Derivatives of oxoisoaporphine alkaloids: a novel class of selective acetylcholinesterase inhibitors.
A series of 9-aminoalkanamido-1-azabenzanthrones derviatives (3a-i Ar-NHCO(CH(2))(n)NR(1)R(2)) and their quaternary methiodide salts (4a-g Ar-NHCO(CH(2))(n)N(+)(CH(3))R(1)R(2)I(-)) were designed and synthesized as acetylcholinesterase (AChE) or butyrylcholinesterase (BuChE) inhibitors. The synthetic compounds exhibited high AChE inhibitory activity with IC(50) values in the nanomolar range and high selectivity for AChE over BuChE (45- to 1980-fold). The structure-activity relationships (SARs) were discussed.
Tang
Huang
H
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510080, People's Republic of China.
Ning
Fang-Xian
FX
Wei
Yong-Biao
YB
Huang
Shi-Liang
SL
Huang
Zhi-Shu
ZS
Chan
Albert Sun-Chi
AS
Gu
Lian-Quan
LQ
D000110:Acetylcholinesterase / Q000737:chemistry*; D000470:Alkaloids / Q000737:chemistry*; D002091:Butyrylcholinesterase / Q000737:chemistry*; D002219:Carbamates / Q000737:chemistry; D002412:Cations; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D020836:Protein Structure, Quaternary; D013329:Structure-Activity Relationship
D000470:Alkaloids; D002219:Carbamates; D002412:Cations; D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase