Neurosteroid-like Inhibitors of N-Methyl-D-aspartate Receptor: Substituted 2-Sulfates and 2-Hemisuccinates of Perhydrophenanthrene

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F16%3A00461780" target="_blank" >RIV/67985823:_____/16:00461780 - isvavai.cz</a>

Alternative codes found

RIV/61388963:_____/16:00461780

Result on the web

<a href="http://dx.doi.org/10.1021/acs.jmedchem.6b00079" target="_blank" >http://dx.doi.org/10.1021/acs.jmedchem.6b00079</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jmedchem.6b00079" target="_blank" >10.1021/acs.jmedchem.6b00079</a>

Result language

angličtina

Original language name

Neurosteroid-like Inhibitors of N-Methyl-D-aspartate Receptor: Substituted 2-Sulfates and 2-Hemisuccinates of Perhydrophenanthrene

Original language description

N-Methyl-n-aspartate receptors (NMDARs) display a critical role in various diseases of the central nervous system. The activity of NMDARs can be modulated by neurosteroids. Herein, we report a structure activity relationship study for perhydrophenanthrene analogues possessing a framework that mimics the steroidal ring system. This study comprises the design, synthesis, and assessment of the biological activity of a library of perhydrophenanthrene 2-sulfates and 2-hemisuccinates (1-10). Their ability to modulate NMDAR-induced currents was tested on recombinant GluN1/GluN2B receptors. Our results demonstrate that such structural optimization leads to compounds that are inhibitors of NMDARs. Notably, compound 9 (IC50 = 15.6 mu M) was assessed as a more potent inhibitor of NMDAR-induced currents than the known endogenous neurosteroid, pregnanolone sulfate (IC50 = 24.6 mu M).

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

ED - Physiology

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Medicinal Chemistry

ISSN

0022-2623

e-ISSN

—

Volume of the periodical

59

Issue of the periodical within the volume

10

Country of publishing house

US - UNITED STATES

Number of pages

16

Pages from-to

4724-4739

UT code for WoS article

000376840600024

EID of the result in the Scopus database

2-s2.0-84971656746