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药物化学

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王磊博士-教授

发布时间:2020-11-10   浏览次数:0

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王磊,教授,博士研究生导师。本科及硕士毕业于中国药科大学药物化学专业,博士毕业于美国Duquesne University药物化学专业。现任8883net新浦京游戏副院长,兼任药学国家级实验教学示范中心主任,河北省药学会药物化学专业委员会主任委员,8883net新浦京游戏药物化学学科/专业负责人。主要从事药物分子设计与合成、药物作用的分子机制和新药研究。主持国家自然科学基金、教育部科学技术研究重点项目、河北省科技厅重点研发计划项目、河北省自然科学基金重点项目等。入选河北省“三三三人才工程”。

主持科研项目

1.国家自然科学基金面上项目,82073681,设计合成FR-β/PI3Kγ靶向嵌合分子调控TAM极化作用及抗肿瘤免疫机制研究,2021/01-2024/12,55万元,在研,主持。

2.河北省自然科学基金重点项目,H2022206327,螺吲哚天然产物骨架及新型手性高价碘催化剂的设计与合成研究,2022/07-2024/12,30万元,在研,主持。

3.河北省科技厅重点研发计划项目,19274801D,新型高选择性多机制靶向抗代谢小分子药物的设计、筛选与评价,2019/07-2022/09,30万元,结题,主持。

4.国家自然科学基金青年基金,81202401,PCFT 为转运靶的新型选择性GARFTase 抑制剂的研究,2013/01-2015/12,23万元,结题,主持。

5.教育部科学技术研究重点项目,212014,特异性被PCFT转运的新型GARFTase抑制剂的研究,2012/01-2014/12,5万元,结题,主持。

6.中国博士后基金特别资助项目,2014T70228,GARFTase抑制剂偶联抗肿瘤药物小分子的合成及活性研究,2014/07-2015/07,15万元,结题,主持。

7.中国博士后基金一等资助项目,2013M540214,新型高选择性甘氨酰核苷酸甲基转移酶抑制剂的研究,2013/07-2013/07,8万元,结题,主持。

8.河北省自然科学基金面上项目,H2020206584,基于FR-β/PI3Kγ的嵌合分子设计、合成及靶向调控肿瘤相关巨噬细胞极化作用,2020/01-2022/12,10万元,结题,主持。

9.河北省自然科学基金面上项目,H2017206291,多靶点叶酸类似物小分子作为高选择性靶向抗肿瘤药物的探索,2017/01-2019.12,6万元,结题,主持。

10.河北省自然科学基金青年基金,H2013206211,PCFT为转运靶的新型选择性GARFTase抑制剂的研究,2013/01-2015.12,3万元,结题,主持。

11.河北省教育厅科学技术研究重点项目,ZD2015112,协同抑制嘌呤和嘧啶从头合成的新型非经典叶酸拮抗剂的设计、合成与生物活性研究,2015/01-2017/12,5万元,结题,主持。

代表论文

1.Zhang, Y.; Luo, Z., Guo, L., Zhang, H.; Su, T.; Tan, Z.; Ren, Q.; Zhang, C.; Fu, Y.; Xing, R.; Guo, R.; Shi, X.; Guo, H.; Liu, Y. *; Wang, L. * Discovery of novel tumor-targeted near-infrared probes with 6-substituted pyrrolo[2,3-d]pyrimidines as targeting ligands. European Journal of Medicinal Chemistry, 2023, DOI: 10.1016/j.ejmech.2023.115914.

2.Guo, R.; Cui, M.; Li, X.; Wu, M.; Xu, F.; Zhang, Y.; Wang, C.; Feng, P.; Wang, J.; Huo, S.; Luo, Z.; Xing, R.; Gu, J.; Shi, X. *; Liu, Y. *; Wang, L. * Design, synthesis and biological evaluation of pyrrolopyrimidine derivatives as novel and selective positive modulator of the small conductance Ca2+-activated K+ channels. European Journal of Medicinal Chemistry, 2023, DOI: 10.1016/j.ejmech.2023.115353.

3.Sun, Z.; Xue, S.; Zhang, Y.; Xin, S.; Guo, R.; Shi, X.; Fu, Y.; Guo, H.; Liu, Y.; Wang, L.* λ3-Iodane/Lewis Acid Mediated Intramolecular Cross-Nucleophile Coupling of β-Amino Acrylates: Chemodivergent Syntheses of Indole Alkaloidal Frameworks. Organic Letters, 2022, 24, 5381-5385.

4.Gao, T.; Zhang, C.; Shi, X.; Guo, R.; Zhang, K.; Gu, J.; Li, L.; Li, S.; Zheng, Q.; Cui, M.; Cui, M.; Gao, X.; Liu, Y.*; Wang, L.* Targeting dihydrofolate reductase: Design, synthesis and biological evaluation of novel 6-substituted pyrrolo[2,3-d]pyrimidines as nonclassical antifolates and as potential antitumor agents. European Journal of Medicinal Chemistry, 2019, 178, 329-340.

5.Xing, R.; Zhang, H.; Yuan, J.; Zhang, K.; Li, L.; Guo, H.; Zhao, L.; Zhang, C.; Li, S.; Gao, T.; Liu, Y.*; Wang, L.* Novel 6-substituted benzoyl and non-benzoyl straight chain pyrrolo[2,3-d]pyrimidines as potential antitumor agents with multitargeted inhibition of TS, GARFTase and AICARFTase. European Journal of Medicinal Chemistry, 2017, 139, 531-541.

6.Liu, Y.; Li, M.; Zhang, H.; Yuan, J.; Zhang, C.; Zhang, K.; Guo, H.; Zhao, L.; Du, Y.; Wang, L.*; Ren, L.* Design, synthesis and biological evaluation of 6-substituted pyrrolo[2,3-d]pyrimidines as dual inhibitors of TS and AICARFTase and as potential antitumor agents. European Journal of Medicinal Chemistry, 2016, 115, 245-256.

7.Wang, L.; Wallace, A.; Raghavan, S.; Deis, S.M.; Wilson, M.R.; Yang, S.; Polin, L.; White, K.; Kushner, J.; Orr, S.; George, C.; O'Connor, C.; Hou, Z.; Mitchell-Ryan, S.; Dann, C.E. 3rd; Matherly, L.H.; Gangjee, A. 6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Regioisomers as Targeted Antifolates for Folate Receptor α and the Proton-Coupled Folate Transporter in Human Tumors. Journal of Medicinal Chemistry, 2015, 58, 6938-6959.

8.Liu, Y.; Zhang, C.; Zhang, H.; Li, M.; Yuan, J.; Zhang, Y.; Zhou, J.; Guo, H.; Zhao, L.; Du, Y.; Wang, L.*; Ren, L.* Synthesis and antitumor activity of a novel series of 6-substituted pyrrolo[2,3-d]pyrimidines as potential nonclassical antifolates targeting both thymidylate and purine nucleotide biosynthesis. European Journal of Medicinal Chemistry, 2015, 93, 142-155.

9.Wang, L.; Cherian, C; Kugel-Desmoulin, S.; Mitchell-Ryan, S; Hou, Z.; Matherly, L. H. and Gangjee, A. Synthesis and Biological Activity of 6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Regioisomers as Inhibitors of de Novo Purine Biosynthesis with Selectivity for Cellular Uptake by High Affinity Folate Receptors and the Proton-Coupled Folate Transporter over the Reduced Folate Carrier. Journal of Medicinal Chemistry, 2012, 55, 1758-1770.

10.Wang, L.; Kugel-Desmoulin, S.; Cherian, C; Polin, L.; White, K.; Kushner, J.; Fulterer, A.; Chang, M.; Mitchell-Ryan, S.; Stout, M.; Romero, M. F.; Hou, Z.; Matherly, L. H. and Gangjee, A. Synthesis, Biological and Antitumor Activity of a Highly Potent 6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Antifolate Inhibitor with Proton-Coupled Folate Transporter and Folate Receptor Selectivity over the Reduced Folate Carrier That Inhibits β-Glycinamide Ribonucleotide Formyltransferase. Journal of Medicinal Chemistry, 2011, 54, 7150–7164. 

11.Wang, L.; Cherian, C; Kugel-Desmoulin, S.; Polin, L.; Deng, Y.; Wu, J.; Hou, Z.; White, K.; Kushner, J.; Matherly, L. H. and Gangjee, A. Synthesis and Antitumor Activity of a Novel Series of 6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Antifolate Inhibitors of Purine Biosynthesis with Selectivity for High Affinity Folate Receptors and the Proton-Coupled Folate Transporter over the Reduced Folate Carrier for Cellular Entry. Journal of Medicinal Chemistry, 2010, 53, 1306–1318.    

授权专利

1.王磊,孙增辉,刘诣,郭冉,石晓伟,郭会彩,薛世麟,二氢吡啶螺[3,4’]吲哚和四氢吡啶并呋喃[2,3-b]吲哚-5-酮类生物碱骨架及其制备,发明专利,专利号:ZL202210796716.1

2.王磊,孙增辉,刘诣,郭冉,石晓伟,郭会彩,薛世麟,一种吖庚因并[4,5-b]吲哚生物碱骨架化合物及其制备方法,发明专利,专利号:ZL202210792284.7

3.王磊,刘诣,张丛颖,高天丰,具有抗肿瘤活性的吡咯并嘧啶化合物及其用途,发明专利,专利号:ZL201910476123.5

4.王磊,刘诣,薛世麟,吡咯并[2,3-d]嘧啶类化合物及其用途,发明专利,专利号:ZL201510046191.X