Benzoxazin-4-ones as novel, easily accessible inhibitors for rhomboid proteases

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F18%3A00490165" target="_blank" >RIV/61388963:_____/18:00490165 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.bmcl.2017.12.056" target="_blank" >http://dx.doi.org/10.1016/j.bmcl.2017.12.056</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmcl.2017.12.056" target="_blank" >10.1016/j.bmcl.2017.12.056</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Benzoxazin-4-ones as novel, easily accessible inhibitors for rhomboid proteases

Popis výsledku v původním jazyce

Rhomboid proteases form one of the most widespread intramembrane protease families. They have been implicated in variety of human diseases. The currently reported rhomboid inhibitors display some selectivity, but their construction involves multistep synthesis protocols. Here, we report benzoxazin-4-ones as novel inhibitors of rhomboid proteases with a covalent, but slow reversible inhibition mechanism. Benzoxazin-4-ones can be synthesized from anthranilic acid derivatives in a one-step synthesis, making them easily accessible. We demonstrate that an alkoxy substituent at the 2-position is crucial for potency and results in low micromolar inhibitors of rhomboid proteases. Hence, we expect that these compounds will allow rapid synthesis and optimization of inhibitors of rhomboids from different organisms.

Název v anglickém jazyce

Benzoxazin-4-ones as novel, easily accessible inhibitors for rhomboid proteases

Popis výsledku anglicky

Rhomboid proteases form one of the most widespread intramembrane protease families. They have been implicated in variety of human diseases. The currently reported rhomboid inhibitors display some selectivity, but their construction involves multistep synthesis protocols. Here, we report benzoxazin-4-ones as novel inhibitors of rhomboid proteases with a covalent, but slow reversible inhibition mechanism. Benzoxazin-4-ones can be synthesized from anthranilic acid derivatives in a one-step synthesis, making them easily accessible. We demonstrate that an alkoxy substituent at the 2-position is crucial for potency and results in low micromolar inhibitors of rhomboid proteases. Hence, we expect that these compounds will allow rapid synthesis and optimization of inhibitors of rhomboids from different organisms.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

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

Bioorganic and Medicinal Chemistry Letters

ISSN

0960-894X

e-ISSN

—

Svazek periodika

28

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

5

Strana od-do

1423-1427

Kód UT WoS článku

000429408300030

EID výsledku v databázi Scopus

2-s2.0-85042592943