N′-(Arylsulfonyl) pyrazoline-1-carboxamidines as novel, neutral 5-hydroxytryptamine 6 receptor (5-HT6R) antagonists with unique structural features

…, J Venhorst, WI Iwema Bakker…

Index: Van Loevezijn, Arnold; Venhorst, Jennifer; Iwema Bakker, Wouter I.; De Korte, Cor G.; De Looff, Wouter; Verhoog, Stefan; Van Wees, Jan-Willem; Van Hoeve, Martijn; Van De Woestijne, Rob P.; Van Der Neut, Martina A. W.; Borst, Alice J. M.; Van Dongen, Maria J. P.; De Bruin, Natasja M. W. J.; Keizer, Hiskias G.; Kruse, Chris G. Journal of Medicinal Chemistry, 2011 , vol. 54, # 20 p. 7030 - 7054

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Citation Number: 26

Abstract

The 5-HT6 receptor (5-HT6R) has been in the spotlight for several years regarding CNS- related diseases. We set out to discover novel, neutral 5-HT6R antagonists to improve off- target selectivity compared to basic amine-containing scaffolds dominating the field. High- throughput screening identified the N′-(sulfonyl) pyrazoline-1-carboxamidine scaffold as a promising neutral core for starting hit-to-lead. Medicinal chemistry, molecular modeling, ...