Discovery and Structural Optimization of 4-(Aminomethyl)benzamides as Potent Entry Inhibitors of Ebola and Marburg Virus Infections.
2020
The
recent Ebola epidemics in West Africa underscore the great
need for effective and practical therapies for future Ebola virus
outbreaks. We have discovered a new series of remarkably potent small
molecule inhibitors of Ebola virus entry. These 4-(aminomethyl)benzamide-based
inhibitors are also effective against Marburg virus. Synthetic routes
to these compounds allowed for the preparation of a wide variety of
structures, including a conformationally restrained subset of indolines
(compounds 41–50). Compounds 20, 23, 32, 33, and 35 are superior inhibitors of Ebola (Mayinga) and Marburg
(Angola) infectious viruses. Representative compounds (20, 32, and 35) have shown good metabolic
stability in plasma and liver microsomes (rat and human), and 32 did not inhibit CYP3A4 nor CYP2C9. These 4-(aminomethyl)benzamides
are suitable for further optimization as inhibitors of filovirus entry,
with the potential to be developed as therapeutic agents for the treatment
and control of Ebola virus infections.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
42
References
6
Citations
NaN
KQI