Structure-activity relationships of trimethoxybenzyl piperazine N-type calcium channel inhibitors.
Bioorg Med Chem Lett
; 22(12): 4153-8, 2012 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-22579422
ABSTRACT
We previously reported the small organic N-type calcium channel blocker NP078585 that while efficacious in animal models for pain, exhibited modest L-type calcium channel selectivity and substantial off-target inhibition against the hERG potassium channel. Structure-activity studies to optimize NP078585 preclinical properties resulted in compound 16, which maintained high potency for N-type calcium channel blockade, and possessed excellent selectivity over the hERG (~120-fold) and L-type (~3600-fold) channels. Compound 16 shows significant anti-hyperalgesic activity in the spinal nerve ligation model of neuropathic pain and is also efficacious in the rat formalin model of inflammatory pain.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piperazinas
/
Nervos Espinhais
/
Bloqueadores dos Canais de Cálcio
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Canais de Cálcio Tipo N
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Hiperalgesia
/
Analgésicos
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Neuralgia
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article