3区 · 医学
Article
作者: Eastman, Kyle ; Yin, Zhiwei ; Kadow, John F. ; Fang, Hua ; Hanumegowda, Umesh ; Wang, Ying-Kai ; Roberts, Susan B. ; Zhu, Juliang ; Zhang, Zhongxing ; Zhuo, Xiaoliang ; Zvyaga, Tatyana ; Mosure, Kathy ; Lemm, Julie ; Parker, Dawn ; Haarhoff, Zuzana ; Rigat, Karen ; Wang, Tao ; Parcella, Kyle ; Tuttle, Maria ; Donoso, Maria ; Liu, Mengping ; Grant-Young, Katharine A. ; Yeung, Kap-Sun ; Meanwell, Nicholas A. ; Soars, Matthew G.
Iterative structure-activity analyses in a class of highly functionalized furo[2,3-b]pyridines led to the identification of the second generation pan-genotypic hepatitis C virus NS5B polymerase primer grip inhibitor BMT-052 (14), a potential clinical candidate. The key challenge of poor metabolic stability was overcome by strategic incorporation of deuterium at potential metabolic soft spots. The preclinical profile and status of BMT-052 (14) is described.