个人简历

1988年毕业于北京医科大学药学院，同年留校从事有机化学的教学与科研工作。历任北京大学药学院助教、讲师、副教授。2008年在日本进修。在此期间，参与了多项课题的研究，其中包括与北京市科委下属研究所合作的紫杉醇的半合成；糖苷酶抑制剂以及血管紧张素II受体拮抗剂的活性测定。2000年起，一直从事抗艾滋病药物的研究工作，承担和参与科技部“十一五支撑计划”、国家自然科学基金、教育部基金及北大方正基金等项目。通过对HIV病毒复制过程中的靶点进行了详尽研究，利用计算机分子模拟，结合酶与抑制剂复合晶体结构及相关构效关系，设计了多种类型的单靶点及双靶点抑制剂，期望通过产生协同效应，减少交叉耐药而达到最佳的治疗效果。其中发现了多个具有自主知识产权、高效低毒且对变异株具有较好抑制活性的抗HIV逆转录酶抑制剂。其中一个化合物已进入临床前研究。到目前已完成了合成工艺改进，化合物稳定性测试及相关质量标准，药效学，急毒，药代等研究。在此工作基础上，课题组将目光从对病毒的防治转向对宿主细胞STING蛋白的激动来诱导天然免疫反应，从而达到抗HIV病毒的功效。为了扩展研究成果，近年来，课题组与302肝病所以及本校的感染病研究所进行合作进行了抗乙肝病毒药物的研究，从中发现了一些对乙肝病毒及其耐药株具有较好活性的化合物。

研究领域

对HIV、HBV病毒作用的靶点、抑制剂的作用机理、构构关系及耐药问题进行研究。结合计算机辅助药物设计、分子模拟等技术，设计多种类型的单靶点及多靶点抑制剂，希望从中找到各项性能更为优良的抗耐药性的抗病毒先导化合物。

近期论文

Amin Li, Yabo Ouyang, Ziyun Wang, Yuanyuan Cao, Xiangyi Liu, Li Ran, Chao Li, Li Li, Liang Zhang, Kang Qiao, Weisi Xu, Yang Huang, Zhili Zhang, Chao Tian, Zhenming Liu, Shibo Jiang, Yiming Shao, Yansheng Du, Liyang Ma*, Xiaowei Wang*, and Junyi Liu* Novel Pyridinone Derivatives As Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) with High Potency against NNRTI-Resistant HIV-1 Strains . Journal of Medicinal Chemistry,56, 3593-3608, 2013. Xiaowei Wang#, Jianfang Zhang#, Yang Huang#, Ruiping Wang, Liang Zhang, Kang Qiao, Li Li, Chang Liu, Yabo Ouyang, Weisi Xu, Zhili Zhang, Liangren Zhang, Shibo Jiang, Yimin Shao, Liying Ma* and Junyi Liu*. Design, Synthesis and Biological Evaluation of 1-[(2-benzyloxyl/alkoxyl) methyl]-5-halo-6–aryl uracils as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Improved Drug Resistance Profile. Journal of Medicinal Chemistry,55, 2242-2250, 2012. Xianling Ning, Ying Guo, Xiaowei Wang, Xiaoyan Ma, Chao Tian, Xueqi Shi, Renzong Zhu, Can Cheng, Yansheng Du, Zhizhong Ma, zhili Zhang,* and Junyi Liu* Design, Synthesis, and Biological Evaluation of (E)？3,4-Dihydroxystyryl Aralkyl Sulfones and Sulfoxides as Novel Multifunctional Neuroprotective Agents.J. Med. Chem. 2014,57, 4302？4312. Zhili Zhang, Chao Tian, Shouxin Zhou, Wei Wang, Ying Guo, Jie Xia, Zhenming Liu, Biao Wang, Xiaowei Wang, Bernard T. Golding, Roger J. Griff, Yansheng Du, Junyi Liu*. Mechanism-based Design, Synthesis and Biological Studies of N5-Substituted Tetrahydrofolate Analogues as Inhibitors of Cobalamin-dependent Methionine Synthase and Potential Anticancer Agents. Euro. J. Med. Chem.58，228-236, 2012 Yuanyuan Cao, Yu Zhang, Shaotong Wu, Quanzhi Yang, Xuefeng Sun, Jianxiong Zhao, Fen Pei, Ying Guo , Chao Tian , Zhili Zhang , Haining Wang, Liying Ma, Junyi Liu*, Xiaowei Wang*. Synthesis and biological evaluation of pyridinone analogues as Novel potent HIV-1 NNRTIs. Bioorg. Med. Chem. 23 (2015) 149–159. Yu Zhang, Xuefeng Sun,Ningning Fan,Jianxiong Zhao,Jing Tu,Xiangmei Chen,Junyi Liu* and Xiaowei Wang*. 5-Iodo-2-arylalkyl thio-6-aryl pyrimidin-4(3H)-ones as non-nucleoside anti-HBV agents. Med. Chem. Commun., 2015, 6, 1438–1443 Shaotong Wu, Qianqian Yin, Liang Zhao, Ningning Fan, Xiaowan Tang, Jianxiong Zhao, Tao Sheng, Ying Guo, Chao Tian, Zhili Zhang, Weisi Xu, Zhenming Liu, Shibo Jiang, Liying Ma,* Junyi Liu* and Xiaowei Wang*, A stereo configuration-activity study of 3-iodo-4-(2-methylcyclohexyloxy)-6-phenethylpyridin-2 (2H)-ones as potency inhibitors of HIV-1 variants. Org. Biomol. Chem.2015, DOI: 10.1039/c5ob02154e Weisi Xu,Jianxiong Zhao, Jianping Sun, Qianqian Yin,Yan Wang, Yang Jiao, Junyi Liu, ShiboJiang, Yiming Shao, Xiaowei Wang,* and Liying Ma.* The HEPT analogue, 1-((benzyloxy) methyl)-6-(3, 5-dimethylbenzyl)-5- iodopyrimidine-2, 4(1H, 3H)-dione (WPR-6), is active against a broad spectrum of HIV-1 strains of different subtypes with drug-resistance. Antimicrob. Agents Chemother. 2015, 59:8 4882-4888 Tong-Bo Zhang,Yuan-Yuan Cao, Shao-Tong Wu, Yu Zhang, Ying Guo,Jian-Xiong Zhao, Xue-Feng Sun,Quan-Zhi Yang,Zhi-Li Zhang, Chao Tian, Jun-Yi Liu]*and Xiao-Wei Wang.*An approach to synthesis of pyrimido[b]azepines via Ruthenium-catalyzed ring-closing metathesis. Synthesis 2015, 47, 3292–3300 Zhang Tongbo, Wu Shaotong, Cao Yuanyuan, Fu Yuhong, Guo Ying, Zhang Liang, Li Li, Zhou Han, Liu Xiangyi, Li Chao, Tang Xiaowan, Zhang Zhili, Tian Chao, Wang Xiaowei*,Liu Junyi*. Rapid Access to 10-(Cyclohexylimino)-7,9-diazaspiro[4.5]decane-6,8-dione Derivatives for HIV-1 Reverse Transcriptase Inhibition via Ruthenium-Catalyzed Ring-Closing Metathesis . Synthesis. 45, 2273-2279,2013. Liang Zhang, Xiaowan Tang, Yuanyuan Cao, Shaotong Wu, Yu Zhang , Jianxiong Zhao, Ying Guo, Chao Tian , Zhili Zhang , Junyi Liu,* and Xiaowei Wang*. Synthesis and Biological Evaluation of Novel 2-Arylalkylthio-5-iodine-6-substituted- benzyl-pyrimidine-4(3H)-ones as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor. Molecules 2014, 19, 7104-7121. Yang Huang# , Xiaowei Wang#, Xiaoling Yu, Lin Yuan, Ying Guo, Weisi Xu, Tiejun Liu, Junyi Liu, Yiming Shao* and Liying Ma*.Inhibitory activity of 9-phenylcyclohepta[d]pyrimidinedione derivatives against different strains of HIV-1 as non-nucleoside reverse transcriptase inhibitors. Virology Journal, 8, 230-236, 2011. Gong Li, Xiaowei Wang*, Chao Tian, Tongbo Zhang, Zhili Zhang, Junyi Liu*. Rapid access to multi-substituted pyrimido[4,5-b][1,4] diazepine-2,4,6-trione and pyrimido[4,5-b][1,4]diazepine-2,4-dione as novel and versatile scaffolds for drug discovery. Tetrahedron Letters53 (2012) 5193–5196. Hua Qin, Jianfang Zhang, Chang Liu, Ying Guo, Siwei Zhang, Zhili Zhang, Xiaowei Wang, Liangren Zhang, Junyi Liu*, Synthesis and biological evaluation of novel 2-arylalkylthio-4-amino-6-benzyl pyrimidines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors, Bioorganic Medicinal Chemistry Letter. 20 , 3003–3005, 2010 Hua Qin, Chang Liu, Ying Guo, Ruiping Wang, Jianfang Zhang, Liying Ma, Zhili Zhang, Xiaowei Wang, Yuxin Cui, Junyi Liu*. Synthesis and biological evaluation of novel C5 halogen-functionalized S-DABO as potent HIV-1 non-nucleoside reverse transcriptase inhibitors. Bioorganic & Medicinal Chemistry2010, 18: 3231–3237. Xiao Lu, Yanli Chen, Ying Guo, Zhenming Liu, Yawei Shi, Yang Xu, Xiaowei Wang and Junyi Liu, The Design and Synthesis of N-1 alkylated 5-aminoaryalkyl substituted 6-methyluracils as potential non-nucleoside HIV-1 RT Inhibitors Bioorganic Medicinal Chemistry15 (2007) 7399–7407 Xiaowei Wang, Qinghua Lou, Ying Guo, Yang Xu, Zhili Zhang and Junyi Liu，The design and synthesis of 9-phenylcyclohepta[d] pyrimidine-2, 4-dione derivatives as potent non- nucleoside inhibitors of HIV reverse transcriptase.Organic & Biomolecular Chemistry2006, 4, 3252–3258 Li Li, Liying Ma, Xiaowei Wang*, Junyi Liu*. New efficient and flexible synthetic route to Emivirine and its analogs.Journal of Heterocyclic Chemistry, 50, 164-168, 2013.