Discovery and structure-based design of a new series of potent and selective PPARδ agonists utilizing a virtual screening method

Bioorg Med Chem Lett. 2022 Mar 1:59:128567. doi: 10.1016/j.bmcl.2022.128567. Epub 2022 Jan 19.

Abstract

Novel PPARδ agonists, 2-(1-piperidinyl)-1,3-benzothiazole derivatives were discovered by our proprietary docking-based virtual screening technique. Compound 1 as the initial hit was effectively modified to acquire PPARδ agonist activity, resulting in the discovery of compound 12 with high agonistic potency for PPARδ and selectivity over PPARα and PPARγ. Compound 12 also had good ADME profiles and showed in vivo efficacy as a lead.

Keywords: Docking simulation; Metabolic syndrome; Selective PPARδ agonist; Virtual screening.

MeSH terms

  • Benzothiazoles / chemical synthesis
  • Benzothiazoles / chemistry
  • Benzothiazoles / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Drug Evaluation, Preclinical
  • Humans
  • Molecular Structure
  • PPAR alpha / agonists
  • PPAR delta / agonists*
  • PPAR gamma / agonists
  • Structure-Activity Relationship

Substances

  • Benzothiazoles
  • PPAR alpha
  • PPAR delta
  • PPAR gamma