2. Academic Validation
  3. Design and synthesis of novel 6-aryl substituted 4-anilinequinazoline derivatives as potential PI3Kδ inhibitors

Design and synthesis of novel 6-aryl substituted 4-anilinequinazoline derivatives as potential PI3Kδ inhibitors

  • Bioorg Med Chem Lett. 2017 May 1;27(9):1972-1977. doi: 10.1016/j.bmcl.2017.03.020.
Minhang Xin 1,  Yuan-Yuan Hei 1,  Hao Zhang 1,  Ying Shen 1,  San-Qi Zhang 2
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No 76, Yanta West Road, Xi'an 710061, PR China.
  • 2 Department of Medicinal Chemistry, School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No 76, Yanta West Road, Xi'an 710061, PR China. Electronic address: sqzhang@xjtu.edu.cn.
PMID: 28325601 DOI: 10.1016/j.bmcl.2017.03.020
Abstract

In this study, a series of new 6-aryl substituted 4-anilinequinazolines was designed and synthesized as PI3Kδ inhibitors based on our reported chemical structures. The preliminary structure-activity relationship (SAR) was established, and compounds 13h and 13k displayed most potent PI3Kδ inhibitory activities with the IC50 values of 9.3nM and 9.7nM, respectively. Compound 13h demonstrated similar anti-proliferative profiles to idelalisib against three human B cell lines. Three key hydrogen bonding interactions were found in the docking of 13h with PI3Kδ Enzyme. These results suggest that compound 13h possessed nanomolar PI3Kδ inhibitory activity and distinctive chemical structure, deserving further structural optimization.

Keywords

6-Aryl substituted 4-anilinequinazolines; Drug design; PI3Kδ inhibitors; Structure-activity relationship.

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