Design, synthesis, and evaluation of new type of L-amino acids containing pyridine moiety as nitric oxide synthase inhibitor
Design, synthesis, and evaluation of new type of L-amino acids containing pyridine moiety as nitric oxide synthase inhibitor
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DOI：
10.1016/j.bmc.2006.01.020
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发表时间：
2006-05-15
影响因子：
3.5
通讯作者：
Higuchi, T
中科院分区：
文献类型：
--
作者：
Ijuin, R;Umezawa, N;Higuchi, T
设计并合成了新的氨基酸 7-12 作为人一氧化氮合酶 (NOS) 的候选抑制剂。含2-氨基吡啶的L-氨基酸8对所有人类NOS同工酶均具有有效的抑制活性。然而，区域异构体9和10以及含2-甲基吡啶的化合物11的抑制活性要低得多。人 NOS 同工酶也被 7 抑制，7 的吡啶部分缺少氨基。进行了计算对接研究以探讨抑制作用的机制。 (c) 2006 Elsevier Ltd. 保留所有权利。
New amino acids 7-12 were designed and synthesized as candidate inhibitors of human nitric oxide synthase (NOS). The 2-aminopyridine-containing L-amino acids 8 had potent inhibitory activity toward all of the human NOS isozymes. However, the regioisomers 9 and 10, and 2-methylpyridine-containing compound 11 had much lower inhibitory activity. Human NOS isozymes were also inhibited by 7, which lacks an amino group on the pyridine moiety. A computational docking study was carried out to investigate the mechanism of the inhibitory effect. (c) 2006 Elsevier Ltd. All rights reserved.