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

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.

SUBMITTER: Zhang X

PROVIDER: S-EPMC7549109 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Zhang Xuejun X Sheng Xijun X Shen Jie J Zhang Shoubo S Sun Wenjie W Shen Chunli C Li Yi Y Wang Jun J Lv Huqiang H Cui Minghui M Zhu Yuchuan Y Huang Lei L Hao Dongling D Qi Zhibo Z Sun Guanglong G Mao Weifeng W Pan Yan Y Shen Liang L Li Xin X Hu Guoping G Gong Zhen Z Han Shuhua S Li Jian J Chen Shuhui S Tu Ronghua R Wang Xuehai X Wu Chengde C

ACS medicinal chemistry letters 20191211 10

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. ...[more]

PMID: 33062165

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