Johns Hopkins University

Evangelos Moudrianakis

Ru Chih C Huang

Jih Ru Hwu

Ming-Hua Hsu

Apostolos Gittis

Julie A Dohm

Reaction of nordihydroguaiaretic acid with various alkyl chlorides, 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 (Scheme 1 and Scheme 2). Among these derivatives, the nitrogen-containing compounds were converted to the corresponding hydrochloride salts. Having good solubility, these NDGA derivatives were found to be stable in aqueous solution. These new compounds exerted potent activities against HIV Tat-regulated transactivation in cos-7 cells. The most active transcription inhibitor compound of this series 5b (PN, Tetrapiperidino NDGA, meso-2,3-dimethyl-1,4-bis(3,4-[2-(piperidino)ethoxypehnyl])butane tetrakishydrochloride salt) has an ICof 0.88 &#x3bc;

Heterocyclic and carbonate derivatives of NDGA and their use as new anti-HIV and anti-cancer agents

Reaction of nordihydroguaiaretic acid with various alkyl chlorides, 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 (Scheme 1 and Scheme 2). Among these derivatives, the nitrogen-containing compounds were converted to the corresponding hydrochloride salts. Having good solubility, these NDGA derivatives were found to be stable in aqueous solution. These new compounds exerted potent activities against HIV Tat-regulated transactivation in cos-7 cells. The most active transcription inhibitor compound of this series 5b (PN, Tetrapiperidino NDGA, meso-2,3-dimethyl-1,4-bis(3,4-[2-(piperidino)ethoxyphenyl])butane tetrakishydrochloride salt) has an ICof 0.88 &#x3bc;

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Baltimore, MD, United States of America

Evangelos Moudrianakis