Development of Tetrahydroindazole-Based Potent and Selective Sigma-2 Receptor Ligands

Iredia D. Iyamu, Wei Lv, Neha Malik, Rama K. Mishra, Gary E. Schiltz*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

The sigma-2 receptor has been shown to play important roles in a number of important diseases, including central nervous system (CNS) disorders and cancer. However, mechanisms by which sigma-2 contributes to these diseases remain unclear. The development of new sigma-2 ligands that can be used to probe the function of this protein and potentially as drug discovery leads is therefore of great importance. Herein we report the development of a series of tetrahydroindazole compounds that are highly potent and selective for sigma-2. Structure–activity relationship data were used to generate a pharmacophore model that summarizes the common features present in the potent ligands. Assays for solubility and microsomal stability showed that several members of this compound series possess promising characteristics for further development of useful chemical probes or drug discovery leads.

Original languageEnglish (US)
Pages (from-to)1248-1256
Number of pages9
JournalChemMedChem
Volume14
Issue number13
DOIs
StatePublished - Jul 3 2019

Keywords

  • pharmacophores
  • sigma-1
  • sigma-2
  • solubility
  • tetrahydroindazoles

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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