NOVEL MODIFIED CURCUMINS AND THEIR USES

摘要

This invention provides a compound having the structure;;wherein α, β, A, B, and R1-R4 are defined herein. This invention also provides pharmaceutical compositions comprising the above compounds, a method of accelerating the healing of a wound, a method of inhibiting the activity and/or levels of a matrix metalloproteinase (MMP), a method of inhibiting the production of a cytokine in a population of cells, a method of inhibiting the production of a growth factor in a population of cells, and a method of inhibiting NFκ-B activation in a population of cells.

主权项

1. A compound having the structure,wherein
bond α and β are each, independently, present or absent; A is an aromatic or heteroaromatic ring; B is an aromatic or heteroaromatic ring; R1 is pyridine, imidazol, oxazole, thiazole, pyridine, pyridazine, pyrazine, pyrimidine, morpholine, C1-10 alkyl, C2-10 alkenyl, C1-10 alkynyl, aryl, heteroaryl, heterocyclyl, or wherein R13, R14, R15, R16, and R17 are each independently, H, halogen, —OCZ3, —CZ3, —OCH2CH(OH)CH2OH, —OCH(CH2OH)2, —NO2, OCH3, —CN, —NR18R19, —SR18, —CO2R18, —OR20, —COR20, —CSR20, —NHCOR18, —SOR18, —POR17, —C(═S)R18, —C(═NF)R18, C(═NR18)R18, —C(═N)R18, —POR18, —P(═O)(OR18)(OR19), —P(OR18)(OR18), —C(═S)R18, —NHR18R19+, —C(═O)-heterocyclyl, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, heteroaryl, or heterocyclyl,
wherein Z is halogen, andR18, R19, and R20 are each, independently, H, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, heteroaryl, or heterocyclyl; R2 is H, —CH3, —OR21, —CO2R21, —CF3, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, aryl, heteroaryl, or heterocyclyl,
wherein R21 is, H, CF3, —CH3, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, or —C(═O)-heterocyclyl; and R3 and R4 are each independently, halogen, —NO2, —NR22R23, —NHR22R23+, —SR22, —SO2R22, —SO3R22, —OR22, —CO2R22, —CF3, —POR22, —P(═O)(OR22)(OR23), or —P(OR22)(OR23),
wherein R22 and R23 are each, H, —CF3, —CH3, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, aryl, heteroaryl, heterocyclyl, or —C(═O)-heterocyclyl, and wherein each occurrence in the compound of alkyl, alkenyl, or alkynyl is branched or unbranched, unsubstituted or substituted; and when α and β are present, A is phenyl with R3 at the para position, B is phenyl with R4 at the para position, R2 is H, R3 is —OH or —N(CH3)2, and R4 is —OH or —N(CH3)2, then R1 is other than unsubstituted phenyl,or a salt thereof.