The prevalence of Alzheimer's Disease (AD) is growing and so will be the societal burden across the world due to the ageing of the population and the abscence of treatment. AD comprises a continuum of progressive neurodegenerative pathologies associated with cognitive, functional, and behavioral deficits. The earliest stages of AD include microscopic changes in the form of A-beta plaques arising from A-beta 42 aggregations. 

Modulation of gamma-secretase appears as a safe approach to lower toxic A-beta 42. Here, we present our contribution to the field which has led to the identification of our clinical candidate RO7185876. Furthermore, in the frame of this project, we also discovered that bridge piperidine coul dbe use as a superior phenyl bioisoster.