Discovery of imidazopyridine derivatives as highly potent respiratory syncytial virus fusion inhibitors.
A series of imidazolepyridine derivatives were designed and synthesized according to the established docking studies. The imidazopyridine derivatives were found to have good potency and physical-chemical properties. Several highly potent compounds such as 8ji, 8jl, and 8jm were identified with single nanomolar activities. The most potent compound 8jm showed an IC50 of 3 nM, lower microsome clearance and no CYP inhibition. The profile of 8jm appeared to be superior to BMS433771, and supported further optimization.
Medicinal Chemistry, Molecular Design and Chemical Biology, and Infectious Diseases, Pharmaceutical Research and Early Development, Roche Innovation Center Shanghai , Building 5, Lane 720, Cai Lun Road, Shanghai 201203, China.
Song
S
Feng
Medicinal Chemistry, Molecular Design and Chemical Biology, and Infectious Diseases, Pharmaceutical Research and Early Development, Roche Innovation Center Shanghai , Building 5, Lane 720, Cai Lun Road, Shanghai 201203, China.
Di
D
Hong
Medicinal Chemistry, Molecular Design and Chemical Biology, and Infectious Diseases, Pharmaceutical Research and Early Development, Roche Innovation Center Shanghai , Building 5, Lane 720, Cai Lun Road, Shanghai 201203, China.
Baoxia
B
Wang
Medicinal Chemistry, Molecular Design and Chemical Biology, and Infectious Diseases, Pharmaceutical Research and Early Development, Roche Innovation Center Shanghai , Building 5, Lane 720, Cai Lun Road, Shanghai 201203, China.
Xiufang
X
Zheng
Medicinal Chemistry, Molecular Design and Chemical Biology, and Infectious Diseases, Pharmaceutical Research and Early Development, Roche Innovation Center Shanghai , Building 5, Lane 720, Cai Lun Road, Shanghai 201203, China.
Kun
K
Miao
Medicinal Chemistry, Molecular Design and Chemical Biology, and Infectious Diseases, Pharmaceutical Research and Early Development, Roche Innovation Center Shanghai , Building 5, Lane 720, Cai Lun Road, Shanghai 201203, China.
Lisha
L
Wang
Medicinal Chemistry, Molecular Design and Chemical Biology, and Infectious Diseases, Pharmaceutical Research and Early Development, Roche Innovation Center Shanghai , Building 5, Lane 720, Cai Lun Road, Shanghai 201203, China.
Hongying
H
Yun
Medicinal Chemistry, Molecular Design and Chemical Biology, and Infectious Diseases, Pharmaceutical Research and Early Development, Roche Innovation Center Shanghai , Building 5, Lane 720, Cai Lun Road, Shanghai 201203, China.
Lu
L
Gao
Medicinal Chemistry, Molecular Design and Chemical Biology, and Infectious Diseases, Pharmaceutical Research and Early Development, Roche Innovation Center Shanghai , Building 5, Lane 720, Cai Lun Road, Shanghai 201203, China.
Shuhai
S
Zhao
Medicinal Chemistry, Molecular Design and Chemical Biology, and Infectious Diseases, Pharmaceutical Research and Early Development, Roche Innovation Center Shanghai , Building 5, Lane 720, Cai Lun Road, Shanghai 201203, China.
Hong C
HC
Shen
Respiratory syncytial virus (RSV); antiviral; fusion inhibitors; heterocycle; imidazopyridine; virus