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Development of Tetrahydroindazole‐Based Potent and Selective Sigma‐2 Receptor Ligands
Author(s) -
Iyamu Iredia D.,
Lv Wei,
Malik Neha,
Mishra Rama K.,
Schiltz Gary E.
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900203
Subject(s) - sigma receptor , sigma 1 receptor , chemistry , receptor , computational biology , stereochemistry , pharmacology , combinatorial chemistry , biology , biochemistry , agonist
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.