Cyclopropyl- and methyl-containing inhibitors of neuronal nitric oxide synthase

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F13%3A10190173" target="_blank" >RIV/00216208:11110/13:10190173 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.bmc.2012.12.019" target="_blank" >http://dx.doi.org/10.1016/j.bmc.2012.12.019</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmc.2012.12.019" target="_blank" >10.1016/j.bmc.2012.12.019</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Cyclopropyl- and methyl-containing inhibitors of neuronal nitric oxide synthase

Popis výsledku v původním jazyce

Inhibitors of neuronal nitric oxide synthase have been proposed as therapeutics for the treatment of different types of neurological disorders. On the basis of a cis-3,4-pyrrolidine scaffold, a series of trans-cyclopropyl- and methyl-containing nNOS inhibitors have been synthesized. The insertion of a rigid electron-withdrawing cyclopropyl ring decreases the basicity of the adjacent amino group, which resulted in decreased inhibitory activity of these inhibitors compared to the parent compound. Nonetheless, three of them exhibited double-digit nanomolar inhibition with high nNOS selectivity on the basis of in vitro enzyme assays. Crystal structures of nNOS and eNOS with these inhibitors bound provide a basis for detailed structure-activity relationship(SAR) studies. The conclusions from these studies will be used as a guide in the future development of selective NOS inhibitors.

Název v anglickém jazyce

Cyclopropyl- and methyl-containing inhibitors of neuronal nitric oxide synthase

Popis výsledku anglicky

Inhibitors of neuronal nitric oxide synthase have been proposed as therapeutics for the treatment of different types of neurological disorders. On the basis of a cis-3,4-pyrrolidine scaffold, a series of trans-cyclopropyl- and methyl-containing nNOS inhibitors have been synthesized. The insertion of a rigid electron-withdrawing cyclopropyl ring decreases the basicity of the adjacent amino group, which resulted in decreased inhibitory activity of these inhibitors compared to the parent compound. Nonetheless, three of them exhibited double-digit nanomolar inhibition with high nNOS selectivity on the basis of in vitro enzyme assays. Crystal structures of nNOS and eNOS with these inhibitors bound provide a basis for detailed structure-activity relationship(SAR) studies. The conclusions from these studies will be used as a guide in the future development of selective NOS inhibitors.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

—

Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2013

Kód důvěrnosti údajů

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

Název periodika

Bioorganic and Medicinal Chemistry

ISSN

0968-0896

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

1333-1343

Kód UT WoS článku

000314689200033

EID výsledku v databázi Scopus

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