Discovery of tetrahydroindazoles as a novel class of potent and in vivo efficacious gamma secretase modulators

Publication date: 23 July 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 12
Author(s): Kai Gerlach, Scott Hobson, Christian Eickmeier, Ulrike Groß, Clemens Braun, Peter Sieger, Michel Garneau, Stefan Hoerer, Niklas Heine
The identification and optimization of a novel series of centrally efficacious gamma secretase modulators (GSMs) offering an alternative to the privileged aryl imidazole motif is described. Chiral bicyclic tetrahydroindazolyl amine substituted triazolopyridines were identified as structurally distinct novel series of GSMs. Representative compound BI-1408 ((R)-42) was demonstrated to be centrally efficacious in rats at a 30 mg/kg oral dose.

Graphical abstract

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