张小虎Xiaohu (Jason) Zhang,Ph.D.

张小虎.bmp

姓  名:张小虎

职称职务:特聘教授

联系电话:65880380

电子邮箱:xiaohuzhang@suda.edu.cn

办公地址:云轩楼1427

 

 

 

一、学习工作经历

1、学历背景:

1986.9-1990.6:北京大学,理学学士

1992.9-1997.11Rutgers University,美国新泽西州立大学,博士

2、工作经历:

1990.8-1992.7:内蒙古金属材料研究所,工程师

1998.3-1999.6Chromagen Inc., San Diego, CA, USA. 研究员

1999.6-2000.10Stratagenean Agilent company,研究员,项目经理

2000.10-2008.2Neurocrine Biosciences,资深研究员

2008.3-2012.4BioDuroa PPD company,北京,总监,资深总监,执行总监

2012.4-至今:苏州大学药学院,特聘教授

二、研究方向

1)靶向中枢神经系统重大疾病的药物研发:以帕金森氏病、抑郁症、药物成瘾为靶向,寻找和发现新型小分子药物。

2)新型抗肿瘤药物的研发:专注于胚胎通路(刺猬通路拮抗剂,豪猪蛋白拮抗剂等)的候选药物研发。

三、主要科研支持

国家自然科学基金项目:腺苷受体拮抗剂抗帕金森综合症的研究(2013-2016

国家自然科学基金项目:刺猬通路拮抗剂抗肿瘤药物的研发(2015-2018

苏州大学科研启动基金等

四、主要研究成果

 

Publications

 

1Exploration of the linkage elements of porcupine antagonists led to potent Wnt signaling pathway inhibitors. Dong, Y.; Li, K.; Xu, Z.; Ma, H.; Zheng, J.; Hu, Z.; He, S.; Wu, Y.; Sun, Z.; Luo, L.; Li, J.; Zhang, H.; Zhang, X.* Bioorg. Med. Chem. 2015, http://dx.doi.org/10.1016/j.bmc.2015.09.048

 

2Discovery of a 6-(pyridin-3-yl)benzo[d]thiazole template for optimization of hedgehog and PI3K/AKT/mTOR dual inhibitors, Yang, Z.; Ma, H.; Sun, Z.; Luo, L.; Tian, S.; Zheng, J.; Zhang, X.* Bioorg. Med. Chem. Lett. 2015, 25, 3665-3670.

 

3Design, synthesis and evaluation of a series of non-steroidal anti-inflammatory drug conjugates as novel neuroinflammatory inhibitors. Xu, Z.; Wu, J.; Zheng, J.; Ma, H.; Zhang, H.; Zhen, X.; Zheng, L.*; Zhang, X.* International Immunopharmacology 2015, 25(2), 528-537.

4Anti-inflammatory effects of glaucocalyxin B in microglia cells. Gan, P.; Zhang, L.; Chen, Y.; Zhang, Y.; Zhang, F.; Zhou, X.; Gao, B.; Zhen, X.; Zhang, X.; Zhang, J.; Zheng, L.* Journal of Pharmacological Sciences 2015, 128(1), 35-46. 

5Design, synthesis, and structure-activity-relationship of tetrahydrothiazolopyridine derivatives as potent smoothened antagonists. Ma, H.; Lu, W.; Sun, Z.; Luo L. *; Geng, D.; Yang, Z.; Li E.; Zheng, J.; Wang, M.; Zhang, H.; Yang, S.; Zhang, X.* European Journal of Medicinal Chemistry 2015, 89, 721-732.

 

6Optimization of 6-heterocyclic-2-(1H-pyrazol-1-yl)-N-(pyridin-2-yl) pyrimidin-4-amine as potent adenosine A2A receptor antagonists for the treatment of Parkinson ’s disease. Zheng, J.; Yang, Z.; Li, X.; Li, L.; Ma, H.; Wang, M.; Zhang, H.; Zhen, X.*; Zhang, X.* ACS Chemical Neuroscience 2014, 5, 674-682.

 

7Scaffold hopping approach to a new series of smoothened antagonists. Lu, W.; Geng, D.; Sun, Z.; Yang, Z.; Ma, H.; Zheng, J., Zhang, X.* Bioorg. Med. Chem. Lett. 2014, 24, 2300-2304.

 

8Replacement of amide with bioisosteres led to a new series of potent adenosine A2A receptor antagonists.  Yang, Z.; Li, X.; Ma, H.; Zheng, J.; Zhen, X.; Zhang, X.* Bioorg. Med. Chem. Lett. 2014, 24, 152-155.

 

9Cyclopamine, a naturally occurring alkaloid, and its analogues may find wide applications in cancer therapy.  Ma, H.; Li, H.; Zhang, X.* Curr. Top. Med. Chem. 2013, 13, 2208-2215.

 

10Pyrrolopyrazines as selective spleen tyrosine kinase inhibitors.  Fernando Padilla, Niala Bhagirath, Shaoqing Chen, Eric Chiao, David Michael Goldstein, Johannes Cornelius Hermann, Jonathan Hsu, Joshua J. Kennedy-Smith, Andreas Kuglstatter, Cheng Liao, Wenjian Liu, Lee E. Lowrie, Jr., Kin-Chun Luk , Stephen M. Lynch, John Menke, Linghao Niu, Timothy D. Owens, Counde O-Yang, Aruna Railkar, Ryan C. Schoenfeld, Michelle Slade, Sandra Steiner, Yun-Chou Tan, Armando G. Villasenor, Ce Wang, Jutta Wanner, Wenwei Xie, Daigen Xu, Xiaohu Zhang, Mingyan Zhou, Matthew Charles Lucas  J. Med. Chem., 2013, 56, 1677.

 

11Rational design of highly selective spleen tyrosine kinase inhibitors.  Matthew Charles Lucas, David Michael Goldstein, Johannes Cornelius Hermann, Andreas Kuglstatter, Wenjian Liu, Kin-Chun Luk , Fernando Padilla, Michelle Slade, Jutta Wanner, Wenwei Xie, Xiaohu Zhang, Cheng Liao  J. Med. Chem., 2012, 55 10414

 

12Discovery of NBI-77860/GSK561679, a potent Corticotropin Releasing Factor (CRF1) Receptor Antagonist with Improved Pharmacokinetic Properties.  Tellow, J.; Lanier-Gross, M.; Moorjani, M.; Lin, E.; Luo, Z.; Slee, D.; Zhang, X.; Hoare, S.; Grigoriadis, D.; Denis, Y.; Di Fabio, R.; Modugno, E.; Saunders, J.; Williams, J.  Bioorganic and Medicinal Chemistry Letters. 2010, 20 (24), 7259.

 

13Report of 2-Amino-N-Pyrimidin-4-yl Acetamides as A2A Receptor Antagonists with Improved Drug Like Properties and In Vivo Efficacy.  Lanier, M.; Luo, Z.; Chen, Y.; Lin, E.; Moorjani, M.; Slee, D.; Tellew, J.; Zhang, X.; Lechner, S.; Markison, S.; Joswig., Kargo, W.; Piercey, J.; Santos, M.; Malany, S.; Gross R.; Williams, J.; Castro-Palomino, J.; Crespo, M.; Prat, M.; Gual, S.; Diaz, J.; Wen, J.; O’Brien, Z.; Saunders, J.  Journal of Medicinal Chemistry.  2009, 52 (3), 709.

 

14Lead Optimization of 4-Acetylamino-2-(3, 5-dimethylpyrazol-1-yl)-6-pyridylpyrimidines as Adenosine A2A Antagonists for the Treatment of Parkinson’s Disease.  Zhang, X.; Tellew, J.; Luo, Z.; Moorjani, M.; Lin, E.; Lanier, M.; Chen, Y.; Williams, J.; Saunders, J.; Lechner, S.; Markison, S.; Joswig, T.; Malany, S.; Santos, M.; Gross R.; Wen, J.; O’Brien, Z.; Slee, D.  Journal of Medicinal Chemistry. 2008, 51 (22), 7099.

 

15Identification of Novel, Water Soluble, 2-Amino-N-Pyrimidin-4-yl Acetamides as A2A Receptor Antagonists with In Vivo Efficacy.  Slee, D.; Zhang, X.; Moorjani, M.; Lin, E.; Lanier, M.; Chen, Y.; Rueter, J.; Lechner, S.; Markison, S.; Malany, S.; Joswig, T.; Santos, M.; Gross R.; Williams, J.; Castro-Palomino, J.; Crespo, M.; Prat, M.; Gual, S.; Diaz, J.; Wen, J.; O’Brien, Z.; Saunders, J.  Journal of Medicinal Chemistry. 2008, 51 (3), 400.

 

162-Amino-N-Pyrimidin-4-yl Acetamides as A2A Receptor Antagonists: Part 1: SAR and Optimization of Heterocyclic Substituents.  Slee, D.; Chen, Y.; Zhang, X.; Moorjani, M.; Lanier, M.; Lin, E.; Rueter, J.; Williams, J.; Lechner, S.; Markison, S.; Malany, S.; Santos, M.; Gross R.; Jalali, K.; Sai, Y.; Zou, Z.; Yang, C.; Castro-Palomino, J.; Crespo, M.; Prat, M.; Gual, S.; Diaz, J.; Wen, J.; Saunders, J.  Journal of Medicinal Chemistry. 2008, 51 (6), 1719.

 

172-Amino-N-Pyrimidin-4-yl Acetamides as A2A Receptor Antagonists: Part 2: Reduction of hERG Activity, Observed Species Selectivity and SAR.  Slee, D.; Moorjani, M.; Zhang, X.; Lin, E.; Lanier, M.; Chen, Y.; Rueter, J.; Lechner, S.; Markison, S.; Malany, S.; Joswig., T.; Santos, M.; Gross R.; Williams, J.; Castro-Palomino, J.; Crespo, M.; Prat, M.; Gual, S.; Diaz, J.; Jalali, K.; Sai, Y.; Zou, Z.; Yang, C.; Wen, J.; O’Brien, Z.; Petroski, R.; Saunders, J.  Journal of Medicinal Chemistry. 2008, 51 (6), 1730.

 

18Synthesis of N-Pyrimidinyl-2-Phenoxyacetamides as Adenosine A2A Receptor Antagonists.  Zhang, X.; Rueter, J.; Chen, Y.; Moorjani, M.; Lanier, M.; Lin, E.; Gross R.; Tellew, J.; Williams, J.; Lechner, S.; Markison, S.; Joswig, T.; Malany, S.; Santos, M.; Castro-Palomino, J.; Crespo, M.; Prat, M.; Gual, S.; Diaz, J.; Saunders, J.; Slee, D.  Bioorganic and Medicinal Chemistry Letters.  2008, 18 (6), 1778.

 

192, 6-Diaryl-4-Phenacylaminopyrimidines as Potent and Selective Adenosine A2A Antagonists with Reduced hERG Liability.  Moorjani, M.; Zhang, X.; Chen, Y.; Lin, E.; Rueter, J.; Gross, R.; Lanier, M.; Tellew., J.; Williams, J.; Lechner, S.; Markison, S.; Malany, S.; Santos, M.; Ekhlassi, P.; Castro-Palomino, J.; Crespo, M.; Prat, M.; Gual, S.; Diaz, J.; Saunders, J.; Slee, D.  Bioorganic and Medicinal Chemistry Letters. 2008, 18 (4), 1269.

 

202,6-Diaryl-4-acylaminopyrimidines as Potent and Selective Adenosine A2A Antagonist with Improved Solubility and Metabolic Stability.  Moorjani, M.; Lou, Z.; Lin, E.; Vong, B.; Chen, Y.; Zhang, X.; Rueter, J.; Gross, R.; Lanier, M.; Tellew, J.; Williams, J.; Lechner, S.; Malany, S.; Santos, M.; Crespo, M.; Diaz, J.; Saunders, J.; Slee, D.  Bioorganic and Medicinal Chemistry Letters. 2008, 18 (20), 5402.

 

21Design and Synthesis of Tricyclic Imidazo [4, 5-b] pyridine-2-ones as Corticotropin-Releasing Factor-1 Antagonists.  Guo, Z.; Tellew, J.; Gross, R.; Dyck, B.; Grey, J.; Haddach, M.; Kiankarimi, M.; Lanier, M.; Li, B.; Luo, Z.; MaCarthy, J.; Moorjani, M.; Saunders, J.; Sullivan, R.; Zhang, X.; Zamani-Kord, S.; Grigoriadis, D.; Crowe, P.; Chen, T.; Williams, J.  Journal of Medicinal Chemistry 2005, 48 (16), 5104.

 

22Potent, Orally Active Corticotropin-Releasing Factor Receptor-1 Antagonists Containing a Tricyclic Pyrrolopyridine or Pyrazolopyridine Core. Dyck, B.; Grigoriadis, D.; Gross, R.; Guo, Z.; Marinkovic, D.; McCarthy, J.; Moorjani, M.; Regan, C.; Saunders, J.; Schwaebe, M.; Szabo, T.; Williams, J.; Zhang, X.; Bozigian, H.; Chen, T. K.  Journal of Medicinal Chemistry 2005, 48 (12), 4100.

 

23Fluorescence-Based Single-Tube Assays for Rapid Detection of Human Gene Mutations.  Hu, X.; Chen, L.; Belachew, B.; Huang, H.; Zhang, X.  Strategies, 2000, 13:71-73.

 

24High Yield Protection of Purine Ribonucleosides for Phosphoramidite RNA synthesis. Song, Q.; Wang, W.; Fischer, A.; Zhang, X.; Gaffney, B. L.; Jones, R. A.  Tetrahedron Letters, 1999, 40, 4153.

 

2515N NMR of Two Specifically Labeled RNA Fragments Containing Tandem GA Pairs.  Zhang, X.; Gaffney, B.; Jones, R. A.  J. Am. Chem. Soc. 1998, 120, 6625.

 

2615N NMR of a Specifically Labeled RNA Fragments Containing GU Pairs.  Zhang, X.; Gaffney, B.; Jones, R. A.  J. Am. Chem. Soc. 1998, 120, 615.

 

27High Yield Protection of Purine Ribonucleosides for H-Phosphonate RNA Synthesis.  Zhang, X.; Abad, J. L.; Huang, Q.; Zeng, F.; Gaffney, B.; Jones, R. A.  Tetrahedron Letters 1997, 38, 7135.

 

28Probing GU pairing in RNA Using 15N NMR.  Zhang, X.; Gaffney, B. L.; Jones, R. A. Structure, Motion, Interaction and Expression of Biological Macromolecules, Proceedings of the Conversation in the Discipline Biomelocular Stereodynamics, 10th, Albany, June 17-21, 1997. 2, 175-180.

 

2915N NMR of a Specifically Labeled RNA Fragment Containing Intrahelical GU Wobble Pairs.  Zhang, X.; Gaffney, B.; Jones, R. A.  J. Am. Chem. Soc. 1997, 119, 6432.

 

30RNA Synthesis Using a Universal, Base-Stable Allyl Linker.  Zhang, X.; Gaffney, B.; Jones, R. A.  Nucl. Acids Res. 1997, 25, 3980.

 

31Specific Labeling Approaches to Guanine and Adenine Imino and Amino Assignments in the AMP-RNA Aptamer Complex.  Jiang, F.; Patel, D.J.; Zhang, X.; Zhao, H.; Jones, R. A. Journal of Biomolecular NMR 1997, 9, 55.

 

32A Universal Allyl Linker for Solid Phase Synthesis.  Zhang, X.; Jones, R. A.  Tetrahedron Letters 1996, 37, 3789.

 

 

 

专利:

专利申请:具有腺苷受体拮抗剂活性的杂环氨基嘧啶化合物等两项中国专利申请(201310608492.8, 201310666030.1), 国际专利申请一项WO2015085909

 

专利申请:具有刺猬通路拮抗剂活性的吡啶杂环化合物及其用途等五项中国专利申请 (201310014254.4, 201310057744.2, 201310465383.5, 201310463448.2201310463448.2.) 国际专利申请一项WO2014113191

 

Pyrrolopyrazine kinase inhibitors.  Chen, Shaoqing; De Vicente Fidalgo, Javier; Hamilton, Matthew Michael; Hermann, Johannes Cornelius; Kennedy-Smith, Joshua; Li, Hongju; Lovey, Allen John; Lucas, Matthew C.; Luk, Kin-Chun Thomas; Lynch, Stephen M.; O'Yang, Counde; Padilla, Fernando; Schoenfeld, Ryan Craig; Sidduri, Achyutharao; Soth, Michael; Wang, Ce; Wovkulich, Peter Michael, Xiaohu Zhang. (with Roche) WO 2013030138, 2013.

 

Triazolopyridine compounds.  Hermann, J.; Lowrie Jr., L.; Lucas, M.; Luk, K.; Padilla, F.; Wanner, J.; Xie, W.; Zhang, X. (with Roche) WO2012163724, 2012.

 

Thiazolopyrimidine compounds as SYK inhibitors for the treatment of auto-immune and inflammation diseases.  Hermann, J.; Lowrie Jr., L.; Lucas, M.; Luk, K.; Padilla, F.; Wanner, J.; Xie, W.; Zhang, X. (with Roche) WO2012130780, 2012.

 

Preparation of pyrazolopyrimidines as inhibitors of DYRK1A and DYRK1B.  Liu, W.; Luk, K.; Zhang, X. (with Roche) US 20120184508 A1, 2012.

 

Preparation of aminopyridazine derivatives and analogs for use as histamine H4 receptor modulators.  Cai, H; Chavez, F; Dunford, P.; Greenspan, A; Meduna, S; Quiroz, J; Savall, B.; Tays, K.; Thurmond, R.; Wei, J.; Wolin, R.; Zhang, X (with J&J). World Patent, WO2009152325, 2009.

 

Substituted pyrimidines as adenosine receptor antagonists. Chen, Y.; Moorjani, M.; Slee, D.; Tellow, J.; Zhang, X.  World Patent, WO2008116185, 2008.

 

Phenoxy-substituted pyrimidines as adenosine receptor antagonists.  Slee, D.; Zhang, X.; Rueter, J. K.; Lin, E.; Crespo, M. I.; Castro, J. World Patent, WO2007084914, 2007.

 

Substituted Pyrimidines as adenosine receptor antagonists.  Slee, D.; Lanier, M.; Vong, B.; Chen, Y.; Zhang, X.; Lin, E.; Moorjani, M., Castro, J. World Patent, WO2006110884, 2006.

 

Preparation of pyrazolo [1, 5-a] pyrimidines as corticotrophin-releasing factor (CRF) receptor antagonists.  Lanier, M.; Luo, Z.; Moorjani, M.; Tellew, J.; Williams, J.; Zhang, X.  World Patent, WO2006044958, 2006.

 

Preparation of pyrazolopyrimidines as CRF receptor antagonists.  Luo, Z.; Slee, D.; Tellew, J.; Williams, J.; Zhang, X.  World Patent, WO2005063756. 2005. 

 

Preparation of pyrazolopyrimidines as CRF receptor antagonists.  Luo, Z.; Slee, D.; Tellew, J.; Williams, J.; Zhang, X.  World Patent, WO2005063755. 2005.

 

Preparation of Peptides as Ligands of Melanocortin Receptors.  Dyck, B. P.; Goodfellow, V.; Phillips, T.; Parker, J.; Zhang, X.; Chen, C.; Tran, J. A.; Pontillo, J.; Tucci, F. C. World Patent, WO2003031410. 2003.

 

Universal Allyl Linker for Solid-Phase Nucleic Acid Synthesis. Zhang, X.; Jones, R. A. United States Patent, US6005125. 1999.