474295-93-7Relevant articles and documents
A conformational restriction approach to the development of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease
Toda, Narihiro,Tago, Keiko,Marumoto, Shinji,Takami, Kazuko,Ori, Mayuko,Yamada, Naho,Koyama, Kazuo,Naruto, Shunji,Abe, Kazumi,Yamazaki, Reina,Hara, Takao,Aoyagi, Atsushi,Abe, Yasuyuki,Kaneko, Tsugio,Kogen, Hiroshi
, p. 4389 - 4415 (2007/10/03)
Alzheimer's disease (AD) has been treated with acetylcholinesterase (AChE) inhibitors such as donepezil. However, the clinical usefulness of AChE inhibitors is limited mainly due to their adverse peripheral effects. Depression seen in AD patients has been treated with serotonin transporter (SERT) inhibitors. We considered that combining SERT and AChE inhibition could improve the clinical usefulness of AChE inhibitors. In a previous paper, we found a potential dual inhibitor, 1, of AChE (IC50=101 nM) and SERT (IC50=42 nM), but its AChE inhibition activity was less than donepezil (IC50=10 nM). Here, we report the conformationally restricted (R)-18a considerably enhanced inhibitory activity against AChE (IC50=14 nM) and SERT (IC50=6 nM).
Design and synthesis of dual inhibitors of acetylcholinesterase and serotonin transporter targeting potential agents for Alzheimer's disease.
Kogen, Hiroshi,Toda, Narihiro,Tago, Keiko,Marumoto, Shinji,Takami, Kazuko,Ori, Mayuko,Yamada, Naho,Koyama, Kazuo,Naruto, Shunji,Abe, Kazumi,Yamazaki, Reina,Hara, Takao,Aoyagi, Atsushi,Abe, Yasuyuki,Kaneko, Tsugio
, p. 3359 - 3362 (2007/10/03)
Highly efficient acetylcholinesterase (AChE) and serotonin transporter (SERT) dual inhibitors, (S)-4 and (R)-13 were designed and synthesized on the basis of the hypothetical model of AChE active site. Both compounds showed potent inhibitory activities against AChE and SERT. [structure: see text]
