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| 引用本文： | ������,������,����ǿ,л�Ƿ�,��Ϊ��,������,����,��־��,�Թ���. Na+�����������ǹ�ת����2���Ƽ���������Ƭ����������Ч��ϵ�ձ��Ե��о�[J]. 中国药学杂志, 2015, 50(22): 1946-1953. DOI: 10.11669/cpj.2015.22.003 |
| 作者姓名： | ������ ������ ����ǿ л�Ƿ� ��Ϊ�� ������ ���� ��־�� �Թ��� |
| 作者单位： | 1. ??????????????,??? ???? 273155; 2. ???????о???????????????????????????????,??? 300193 |
| 摘 要： | |
| 关 键 词： | SGLT2????? 3-???????? 6-???????? ??Ч??? ??? |
Generality of Structure-Activity Relationship of Deoxylations of the Sugar Moiety in SGLT2 Inhibitors |
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| JIANG Lin-lin,WANG Yu-li,LIU Yu-qiang,XIE Ya-fei,XU Wei-ren,TANG Li-da,YIN Ling,GAO Zhi-gang,ZHAO Gui-long. Generality of Structure-Activity Relationship of Deoxylations of the Sugar Moiety in SGLT2 Inhibitors[J]. Chinese Pharmaceutical Journal, 2015, 50(22): 1946-1953. DOI: 10.11669/cpj.2015.22.003 | |
| Authors: | JIANG Lin-lin WANG Yu-li LIU Yu-qiang XIE Ya-fei XU Wei-ren TANG Li-da YIN Ling GAO Zhi-gang ZHAO Gui-long |
| Affiliation: | 1.Department of Chemistry and Chemical Engineering,Jining University, Qufu 273155,China; 2.Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research Co., Ltd, Tianjin 300193, China |
| Abstract: | ??OBJECTIVE To study the generality of the structure-activity relationships(SARs)of 3-deoxylation and 6-deoxylation of the sugar moiety in SGLT2 inhibitors. METHODS Based on the earlier study, 3-deoxycanagliflozin(compound 5), 6-deoxyipragliflozin(compound 6), 6-deoxyempagliflozin(compound 7)and 3-deoxyempagliflozin(compound 8)were synthesized and evaluated by in vitro hSGLT2 and hSGLT1 inhibitory assay. RESULTS The deoxylated SGLT2 inhibitors were synthesized from their corresponding aryl halides 9a-9c and 3-/6-deoxylated perbenzylated gluconolactones 11a-11b.In vitro hSGLT2 and hSGLT1 inhibitory assay showed that compounds 5 and 8 almost lost SGLT2 inhibitory activity, while compounds 6 and 7 exhibited similar activities to their corresponding parent compounds. CONCLUSION It seems a general rule that 6-deoxylation of the sugar moiety in SGLT2 inhibitors has no effect on the SGLT2 inhibitory activity, whereas the effect of 3-deoxylation on SGLT2 inhibitory activity depends on the structures of the specific SGLT2 inhibitors, which does not show a universal rule. |
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