Discovery of N -[(2 s)-5-(6-fluoro-3-pyridinyl)-2,3-dihydro-1 H -inden-2-yl]-2-propanesulfonamide, a novel clinical AMPA receptor positive modulator

摘要

A series of AMPA receptor positive allosteric modulators has been optimized from poorly penetrant leads to identify molecules with excellent preclinical pharmacokinetics and CNS penetration. These discoveries led to 17i, a potent, efficacious CNS penetrant molecule with an excellent pharmacokinetic profile across preclinical species, which is well tolerated and is also orally bioavailable in humans.