Synthesis of Novel Tacrine Analogs as Reversible, Potent and Selective Cholinesterase Inhibitors and Methods for their Use

Reference #:

1995-073

Inventors/Contributors

Stephen W. Brimijoin, Ph.D., Yuan-Ping Pang, Ph.D.

Description

An efficient and economical synthesis for novel, more lipophilic tacrine analogs has been developed. These analogs found up to 10,000 fold more selective and 1,000 fold more potent in inhibiting reversible acetylcholinesterase (AChE) than tacrine. May be used as (I) tools to evaluate the role of AChE inhibition by tacrine in treating Alzheimer's Disease (AD), (ii) insecticides, (iii) drugs for killing parasites, (iv) blockers of K+ channel and the NMDA receptor channel, and (v) improved therapeutics for AD. Derivatives can be made with the same synthetic method, and may be used as (vi) prophylactic or therapeutic antidotes for chemical warfare agents and (vii) reversible, selective and potent butyrylcholinesterase (BChE) inhibitors to evaluate a permissive or causative role of glial BChE in the neuropathology of AD.

Patent Status

	U.S. Patent Number 5,783,584 Issued July 21, 1998 U.S. Patent Number 5,886,007 Issued May 23, 1999