New nordihydroguaiaretic acid derivatives as anti-HIV agents.
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.
Hwu
Jih Ru
JR
Department of Chemistry, National Tsing Hua University, 101, Section 2, Kuang-fu Road, Hsinchu 30013, Taiwan, ROC. jrhwu@mx.nthu.edu.tw
Hsu
Ming-Hua
MH
Huang
Ru Chih C
RC
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D019556:COS Cells; D049109:Cell Proliferation; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003587:Cytomegalovirus / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009637:Masoprocol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology*; D010957:Plasmids; D015533:Transcriptional Activation / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
D019380:Anti-HIV Agents; D004279:DNA, Viral; D010880:Piperidines; C529308:meso-2,3-dimethyl-1,4-bis(3,4-(2-(piperdino)ethoxyphenyl))butane tetrakishydrochloride; D054322:tat Gene Products, Human Immunodeficiency Virus; D009637:Masoprocol; D000469:Alkaline Phosphatase