New Imidazopyridines with Phosphodiesterase 4 and 7 Inhibitory Activity and Their Efficacy in Animal Models of Inflammatory and Autoimmune Diseases
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F21%3A73608265" target="_blank" >RIV/61989592:15310/21:73608265 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0223523420308266" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0223523420308266</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejmech.2020.112854" target="_blank" >10.1016/j.ejmech.2020.112854</a>
Alternative languages
Result language
angličtina
Original language name
New Imidazopyridines with Phosphodiesterase 4 and 7 Inhibitory Activity and Their Efficacy in Animal Models of Inflammatory and Autoimmune Diseases
Original language description
Herein, we describe the rapid synthesis of a focused library of trisubstituted imidazo[4,5 b]pyridines and imidazo[4,5-c]pyridines from 2,4-dichloro-3-nitropyridine using the combination of solution-phase/solid-phase chemistry as new potential anti-inflammatory agents in the treatment of autoimmune diseases. Structure-activity relationship studies, followed by the structure optimization, provided hit compounds (17 and 28) which inhibited phosphodiesterase 4 (PDE4) with IC50 values comparable to rolipram and displayed different inhibitory potency against phosphodiesterase 7 (PDE7). Among them, compound 17 showed a beneficial effect in all the studied animal models of inflammatory and autoimmune diseases (concanavalin A-induced hepatitis, lipopolysaccharide-induced endotoxemia, collagen induced arthritis, and MOG35-55-induced encephalomyelitis). In addition, compound 17 showed a favorable pharmacokinetic profile after intraperitoneal administration; it was characterized by a fast absorption from the peritoneal cavity and a relatively long terminal half-life in rats. It was found to penetrate brain barrier in mice. The performed experiments sheds light on the impact of PDE7A inhibition for the efficacy of PDE4 inhibitors in these disease conditions.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10401 - Organic chemistry
Result continuities
Project
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Continuities
N - Vyzkumna aktivita podporovana z neverejnych zdroju
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN
0223-5234
e-ISSN
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Volume of the periodical
209
Issue of the periodical within the volume
JAN
Country of publishing house
FR - FRANCE
Number of pages
18
Pages from-to
"112854-1"-"112854-18"
UT code for WoS article
000600418500005
EID of the result in the Scopus database
2-s2.0-85091913177