Design and synthesis of a novel series of cyanoindole derivatives as potent γ-secretase modulators. Issue 14 (15th July 2019)

• Record Type: Journal Article
• Authors: Bischoff, François P.; Velter, Adriana Ingrid; Minne, Garrett; Pieters, Serge; Berthelot, Didier; De Cleyn, Michel; Gijsen, Harrie J.M.; Macdonald, Gregor; Surkyn, Michel; Van Brandt, Sven; Van Roosbroeck, Yves; Zavattaro, Chiara; Mercken, Marc; Austin, Nigel; Dhuyvetter, Deborah; Borghys, Herman; Ahmad, Ishtiyaque; Samanta, Swapan Kumar
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 14(2019)
• Page Start: 1737
• Page End: 1745
• Publication Date: 2019-07-15
• Subjects: Alzheimer's disease -- γ-Secretase -- γ-Secretase modulators -- GSMs; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.05.023
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: The discovery, design and synthesis of a new series of GSMs is described. The classical imidazole heterocycle has been replaced by a cyano group attached to an indole nucleus. The exploration of this series has led to compound 26-S which combined high in vitro and in vivo potency with an acceptable drug-like profile.