- 著者
- Katsuhiko Sekimata Tomohiro Sato Naoki Sakai Hisami Watanabe Chiemi Mishima-Tsumagari Tomonori Taguri Takehisa Matsumoto Yoshifumi Fujii Noriko Handa Teruki Honma Akiko Tanaka Mikako Shirouzu Shigeyuki Yokoyama Kohei Miyazono Yoshinobu Hashizume Hiroo Koyama
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.67, no.3, pp.224-235, 2019-03-01 (Released:2019-03-01)
- 参考文献数
- 17
- 被引用文献数
- 11
Mutant activin receptor-like kinase-2 (ALK2) was reported to be closely associated with the pathogenesis of fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG), and therefore presents an attractive target for therapeutic intervention. Through in silico virtual screenings and structure–activity relationship studies assisted by X-ray crystallographic analyses, a novel series of bis-heteroaryl pyrazole was identified as potent inhibitors of ALK2 (R206H). Derived from in silico hit compound RK-59638 (6a), compound 18p was identified as a potent inhibitor of ALK2 (R206H) with good aqueous solubility, liver microsomal stability, and oral bioavailability.