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Updated: Jul 16, 2025

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Published on: January 22, 2019
Discovery of novel pyrido[3,2-d]pyrimidine derivatives as selective and potent PI3Kδ inhibitors
Huanrong Bai1, Jiajia Sun1, Hao Lei1
1School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Abstract:
The δ isoform of class I PI3K (PI3Kδ) has been shown as a promising target for the treatment of hematologic malignancies and immune diseases. Herein, a series of pyrido[3,2-d]pyrimidine derivatives were designed, synthesized and evaluated for the preliminary bioactivity. Compared with idelalisib, compound S5 exhibited excellent enzyme activity against PI3Kδ (IC50 = 2.82 nM) and strong antiproliferation activity against SU-DHL-6 cells (IC50 = 0.035 μM). Besides, S5 inhibited the phosphorylation of Akt, which is downstream of PI3Kδ, in concentration-dependent manner. In view of the significant improvement in potency of PI3Kδ and selectivity over other PI3K isoforms, Compound S5 deserved further investigation as a promising PI3Kδ inhibitor.
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