Alpha-arylmethoxyacrylate derivative, preparation method thereof, and pharmaceutical composition containing same

摘要

The present invention relates to an alpha-arylmethoxyacrylate derivative, a preparation method thereof and a pharmaceutical composition comprising the same, and the alpha-arylmethoxyacrylate derivative is inhibitory of HIF, which plays an important role in the regulation of genes associated with energy metabolism, vasomotion, angiogenesis and apoptosis and in the response of cells under hypoxic conditions, so that it can be used for preventing or treating of diseases such as cancer, arthritis, psoriasis, diabetic retinopathy and macular degeneration.

主权项

1. A method for treating pancreatic cancer, psoriasis, diabetic retinopathy, or macular degeneration in a subject in need thereof, comprising administering to the subject an alpha-arylmethoxyacrylate of the following formula 1, or a pharmaceutically acceptable salt, a hydrate, or a solvate thereof: wherein
R1 and R5 are each independently H, hydroxy, halogen, C1-6alkyl, or C1-6alkoxy; R2, R3 and R4 are each independently H, hydroxy, halogen, formyl, C1-6alkyl, C1-6alkoxy, C3-6 heteroaryl, or any one of formulae A to C: wherein n is an integer of 0 to 4; R11 is H, hydroxy, cyano, C1-4alkyl, C2-6alkenyl, C1-6alkoxy, C1-4alkoxyC1-4alkyl, C3-8cycloalkylC1-4alkyl, or C2-7heterocycloalkylC1-4alkyl, C1-4alkylamino, or diC1-4alkylamino; R12 and R13 are each independently H, halogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C3-8cycloalkylC1-4alkyl, C2-7heterocycloalkylC1-4alkyl, C6-12aryl, C6-12arylC1-4alkyl, C6-12aryloxyC1-4alkyl, or C3-6heteroarylC1-4alkyl, or combine together to form C2-7heterocycloalkyl; and R14 is H, hydroxy, C3-8cycloalkyl, C2-7heterocycloalkyl, C6-12aryl, C6-12 arylC1-4alkyl, C6-12aryloxy, C3-6heteroaryl, C1-4alkylamino, diC1-4alkylamino, or said alkyl, alkenyl and alkoxy each independently being optionally substituted with one or more substituents selected from the group consisting of hydroxy, halogen, nitro and cyano; said cycloalkyl, heterocycloalkyl, aryl and heteroaryl each independently being optionally substituted with one or more substituents selected from the group consisting of halogen, nitro, cyano, C1-4alkyl and C1-4alkoxy; and said heterocycloalkyl and heteroaryl each independently comprising at least one atom of N or O.