Masanori Baba

HEPT: From an investigation of lithiation of nucleosides towards a rational design of non-nucleoside reverse transcriptase inhibitors of HIV-1

Publisher Summary This chapter presents the alpha lithiation reaction at the base moiety of purine, imidazole, and pyrimidine nucleosides for the synthesis of their analogs and an anti-HIV-1 (Human Immunodeficiency Virus Type 1) lead compound HEPT which resulted from the lithiation studies. Lithiation chemistry of aromatic compounds started with a halogenlithium exchange reaction reflecting the historical finding that an aryllithium can be generated by treatment of an aryl halide with alkyllithium. The anti-HIV-1 activity of HEPT is only marginal when compared with that of AZT and ddC, but HEPT was found to be much less toxic than these nucleoside derivatives. In terms of activity (EC 50 ) and cytotoxicity (CC 50 ), HEPT is almost comparable to ddA. A salient feature of this compound lies in its highly specific antiviral property. When the activity of HEPT was examined by changing the virus as well as the cells, HEPT was uniformly active to various strains of HIV-1, but not to other retroviruses, including HIV-2, and other DNA viruses.