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Updated: Jun 28, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Novel piperidinylpyrimidine derivatives as inhibitors of HIV-1 LTR activation
Norio Fujiwara1, Takashi Nakajima, Yutaka Ueda
1Drug Research Division, Dainippon Sumitomo Pharma Co., Ltd, Enoki 33-94, Suita, Osaka 564-0053, Japan. norio-fujiwara@ds-pharma.co.jp
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.
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