A new series of physostigmine analogues 3a--3j with modifications at the C3a and C5 positions was de- signed and synthesized. Bioassay of the synthetic analogues 3a--3j, along with the previous synthesized C3a-ethyl-C...A new series of physostigmine analogues 3a--3j with modifications at the C3a and C5 positions was de- signed and synthesized. Bioassay of the synthetic analogues 3a--3j, along with the previous synthesized C3a-ethyl-C5-triazole physostigmine analogues laJlg and 2a--2j was performed, which indicates that the replace- ment of the carbamoyl moiety of C3a-ethyl-C5-triazole analogues 1 and 2 with a triazole moiety decreased acetyl- cholinesterase（AchE） inhibitory activity, whereas the introduction of heterocycles into the triazole ring increased both AChE and butyrylcholinesterase（BchE） inhibitory activities. Structure-activity relationship（SAR） studies of C3a-methyl-C5-triazole analogues 3 reveal the C3a-methyl substituent is important for AChE and BChE inhibition and the introduction of a second ionizable N center improved the binding of the synthetic analogues to both AChE and BChE.展开更多
基金Supported by the National Natural Science Foundation of China（No.21202209）, the National Science ＆ Technology Major Project of China（No.2011ZX09401-304）, the Fundamental Research Funds for the Central Universities, China （No.CQDXWL-2012-131） and the Natural Science Foundation Project of Chongqing Science and Technology Commission, China（No.cstc2012jjA10087）.
文摘A new series of physostigmine analogues 3a--3j with modifications at the C3a and C5 positions was de- signed and synthesized. Bioassay of the synthetic analogues 3a--3j, along with the previous synthesized C3a-ethyl-C5-triazole physostigmine analogues laJlg and 2a--2j was performed, which indicates that the replace- ment of the carbamoyl moiety of C3a-ethyl-C5-triazole analogues 1 and 2 with a triazole moiety decreased acetyl- cholinesterase（AchE） inhibitory activity, whereas the introduction of heterocycles into the triazole ring increased both AChE and butyrylcholinesterase（BchE） inhibitory activities. Structure-activity relationship（SAR） studies of C3a-methyl-C5-triazole analogues 3 reveal the C3a-methyl substituent is important for AChE and BChE inhibition and the introduction of a second ionizable N center improved the binding of the synthetic analogues to both AChE and BChE.
