Wang, Beilei; Deng, Yuanxin; Chen, Yongfei; Yu, Kailin; Wang, Aoli; Liang, Qianmao; Wang, Wei; Chen, Cheng; Wu, Hong; Hu, Chen; Miao, Weili; Hur, Wooyoung; Wang, Wenchao; Hu, Zhenquan; Weisberg, Ellen L.; Wang, Jinhua; Ren, Tao; Wang, Yinsheng; Gray, Nathanael S.; Liu, Qingsong; Liu, Jing published the artcile< Structure-activity relationship investigation for benzonaphthyridinone derivatives as novel potent Bruton's tyrosine kinase (BTK) irreversible inhibitors>, Synthetic Route of 1223001-51-1, the main research area is benzo naphthyridinone derivative structure preparation Bruton’s tyrosine kinase cancer; B-Cell lymphoma; BTK; Irreversible inhibitor; Kinase inhibitor; Structure-activity relationship.
Through a structure-based drug design approach, a tricyclic benzonaphthyridinone pharmacophore was used as a starting point for carrying out detailed medicinal structure-activity relationhip (SAR) studies geared toward characterization of a panel of proposed BTK inhibitors, including 6 (QL-X-138), 7 (BMX-IN-1) and 8 (QL47). These studies led to the discovery of the novel potent irreversible BTK inhibitor, compound 18 (CHMFL-BTK-11). Kinetic anal. of compound 18 revealed an irreversible binding efficacy (kinact/Ki) of 0.01 μM-1s-1. Compound 18 potently inhibited BTK kinase Y223 auto-phosphorylation (EC50 < 100 nM), arrested cell cycle in G0/G1 phase, and induced apoptosis in Ramos, MOLM13 and Pfeiffer cells. We believe these features would make 18 a good pharmacol. tool for studying BTK-related pathologies. European Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Synthetic Route of 1223001-51-1.
Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem