European Journal of Medicinal Chemistry p. 673 - 687 (1992)
Update date:2022-09-26
Han, SY
Sweeney, JE
Bachman, ES
Schweiger, EJ
Forloni, G
et al.
We conducted structural and pharmacological studies of galanthamine, a cortical acetylcholinesterase (AChE) inhibitor, and 19 structural analogs.Systematic derivatization of galanthamine at the cyclohexene ring, tertialy amino, hydroxyl, methoxyl functions indicated that these structural features are essential for biological activity.Molecular modeling studies suggested that the low energy conformations of the analogs are similar to that of the parent.One derivative, galanthamine n-butyl carbamate, had an LD50 of over 100 mg/kg (ip) in mice.In a passive avoidanceparadigm, this analog improved performance in a dose-dependant fashion with a peak effect at 0.1 mg/kg in control and 0.5 mg/kg in basal forebrain lesioned mice.In the same paradigm, the peak effect of the parent compound is a 6-fold higher dose.With this surprisingly high therapeutic ratio, this compound may be of interest in treating cholinergic deficits of the central nervous system such as Alzheimer's desease. galanthamine derivatives / molecular modeling / avetylcholinesterase inhibitor / Alzheimer's desease / passive avoidance / basal forebrain lesion
View MoreContact:86-18641848178
Address:
Office Address: Rm.905 Yinhe Building,No.68 Yuexiu Rd,Hexi district,Tianjin,300201.China.
Factory Address: #65,Antai Road,Yimatu Fluorochemical industrial Park,Fuxin City,Liaoning Province,123129,China.
YanCheng LongShen Chemical Co.,Ltd.
Contact:+86-515-86668866
Address:No.13,Weiyi Road,Funing Aoyang Industrial Park
Hangzhou Pharma & Chem Co.,Ltd.
Contact:+86-571-87040515
Address:No,139Qingchun Rd
Contact:+33-5-34012600
Address:28 ZA des Pignès
Contact:86-25-84683399
Address:605, Phoenix Herui Plaza, No.389, South Taiping Road, Nanjing, China 210002
Doi:10.1021/jm00072a007
(1993)Doi:10.1021/ja01634a039
(1954)Doi:10.1007/s10593-020-02673-w
(2020)Doi:10.1002/jhet.5570320203
(1995)Doi:10.1021/ja00199a055
(1989)Doi:10.1016/j.ica.2010.02.020
(2010)