Phenylpyridine-2-ylguanidines and rigid mimetics as novel inhibitors of TNFα overproduction: Beneficial action in models of neuropathic pain and of acute lung inflammation.
Eur J Med Chem
; 147: 163-182, 2018 Mar 10.
Article
en En
| MEDLINE
| ID: mdl-29432948
ABSTRACT
4-phenylpyridin-2-yl-guanidine (5b) a new inhibitor of the overproduction of pro-inflammatory cytokines (TNFα and Il1ß) was identified from a high-throughput screening of a chemical library on human peripheral blood mononuclear cells (PBMCs) after LPS stimulation. Derivatives, homologues and rigid mimetics of 5b were designed and synthesized, and their cytotoxicity and ability to inhibit TNFα overproduction were evaluated. Among them, compound 5b and its mimetic 12 (2-aminodihydroquinazoline) showed similar inhibitory activities, and were evaluated in vivo in models of lung inflammation and neuropathic pain in mice. In particular, compound 12 proved to be active (5â¯mg/kg, ip) in both models.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Antiinflamatorios no Esteroideos
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Factor de Necrosis Tumoral alfa
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Lesión Pulmonar Aguda
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Guanidinas
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Inflamación
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Modelos Biológicos
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Neuralgia
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
Eur J Med Chem
Año:
2018
Tipo del documento:
Article
País de afiliación:
Francia