SAR investigations on a novel class of gamma-secretase modulators based on a unique scaffold

In this communication we present details of our analog efforts within a novel series of gamma-secretase modulating compounds. Esters and carbamates were investigated as bioisosteres for a glycoside moiety present in an initial hit isolated from black cohosh extract. We identified elements within each series that retain the potency and selectivity of the initial lead while improving physicochemical properties.