2019年
Bis-Heteroaryl Pyrazoles: Identification of Orally Bioavailable Inhibitors of Activin Receptor-Like Kinase-2 (R206H).
Chemical & pharmaceutical bulletin
- 巻
- 67
- 号
- 3
- 開始ページ
- 224
- 終了ページ
- 235
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1248/cpb.c18-00598
- 出版者・発行元
- PHARMACEUTICAL SOC JAPAN
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.
- リンク情報
- ID情報
-
- DOI : 10.1248/cpb.c18-00598
- ISSN : 0009-2363
- PubMed ID : 30828000
- Web of Science ID : WOS:000460366300010