Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F18%3A00489202" target="_blank" >RIV/67985823:_____/18:00489202 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1111/cbdd.13059" target="_blank" >http://dx.doi.org/10.1111/cbdd.13059</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/cbdd.13059" target="_blank" >10.1111/cbdd.13059</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes

Popis výsledku v původním jazyce

Muscarinic receptors are known to play important biological roles and are drug targets for several human diseases. In a pilot study, novel muscarinic antagonists were synthesized and used as chemical probes to obtain additional information of the muscarinic pharmacophore. The design of these ligands made use of current orthosteric and allosteric models of drug-receptor interactions together with chemical motifs known to achieve muscarinic receptor selectivity. This approach has led to the discovery of several non-competitive muscarinic ligands that strongly bind at a secondary receptor site. These compounds were found to be non-competitive antagonists that completely abolished carbachol activation in functional assays. Several of these compounds antagonized functional response to carbachol with great potency at M-1 and M-4 than at the rest of receptor subtypes.

Název v anglickém jazyce

Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes

Popis výsledku anglicky

Muscarinic receptors are known to play important biological roles and are drug targets for several human diseases. In a pilot study, novel muscarinic antagonists were synthesized and used as chemical probes to obtain additional information of the muscarinic pharmacophore. The design of these ligands made use of current orthosteric and allosteric models of drug-receptor interactions together with chemical motifs known to achieve muscarinic receptor selectivity. This approach has led to the discovery of several non-competitive muscarinic ligands that strongly bind at a secondary receptor site. These compounds were found to be non-competitive antagonists that completely abolished carbachol activation in functional assays. Several of these compounds antagonized functional response to carbachol with great potency at M-1 and M-4 than at the rest of receptor subtypes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Chemical Biology & Drug Design

ISSN

1747-0277

e-ISSN

—

Svazek periodika

91

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

93-104

Kód UT WoS článku

000418803800008

EID výsledku v databázi Scopus

2-s2.0-85024390786