2. Academic Validation
  3. Discovery and Evaluation of Pyrazolo[3,4- d]pyridazinone as a Potent and Orally Active Irreversible BTK Inhibitor

Discovery and Evaluation of Pyrazolo[3,4- d]pyridazinone as a Potent and Orally Active Irreversible BTK Inhibitor

  • ACS Med Chem Lett. 2019 Dec 11;11(10):1863-1868. doi: 10.1021/acsmedchemlett.9b00395.
Xuejun Zhang 1 2,  Xijun Sheng 1 2,  Jie Shen 1 2,  Shoubo Zhang 1 2,  Wenjie Sun 1 2,  Chunli Shen 3,  Yi Li 3,  Jun Wang 3,  Huqiang Lv 3,  Minghui Cui 3,  Yuchuan Zhu 3,  Lei Huang 3,  Dongling Hao 3,  Zhibo Qi 3,  Guanglong Sun 3,  Weifeng Mao 3,  Yan Pan 3,  Liang Shen 3,  Xin Li 3,  Guoping Hu 3,  Zhen Gong 3,  Shuhua Han 3,  Jian Li 3,  Shuhui Chen 3,  Ronghua Tu 1 2,  Xuehai Wang 2,  Chengde Wu 3
Affiliations

Affiliations

  • 1 Hubei Bio-Pharmaceutical Industrial Technological Institute Inc., No. 666 High Tech Avenue, East Lake High Tech Development Zone, Wuhan, Hubei 430075, China.
  • 2 Humanwell Healthcare (Group) Co., Ltd., No. 666 High Tech Avenue, East Lake High Tech Development Zone, Wuhan, Hubei 430075, China.
  • 3 Domestic Discovery Service Unit, WuXi AppTec, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
PMID: 33062165 DOI: 10.1021/acsmedchemlett.9b00395
Abstract

The identification and lead optimization of a series of pyrazolo[3,4-d]pyridazinone derivatives are described as a novel class of potent irreversible Btk inhibitors, resulting in the discovery of compound 8. Compound 8 exhibited high potency against Btk kinase and acceptable PK profile. Furthermore, compound 8 demonstrated significant in vivo efficacy in a mouse-collagen-induced arthritis (CIA) model.

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