Design, synthesis, and preliminary evaluation of 4-(6-(3-nitroguanidino)hexanamido)pyrrolidine derivatives as potential iNOS inhibitors.
Design, synthesis, and preliminary evaluation of 4-(6-(3-nitroguanidino)hexanamido)pyrrolidine derivatives as potential iNOS inhibitors.
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DOI：
10.1016/j.bmc.2007.04.030
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发表时间：
2008
影响因子：
3.5
通讯作者：
Feng Liu;H. Fang;Huawei Zhu;Qiang Wang;Yue Yang;Wenfang Xu
中科院分区：
文献类型：
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作者：
Feng Liu;H. Fang;Huawei Zhu;Qiang Wang;Yue Yang;Wenfang Xu
合成了一系列4-(6-（3-硝基胍）己胺吡咯烷衍生物，并对其抑制诱导型一氧化氮合酶（iNOS）异构体的能力进行了评价。所有目标化合物均由商业反式-4-羟基-l-脯氨酸经11步制备而成。初步药理试验结果表明，化合物17、21、30与NOS抑制剂NG-nitroarginine（L-NNA）的IC50分别为2.36、2.68、2.5μM，可作为未来开发新型iNOS抑制剂的先导化合物。
A series of 4-(6-(3-nitroguanidino)hexanamido)pyrrolidine derivatives were synthesized and evaluated for their abilities to inhibit inducible nitric oxide synthase (iNOS) isoform. All target compounds were prepared in 11 steps from commercially trans-4-hydroxy-l-proline. The preliminary pharmacological test showed that three compounds, 17, 21, and 30, have the good potency (IC50=2.36, 2.68, 2.5μM, respectively) which are compared to the NOS inhibitor NG-nitroarginine(L-NNA) (IC50=14.74μM), and could be used as lead compounds for exploring new iNOS inhibitors in the future.