Discovery of orally bioavailable phenyltetrazolium derivatives for the acute treatment and the secondary prevention of ischemic stroke.
Eur J Med Chem
; 275: 116542, 2024 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-38875807
ABSTRACT
The potential for secondary stroke prevention, which can significantly reduce the risk of recurrent strokes by almost 90%, underscores its critical importance. N-butylphthalide (NBP) has emerged as a promising treatment for acute cerebral ischemia, yet its efficacy for secondary stroke prevention is hindered by inadequate pharmacokinetic properties. This study, driven by a comprehensive structural analysis, the iterative process of structure optimization culminated in the identification of compound B4, which demonstrated exceptional neuroprotective efficacy and remarkable oral exposure and oral bioavailability. Notably, in an in vivo transient middle cerebral artery occlusion (tMCAO) model, B4 substantially attenuated infarct volumes, surpassing the effectiveness of NBP. While oral treatment with B4 exhibited stronger prevention potency than NBP in photothrombotic (PT) model. In summary, compound B4, with its impressive oral bioavailability and potent neuroprotective effects, offers promise for both acute ischemic stroke treatment and secondary stroke prevention.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Sais de Tetrazólio
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Fármacos Neuroprotetores
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Prevenção Secundária
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AVC Isquêmico
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China