Biaryl compound, preparation method and use thereof
AssigneeFudan University
InventorsYonghui Wang, Yafei Huang, Ruomeng Qiu, Ting Tang
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Abstract
The present invention belongs to the technical field of chemical pharmaceuticals, and relates to a compound represented by general formula (I) or formula (II) and a preparation method thereof. The compounds are biaryl derivatives with RORγt activation activity. The biaryl derivatives disclosed in this invention can effectively activate the RORγt protein receptor, and thereby promote the differentiation of Th17 cells and increasing the production of IL-17, which can be used as an immune modulator for the treatment of various cancers or viral infection-related diseases.
Claims12
A compound of formula (I) or (II) or a pharmaceutically acceptable salt thereof:
- wherein:
- R1, R2 and R3 are each independently selected from a group consisting of hydrogen, R11-substituted C1-C6 alkyl, R11-substituted C3-C8 cycloalkyl, R11-substituted C3-C8 heterocycloalkyl, —C(O)R9, —C(O)NR9R10, —NR9C(O)R10, —OR9 and —NR9R10;
- or any two of R1, R2 and R3 form C2-C8 alkyl alkenyl or C3-C7 cycloalkyl alkenyl, or R1, R2 and R3 form C2-C6 alkyl alkynyl;
- or any two of R1, R2 and R3 form C3-C8 cycloalkyl or C3-C8 heterocycloalkyl;
- R1′ is selected from a group consisting of hydrogen, C3-C6 alkyl, C1-C6 cycloalkyl, C3-C6 heterocycloalkyl and C1-C6 alkyl acyl;
- R4 is optionally selected from a group consisting of hydrogen, —OCF3, —OCHF2, —CF3, halogen, —CN, C1-C3 alkyl, C1-C3 alkoxyl, aryl, heteroaryl, and —OR9-substituted heterocycloalkyl;
- X, Y are each independently selected from a group consisting of hydrogen, halogen, —CN, —OCF3, —CF3, C1-C6 alkyl, C3-C8 cycloalkyl, C3-C8 heterocycloalkyl, aryl, heteroaryl, C1-C3 alkoxyl, C1-C3 alkyl amino, C1-C3 acyl, C1-C3 acyloxyl and C1-C3 amide;
- R5 is optionally selected from
- R6 and R7 are each independently selected from a group consisting of hydrogen, hydroxyl, halogen, —CN, —OCF3, —CF3 and C1-C3 alkyl;
- or R6 and R7 form C3-C8 cycloalkyl or C3-C8 heterocycloalkyl;
- R8 is optionally selected from a group consisting of C1-C8 alkyl, C3-C8 cycloalkyl, C3-C8 heterocycloalkyl, phenyl substituted with one or more R31;
- and heteroaryl substituted with one or more R31;
- R9, R10 are each independently selected from a group consisting of hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl and C3-C8 heterocycloalkyl, or R9 and R10 form a cyclic group having four to seven ring members together with the nitrogen atom to which they attach;
- the cyclic group contains or does not contain a second heteroatom selected from oxygen as a ring member;
- R11 is optionally selected from a group consisting of halogen, —CN, —OCF3, —CF3, C1-C4 alkyl acyl, C1-C4 alkyl amide, C1-C4 alkyl sulfonyl, C1-C4 alkyl sulfonamide, C1-C4 alkyl phosphoryl, C1-C4 alkoxyl and C1-C4 alkyl ester;
- R31 is optionally selected from a group consisting of hydrogen, C1-C8 alkyl, C3-C8 cycloalkyl, halogenated C1-C8 alkyl, halogen, —CN, —CF3, —OCF3, C1-C6 alkyl sulfonyl, —SO2NR9R10, —P(O)R9R10, —OR9, —C(O)OR9, —C(O)R9, —C(O)NR9R10, —NR9R10, —NR9SO2R10 and —NR9C(O)R10;
- m is selected from 0, 1, 2, 3 or 4.
Dependencies are inferred from the claim text.