Synthesis and biological activity of conformationally restricted indole-based inhibitors of neurotropic alphavirus replication: Generation of a three-...
Basic Information
ID: ALA4811294
Journal: Bioorg Med Chem Lett
Title: Synthesis and biological activity of conformationally restricted indole-based inhibitors of neurotropic alphavirus replication: Generation of a three-dimensional pharmacophore.
Authors: Barraza SJ, Sindac JA, Dobry CJ, Delekta PC, Lee PH, Miller DJ, Larsen SD.
Abstract: We have previously reported the development of indole-based CNS-active antivirals for the treatment of neurotropic alphavirus infection, but further optimization is impeded by a lack of knowledge of the molecular target and binding site. Herein we describe the design, synthesis and evaluation of a series of conformationally restricted analogues with the dual objectives of improving potency/selectivity and identifying the most bioactive conformation. Although this campaign was only modestly successful at improving potency, the sharply defined SAR of the rigid analogs enabled the definition of a three-dimensional pharmacophore, which we believe will be of value in further analog design and virtual screening for alternative antiviral leads.
CiteXplore: 34098081
DOI: 10.1016/j.bmcl.2021.128171
Patent ID: ┄