Design and synthesis of dual inhibitors of acetylcholinesterase and serotonin transporter targeting potential agents for Alzheimer's disease

Organic Letters

Volumn 4, Issue 20, 2002, Pages 3359-3362

  Kogen, Hiroshi ^b   Toda, Narihiro ^b   Tago, Keiko ^b   Marumoto, Shinji ^b   Takami, Kazuko ^b   Ori, Mayuko ^b   Yamada, Naho ^b   Koyama, Kazuo ^a   Naruto, Shunji ^a   Abe, Kazumi ^a   Yamazaki, Reina ^a   Hara, Takao ^a   Aoyagi, Atsushi ^a   Abe, Yasuyuki ^a   Kaneko, Tsugio ^a  

^a DAIICHI SANKYO CO   (Japan)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCHOLINESTERASE; CHOLINESTERASE INHIBITOR; SEROTONIN; SEROTONIN UPTAKE INHIBITOR;

ALZHEIMER DISEASE; ARTICLE; BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DESIGN; HUMAN; IC 50; METABOLISM; SYNTHESIS;

ACETYLCHOLINESTERASE; ALZHEIMER DISEASE; BINDING SITES; CHOLINESTERASE INHIBITORS; DRUG DESIGN; HUMANS; INHIBITORY CONCENTRATION 50; MOLECULAR STRUCTURE; SEROTONIN; SEROTONIN UPTAKE INHIBITORS;

EID: 18744366138     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol026418e     Document Type: Article

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29. Since there is no information on the structure of SERT, the reason of the opposite stereochemical preference is unclear.
30. The brain of mouse was isolated 1 h after an oral administration of compounds, and AChE and/or SERT activity were measured. Each symbol represents the mean of five mice. The doses (95% confidence interval) of (S)-4 necessary for 50% inhibition of AChE and SERT in the brain were determined as 13 (11-15) and 2.4 (1.9-2.9) mg/kg, p.o., respectively. Details will be reported soon.
31. The SERT inhibition of R-13 was not determined because a low penetration of the compound into the brain was predicted from the ex vivo study of AChE inhibition.