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Design, synthesis and biological evaluation of spiropyrazolopyridone derivatives as potent dengue virus inhibitors.
- Source :
-
Bioorganic & Medicinal Chemistry Letters . Jun2020, Vol. 30 Issue 11, pN.PAG-N.PAG. 1p. - Publication Year :
- 2020
-
Abstract
- The effective treatment for dengue virus infection continues to be a challenge. We herein reported our continued SAR exploration on the spiropyrazolopyridone scaffold. Introducing different substituents at the 3́- or 5́-site of the pyrazolopyridone core or moving the benzyl chain to the adjacent nitrogen led to a significant loss of potency on DENV-2. While a narrow range of substitutions were tolerated at the para -position of the phenyl ring, di-substitution on the phenyl ring is beneficial for DENV-2 potency and has variable influences on DENV-3 potency depending on the exact compound. Among these molecules, compounds 22 (JMX0376) with 4-chloro-3-fluorobenzyl and 24 (JMX0395) with 2,4-bis(trifluoromethyl)benzyl showed the most potent and broadest inhibitory activities against DENV-1 to −3 with nanomolar to low micromolar EC 50 values. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0960894X
- Volume :
- 30
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Publication Type :
- Academic Journal
- Accession number :
- 142769477
- Full Text :
- https://doi.org/10.1016/j.bmcl.2020.127162