Synthesis and preliminary structure-activity relationships of 1-[(3-fluoro-4-pyridinyl)amino]-3-methyl-1H-indol-5-yl methyl carbamate (P10358), a novel acetylcholinesterase inhibitor

A series of carbamate analogs of besipirdine (HP 749) was synthesized as potential agents with enhanced cholinomimetic properties for the treatment of Alzheimer's disease. Compound 5a (P10358, 1-[3-fluoro-4-pyridinyl)amino]-3-methyl-1H-indol-5-yl methyl carbamate) emerged as a potent, reversible acetylcholinesterase inhibitor that significantly enhanced performance on oral or parenteral administration in learning and memory paradigms.