کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1368738 | 981717 | 2016 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Optimization of N′-(arylsulfonyl)pyrazoline-1-carboxamidines by exploiting a novel interaction site in the 5-HT6 antagonistic binding pocket
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موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
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چکیده انگلیسی
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.
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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 26, Issue 6, 15 March 2016, Pages 1605–1611
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 26, Issue 6, 15 March 2016, Pages 1605–1611
نویسندگان
Arnold van Loevezijn, Jennifer Venhorst, Wouter I. Iwema Bakker, Jos H.M. Lange, Wouter de Looff, Remco Henzen, Jelle de Vries, Rob P. van de Woestijne, Arnold P. den Hartog, Stefan Verhoog, Martina A.W. van der Neut, Natasja M.W.J. de Bruin,