Synthesis and biological evaluation of glycosidase inhibitors: gem-difluoromethylenated nojirimycin analogues

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	Synthesis and biological evaluation of glycosidase inhibitors: gem-difluoromethylenated nojirimycin analogues
	Wang RW(王若文) ; Qiu XL(邱小龙) ; Mikael Bols ; Fernando Ortega-Caballero ; Qing FL(卿凤翎)
刊名	J. Med. Chem.
	2006
卷号	49 期号:10 页码:2989-2997
ISSN号	0022-2623
其他题名	糖甘酶抑制剂的合成与生物化学研究:二氟亚甲基Nojirimycin类似物
通讯作者	卿凤翎
英文摘要	In our ongoing program aimed at the design, synthesis, and biological evaluation of novel gem-difluoromethylenated glycosidase inhibitors, gem-4,4-difluoromethylenated iminosugars (5-9) were synthesized. The biological evaluation of these synthetic iminosugars showed that the gem-difluoromethylenyl group generally reduced the inhibition of glycosidases. However, this was not the case at pH 5.0, where the gem-difluoromethylenated iminosugar 6 was a stronger inhibitor than comparable iminosugars 1 and 36, suggesting that the influence of this group is mainly through its effect on the amine. It is proposed that the unprotonated iminosugar is the species preferably bound by beta-glucosidase, due to the lower pK(a) value of iminosugar 6 than of 1 or 36, leaving iminosugars 1 and 36 mostly protonated at pH 5.0, while iminosugar 6 is not. Iminosugar 6 also displayed good and selective inhibition of beta-glucosidase at pH 6.8.
学科主题	氟化学
收录类别	SCI
原文出处	http://dx.doi.org/10.1021/jm060066q
语种	英语
WOS记录号	WOS:000237555400014
公开日期	2013-02-22
内容类型	期刊论文
源URL	[http://202.127.28.38/handle/331003/17579]
专题	上海有机化学研究所_中科院有机氟化学重点实验室
推荐引用方式 GB/T 7714	Wang RW,Qiu XL,Mikael Bols,et al. Synthesis and biological evaluation of glycosidase inhibitors: gem-difluoromethylenated nojirimycin analogues[J]. J. Med. Chem.,2006,49(10):2989-2997.
APA	王若文,邱小龙,Mikael Bols,Fernando Ortega-Caballero,&卿凤翎.(2006).Synthesis and biological evaluation of glycosidase inhibitors: gem-difluoromethylenated nojirimycin analogues.J. Med. Chem.,49(10),2989-2997.
MLA	王若文,et al."Synthesis and biological evaluation of glycosidase inhibitors: gem-difluoromethylenated nojirimycin analogues".J. Med. Chem. 49.10(2006):2989-2997.