1,3-diphenylpropan-1-ones as allosteric modulators of α7 nACh receptors with analgesic and antioxidant properties.
Future Med Chem
; 8(7): 731-49, 2016 05.
Article
en En
| MEDLINE
| ID: mdl-27161515
ABSTRACT
UNLABELLED Nicotine acethylcholine receptors (nAChRs) play critical roles in cognitive processes, neuroprotection and inflammation. RESULTS:
According to their substituents, 1,3-diphenylpropan-1-one derivatives act as α7 nAChRs negative allosteric modulators (NAM, OMe) or Type I positive allosteric modulators (PAMs, OH). Compounds 7 and 31 were the most effective (989 and 666% enhancement of ACh-induced currents) and potent (EC50 12.9 and 6.85 µM) PAMs. They exhibited strong radical scavenging values. Compound 31, selective over other neuronal nAChR subtypes and with acceptable pharmacokinetic profile, showed antinociceptive effects in a model of inflammatory pain.CONCLUSION:
Compound 31 is a novel, potent and selective α7 nAChR PAM, displaying antioxidant and analgesic activities. The 1,3-diphenylpropan-1-one scaffold could be the base toward more advanced type I PAMs for the treatment of nAChR-mediated diseases.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Propano
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Receptor Nicotínico de Acetilcolina alfa 7
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Analgésicos
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Antioxidantes
Límite:
Animals
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Humans
Idioma:
En
Revista:
Future Med Chem
Año:
2016
Tipo del documento:
Article
País de afiliación:
España