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US 10,647,665 B2Granted
Biaryl urea derivative or salt thereof and preparation process and use for the same
AssigneeFudan University
InventorsYonghui Wang, Yafei Huang, Fazhi Yu, Ting Tang
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Abstract
The present invention discloses a biaryl urea RORγt inhibitor, and specifically relates to a biaryl urea derivative, as represented by formula I, with an RORγt inhibiting activity, and a preparation process thereof, and a pharmaceutical composition comprising the compound. Further disclosed is use of the compound for treating an RORγt-related disease.
Claims10
A compound shown by formula II or a pharmaceutically acceptable salt thereof:
- wherein:
- B is phenyl or pyridyl;
- R1 is optionally selected from a group consisting of hydrogen, methyl, halogen, cyano, hydroxyl, —CF3, —CHF2, and —CH2F;
- R1′ is selected from a group consisting of hydrogen, —OCF3, —OCHF2, —CF3, and heteroaryl;
- R2 is optionally selected from a group consisting of hydrogen, halogen, cyano, hydroxyl, C1-C6 alkyl, halogen-substituted C1-C6 alkyl, C(O)ORa or cycloalkyl substituted C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 oxo(azo)heterocycloalkyl, C1-C6 alkoxyl, halogen-substituted C1-C6 alkoxyl, hydroxyl or C1-C3 alkoxyl substituted C1-C3 alkyl, phenyl, substituted heteroaryloxyl, C2-C6 alkenyl, halogen substituted aromatic ketone group, carboxyl or cyano substituted heteroaryl, —C(O)Ra, —(CH2)nNRa1Ra2, —(CH2)nC(O)ORa, —C(O)NRa1Ra2;
- R3 and R4 each is hydrogen;
- R5 and R6 each is hydrogen;
- R7 is optionally selected from a group consisting of hydrogen, halogen, cyano, hydroxyl, C1-C6 alkyl, halogen-substituted C1-C6 alkyl, C(O)ORa or cycloalkyl substituted C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 oxo(azo)heterocycloalkyl, C1-C6 alkoxyl, halogen-substituted C1-C6 alkoxyl, hydroxyl or C1-C3 alkoxyl substituted C1-C3 alkyl, phenyl, substituted phenyl, phenoxyl, substituted phenoxyl, heterocyclyl, heterocyclooxyl, heteroaryl, heteroaryloxyl, C2-C6 alkenyl, halogen-substituted aromatic ketone group, carboxyl or cyano substituted heteroaryl, —C(O)Ra, —(CH2)nNRa1Ra2, —(CH2)nC(O)ORa and —C(O)NRa1Ra2;
- Y is a covalent bond;
- when R8 is
- wherein Z is O, and R9 is methyl, ethyl, or —NH2;
- or
- Y is —CRa1Ra2, when R8 is
- Ra, Ra1 and Ra2 are each independently selected from hydrogen or C1-C3 alkyl;
- m, r, t and n are each independently selected from any integer value of 0˜2.
12 more elements
A compound shown by formula II or a pharmaceutically acceptable salt thereof:
- wherein:
- B is phenyl or pyridyl;
- R1 is optionally selected from a group consisting of hydrogen, methyl, halogen, cyano, hydroxyl, —CF3, —CHF2, and —CH2F;
- R1′ is selected from a group consisting of hydrogen, —OCF3, —OCHF2, —CF3 and heteroaryl;
- R2 is optionally selected from a group consisting of hydrogen, halogen, cyano, hydroxyl, C1-C6 alkyl, halogen-substituted C1-C6 alkyl, C(O)ORa or cycloalkyl substituted C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 oxo(azo)heterocycloalkyl, C1-C6 alkoxyl, halogen-substituted C1-C6 alkoxyl, hydroxyl or C1-C3 alkoxyl substituted C1-C3 alkyl, phenyl, substituted heteroaryloxyl, C2-C6 alkenyl, halogen substituted aromatic ketone group, carboxyl or cyano substituted heteroaryl, —C(O)Ra, —(CH2)nNRa1Ra2, —(CH2)nC(O)ORa, —C(O)NRa1Ra2;
- R3 and R4 each is hydrogen, one of R5 and R6 is hydrogen, the other of R5 and R6 is C1-C3 alkyl or C1-C3 alkyl hydroxyl;
- or
- one of R3 and R4 is hydrogen, the other one of R3 and R4 is C1-C3 alkyl, R5 and R6 each is hydrogen;
- R7 is optionally selected from a group consisting of hydrogen, halogen, cyano, hydroxyl, C1-C6 alkyl, halogen-substituted C1-C6 alkyl, C(O)ORa or cycloalkyl substituted C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 oxo(azo)heterocycloalkyl, C1-C6 alkoxyl, halogen-substituted C1-C6 alkoxyl, hydroxyl or C1-C3 alkoxyl substituted C1-C3 alkyl, phenyl, substituted phenyl, phenoxyl, substituted phenoxyl, heterocyclyl, heterocyclooxyl, heteroaryl, heteroaryloxyl, C2-C6 alkenyl, halogen-substituted aromatic ketone group, carboxyl or cyano substituted heteroaryl, —C(O)Ra, —(CH2)nNRa1Ra2, —(CH2)nC(O)ORa and —C(O)NRa1Ra2;
- Y is a covalent bond, when R8 is
- wherein Z is O, and R9 is methyl or ethyl;
- or
- Y is —CRa1Ra2, when R8 is
- Ra, Ra1 and Ra2 are each independently selected from hydrogen or C1-C3 alkyl;
- m, r, t and n are each independently selected from any integer value of 0˜2.
12 more elements
Dependencies are inferred from the claim text.