在药物研发中优势片段杂交策略的应用(2)

2019-10-31  未知 admin

随后另有研究人员通过分子对接及优势片段杂交策略，发现了新型的吡啶酰胺及吡啶酮类衍生物对HIV有较强的抑制活性。

基于优势片段杂交策略在药物设计中具有思路清晰、研发时间短及成本低等优势，但是在实际操作时需要借助一部分外界的力量，如药物与靶点的晶体结构及分子对接技术等，另外在进行分子杂交过程中可能会导致目标化合物的分子量过大、理化性质发生改变等缺点。

参考文献

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[2] Pelz NF, Bian ZG, Zhao B, et al. Discovery of 2-Indole-acylsulfonamide Myeloid Cell Leukemia 1 (Mcl-1)Inhibitors Using Fragment-Based Methods [J]. Journal of Medicinal Chemistry,2013, 56(1): 15-30.

[3] Hutton JA.Goncalves V, BranniganJA,et al. Structure-based design of potent and selective LeishmaniaN-myristoyltransferase inhibitors [J]. Journal of medicinal chemistry, 2014,57(20): 8664-8670.

[4] Liu ZQ, Chen WM, Zhan P, etal. Design, synthesis and anti-HIV evaluation of novel diarylnicotinamidederivatives (DANAs) targeting the entrance channel of the NNRTI binding pocketthrough structure-guided molecular hybridization [J]. European Journal ofMedicinal Chemistry, 2014, 87: 52-62.

[5] Chen WM, Zhan P, Rai D, et al. Discoveryof 2-pyridone derivatives as potent HIV-1 NNRTIs using molecular hybridizationbased on crystallographic overlays [J]. Bioorganic & MedicinalChemistry, 2014, 22: 1863–1872.

原标题：优势片段杂交策略在药物研发中的应用