Design, synthesis, evaluation and QSAR analysis of N(1)-substituted norcymserine derivatives as selective butyrylcholinesterase inhibitors.
We synthesized a series of N(1)-substituted norcymserine derivatives 7a-p and evaluated their anti-cholinesterase activities. In vitro evaluation showed that the pyridinylethyl derivatives 7m-o and the piperidinylethyl derivative 7p improved the anti-butyrylcholinesterase activity by approximately threefold compared to N(1)-phenethylnorcymserine (PEC, 2). A quantitative structure-activity relationship (QSAR) study indicated that logS might be a key feature of the improved compounds.
Department of Neuroscience for Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Jun
J
Takahashi
Ichiro
I
Hijikuro
Takeshi
T
Kihara
Modachur G
MG
Murugesh
Shinichiro
S
Fuse
Ryo
R
Kunimoto
Yoshinori
Y
Tsumura
Akinori
A
Akaike
Tetsuhiro
T
Niidome
Yasushi
Y
Okuno
Takashi
T
Takahashi
Hachiro
H
Sugimoto
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010830:Physostigmine / Q000031:analogs & derivatives* / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D010830:Physostigmine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase