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ID: ALA1142540

Journal: Bioorg Med Chem

Title: Novel piperidinylpyrimidine derivatives as inhibitors of HIV-1 LTR activation.

Authors: Fujiwara N, Nakajima T, Ueda Y, Fujita H, Kawakami H.

Abstract: Piperidinylpyrimidine derivatives, previously prepared as inhibitors of TNF-alpha production, were evaluated for their inhibitory activity against HIV-1 LTR activation. Some of these derivatives inhibited activation of HIV-1 LTR-directed CAT gene expression induced by PMA in Jurkat cells. In this report, we describe SAR in this series of compounds and show that the 3,4-methylenedioxybenzoyl (piperonyloyl) group on the nitrogen of piperidine and lipophilic substitution at the C(6)-position of pyrimidine are important for this inhibitory activity. Some of the synthesized compounds also inhibited HIV-1 LTR transactivation induced by viral protein Tat. These results suggest that piperidinylpyrimidines are useful as potent AIDS therapeutics that directly inhibit HIV-1 LTR activation and indirectly suppress TNF-alpha production.

CiteXplore: 18926711

DOI: 10.1016/j.bmc.2008.09.059