2. Academic Validation
  3. Design and synthesis of boron-containing diphenylpyrimidines as potent BTK and JAK3 dual inhibitors

Design and synthesis of boron-containing diphenylpyrimidines as potent BTK and JAK3 dual inhibitors

  • Bioorg Med Chem. 2020 Jan 15;28(2):115236. doi: 10.1016/j.bmc.2019.115236.
Jing Ren 1,  Wei Shi 1,  Damin Zhao 1,  Qinglin Wang 1,  Xiayun Chang 1,  Xiangyi He 1,  Xiaojin Wang 1,  Yong Gao 1,  Peng Lu 1,  Xiquan Zhang 1,  Hongjiang Xu 2,  Yinsheng Zhang 3
Affiliations

Affiliations

  • 1 Institute for Innovative Drug Discovery, Chia Tai Tianqing Pharmaceutical Group Co., Ltd, 1099 Fuying Road, Jiangning District, Nanjing, Jiangsu Province, China.
  • 2 Institute for Innovative Drug Discovery, Chia Tai Tianqing Pharmaceutical Group Co., Ltd, 1099 Fuying Road, Jiangning District, Nanjing, Jiangsu Province, China. Electronic address: xuhongjiang@cttq.com.
  • 3 Institute for Innovative Drug Discovery, Chia Tai Tianqing Pharmaceutical Group Co., Ltd, 1099 Fuying Road, Jiangning District, Nanjing, Jiangsu Province, China. Electronic address: zys@cttq.com.
PMID: 31843459 DOI: 10.1016/j.bmc.2019.115236
Abstract

Bruton's tyrosine kinase (Btk) and Janus kinase 3 (JAK3) are very promising targets for hematological malignancies and autoimmune diseases. In recent years, a few compounds have been approved as a marketed medicine, and several are undergoing clinical trials. By recombining the dominant backbone of known active compounds, constructing a foused library, and screening a broad panel of kinases, we found a class of compounds with dual activities of anti-BTK and anti-JAK3. Some of the compounds have shown 10-folds more active in the Enzyme and cell-based assays than a known active compound. Furthermore, liver microsome stability experiments show that these compounds have better stability than ibrutinib. These explorations offered new clues to discover benzoxaborole fragment and pyrimidine scaffold as more effective Btk and JAK3 dual inhibitors.

Keywords

Autoimmune diseases; BTK; Benzoxaborole; Dual inhibitor; Hematological; JAK3; Pyrimidine.

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