Design, synthesis and structure-activity relationship study of piperazinone-containing thieno[3, 2-d]pyrimidine derivatives as new PI3Kδ inhibitors. Issue 20 (15th October 2020)

• Record Type: Journal Article
• Authors: Wang, Ning-Yu; Zuo, Wei-Qiong; Hu, Rong; Wang, Wan-Li; Zhu, Yong-Xia; Xu, Ying; Yu, Luo-Ting; Liu, Zhi-Hao
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 20(2020)
• Publication Date: 2020-10-15
• Subjects: PI3Kδ -- SAR -- Thieno[3, 2-d]pyrimidine -- Piperazinone -- Antiproliferative activity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127479
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Two classes of piperazinone-containing thieno[3, 2- d ]pyrimidines were designed and synthesized as new PI3Kδ inhibitors in this study. Detailed SAR study with respect to the piperazinone substituents at the 6-position of thieno[3, 2- d ]pyrimidine core demonstrated that piperazinone-containing thieno[3, 2- d ]pyrimidines would be more potent and selective for PI3Kδ than their piperazine counterparts, which led to the discovery of several potent PI3Kδ inhibitors with comparable or better antiproliferative activity against a panel of non-Hodgkin lymphoma (NHL) cell lines as compared with idelalisib. Our study will promote the development of new PI3Kδ inhibitors based on piperazinone-containing thieno[3, 2- d ]pyrimidine scaffold.