@article{1302b20e26e4478297eb3a758b8de78b,
title = "From dopamine 4 to sigma 1: Synthesis, SAR and biological characterization of a piperidine scaffold of σ1 modulators",
abstract = "The sigma 1 receptor is a multifunctional receptor with wide distribution in the nervous system and its function has been implicated with a number of neurological disorders including dementia and Alzheimer's disease (AD) and other neurodegenerative disorders. In addition, modulators of σ1 have been advanced into clinical trials for the treatment of pain. Starting from our previously disclosed piperidine scaffold, we have identified a class of potent sigma 1 modulators. This work highlights the key SAR components that lead to the divergence in D4 and σ1 activity. In addition, we further profile lead compounds in a panel of off-target receptors, in vitro and in vivo pharmacokinetic studies. This has culminated in the discovery of multiple σ1 receptor modulators with properties that will allow for study in animal models.",
keywords = "Dopamine 4 receptor, Modulators, SAR, Selectivity, Sigma 1 receptor",
author = "Tolentino, {Kirsten T.} and Viktoriya Mashinson and Sharma, {Manish K.} and Chhonker, {Yashpal S.} and Murry, {Daryl J.} and Hopkins, {Corey R.}",
note = "Funding Information: This work was generously supported by a grant from the US National Institutes of Health ( NINDS: R01NS119266 ) to C.R.H. The authors would like to thank Q2 Solutions (Indianapolis, IN USA) and Pharmaron, Inc. (Louisville, KY) for the in vitro and in vivo DMPK experiments. Funding Information: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Corey R. Hopkins reports financial support was provided by National Institute of Neurological Disorders and Stroke. Corey R. Hopkins reports a relationship with National Institute of Neurological Disorders and Stroke that includes: funding grants.This work was generously supported by a grant from the US National Institutes of Health (NINDS: R01NS119266) to C.R.H. The authors would like to thank Q2 Solutions (Indianapolis, IN USA) and Pharmaron, Inc. (Louisville, KY) for the in vitro and in vivo DMPK experiments. Publisher Copyright: {\textcopyright} 2022 Elsevier Masson SAS",
year = "2022",
month = dec,
day = "15",
doi = "10.1016/j.ejmech.2022.114840",
language = "English (US)",
volume = "244",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",
}