| Autor: |
Loevezijn, A. van, Venhorst, J., Iwema Bakker, W.I., Lange, J.H.M., Looff, W. de, Henzen, R., Vries, J. de, Woestijne, R.P. van de, Hartog, A.P. den, Verhoog, S., Neut, M.A.W. van der, Bruin, N.M.W.J. de, Kruse, C.G. |
| Přispěvatelé: |
Publica |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Popis: |
The discovery of non-basic N'-(arylsulfonyl)pyrazoline-1-carboxamidines as 5-HT6 antagonists with unique structural features was recently disclosed. Here we describe how this structural class was further developed by addressing an unexplored interaction site of the 5-HT6 receptor. Compound 13 resulting from this effort is a highly potent and selective 5-HT6 antagonist with improved metabolic stability. It is furthermore devoid of hERG affinity. Despite its modest CNS/plasma ratio, a high brain free fraction ensured substantial exposure to allow for rodent cognition studies. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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