Compound 94

Compound 94 is a first-in-class, small molecule dual inhibitor of butyrylcholinesterase (BChE) and p38α mitogen-activated protein kinase (p38α MAPK). Developed as a multi-target directed ligand (MTDL) for the treatment of Alzheimer's disease, it is designed to simultaneously address cholinergic deficits and neuroinflammation, two primary drivers of neurodegeneration. Preclinical studies have shown that Compound 94 possesses balanced inhibitory activity against both targets and can effectively cross the blood-brain barrier. In vivo, the compound significantly improved cognitive function in mouse models of dementia induced by scopolamine and lipopolysaccharide (LPS), while also reducing the production of proinflammatory markers such as TNF-α and IL-6 in vitro and ex vivo. The compound's design was optimized using structure-based drug design and a library of known p38α MAPK inhibitors.