Skip to main content

Central Selective Acetylcholinesterase Inhibitor with Neurotrophic Activity Structure-Activity Relationships of TAK-147 and Related Compounds

Buy Article:

$63.00 plus tax (Refund Policy)


A series of benzylamino inhibitors of acetylcholinesterase (AChE) have been designed based on a working hypothesis of the enzymes active site. These compounds were tested for their inhibitory activities on AChE and potent inhibitors were further evaluated in terms of central selectivity. These studies led to a discovery of 3-(1-(phenylmethyl)-4-piperidinyl)-1-( 2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone fumarate (TAK-147). Pharmacokinetic study has shown that the compound has high central selectivity, as demonstrated by rapid elimination from plasma and long-term existence in the brain. As a consequence, TAK-147 ameliorates impairments of learning and memory in various animal models without producing peripheral side effects. TAK-147 also activates the monoaminergic systems and energy metabolism. Furthermore, TAK-147 was revealed to have NGF-like neurotrophic activity on central cholinergic neurons at concentrations where it inhibits AChE activity. Therefore, TAK-147 is expected not only to ameliorate the clinical symptoms in Alzheimers disease via AChE inhibition but to prevent or slow the progression of the disease via its neurotrophic action. TAK-147 is now under clinical trial as a therapeutic drug for Alzheimers disease. This article reviews design and structure-activity relationships of TAK-147 and related compounds. Preclinical pharmacology of TAK-147 is also summarized.

Keywords: ChAT activity Neurotrophic activity; NGF like neurotrophic activity; Phenylmethy 4 piperidinyl; TAK 147; acetylchoinesterase AChE; alzhemier s disease; amelioring effect; behavioral depression monoamine metabolism; benzylamino inhibitors; central selective acetylcholinesterase inhibitor; central selective inhibitors; docking analysis; donepezil; learning; memory impairment; neurotrophic activity; pharmacokinetics; pharmacology; phthalimdie; physostigmine; rivastigmine; tacrine THA; tetrahydro 1H1 benzaazepin 8 yl propanone fumarate; torpedo californica

Document Type: Review Article


Publication date: March 1, 2000

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Partial Open Access Content
Partial Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more