Discovery of Pyrazolopyrimidine Derivatives as Novel Dual Inhibitors of BTK and PI3Kδ

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• 作者：Brahmam Pujala ; Anil K. Agarwal ; Sandip Middya ; Monali Banerjee ; Arjun Surya ; Anjan K. Nayak ; Ashu Gupta ; Sweta Khare ; Rambabu Guguloth ; Nitin A. Randive ; Bharat U. Shinde ; Anamika Thakur ; Dhananjay I. Patel ; Mohd. Raja ; Michael J. Green ; Jennifer Alfaro ; Patricio Avila ; Felipe Pérez de Arce ; Ramona G. Almirez ; Stacy Kanno ; Sebastián Bernales ; David T. Hung ; Sarvajit Chakravarty ; Emma McCullagh ; Kevin P. Quinn ; Roopa Rai ; Son M. Pham
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：December 8, 2016
• 年：2016
• 卷：7
• 期：12
• 页码：1161-1166
• 全文大小：337K
• ISSN：1948-5875

文摘

The aberrant activation of B-cells has been implicated in several types of cancers and hematological disorders. BTK and PI3Kδ are kinases responsible for B-cell signal transduction, and inhibitors of these enzymes have demonstrated clinical benefit in certain types of lymphoma. Simultaneous inhibition of these pathways could result in more robust responses or overcome resistance as observed in single agent use. We report a series of novel compounds that have low nanomolar potency against both BTK and PI3Kδ as well as acceptable PK properties that could be useful in the development of treatments against B-cell related diseases.