于丽芳

药物化学及相关的化学生物学

《药学学科研究进展》

《药物化学前沿》

《有机化学及实验》

国家自然科学基金面上项目

国家自然科学基金青年项目

国家科技重大专项子课题任务

上海市自然科学基金

上海市教委科技创新项目

新药国家重点实验室开放课题

中国科学院受体结构与功能重点实验室开放课题

1)      Wei Zhang,# Shichun Lun,# Shuang-Shuang Wang,# Yan-Peng Cai, Fan Yang, Jie Tang, William R. Bishai,* and Li-Fang Yu* Structure-Based Optimization of Coumestan Derivatives as Polyketide Synthase 13-Thioesterase(Pks13-TE) Inhibitors with Improved hERG Profiles for Mycobacterium tuberculosis Treatment. J. Med. Chem. 2022, Just accepted.

2)      Liping Liu, Rui Zhu, Jiacheng Li, Yuan Pei, Shuangshuang Wang, Pan Xu, Mingyu Wang, Yu Wen, Hao Zhang, Daohai Du, Hong Ding, Hualiang Jiang, Kaixian Chen, Bing Zhou, Lifang Yu,* and Cheng Luo* Computational and Structure-Based Development of High Potent Cell-Active Covalent Inhibitor Targeting the Peptidyl-Prolyl Isomerase NIMA-Interacting‑1 (Pin1) J. Med. Chem. 2022, 65, 2174.

3)      Bei-Er Jiang, Jiaxin Hu, Hao Liu, Zhitao Liu, Yu Wen, Mingyao Liu, Han-Kun Zhang, Xiufeng Pang,* Li-Fang Yu* Design, synthesis, and biological evaluation of indole-based hydroxamic acid derivatives as histone deacetylase inhibitors. Eur.J. Med. Chem. 2022, 227, 113893.

4)      Yanpeng Cai, Wei Zhang, Shichun Lun, Tongtong Zhu, Weijun Xu, Fan Yang, Jie Tang, William R. Bishai,* and Lifang Yu* Design, Synthesis and Biological Evaluation of N-phenylindole Derivatives as Pks13 Inhibitors against Mycobacterium tuberculosis. Molecules 2022, 27, 2844-2862.

5)      Bei-Er Jiang, Xingwu Jiang, Qiansen Zhang, Qiuwen Liang, Zi-Liang Qiu, Xiang-Bai Sun, Jun-Jie Yang, Si Chen, Chunyang Yi, Xiaolei Chai, Mingyao Liu, Li-Fang Yu,* Weiqiang Lu,*and Han-Kun Zhang* From a Designer Drug to the Discovery of Selective Cannabinoid Type 2 Receptor Agonists with Favorable Pharmacokinetic Profiles for the Treatment of Systemic Sclerosis. J. Med. Chem. 2021, 64, 385.

6)      Wei Zhang, Ling-ling Liu, Shichun Lun, Shuang-Shuang Wang, Shiqi Xiao, Hendra Gunosewoyo, Fan Yang, Jie Tang, William R. Bishai*, Li-Fang Yu* Design and synthesis of mycobacterial pks13 inhibitors: conformationally rigid tetracyclic molecules. Eur.J. Med. Chem. 2021, 213, 113202.

7)      Shichun Lun, Shiqi Xiao, Wei Zhang, Shuangshuang Wang, Hendra Gunosewoyo, Li-Fang Yu*, William R. Bishai*. Therapeutic potential of coumestan Pks13 inhibitors for tuberculosis. Antimicrob. Agents Chemother.2021, 65(5), e02190-20.

8)      Jun-Jie Shi, Qi-Hui Jiang, Tian-Ning Zhang, Hao Sun, Wen-Wen Shi, Hendra Gunosewoyo, Fan Yang, Jie Tang, Tao Pang* and Li-Fang Yu*. Sigma-1 Receptor Agonist TS-157 Improves Motor Functional Recovery by Promoting Neurite Outgrowth and pERK in Rats with Focal Cerebral Ischemia. Molecules 2021, 26, 1212.

9)      Shi JJ, Jia KH, Sun H, Gunosewoyo H, Yang F, Tang J, Luo J, Yu LF*. Synthesis and Pharmacological Evaluation of σ2 Receptor Ligands Based on a 3-Alkoxyisoxazole Scaffold: Potential Antitumor Effects against Osteosarcoma. ChemMedChem 2021, 16, 524.

10)  吕润秋，张维，于丽芳* 靶向分枝菌酸生物合成的抗结核化合物研究进展《有机化学》2021, Doi: 10.6023/cjoc202012008.

11)  Jianpeng Yin, Desheng Zhan, Hui Ma, Huanan Liu, Lifang Yu, Yangming Zhang,* and Fajun Nan* Optimization and Development of a Scalable Palladium-Catalyzed C−H Activation Process for the Geometry-Selective Preparation of Kilograms of YLF466D, a Potent AMP-Activated Protein Kinase Activator. Org. Process Res. & Dev. 2021, 25, 2260-2269.

12)  Huiqing Chen, Jie Tang, Ting Liu, Li-Fang Yu, Dong Xing, Fan Yang Enantioselective synthesis of chiral 3-alkyl-3-nitro-4-chromanones via chiral thiourea-catalysed intramolecular Michael-type cyclization. Org. Biomol. Chem. 2021, 19, 7403.

13)  Shahinda S R Alsayed, Amreena Suri, Anders W Bailey, Samuel Lane, Eryn L Werry, Chiang-Ching Huang, Li-Fang Yu, Michael Kassiou, Simone Treiger Sredni, Hendra Gunosewoyo Synthesis and antitumour evaluation of indole-2-carboxamides against paediatric brain cancer cells. RSC Med. Chem. 2021, 12, 1910.

14)  裴方宁，杨帆，汤杰，于丽芳* 具有偏向性的大麻素受体配体研究进展，《药学进展》2020，44，790.

15)  韦媛媛，杨帆，汤杰，于丽芳* 抗结核药物的研究进展，《中国药科大学学报》2020，51，231.

16)  Wang, Fangqin; Jiang, Xuefeng; Xiang, Huaijiang; Wang, Ning; Zhang, Yunjing; Yao, Xi; Wang, Ping; Pan, Hao; Yu, Lifang; Cheng, Yunfeng; Hu, Yongzhou; Lin, Weiqiang*; Li, Xin* An inherently kidney-targeting near-infrared fluorophore based probe for early detection of acute kidney injury. Biosensors and Bioelectronics, 2021, 172: 0-112756.

17)  Wang, Z.C.; Wang, J.; Chen, H.; Tang, J.; Bian, A.W.; Liu, T.; Yu, L. F.; Yi, Z.*; Yang, F.* Synthesis and anticancer activity of novel 9,13-disubstituted berberine derivatives. Bioorg. Med. Chem. Lett.2020, 30,126821.

18)  Wang, Zhi-Cheng; Wei, Bingyan; Pei, Fang-Ning; Yang, Teng; Tang, Jie; Yang, Song; Yu, Li-Fang; Yang, Cai-Guang*; Yang, Fan*. Capsaicin derivatives with nitrothiophene substituents: Design, synthesis and antibacterial activity against multidrug-resistant S. aureu. Eur.J. Med. Chem. 2020, 198: 0-112352.

19)  Lin, Ying; Xing, Dong; Wu, Wen-Biao; Xu, Gao-Ya; Yu, Li-Fang; Tang, Jie; Zhou, Yu-Bo; Li, Jia*; Yang, Fan* Design, Synthesis, and In Vitro Evaluation of Benzofuro[3,2-c]Quinoline Derivatives as Potential Antileukemia Agents. Molecules2020, 25, 0-203.

20)  Hu, Min-Qi; Li, Heng; Lin, Ying; Zhang, Ying; Tang, Jie; Zuo, Jian-Ping; Yu, Li-Fang; Tong, Xian-Kun*; Tang, Wei*; Yang, Fan*. 1-Phenyl-N-(benzothiazol-2-yl)methanimine derivatives as Middle East respiratory syndrome coronavirus inhibitors. RSC Adv.2020, 10, 43299.

21)  Zhang, W.; Lun, S.; Liu, L. L.; Xiao, S.; Duan, G.; Gunosewoyo, H.; Yang, F.*; Tang, J.; Bishai, W. R. *; Yu, L. F.* Identification of Novel Coumestan Derivatives as Polyketide Synthase 13 Inhibitors Against Mycobacterium tuberculosis. Part II J. Med. Chem. 2019, 62, 3575-3589.

22)  Ji, Y. Y.; Wang, Z. L.; Pei, F. N.; Shi, J. J.; Li, J. J.; Gunosewoyo, H.; Yang, F.; Tang, J.; Xie, X. *; Yu, L. F. * Introducing nitrogen atoms to amidoalkylindoles: potent and selective cannabinoid type 2 receptor agonists with improved aqueous solubility. Med. Chem. Comm.2019, 10, 2131-2139.

23)  Jiang, H.; Jin, J.; Duan, Y.; Xie, Z.; Li, Y.; Gao, A.; Gu, M.; Zhang, X.; Peng, C.; Xia, C.; Dong, T.; Li, H.; Yu, L.; Tang, J.; Yang, F.*; Li, J.*; Li, J.* Mitochondrial Uncoupling Coordinated With PDH Activation Safely Ameliorates Hyperglycemia via Promoting Glucose Oxidation. Diabetes. 2019, 68, 2197-2209.

24)  Zhang, W.; Lun, S.; Wang, S. H.; Jiang, X. W.; Yang, F.; Tang, J.; Manson, A. L.; Earl, A. M.; Gunosewoyo, H.; Bishai, W. R.; Yu, L. F. Identification of Novel Coumestan Derivatives as Polyketide Synthase 13 Inhibitors against Mycobacterium tuberculosis. J. Med. Chem. 2018, 61, 791–803.

25)  Shi, Y.; Wu, Y. R.; Su, M. B.; Shen, D. H.; Gunosewoyo, H.; Yang, F.; Li, J.; Tang, J.; Zhou, Y. B.*; Yu, L. F.* Novel spirocyclic tranylcypromine derivatives as lysine-specific demethylase 1 (LSD1) inhibitors. RSC Advances 2018, 8, 1666–1676.

26)  Sun, H.; Wang, Y. J.; Shi, W. W.; Yang, F.; Tang, J.; Pang, T.*; Yu, L. F.* Discovery of N-Cyclobutylaminoethoxyisoxazole Derivatives as Novel Sigma-1 Receptor Ligands with Neurite Outgrowth Efficacy in Cells. RSC Advances 2018, 8, 7080–7088.

27)  Shi, Y.; Duan, Y. H.; Ji, Y. Y.; Wang, Z. L.; Wu, Y. R.; Gunosewoyo, H.; Xie, X.* Yu, L. F.*Amidoalkylindoles as Potent and Selective Cannabinoid Type 2 Receptor Agonists with in Vivo Efficacy in a Mouse Model of Multiple Sclerosis. J. Med. Chem. 2017, 60, 7067–7083.

28)  Ji, Y. Y.; Lin, S. D.; Wang, Y. J.; Su, M. B.; Zhang, W.; Gunosewoyo, H.; Yang, F.; Li, J.; Tang, J.; Zhou, Y. B.*; Yu, L. F.* Tying up tranylcypromine: Novel selective histone lysine specific demethylase 1 (LSD1) inhibitors. Eur. J. Med. Chem. 2017, 141, 101–112.

29)  Wang, S.; Xu, L.; Lu, Y. T.; Liu, Y. F.; Han, B.; Liu, T.; Tang, J.; Li, J.; Wu, J. P.;* Li, J. Y.;* Yu, L. F.;* Yang, F.* Discovery of Benzofuran-3(2H)-one Derivatives as Novel DRAK2 Inhibitors that Protect Islet β-Cells from Apoptosis. Eur. J. Med. Chem. 2017, 127, 195–208.

30)  Gunosewoyo, H.; Yu, L. F.; Munoz, L.; Kassiou, M.* Kinase Targets in Central Nervous System Drug Discovery. Future Med. Chem., 2017, 9(3), 303–314.

31)  Wang, J.; Yang, T.; Chen, H.; Xu, Y. N.; Yu, L. F.; Liu, T.; Tang, J.; Yi, Z. F.; Yang, C. G.; Xue, W.*; Yang, F.* The Synthesis and Antistaphylococcal Activity of 9, 13-Disubstituted Berberine Derivatives. Eur. J. Med. Chem. 2017, 127, 424–433.

32)  Sun, H.; Shi, M.; Zhang, W.; Zheng, Y. M.; Xu, Y.; Shi, J. J.; Liu, T.; Gunosewoyo, H.; Pang, T.; Gao, Z. B.; Yang, F.; Tang, J.*; Yu, L. F.* Development of Novel Alkoxyisoxazoles as Sigma-1 Receptor Antagonists with Anti-Nociceptive Efficacy. J. Med. Chem.2016, 59, 6329–6343.

33)  Zhang, H. K.; Eaton, J. B.; Fedolak, A.; Gunosewoyo, H.; Onajole, O. P.; Brunner, D.; Lukas, R. J.;Yu, L. F.*; Kozikowski, A. P.* Synthesis and Biological Evaluation of Novel Hybrids of Highly Potent and Selective α4β2-Nicotinic Acetylcholine Receptor (nAChR) Partial Agonists. Eur. J. Med. Chem. 2016, 124, 689–697.

34)  Zhang, H. K.; Gunosewoyo, H.; Yan, F.; Tang, J.;Yu, L. F.* Development of Antidepressant Drugs Through Targeting α4β2-Nicotinic Acetylcholine Receptors. Nicotinic Acetylcholine Receptor Technologies. Li, M. D., Ed.; Springer New York: New York, NY, 2016; 117, pp 207–225.

35)  Zhang, J. F.; Qiu, J. K.; Xiao, C. M.; Yu, L. F.; Yang, F.*, Tang, J.* Tandem Demethylation/annulation/oxidation of 2,3-Bis(2-methoxyphenyl)-3-oxopropanals for One-Pot Construction of Coumestans. Eur. J. Org. Chem. 2016, 3380–3385.

36)  Mao, S. W.; Chen, H.; Yu, L. F.; Lv, F.; Xing, Y. J.; Liu, T.; Xie, J.; Tang, J.; Yi, Z. F.*, Yang, F.* Novel 3,4-seco Bile Acid Diamides as Selective Anticancer Proliferation and Migration Agents. Eur. J. Med. Chem. 2016, 122, 574–583.

37)  Wang, S.; Zhao, C.; Liu, T.; Yu, L. F.; Yang, F.*, Tang, J.* Efficient Construction of 3-Arylquinolin-4(1H)-ones via in situ Meinwald Rearrangement/intramolecular Reductive Cyclization of 2’-Nitrochalcone Epoxides. Tetrahedron 2016, 72, 7025‒7031.

38)  Zhang, J.; Guan, F.; Qiu, J.; Fang, Y.; Yu, L.; Li, J.; Yang, F.; Zhang, X.; Li, J.; Tang, J.* Design, synthesis, in vitro antiproliferative activity evaluation of 2-alkanoylamidothiophene-3-carboxamide derivatives. Heterocycles 2016, 92, 2166–2200.

39)  Mao, S. W.; Shuai, L.; He, H. B.; Pan, N.; Gao, L. X.; Yu, L. F.; Li, J.; Li, J. Y.*, Yang, F.* Synthesis and Biological Evaluation of Novel 2,3-Pyrazole Ring-substituted-4,4-dimethyl Lithocholic Acid Derivatives as Selective Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitors with Cellular Efficacy. RSC Adv.2015, 5, 106551–106560.

40)  Wang, J.; Tang, J.; Yu, L. F.; Li, J.; Li, J. Y.; Yang, F.* Berberine Analogues: Progress towards Versatile Applications. Heterocycles 2015, 91, 2233–2270.

41)  Yu, L. F.; Zhang, H. K.; Caldarone, B.; Eaton, J. B.; Lukas, R. J.; Kozikowski, A. P.* Recent Developments in Novel Antidepressants Targeting α4β2-Nicotinic Acetylcholine Receptors. J. Med. Chem.2014, 57, 8204–8223.

42)  Yu, L. F.; Eaton, J. B.; Zhang, H. K.; Hanania, T.; Li, G. N.; van Breemen, R. B.; Whiteaker, P.; Liu, Q.; Wu, J.; Chang, Y. C.; Lukas, R. J.; Brunner, D.; Kozikowski, A. P.* The Potent and Selective α4β2*/α6*-Nicotinic Acetylcholine Receptor (nAChR) Partial Agonist 2-[5-[5-((S)Azetidin-2-ylmethoxy)-3-pyridinyl]-3-isoxazolyl]ethanol (LF-3-88) Demonstrates Anti-depressive-like Behaviour in Animal Models and a Favorable ADME-Tox profile. Pharmacol. Res. & Persp. 2014, 2, 1‒14.

43)  Ruan, L. B.; Shi, M.; Mao, S. W.; Yu, L. F.; Yang, F.*; Tang, J.* An Efficient Approach to Construct 2-Arylbenzo[b]furans from 2-Methoxychalcone Epoxides. Tetrahedron 2014, 70, 1065‒1070.

44)  Yu, L. F.; Li, Y. Y.; Su, M. B.; Zhang, M.; Zhang, W.; Zhang, L. N.; Pang, T.; Zhang R. T.; Liu, B.; Li, J. Y.; Li, J.*; Nan, F. J.* Development of Novel Alkene Oxindole Derivatives As Orally Efficacious AMP-Activated Protein Kinase Activators. ACS Med. Chem. Lett. 2013, 4, 475‒480.

45)  Yuan, Y.; Yu, L. F. (共同第一作者); Qiu, X.; Kozikowski, A. P.*; van Breemen, R.* Pharmacokinetics and Brain Penetration of LF-3-88, (2-[5-[5-(2(S)-Azetidinylmethoxyl)-3-pyridyl]-3-isoxazolyl]ethanol, a Selective α4β2-nAChR Partial Agonist and Promising Antidepressant. J. Chromatogr. B. 2013, 912, 38‒42.

46)  Li, Y.Y.; Yu, L.F. (共同第一作者); Zhang, L.N.; Qiu, B.Y.; Su, M.B.; Wu, F.; Chen, D.K.; Pang T.; Gu, M.; Zhang, W.; Ma, W.P.; Jiang, H.W.; Li, J.Y.; Nan, F.J.*; Li, J.* Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice. Toxicol. Appl. Pharmacol.2013, 273 (2), 325–334.

47)  Zhang, H.; Yu, L. F.; Eaton, J. B.; Whiteaker, P.; Onajole, O. K.; Hanania, T.; Brunner, D.; Lukas, R. J.; Kozikowski, A. P.* Chemistry, Pharmacology, and Behavioral Studies Identify Chiral Cyclopropanes as Selective α4β2-Nicotinic Acetylcholine Receptor Partial Agonists Exhibiting an Antidepressant Profile. Part II. J. Med. Chem.2013, 56, 5495–5504.

48)  Yu, L. F.; Eaton, J. B.; Fedolak, A.; Zhang, H. K.; Hanania, T.; Brunner, D.; Lukas, R. J.; Kozikowski, A. P.* Discovery of Highly Potent and Selective α4β2-Nicotinic Acetylcholine Receptor (nAChR) Partial Agonists Containing an Isoxazolylpyridine Ether Scaffold that Demonstrate Antidepressant-like Activity. Part II. J. Med. Chem.2012, 55, 9998‒10009.

49)  Yu, L. F.; Zhang, H. K.; Gunosewoyo, H.; Kozikowski, A. P.* From α4β2 Nicotinic Ligands to the Discovery of σ1 Receptor Ligands: Pharmacophore Analysis and Rational Design. ACS Med. Chem. Lett.2012, 3, 1054‒1058.

50)  Yu, L. F.; Tϋckmantel, W.; Eaton, J. B.; Caldarone, B.; Fedolak, A.; Hanania, T.; Brunner, D.; Lukas, R. J.; Kozikowski, A. P.* Identification of novel α4β2-nicotinic acetylcholine receptor (nAChR) agonists based on an isoxazole ether scaffold that demonstrate antidepressant-like activity. J. Med. Chem. 2012, 55, 812‒823.

51)  Zhang, H. K.; Eaton, J. B.; Yu, L. F.; Nys, M.; Mazzolari, A.; van Elk, R.; Smit, A. B.; Alexandrov, V.; Hanania, T.; Sabath, E.; Fedolak, A.; Brunner, D.*; Lukas, R. J.*; Vistoli, G.*; Ulens, C.*; Kozikowski, A. P.* Insights into the Structural Determinants Required for High Affinity Binding of Chiral Cyclopropane-Containing Ligands to α4β2-Nicotinic Acetylcholine Receptors; An Integrated Approach to Behaviorally Active Nicotinic Ligands. J. Med. Chem.2012, 55, 8028‒8037.

52)  Zhang, H.; Tϋckmantel, W.; Eaton, J. B.; Yuen, P. W.; Yu, L. F.; Bajjuri, K. M.; Fedolak, A.; Wang, D.; Ghavami, A.; Caldarone, B.; Paterson, N. E.; Lowe, D. A.; Brunner, D.; Lukas, R. J.; Kozikowski, A. P.* Chemistry and behavioral studies identify chiral cyclopropanes as selective α4β2-nicotinic acetylcholine receptor partial agonists exhibiting an antidepressant profile. J. Med. Chem. 2012, 55, 717‒724.

53)  Liu, J.; Yu, L. F.; Eaton, J. B.; Caldarone, B.; Cavino, K.; Ruiz, C.; Terry, M.; Fedolak, A.; Wang, D.; Ghavami, A.; Lowe, D. A.; Brunner, D.; Lukas, R. J.; Kozikowski, A. P.* Discovery of isoxazole analogues of sazetidine-A as selective α4β2-nicotinic acetylcholine receptor partial agonists for the treatment of depression. J. Med. Chem.2011, 54, 7280‒7288.

54)  Yu, L. F.; Hu, H. N.; Nan, F. J.* Total synthesis of lathyranoic acid A. J. Org. Chem.2011, 76, 1448‒1451.

55)  Yu, L. F.; Qiu, B. Y.; Nan, F. J.; Li, J.* AMPK activators as novel therapeutics for type 2 diabetes. Curr. Top. Med. Chem.2010, 10, 397‒410.

56)  Zang, Y.; Yu, L. F.; Nan, F. J.; Feng, L. Y.; Li, J.* AMP-activated protein kinase is involved in neural stem cell growth suppression and cell cycle arrest by 5-aminoimidazole-4-carboxamide-1-α-D-ribofuranoside and glucose deprivation by down-regulating phospho-retinoblastoma protein and cyclin D. J. Biol. Chem.2009, 284, 6175‒6184.

57)  Zang, Y.; Yu, L. F.; Pang, T.; Fang, L. P.; Feng, X.; Wen, T. Q.; Nan, F. J.; Feng, L. Y.; Li, J.* AICAR induces astroglial differentiation of neural stem cells via activating the JAK/STAT3 pathway independently of AMP-activated protein kinase. J. Biol. Chem.2008, 283, 6201‒6208.

58)  Pang, T.; Zhang, Z. S.; Gu, M.; Qiu, B. Y.; Yu, L. F.; Cao, P. R.; Shao, W.; Su, M. B.; Li, J. Y.; Nan, F. J.; Li, J.* Small molecule antagonizes autoinhibition and activates AMP-activated protein kinase in cells. J. Biol. Chem.2008, 283, 16051‒16060.

2018年中国药学会-施维雅青年药物化学奖

2018年至今华东师范大学紫江青年研究员