Compound having angiogenesis inhibitory activity, method for preparing same, and pharmaceutical composition comprising same

摘要

Disclosed are an anti-angiogenic compound, represented by Chemical Formula I, or a pharmaceutically acceptable salt thereof, a preparation method thereof, and a pharmaceutically acceptable composition including the same. Because the compound of Chemical Formula I potently suppresses the angiogenesis, the compound of Chemical Formula I is applicable to the prevention and treatment of diseases caused by aberrant activity of vascular endothelial growth factor, and available as an anti-angiogenic agent.

主权项

1. A compound of Chemical Formula I, or a pharmaceutically acceptable salt thereof: wherein, X1 and X2 are independently a halogen atom selected from the group consisting of F, Cl, Br, and I, or a hydrogen atom, Y is —NH—; —S—; or —O—, R1 is piperidinyl, piperazinyl, azabicyclo[2.2.2]octanyl, or phenyl, each independently having 1 to 5 substituents selected from the group consisting of benzyl, phenyloxy, 1-pyrimidinylethyl, pyridine methyl, C1-4 alkyl, C3-6 alkene, t-butoxycarboxyl, and malon-2-yl; 1-azabicyclo[2.2.2]oct-3-yl; piperidin-4-yl; piperidin-3-yl; or 1-(6-chloro-5-fluoropyrimidin-4-yl)ethyl piperidin-4-yl, wherein the C1-4 alkyl is substituted with 0 to 3 substituents selected from the group consisting of R3R4N—, hydroxyl, and a halogen atom, wherein R3 and R4 are each independently a C1-4 alkyl, wherein the benzyl, the phenyloxy, the pyrimidinylethyl and the pyridine methyl are independently substituted with 0 to 4 halogen atoms, R2 is C1-4 alkyl with 1 or 2 substituents selected from the group consisting of morpholinyl substituted with 0 to 3 benzyl groups having 0 to 3 halogen substituents, phenyl substituted with 0 to 3 halogen atoms, pyridinyl, pyrimidinyl, piperidinyl and piperazinyl; C5-10 alkyl; C1-4 alkyloxycarbonylamino; C1-4alkoxyC1-4alkyl; toluenesulfonamino; phenyl with 0 to 3 substituents selected from the group consisting of C1-4 alkyl, halogen, nitro and phenoxy; (3,4-dimethoxy)phenyl; pyridinyl with 0 to 3 substituents selected from the group consisting of C1-4 alkyloxycarbonyl and C1-4 alkyl; azepan-2-onyl; 1,3,4-triazolyl; pyrimidinyl substituted with 0 to 3 C1-4 alkyl groups; pyrrolidinyl; thiazolyl substituted with 0 to 2 C1-4 alkyl groups; 2,3-dihydroxy indole substituted with 0 to 3 C1-4 alkyl groups; wherein R5 and R6 are each independently C1-4alkyl, C1-4alkyl sulfanyl or thiol, and R7 and R8 are each independently C1-4 alkyloxycarbonyl, phenyl or benzyl.