Yoichi Iimura

Enantioselective synthesis of (2S)-5-{4-[2-(4-fluorophenoxy)ethyl]piperazin-1-yl}-2-isopropyl-2-phenyl-pentanenitrile dihydrochloride (E2050) using enzyme-catalyzed kinetic resolution

Abstract Immobilized lipase ( Pseudomonas sp.)-catalyzed transesterification of ( RS )-4-cyano-4-isopropyl-4-phenyl-1-butanol 4 in vinyl acetate gave ( S )-4-cyano-4-isopropyl-4-phenyl-1-butyl acetate 3a with high enantiomeric excess values and conversions (95–97% ee, 30–47%, E =90–93), leaving the enantiomerically pure ( R )-alcohol 4 (>99% ee) unreacted. As 3a can be efficiently converted to E2050, use of the immobilized lipase should provide an economical route for large-scale synthesis of E2050.

Discovery of Novel Neuronal Voltage-Dependent Calcium Channel Blockers Based on Emopamil Left Hand as a Bioactive Template

A series of novel neuronal voltage-dependent calcium channel (VDCC) blockers, with inhibitory activity at low micromolar and moderate solubility in water, was discovered by constructing and screening a focused library based on emopamil (1) left hand (ELH) as a bioactive template.

The New Generation of Acetylcholinesterase Inhibitors

Acetylcholinesterase inhibitor has been widely recognized as an effective treatment for Alzheimer’s Disease (AD). It is known to alleviate the symptoms and slow the progression of the disease. Currently, there are four such kind of drugs in the market. These are Tacrine, Rivastigmine, Galantamine and Donepezil. Donepezil, developed by my company, Eisai Co., Ltd., was the second drug approved by the U.S. FDA for the treatment of AD.