氨基)甲基)噻唑-2-基)甲基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-(((5-(哌啶-1-基甲基)噻唑-2-基)甲基)氨基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(((5-(氮杂环庚烷-1-基甲基)噻唑-2-基)甲基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-5-(((5-(吗啉代基甲基)噻唑-2-基)甲基)氨基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-5-(((4-(吗啉-4-羰基)环己基)甲基)氨基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;N-((3s,5s,7s)-金刚烷-1-基)-4-(((3-(2,6-二氧代哌啶-3-基)-2-甲基-4-氧代-3,4-二氢喹唑啉-5-基)氨基)甲基)环己酰胺;N-(4-(((3-(2,6-二氧代哌啶-3-基)-2-甲基-4-氧代-3,4-二氢喹唑啉-5-基)氨基)甲基)苯基)环己酰胺;4-(((3-(2,6-二氧代哌啶-3-基)-2-甲基-4-氧代-3,4-二氢喹唑啉-5-基)氨基)甲基)苯基环己甲酸酯;N-环己基-4-(((3-(2,6-二氧代哌啶-3-基)-2-甲基-4-氧代-3,4-二氢喹唑啉-5-基)氨基)甲基)苯磺酰胺;3-(5-((4-((4-(2-羟基乙基)哌嗪-1-基)甲基)苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;4-(4-(4-(((3-(2,6-二氧代哌啶-3-基)-2-甲基-4-氧代-3,4-二氢喹唑啉-5-基)氨基)甲基)苄基)哌嗪-1-基)-3-氟苯甲腈;3-(2-甲基-4-氧代-6-((4-(哌啶-1-基甲基)苄基)氨基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(6-((4-((3,5-二甲基哌啶-1-基)甲基)苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-6-((4-(硫代吗啉代基甲基)苄基)氨基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(6-((4-(氮杂环庚烷-1-基甲基)苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-6-((4-(吗啉代基甲基)苄基)氨基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-8-((4-(哌啶-1-基甲基)苄基)氨基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(8-((4-((3,5-二甲基哌啶-1-基)甲基)苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-8-((4-(吗啉代基甲基)苄基)氨基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(8-((4-(氮杂环庚烷-1-基甲基)苄基)氨基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((4-(2-(哌啶-1-基)乙基)苄基)氨基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((4-(3-(哌啶-1-基)丙基)苄基)氨基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((4-(哌啶-1-基甲基)苯乙基)氨基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((2-氟苄基)氧基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-((金刚烷-1-基氨基)甲基)苄基)氧基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-(羟基甲基)苄基)氧基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((4-(哌啶-1-基甲基)苄基)氧基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-(氮杂环庚烷-1-基甲基)苄基)氧基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-5-((4-(吗啉代基甲基)苄基)氧基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-(氮杂环庚烷-1-基甲基)-2-氟苄基)氧基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((2-氟-4-(吗啉代基甲基)苄基)氧基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((5-(哌啶-1-基甲基)吡啶-2-基)甲氧基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((5-((3,5-二甲基哌啶-1-基)甲基)吡啶-2-基)甲氧基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((5-(氮杂环庚烷-1-基甲基)吡啶-2-基)甲氧基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-5-((5-(吗啉代基甲基)吡啶-2-基)甲氧基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((5-((金刚烷-1-基氨基)甲基)噻唑-2-基)甲氧基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((5-(哌啶-1-基甲基)噻唑-2-基)甲氧基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((5-(氮杂环庚烷-1-基甲基)噻唑-2-基)甲氧基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-5-((5-(吗啉代基甲基)噻唑-2-基)甲氧基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-5-((4-(吗啉-4-羰基)环己基)甲氧基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;N-(4-(((3-(2,6-二氧代哌啶-3-基)-2-甲基-4-氧代-3,4-二氢喹唑啉-5-基)氧基)甲基)苯基)环 己酰胺;3-(2-甲基-4-氧代-6-((4-(哌啶-1-基甲基)苄基)氧基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(6-((4-(氮杂环庚烷-1-基甲基)苄基)氧基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-6-((4-(吗啉代基甲基)苄基)氧基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-8-((4-(哌啶-1-基甲基)苄基)氧基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-8-((4-(吗啉代基甲基)苄基)氧基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(8-((4-(氮杂环庚烷-1-基甲基)苄基)氧基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((4-(2-(哌啶-1-基)乙基)苄基)氧基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-(4-(哌啶-1-基甲基)苯乙氧基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(苄基硫基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((吡啶-2-基甲基)硫基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((2-氟苄基)硫基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-((金刚烷-1-基氨基)甲基)苄基)硫基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-(羟基甲基)苄基)硫基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((4-(哌啶-1-基甲基)苄基)硫基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-(氮杂环庚烷-1-基甲基)苄基)硫基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-5-((4-(吗啉代基甲基)苄基)硫基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((2-氟-4-(哌啶-1-基甲基)苄基)硫基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-(氮杂环庚烷-1-基甲基)-2-氟苄基)硫基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((2-氟-4-(吗啉代基甲基)苄基)硫基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-(((5-(哌啶-1-基甲基)吡啶-2-基)甲基)硫基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(((5-(氮杂环庚烷-1-基甲基)吡啶-2-基)甲基)硫基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-5-(((5-(吗啉代基甲基)吡啶-2-基)甲基)硫基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-(((5-(哌啶-1-基甲基)噻唑-2-基)甲基)硫基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(((5-(氮杂环庚烷-1-基甲基)噻唑-2-基)甲基)硫基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-5-(((5-(吗啉代基甲基)噻唑-2-基)甲基)硫基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-6-((4-(硫代吗啉代基甲基)苄基)硫基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(6-((4-(氮杂环庚烷-1-基甲基)苄基)硫基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-6-((4-(吗啉代基甲基)苄基)硫基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-8-((4-(哌啶-1-基甲基)苄基)硫基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(8-((4-(氮杂环庚烷-1-基甲基)苄基)硫基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((4-(2-(哌啶-1-基)乙基)苄基)硫基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((4-(哌啶-1-基甲基)苯乙基)硫基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((4-(3-(哌啶-1-基)丙基)苄基)硫基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(4-(4-(氮杂环庚烷-1-基甲基)苯基)丁-1-炔-1-基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-(氮杂环庚烷-1-基甲基)苯基)乙炔基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(4-(氮杂环庚烷-1-基甲基)苯乙基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(4-(氮杂环庚烷-1-基甲基)-2-氟苯乙基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(4-(氮杂环庚烷-1-基甲基)-2-溴苯乙基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(4-((金刚烷-1-基氨基)甲基)苯乙基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-(4-(哌啶-1-基甲基)苯乙基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-5-(4-(吗啉代基甲基)苯乙基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-(4-(硫代吗啉代基甲基)苯乙基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(2-氟-4-(吗啉代基甲基)苯乙基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-(2-(5-(哌啶-1-基甲基)吡啶-2-基)乙基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(2-(5-((3,5-二甲基哌啶-1-基)甲基)吡啶-2-基)乙基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(2-(5-(氮杂环庚烷-1-基甲基)吡啶-2-基)乙基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶- 2,6-二酮;3-(2-甲基-5-(2-(5-(吗啉代基甲基)吡啶-2-基)乙基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(2-(5-((((1R,3R,5S)-金刚烷-1-基)氨基)甲基)噻唑-2-基)乙基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-(2-(5-(哌啶-1-基甲基)噻唑-2-基)乙基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(2-(5-(氮杂环庚烷-1-基甲基)噻唑-2-基)乙基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-5-(2-(5-(吗啉代基甲基)噻唑-2-基)乙基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-6-(4-(哌啶-1-基甲基)苯乙基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(6-(4-(氮杂环庚烷-1-基甲基)苯乙基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-6-(4-(吗啉代基甲基)苯乙基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-8-(4-(哌啶-1-基甲基)苯乙基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-8-(4-(吗啉代基甲基)苯乙基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(8-(4-(氮杂环庚烷-1-基甲基)苯乙基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-(4-(2-(哌啶-1-基)乙基)苯乙基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-(3-(4-(哌啶-1-基甲基)苯基)丙基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-((((1R,3R,5S)-金刚烷-1-基)氨基)甲基)苯基)乙炔基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-(羟基甲基)苯基)乙炔基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((4-(哌啶-1-基甲基)苯基)乙炔基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-5-((4-(吗啉代基甲基)苯基)乙炔基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-(氮杂环庚烷-1-基甲基)-2-氟苯基)乙炔基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((2-氟-4-(吗啉代基甲基)苯基)乙炔基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((5-(哌啶-1-基甲基)吡啶-2-基)乙炔基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((5-((3,5-二甲基哌啶-1-基)甲基)吡啶-2-基)乙炔基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((5-(氮杂环庚烷-1-基甲基)吡啶-2-基)乙炔基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-5-((5-(吗啉代基甲基)吡啶-2-基)乙炔基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二 酮;3-(5-((5-((((1R,3R,5S)-金刚烷-1-基)氨基)甲基)噻唑-2-基)乙炔基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((5-(哌啶-1-基甲基)噻唑-2-基)乙炔基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((5-(氮杂环庚烷-1-基甲基)噻唑-2-基)乙炔基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-5-((5-(吗啉代基甲基)噻唑-2-基)乙炔基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-6-((4-(哌啶-1-基甲基)苯基)乙炔基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(6-((4-(氮杂环庚烷-1-基甲基)苯基)乙炔基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-6-((4-(吗啉代基甲基)苯基)乙炔基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-8-((4-(哌啶-1-基甲基)苯基)乙炔基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-8-((4-(吗啉代基甲基)苯基)乙炔基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((4-(硫代吗啉代基甲基)苯基)乙炔基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(8-((4-(氮杂环庚烷-1-基甲基)苯基)乙炔基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-((4-(氮杂环庚烷-1-基甲基)-2-氟苯基)乙炔基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-((4-(2-(哌啶-1-基)乙基)苯基)乙炔基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-(3-(4-(哌啶-1-基甲基)苯基)丙-1-炔-1-基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(3-(4-(氮杂环庚烷-1-基甲基)苯基)丙-1-炔-1-基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(5-(3-(4-(氮杂环庚烷-1-基甲基)-2-氟苯基)丙-1-炔-1-基)-2-甲基-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮;3-(2-甲基-4-氧代-5-(3-(4-(硫代吗啉代基甲基)苯基)丙-1-炔-1-基)喹唑啉-3(4H)-基)哌啶-2,6-二酮;或3-(2-甲基-5-(3-(4-(吗啉代基甲基)苯基)丙-1-炔-1-基)-4-氧代喹唑啉-3(4H)-基)哌啶-2,6-二酮。
- 药物组合物,其包含如权利要求1至42中任一项所述的式(I)化合物或其医药学上可接受的盐,及至少一种医药学上可接受的载体。
- 如权利要求43所述的药物组合物,进一步包括第二治疗剂。
- 如权利要求1至42中任一项所述的式(I)化合物或其医药学上可接受的盐或如权利要求43或44所述的药物组合物的用途,其用于制备用以预防及/或治疗与TNF-α相关的疾病或病症的药剂。
- 如权利要求45所述的用途,其中所述与TNF-α相关的疾病或病症是选自:肿瘤、感染性疾病、炎性疾病、自身免疫性疾病、贫血、出血性休克、移植排斥反应、多器官功能障碍综合征(MODS)、类肉瘤病、成人呼吸窘迫综合征、充血性心力衰竭、心肌梗塞、翁韦里希特综合征、急性肝功能衰竭或糖尿病。
- 如权利要求45所述的用途,其中所述与TNF-α相关的疾病或病症选自由以下组成的群组:骨髓瘤,包括多发性骨髓瘤、浆细胞骨髓瘤、阴燃骨髓瘤、闷烧多发性骨髓瘤;骨髓纤维化;骨髓疾病;骨髓增生异常综合征(MDS);既往治疗的骨髓增生异常综合征;移植相关的癌症;中性粒细胞减少症;白血病,包括急性髓细胞白血病、慢性粒细胞白血病、B细胞慢性淋巴细胞白血病、与白血病相关的贫血、急性髓性白血病(AML);淋巴瘤,包括弥漫性大B细胞淋巴瘤、非霍奇金淋巴瘤、间变性淋巴瘤、间变性大细胞淋巴瘤、CD20阳性淋巴瘤、套细胞淋巴瘤、原发性淋巴瘤、B细胞淋巴瘤、复发性B细胞非霍奇金淋巴瘤、复发性弥漫性大B细胞淋巴瘤、复发性纵隔(胸腺)大B细胞淋巴瘤、原发性纵隔(胸腺)大B细胞淋巴瘤、复发性转化非霍奇金淋巴瘤、难治性B细胞非霍奇金淋巴瘤、难治性弥漫性大B细胞淋巴瘤、难治性原发性纵隔(胸腺)大B细胞淋巴瘤、难治性转化的非霍奇金淋巴瘤;甲状腺癌;黑色素瘤;肺癌;炎症性肌纤维母细胞瘤;结直肠癌;脑胶质瘤;星形胶质母细胞瘤;卵巢癌;支气管癌;前列腺癌;乳腺癌,包括三阴性乳腺癌、偶发性乳腺癌和考登病患者;胰腺癌;神经母细胞瘤;髓外浆细胞瘤;浆细胞瘤;胃癌;胃肠道间质瘤;食道癌;大肠腺癌;食管鳞状细胞癌;肝癌;肾细胞癌;膀胱癌;子宫内膜癌;脑癌;口腔癌;肉瘤,包括横纹肌肉瘤、各种脂肪源性肿瘤、尤文肉瘤/原始神经外胚层瘤(Ewing/PNETs)、和平滑肌肉瘤;翁韦里希特综合征;自身免疫性疾病,包括类风湿性关节炎、自身免疫性脑脊髓炎、强直性脊柱炎、银屑病、系统性红斑狼疮、多发性硬化症、复发性口腔溃疡、川崎病;炎症性疾病,包括包括克罗恩病和溃疡性结肠炎、、肺炎、骨关节炎、滑膜炎、全身炎症反应综合征、气道炎症、支气管炎;脑型疟疾;艾滋病(AIDS);COVID-19新型冠状病毒感染;感染性休克;脓毒综合征;结核病;细菌性脑膜炎;慢性阻塞性肺疾病;哮喘;出血性休克;器官(包括肾、心脏、肺)或组织移植排斥反应;糖尿病;类肉瘤病;成人呼吸窘迫综合征;充血性心力衰竭;心肌梗塞;恶病质和败血症休克所致的多器官功能衰竭;或急性肝功能衰竭。
- 如权利要求1至42中任一项所述的式(I)化合物或其医药学上可接受的盐,其用于预防及/或治疗与TNF-α相关的疾病或病症。
- 如权利要求48所述的式(I)化合物,或其医药学上可接受的盐,其中所述与TNF- α相关的疾病或病症是选自:肿瘤、感染性疾病、炎症性疾病、自身免疫性疾病、贫血、出血性休克、移植排斥反应、多器官功能障碍综合征(MODS)、类肉瘤病、成人呼吸窘迫综合征、充血性心力衰竭、心肌梗塞、翁韦里希特综合征、急性肝功能衰竭或糖尿病。
- 如权利要求48所述的式(I)化合物,或其医药学上可接受的盐,其中所述与TNF-α相关的疾病或病症选自由以下组成的群组:骨髓瘤,包括多发性骨髓瘤、浆细胞骨髓瘤、阴燃骨髓瘤、闷烧多发性骨髓瘤;骨髓纤维化;骨髓疾病;骨髓增生异常综合征(MDS);既往治疗的骨髓增生异常综合征;移植相关的癌症;中性粒细胞减少症;白血病,包括急性髓细胞白血病、慢性粒细胞白血病、B细胞慢性淋巴细胞白血病、与白血病相关的贫血、急性髓性白血病(AML);淋巴瘤,包括弥漫性大B细胞淋巴瘤、非霍奇金淋巴瘤、间变性淋巴瘤、间变性大细胞淋巴瘤、CD20阳性淋巴瘤、套细胞淋巴瘤、原发性淋巴瘤、B细胞淋巴瘤、复发性B细胞非霍奇金淋巴瘤、复发性弥漫性大B细胞淋巴瘤、复发性纵隔(胸腺)大B细胞淋巴瘤、原发性纵隔(胸腺)大B细胞淋巴瘤、复发性转化非霍奇金淋巴瘤、难治性B细胞非霍奇金淋巴瘤、难治性弥漫性大B细胞淋巴瘤、难治性原发性纵隔(胸腺)大B细胞淋巴瘤、难治性转化的非霍奇金淋巴瘤;甲状腺癌;黑色素瘤;肺癌;炎症性肌纤维母细胞瘤;结直肠癌;脑胶质瘤;星形胶质母细胞瘤;卵巢癌;支气管癌;前列腺癌;乳腺癌,包括三阴性乳腺癌、偶发性乳腺癌和考登病患者;胰腺癌;神经母细胞瘤;髓外浆细胞瘤;浆细胞瘤;胃癌;胃肠道间质瘤;食道癌;大肠腺癌;食管鳞状细胞癌;肝癌;肾细胞癌;膀胱癌;子宫内膜癌;脑癌;口腔癌;肉瘤,包括横纹肌肉瘤、各种脂肪源性肿瘤、尤文肉瘤/原始神经外胚层瘤(Ewing/PNETs)、和平滑肌肉瘤;翁韦里希特综合征;脓毒综合征;自身免疫性疾病,包括类风湿性关节炎、自身免疫性脑脊髓炎、强直性脊柱炎、银屑病、系统性红斑狼疮、多发性硬化症、复发性口腔溃疡、川崎病;炎症性疾病,包括包括克罗恩病和溃疡性结肠炎、肺炎、骨关节炎、滑膜炎、全身炎症反应综合征、气道炎症、支气管炎;脑型疟疾;艾滋病(AIDS);COVID-19新型冠状病毒感染;感染性休克;结核病;细菌性脑膜炎;慢性阻塞性肺疾病;哮喘;出血性休克;器官(包括肾、心脏、肺)或组织移植排斥反应;糖尿病;类肉瘤病;成人呼吸窘迫综合征;充血性心力衰竭;心肌梗塞;恶病质和败血症休克所致的多器官功能衰竭;或急性肝功能衰竭。
- 治疗或预防与TNF-α相关的疾病或病症的方法,其包括向受试者施用治疗有效量的如权利要求1-42中任一项所述的式(I)化合物,或其医药学上可接受的盐,或如权利要求43或44所述的药物组合物。
- 如权利要求51所述的方法,其中所述与TNF-α相关的疾病或病症是选自:肿瘤、感染性疾病、炎性疾病、自身免疫性疾病、贫血、出血性休克、移植排斥反应、多器官功能障碍综合征(MODS)、类肉瘤病、成人呼吸窘迫综合征、充血性心力衰竭、心肌梗塞、翁韦里希特综合征、急性肝功能衰竭或糖尿病。
- 如权利要求51所述的方法,其中所述与TNF-α相关的疾病或病症选自由以下组 成的群组:骨髓瘤,包括多发性骨髓瘤、浆细胞骨髓瘤、阴燃骨髓瘤、闷烧多发性骨髓瘤;骨髓纤维化;骨髓疾病;骨髓增生异常综合征(MDS);既往治疗的骨髓增生异常综合征;移植相关的癌症;中性粒细胞减少症;白血病,包括急性髓细胞白血病、慢性粒细胞白血病、B细胞慢性淋巴细胞白血病、与白血病相关的贫血、急性髓性白血病(AML);淋巴瘤,包括弥漫性大B细胞淋巴瘤、非霍奇金淋巴瘤、间变性淋巴瘤、间变性大细胞淋巴瘤、CD20阳性淋巴瘤、套细胞淋巴瘤、原发性淋巴瘤、B细胞淋巴瘤、复发性B细胞非霍奇金淋巴瘤、复发性弥漫性大B细胞淋巴瘤、复发性纵隔(胸腺)大B细胞淋巴瘤、原发性纵隔(胸腺)大B细胞淋巴瘤、复发性转化非霍奇金淋巴瘤、难治性B细胞非霍奇金淋巴瘤、难治性弥漫性大B细胞淋巴瘤、难治性原发性纵隔(胸腺)大B细胞淋巴瘤、难治性转化的非霍奇金淋巴瘤;甲状腺癌;黑色素瘤;肺癌;炎症性肌纤维母细胞瘤;结直肠癌;脑胶质瘤;星形胶质母细胞瘤;卵巢癌;支气管癌;前列腺癌;乳腺癌,包括三阴性乳腺癌、偶发性乳腺癌和考登病患者;胰腺癌;神经母细胞瘤;髓外浆细胞瘤;浆细胞瘤;胃癌;胃肠道间质瘤;食道癌;大肠腺癌;食管鳞状细胞癌;肝癌;肾细胞癌;膀胱癌;子宫内膜癌;脑癌;口腔癌;肉瘤,包括横纹肌肉瘤、各种脂肪源性肿瘤、尤文肉瘤/原始神经外胚层瘤(Ewing/PNETs)、和平滑肌肉瘤;翁韦里希特综合征;脓毒综合征;自身免疫性疾病,包括复发性口腔溃疡、类风湿性关节炎、自身免疫性脑脊髓炎、强直性脊柱炎、银屑病、系统性红斑狼疮、多发性硬化症、川崎病;炎症性疾病,包括包括克罗恩病和溃疡性结肠炎、肺炎、骨关节炎、滑膜炎、全身炎症反应综合征、气道炎症、支气管炎;脑型疟疾;艾滋病(AIDS);COVID-19新型冠状病毒感染;感染性休克;结核病;细菌性脑膜炎;慢性阻塞性肺疾病;哮喘;出血性休克;器官(包括肾、心脏、肺)或组织移植排斥反应;糖尿病;类肉瘤病;成人呼吸窘迫综合征;充血性心力衰竭;心肌梗塞;恶病质和败血症休克所致的多器官功能衰竭;或急性肝功能衰竭。
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