Citation: Jia-Lin Guo, Yun-Yong Liu, Ya-Zhong Pei. Synthesis and biological evaluation of 3-(piperidin-4-yl)isoxazolo[4,5-d]pyrimidine derivatives as novel PI3Kδ inhibitors[J]. Chinese Chemical Letters, ;2015, 26(10): 1283-1288. doi: 10.1016/j.cclet.2015.05.041 shu

Synthesis and biological evaluation of 3-(piperidin-4-yl)isoxazolo[4,5-d]pyrimidine derivatives as novel PI3Kδ inhibitors

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1 The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China;
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2 Nanjing Gator MediTech Company, Ltd., Nanjing 211300, China

Corresponding author: Ya-Zhong Pei,
Received Date: 1 February 2015
Available Online: 20 May 2015
Fund Project: This work was supported by the National Natural Science Foundation of China (No. 81172914) (No. 81172914)

An efficient synthesis of novel 3-(piperidin-4-yl)isoxazolo[4, 5-d]pyrimidine scaffold has been designed and deveopled. A series of 5-phenylurea derivatives was synthesized using this method. Their cytotoxic activities against breast cancer cell line BT-474 were evaluated by CCK-8 assay. Most of them showed potent anti-proliferative activities, of which compound 20 and 21 exhibited IC₅₀s of 1.565 μmol/L and 1.311 μmol/L, respectively. Furthermore, compound 20 and 21 also showed potent inhibitory activities against PI3Kδ with IC₅₀s of 0.286 μmol/L and 0.452 μmol/L, respectively. These results indicate that these 3-(piperidin-4-yl)isoxazolo[4, 5-d] pyrimidine derivatives are novel antitumor agents through the inhibition of PI3Kδ.
- Synthesis,
- Isoxazolopyrimidine,
- PI3Kδ inhibitors,
- Cytotoxicity
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