1996
DOI: 10.1021/ja9622822
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Identification of a More Potent Analogue of the Naturally Occurring Alkaloid Huperzine A. Predictive Molecular Modeling of Its Interaction with AChE

Abstract: Huperzine A (HA), a potent reversible inhibitor of acetylcholinesterase (AChE), is an important psychotherapeutic agent for improving cognitive function in Alzheimer's patients through the enhancement of central cholinergic tone. This molecule takes on added value in that it has recently been shown to exhibit neuroprotective properties (glutamate toxicity blocking activity) in vitro. Based upon our cumulative SAR information and to some extent the predicted binding site of HA within Torpedo AChE, we chose to i… Show more

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Cited by 111 publications
(48 citation statements)
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“…Some synthetic analogues (e.g. the 10a-methyl derivative) have shown higher levels of activity (Kozikowski et al, 1996;Skolnick, 1997). The alkaloid is already available in the United States in stores and through the internet for 'improving cognitive function' following clinical trials for memory enhancement and cognition in China (Borman, 1998a).…”
Section: Alkaloids Of Current Interestmentioning
confidence: 99%
“…Some synthetic analogues (e.g. the 10a-methyl derivative) have shown higher levels of activity (Kozikowski et al, 1996;Skolnick, 1997). The alkaloid is already available in the United States in stores and through the internet for 'improving cognitive function' following clinical trials for memory enhancement and cognition in China (Borman, 1998a).…”
Section: Alkaloids Of Current Interestmentioning
confidence: 99%
“…Both type of inhibitors stop formation of toxic A . Chemical structures for some of these potency values (Kazikowsky et al, 1996;Harel et al, 1996;Camps et al, 1999;Weihofen et al, 2003) are shown in fig.3. Despite numerous efforts these preventive drugs have not been able to reach our markets due to their poor pharmacodynamics and bioavailability problems.…”
Section: Secretase Inhibitionmentioning
confidence: 99%
“…Compared with the above four AChE inhibitors, Hup A (trade name: Shuangyiping) has better penetration through the blood-brain barrier, higher oral bioavailability and longer duration of AChE inhibitory action. 6,7 Many attempts have been made to synthesize Hup A, Hup A analogs or derivatives since 1989, [8][9][10][11][12][13][14][15][16][17][18][19] however, only very few compounds have obvious and potent anti-AChE activity. For example, ZT-1 is being developed as a new anti-AD drug candidate in both China and Europe.…”
Section: Introductionmentioning
confidence: 99%