title: Derivatives of oxoisoaporphine alkaloids: a novel class of selective acetylcholinesterase inhibitors.
abstract: 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.
authors: School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510080, People's Republic of China.
authors: Huang
authors: H
authors: Tang
authors: Fang-Xian
authors: FX
authors: Ning
authors: Yong-Biao
authors: YB
authors: Wei
authors: Shi-Liang
authors: SL
authors: Huang
authors: Zhi-Shu
authors: ZS
authors: Huang
authors: Albert Sun-Chi
authors: AS
authors: Chan
authors: Lian-Quan
authors: LQ
authors: Gu
mesh_terms: 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
chemical_list: D000470:Alkaloids; D002219:Carbamates; D002412:Cations; D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase