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副研究员

张文轩

职 称:副研究员

所属科室:新药开发研究室

导师类别:硕士生导师

联系方式:wxzhang@www.myhortonhome.com

所属重点实验室:天然药物活性物质与功能国家重点实验室

个人简介

2013年毕业于北京大学,先后获得学士和博士学位。现任bobapp官方下载 新药开发研究室副主任、副研究员、硕士研究生导师、兼任北京药学会药物化学专业委员会委员。在创新药物研发方面,作为主要完成人,开展了调血脂原创候选药IMM-H007(已转让)、治疗非酒精性肝炎(NASH)原创候选药物IMM-H014(已转让)、以及抗耐药菌感染原创候选药物等品种的临床前药学研究开发工作。同时完成了盐酸溴己新等多种仿制药原料药合成工艺研发和注册申报工作,并完成了二十余种重要药物的微量杂质对照品合成工作(百十克级)。相关研究成果在Nat Commun., Eur. J. Med. Chem等国内外著名期刊发表论文三十余篇,申请国际国内专利十余项,并担任Eur. J. Med. Chem.等药物化学期刊审稿人。已获得国家自然科学基金、北京市自然科学基金、北京协和医学院青年基金、国家重大新药创制专项、中国医学科学院创新团队基金等资助。

研究方向

目前主要从事临床亟需创新药物研究和开发工作,包括抗感染、抗肿瘤、代谢性疾病以及其他疾病治疗药物。正在开展研究方向:
1. 抗耐药菌、抗肿瘤、治疗代谢性疾病等化学药物的发现、结构优化和成药性评价研究,包括基于细菌DNA拓扑异构酶与核糖体等靶点的抗菌药物、针对肿瘤干细胞Wnt信号通路的抗肿瘤药物、代谢相关脂肪性肝病治疗药物的研究与开发。
2. 活性天然产物的全合成、结构优化与成药性评价研究。
3. 基于在线分析监控技术平台(PAT)如自动合成仪、在线红外、在线粒度分析和在线颗粒成像等技术的原料药合成&晶型工艺研究与开发。

发表论文


1. Tianlei Li#, Jishun Li#, Zihao Zhu, Yuyuan Chen, Xueyao Li, Qingyun Yang, Jie Xia, Wenxuan Zhang, Chao Zhang,* Weidong Pan* and Song Wu*. Metallaphotoredox -catalyzed C–H activation: regio-selective annulation of allenes with benzamide. Org Chem Front, 2021, 8 (5): 928-935.
2.1. Yuan-Yuan Zhang#, Jie Zhang#, Wen-Xuan Zhang, Yue Wang, Ying-Hong Wang, Qing-Yun Yang* and Song Wu*. Quantitative 1H Nuclear Magnetic Resonance Method for Assessing the Purity of Dipotassium Glycyrrhizinate. Molecules 2021, 26 (12): 3549.
3.2. Hongna Wu#, Jun Wu#, Tong Qin, Xu Lian, Zhongwen Li, Baojie Guo, Jie Hao, Qi Zhou, Tianlei Li, Wenxuan Zhang⁎, Song Wu⁎, The structure optimization of dicarboximide-phenylpyridine conjugates as inhibitor of Wnt signaling Pathway, Chemistry select. 2020,5, 13795 – 13799
4.3. Ming Zhong#, Yao Yu#, Jia-Qi Song, Tian-Wei Jia, Ao-Yun Liu, Teng-Fei Zhao, Hao-Jie He, Mei-Bing Yang, Wenxuan Zhang*, Yang Yang*. Amide-sialoside protein conjugates as neomucin bioshields prevent influenza virus infection. Carbohyd Res, 2020, 495: 108088.
5.4. Xuechen Li, Zhenxin Yan, Mattias Carlström, Jinying Tian, Xiaolin Zhang, Wenxuan Zhang, Song Wu and Fei Ye*, Mangiferin Ameliorates Hyperuricemic Nephropathy Which Is Associated With Downregulation of AQP2 and Increased Urinary Uric Acid Excretion. Front Pharmacol, 2020, 11: 49.
6.5. Hui Hui Guo#, Chen Lin Feng #, Wenxuan Zhang#, Zhi-Gang Luo#, Hong-Juan Zhang, Ting-Ting Zhang, Chen Ma, Yun Zhan, Rui Li, Song Wu, Zeper Abliz, Cong Li, Xiao-Lin Li, Xiao-Lei Ma, Lu-Lu Wang*, Wen-Sheng Zheng*, Yan-Xing Han* & Jian-Dong Jiang*. Liver-target nanotechnology facilitates berberine to ameliorate cardio-metabolic diseases. Nat Commun., 2019, 10(1): 1981.
7.6. Hongna Wu #, Jun Wu#, Wenxuan Zhang*, Zhongwen Li, Jinhui Fang, Xu Lian, Tong Qin, Jie Hao, Qi Zhou, Song Wu*. Discovery and structure-activity relationship study of phthalimide- phenylpyridine conjugate as inhibitor of Wnt pathway, Bioorg. Med. Chem. Lett.,2019, 29: 870~872.
8.7. Tianlei Li, Gang Wen, Jishun Li, Wenxuan Zhang , and Song Wu* , A Useful Synthesis of 2-Acylamino-1,3,4-oxadiazoles from Acylthiosemicarbazides Using Potassium Iodate and the Discovery of New Antibacterial Compounds,Molecules 2019, 24, 1490
9.8. Shao-Yuan Wang, Mei Li, Lu-Yang Miao, Song Wu, Yuan-Feng Tong, Wen-Xuan Zhang, Yu-Yang Zhang & Hua Sun., Protective effects of a novel water-soluble biphenyl compound WLP-S-14 against acute-on-chronic liver failure in rats, J Asian Nat Prod Res, 2019, 21(9), pp. 928-938.
10.9. Yan Yang, Minzhi Liu, Wenxuan Zhang, Yunsong Cao, Changkun Li, and Wei Wang*, Identification and Characterization of Two New 1‑O‑Acyl-glucoseester Forming Glucosyltransferases from Erigeron breviscapus. J. Agric. Food Chem. 2019, 67, 2848−2855.
11.10. Wenxuan Zhang, Wenjie Xue, Yuqing Jia, Gang Wen, Xu Lian, Jing Shen, Ailin Liu and Song Wu*, A Concise Synthesis of (±)-7-O-Galloyltricetiflavan, RSC Adv., 2018, 8, 14389.
12.11. Wenxuan Zhang,#* Jun Wu,# Bo Li, Xu Lian, Jie Xia, Qi Zhou, Song Wu*, Design and synthesis of conformationally constrained salinomycin derivatives, Eur. J. Med. Chem., 2017, 138, 353.
13.12. Gang Wen, Wenxuan Zhang* and Song Wu*, A Novel Synthesis of 4-Acetoxyl 5(4H)-Oxazolones by Direct α-Oxidation of N-Benzoyl Amino-Acid Using Hypervalent Iodine, Molecules 2017, 22, 1102.
14.13. Bo Li#, Jun Wu#, Wenxuan Zhang*, Zhongwen Li, Gang Chen, Qi Zhou, Song Wu*, Synthesis and biological activity of salinomycin-hydroxamic acid conjugates, Bioorg Med Chem Lett, 2017, 27, 1624.
15.14. Lu-Lu Wang, Chen-Lin Feng, Wen-Sheng Zheng, Shuai Huang, Wenxuan Zhang, Hong-Na Wu, Yun Zhan, Yan-Xing Han*, Song Wu*, Jian-Dong Jiang*, Tumor-selective lipopolyplex encapsulated small active RNA hampers colorectal cancer growth in vitro and in orthotopic murine,Biomaterials 2017,141,13-28
16.15. Wenxuan Zhang, Jun Wu, Bo Li, Jie Xia, Hongna Wu, Liu Wang, Jie Hao, Qi Zhou, Song Wu*, Synthesis and biological activity evaluation of 20-epi-salinomycin and its 20-O-acyl derivatives, RSC Adv., 2016, 6, 41885.
17.16. Wenxuan Zhang#, Jun Wu#, Bo Li, Hongna Wu, Liu Wang, Jie Hao, Song Wu*, Qi Zhou*, Structure–activity & structure–toxicity relationship study of salinomycin diastereoisomers and their benzoylated derivatives, Org Biomol Chem, 2016, 14, 2840. (inside cover)
18.17. Wenxuan Zhang#, Jiming Wang#, Xihuan Luo, Xiangbao Meng*, Zhongjun Li*,An attempt to construct the C/D ring system of parkacine by intramolecular cycloaddition of azomethine ylide and alkyne, Tetrahedron Lett., 2016, 57, 1981.
19.18. Wen-Xuan Zhang, Hong-Na Wu, Bo Li, Hong-Lin Wu, Dong-Mei Wang, Song Wu*, The Synthesis of the Metabolites of 2′,3′,5′-Tri-O-acetyl-N6-(3-hydroxyphenyl) Adenosine (WS070117). Molecules, 2015, 21, 8.
20.19. Wenxuan Zhang, Ying Chen, Qingzhao Liang, Hui Li, Hongwei Jin, Liangren Zhang, Xiangbao Meng*, and Zhongjun Li*, Design, Synthesis and Antibacterial Activities of Conformationally Constrained Kanamycin A Derivatives. J. Org. Chem. 2013, 78, 400−409.
21.20. Wenxuan Zhang, Qingzhao Liang, Hui Li, Xiangbao Meng* and Zhongjun Li*, Concise synthesis and antitumor activity of Bengamide E and its analogs, Tetrahedron, 2013, 69, 664-672.

专著

专利


1. 吴松,张文轩,赵欣彤,李天磊,夏杰,杨庆云,张驰,韩遵圣,冯靖,张洁,张坤,刘博,连旭,朱子豪,邵会会,王越,胡宇华, 吡咯酰哌啶胺类化合物及其用途,202110656714.8
2. 王璐璐,张文轩,蒋建东,吴松,一种盐酸小檗碱和水飞蓟宾形成的盐、其制备方法和应用,202110460032.X
3. 刘艾林, 谭文杰, 郑丽舒, 许律捷, 赵君, 吴松, 康洁, 张文轩, 叶飞, 郭鹏飞, 李超,贾皓, 杜冠华没食子儿茶素-7-没食子酸酯在抗冠状病毒药物中的用途, 2021102764452
4. 孙华, 吴松, 张金兰, 张文轩, 王喆, 生宁, 刘宁, 刘威, 陈智伟, 陈子涵, 一类双环吗啉类化合物在预防或治疗糖尿病中的应用, 2021105700170
5. 吴松、孙华、张金兰、张文轩、王喆、杨庆云、姜琳、陈子涵、申静、张洁、张驰、韩遵圣、秦通、张媛媛,一种左旋双环吗啉盐、制备方法和用途,201911190936.4, PCT/CN2020/115410
6. 吴松,李艳,张文轩,安涛,武红娜,申静,连旭,秦通,吡啶酮酰联芳基胺类化合物及其用途,201910171194.4
7. 杨庆云, 吴松, 张金兰, 王琰, 王喆, 符洁, 马春华, 张文轩, 李天磊, 夏杰, 陈谕园,泮托拉唑钠及其起始原料中基因毒性杂质的分析方法,2018104544101
8. 吴松,夏杰,闻刚,冯波,贾雨晴,张文轩,戚燕,杨庆云,张驰, 1-取代苯甲酰基-4-酯酰基氨基硫脲类衍生物、制备方法及作为抗菌药物的用途。ZL201810091202.X(2020)
9. 吴松,周琪,张文轩,吴骏,武红娜,王柳,郝捷,调节WNT信号通路的酰胺类化合物及其用途,201711263401.6.
10. 吴松,周琪,张文轩,吴骏,李波,连旭,王柳,郝捷,盐霉素肟醚生物、其制备方法和抗肿瘤用途,PCT/CN2017/085516.公开日:2017.11.30
11. 吴松,周琪,张文轩,吴骏,李波,王柳,郝捷,盐霉素肟及肟醚生物以及制备方法和抗肿瘤用途,ZL201610347806.7. (2020)
12. 吴松,杜冠华,张文轩,何国荣,李莉,C20位差向异构化盐霉素及其酰化衍生物以及制备方法和抗肿瘤用途,ZL201610922564.X.
13. 吴松,孙华,张文轩,张金兰,张丹,王少媛,武丽萍,童元峰,刘宁,一种双环醇类衍生物及其制备和应用,ZL201610922563.5(2020)
14. 李中军,樊玉平,孟祥豹,张文轩,一种新的卡那霉素A衍生物及其制备方法和用途,2012-7-5,中国,CN101481397.(已授权)

科技奖励

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