Discovery of oxazolidinone-based heterocycles as subtype selective sigma-2 ligands

Benjamin E. Blass; Richie Rashmin Bhandare; Daniel J. Canney

doi:10.1007/s00044-022-02848-4

Discovery of oxazolidinone-based heterocycles as subtype selective sigma-2 ligands

Benjamin E. Blass
, Richie Rashmin Bhandare
, Daniel J. Canney

College of Pharmacy and Health Sciences

Temple University

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

The sigma-2 (σ₂) receptor, also known as the Transmembrane Protein 97 (TMEM97, and MAC30 (Meningioma-associated protein), has been linked to a number of conditions are disease states such as schizophrenia, cancer, Alzheimer’s disease, traumatic brain injury, and neuropathic pain. As part or our on-going effort identify novel σ₂ ligands, we have identified a series of novel, functionalized oxazolidin-2-one sigma-2 ligands (4). Our lead compound (4h) demonstrated high affinity (K_i = 36 nM) and excellent σ₁/σ₂ selectivity (79-fold). Evaluation of its affinity at key CNS targets via the Psychoactive Drug Screening Program (PDSP) also indicated a high degree of selectivity for σ₂ over other receptors. [Figure not available: see fulltext.].

Original language	English
Pages (from-to)	416-425
Number of pages	10
Journal	Medicinal Chemistry Research
Volume	31
Issue number	3
DOIs	https://doi.org/10.1007/s00044-022-02848-4
State	Published - Mar 2022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Oxazolidin-2-one
Sigma receptor
Sigma-1
Sigma-2

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10.1007/s00044-022-02848-4

Cite this

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title = "Discovery of oxazolidinone-based heterocycles as subtype selective sigma-2 ligands",

abstract = "The sigma-2 (σ2) receptor, also known as the Transmembrane Protein 97 (TMEM97, and MAC30 (Meningioma-associated protein), has been linked to a number of conditions are disease states such as schizophrenia, cancer, Alzheimer{\textquoteright}s disease, traumatic brain injury, and neuropathic pain. As part or our on-going effort identify novel σ2 ligands, we have identified a series of novel, functionalized oxazolidin-2-one sigma-2 ligands (4). Our lead compound (4h) demonstrated high affinity (Ki = 36 nM) and excellent σ1/σ2 selectivity (79-fold). Evaluation of its affinity at key CNS targets via the Psychoactive Drug Screening Program (PDSP) also indicated a high degree of selectivity for σ2 over other receptors. [Figure not available: see fulltext.].",

keywords = "Oxazolidin-2-one, Sigma receptor, Sigma-1, Sigma-2",

author = "Blass, \{Benjamin E.\} and Bhandare, \{Richie Rashmin\} and Canney, \{Daniel J.\}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.",

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doi = "10.1007/s00044-022-02848-4",

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TY - JOUR

T1 - Discovery of oxazolidinone-based heterocycles as subtype selective sigma-2 ligands

AU - Blass, Benjamin E.

AU - Bhandare, Richie Rashmin

AU - Canney, Daniel J.

PY - 2022/3

Y1 - 2022/3

N2 - The sigma-2 (σ2) receptor, also known as the Transmembrane Protein 97 (TMEM97, and MAC30 (Meningioma-associated protein), has been linked to a number of conditions are disease states such as schizophrenia, cancer, Alzheimer’s disease, traumatic brain injury, and neuropathic pain. As part or our on-going effort identify novel σ2 ligands, we have identified a series of novel, functionalized oxazolidin-2-one sigma-2 ligands (4). Our lead compound (4h) demonstrated high affinity (Ki = 36 nM) and excellent σ1/σ2 selectivity (79-fold). Evaluation of its affinity at key CNS targets via the Psychoactive Drug Screening Program (PDSP) also indicated a high degree of selectivity for σ2 over other receptors. [Figure not available: see fulltext.].

AB - The sigma-2 (σ2) receptor, also known as the Transmembrane Protein 97 (TMEM97, and MAC30 (Meningioma-associated protein), has been linked to a number of conditions are disease states such as schizophrenia, cancer, Alzheimer’s disease, traumatic brain injury, and neuropathic pain. As part or our on-going effort identify novel σ2 ligands, we have identified a series of novel, functionalized oxazolidin-2-one sigma-2 ligands (4). Our lead compound (4h) demonstrated high affinity (Ki = 36 nM) and excellent σ1/σ2 selectivity (79-fold). Evaluation of its affinity at key CNS targets via the Psychoactive Drug Screening Program (PDSP) also indicated a high degree of selectivity for σ2 over other receptors. [Figure not available: see fulltext.].

KW - Oxazolidin-2-one

KW - Sigma receptor

KW - Sigma-1

KW - Sigma-2

UR - https://www.scopus.com/pages/publications/85123465965

U2 - 10.1007/s00044-022-02848-4

DO - 10.1007/s00044-022-02848-4

M3 - Article

AN - SCOPUS:85123465965

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JO - Medicinal Chemistry Research

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IS - 3

ER -

Discovery of oxazolidinone-based heterocycles as subtype selective sigma-2 ligands

Abstract

UN SDGs

Keywords

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