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: