909187-69-5Relevant articles and documents
A hit deconstruction approach for the discovery of fetal hemoglobin inducers
Benowitz, Andrew B.,Eberl, H. Christian,Erickson-Miller, Connie L.,Gilmartin, Aidan G.,Gore, Elizabeth R.,Montoute, Monica N.,Wu, Zining
supporting information, p. 3676 - 3680 (2018/10/31)
Beta-hemoglobinopathies such as sickle cell disease represent a major global unmet medical need. De-repression of fetal hemoglobin in erythrocytes is a clinically validated approach for the management of sickle cell disease, but the only FDA-approved medicine for this purpose has limitations to its use. We conducted a phenotypic screen in human erythroid progenitor cells to identify molecules with the ability to de-repress fetal hemoglobin, which resulted in the identification of the benzoxaborole-containing hit compound 1. This compound was found to have modest cellular potency and lead-like pharmacokinetics, but no identifiable SAR to enable optimization. Systematic deconstruction of a closely related analog of 1 revealed the fragment-like carboxylic acid 12, which was then optimized to provide tetrazole 31, which had approximately 100-fold improved cellular potency compared to 1, high levels of oral exposure in rats, and excellent solubility.
Synthesis of new acylsulfamoyl benzoxaboroles as potent inhibitors of HCV NS3 protease
Li, Xianfeng,Zhang, Yong-Kang,Liu, Yang,Zhang, Suoming,Ding, Charles Z.,Zhou, Yasheen,Plattner, Jacob J.,Baker, Stephen J.,Liu, Liang,Bu, Wei,Kazmierski, Wieslaw M.,Wright, Lois L.,Smith, Gary K.,Jarvest, Richard L.,Duan, Maosheng,Ji, Jing-Jing,Cooper, Joel P.,Tallant, Matthew D.,Crosby, Renae M.,Creech, Katrina,Ni, Zhi-Jie,Zou, Wuxin,Wright, Jon
experimental part, p. 7493 - 7497 (2011/02/24)
HCV NS3/4A serine protease is essential for the replication of the HCV virus and has been a clinically validated target. A series of HCV NS3/4A protease inhibitors containing a novel acylsulfamoyl benzoxaborole moiety at the P1′ region was synthesized and
