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New nordihydroguaiaretic acid derivatives as anti-HIV agents
Jih Ru Hwu1, Ming-Hua Hsu, Ru Chih C Huang
1Department of Chemistry, National Tsing Hua University, 101, Section 2, Kuang-fu Road, Hsinchu 30013, Taiwan, ROC. jrhwu@mx.nthu.edu.tw
Abstract:
Reaction of nordihydroguaiaretic acid with various alkyl chloride, 1-piperidinecarbonyl chloride, methyl chloroformate, or 1,1'-carbonyldiimidazole under alkaline conditions produced the corresponding phenol ethers, carbamates and carbonates, respectively, in 67-83% yields. Among these derivatives, the nitrogen-containing compounds were converted to the corresponding hydrochloride salts. Having good solubility, these NDGA derivatives were found stable in aqueous solution. These new compounds exerted appealing activity against HIV Tat-regulated transactivation in human epithelial cells. The most potent compound meso-2,3-dimethyl-1,4-bis(3,4-[2-(piperdino)ethoxyphenyl])butane tetrakishydrochloride salt (5b) showed IC(50) value of 0.88 microM.
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