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C Assistant

Location:
Kenilworth, New Jersey, United States
Posted:
October 09, 2016

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ZHI-QIANG YANG, Ph.D.

Phone: 908-***-****(Cell)

acwy9a@r.postjobfree.com

www.linkedin.com/in/yang-zhi-qiang

CHEMISTRY AND DRUG DISCOVERY LEADER

Successful drug discovery/development scientist with over 14 years of experience across therapeutic areas (oncology, CNS, cardiovascular and diabetes), and across modalities from small molecules to large peptides. Inventor of 12 preclinical candidates, 5 moved into First-in-Man and one progressed to Phase II clinical trial. Developed robust processes supporting complex carbohydrate and peptide bioconjugates as preclinical candidates. Extensive managerial experience with internal and external scientists. Led successful collaborative teams with cross- function responsibility to meet delivery objectives. AREAS of EXPERTISE

Structure-Based Drug Design Chemical Analysis Molecular Modeling

Process Development API Quality Control Polymer Chemistry

Peptide/Carbohydrate Chemistry Bioconjugation Chemical Biology EDUCATION

Ph.D., Organic Chemistry, University of Wisconsin-Madison, Madison, WI, 2002 Thesis title: "Synthetic Ligands for L-Selectin and for B-Cell Receptors" Advisor: Professor Laura L. Kiessling

M.S., Organic Chemistry, Chinese Academy of Sciences, Beijing, China, 1993 B.S., Chemistry, Peking University, Beijing, China, 1990 PROFESSIONAL EXPERIENCE

Merck Research Laboratories (West Point, Rahway and Kenilworth) 2004-2016 Associate Principal Scientist, Discovery and Process Chemistry, Merck 2012-2016 External Chemistry Lead, Medicinal Chemistry 2011-2012 Research Fellow, Medicinal Chemistry 2007-2011

Senior Research Chemist, Medicinal Chemistry 2004-2007 Memorial Sloan-Kettering Cancer Center, New York City 2002-2004 Postdoctoral Fellow, Laboratory of Bioorganic Chemistry Advisor: Professor Samuel J. Danishefsky

Total Synthesis of Natural Products as Anticancer Agents

Developed an efficient synthesis for cyclopropyl radicicol (metabolically more stable than epoxide-containing natural product, radicicol) as an Hsp90 inhibitor, which achieved potent anti- tumor effect in rodents. Invented a new methodology using cobalt-complexation of alkynes to promote ring-closing metathesis. Pioneered using “ynolides” as dienophiles to facilitate Diels- Alder reactions.

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Completed total synthesis of natural macrocyclic peptides TMC-95A and B as potent proteasome inhibitors for cancer treatment. Designed and synthesized various analogues for SAR studies. University of Wisconsin-Madison 1996-2002

Research Assistant

Synthesis of Glycoconjugates and Glycopolymers for Selectins and for B-Cell Receptors

Developed efficient syntheses of selectin ligand, tetrasaccharide 6-sulfo sLex. Designed, synthesized and characterized related novel glycolipids and glycopolymers to study carbohydrate- protein interactions, important in regulating inflammation and immune response.

Designed and synthesized CD22 trisaccharide ligand and corresponding glycopeptides and glycopolymers to study B-cell receptor signaling, important for immune disorders and cancer. University of Rhode Island 1994-1996

Teaching Assistant

AWARDS

ACS Meeting Travel Award, University of Wisconsin-Madison, 1999 SCC Scholarship, University of Wisconsin-Madison, 2000 Goodwin postdoctoral fellow, Memorial Sloan Kettering Cancer Center, 2003-2004 Department Excellence Awards, Merck, 2005, 2006.

Quarterly Stock Option Awards, Merck, 2005, 2006

Merck Grand Challenge Award, 2012

Department Excellence Award, Process Chemistry, Merck, RY, 2015. AFFILIATION

American Chemical Society, 2004-current

Board member of Tristate Chinese American Chemical Society, 2014-current PUBLICATIONS

1. Tung, C. -H.; Li, Y.; Yang, Z. -Q. “Hydrophobic Effects on Photochemical and Photophysical Processes. 15. Intramolecular Photodimerization of 2-Naphthoates – Successful Application of Hydrophobic Forces in the Preparation of Large-Ring Compounds.” J. Chem. Soc. Faraday T. 1994, 90, 947-951.

2. Tung, C. -H.; Ying, Y. -M.; Yang, Z. -Q.; Wang, X. -H. “Photochemistry of Substituted Phenyl Phenylacetates within Cyclodextrin Cavities.” Chinese Chem. Lett. 1995, 6, 27-30. 3. Tung, C. -H.; Wang, X. -H.; Ying, Y. -M.; Yang, Z. -Q. “Effects of Silica Surface and External Magnetic-Field on Photochemical Reactions of Phenyl-Esters.” Res. Chem. Intermediat. 1995, 21, 613-620.

4. Yang, Z. -Q.; Puffer, E. B.; Pontrello, J. K.; Kiessling, L. L. “Synthesis of a Multivalent Display of a CD22-Binding Trisaccharide.” Carbohydr. Res. 2002, 337, 1605-1613. 5. Genbacev, O. D.; Prakobphol, A.; Foulk, R. A.; Krtolica, A. R.; Ilic, D.; Singer, M. S.; Yang, Z. -Q.; Kiessling, L. L.; Rosen, S. D. Fisher, S. "Trophoblast L-Selectin-Mediated Adhesion at the Maternal- Fetal Interface." Science 2002, 299, 405-408.

6. Yang, Z.-Q.; Danishefsky, S. J. “A Concise Route to Benzofused Macrolactones via Ynolides: Cycloproparadicicol.” J. Am. Chem. Soc. 2003, 125, 9602-9603.

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7. Yang, Z.-Q.; Kwok, B. H. B.; Lin, S.; Koldobskiy, M.; Crews, C. M.; Danishefsky, S. J. “Simplified Synthetic TMC-95A/B Analogues Retain the Potency of Proteasome Inhibition.” ChemBioChem. 2003, 4, 508-513.

8. Mowery, P.; Yang, Z. -Q.; Gordon, E. J.; Dwir, O.; Spencer, A. G.; Alon, R.; Kiessling, L. L. “Synthetic Glycoprotein Mimics Inhibit L-Selectin-Mediated Rolling and Promote L-Selectin Shedding.” Chem. Biol. 2004, 11, 725-732.

9. Lin, S.; Yang, Z.-Q.; Kwok, B. H. B; Koldobskiy, M.; Crews, C. M.; Danishefsky, S. J. “Total synthesis of TMC-95A and -B via a new reaction leading to Z-enamides. Some preliminary findings as to SAR.” J. Am. Chem. Soc. 2004, 126, 6347-6355.

10. Yang, Z.-Q.; Geng, X.; Solit, D.; Pratilas, C. A.; Rosen, N.; Danishefsky, S. J. “New efficient synthesis of resorcinylic macrolides via ynolides: Establishment of cycloproparadicicol as synthetically feasible preclinical anticancer agent based on Hsp90 as the target.” J. Am. Chem. Soc. 2004, 126, 7881-7889.

11. Geng, X.; Yang, Z.-Q.; Danishefsky, S. J. “Synthetic development of radicicol and cycloproparadicicol: Highly promising anticancer agents targeting hsp90.” Synlett, 2004, 8, 1325- 1333.

12. Yang, Z.-Q. “Agonists and antagonists for group III metabotropic glutamate receptors 6, 7 and 8” Curr.Top. Med. Chem., 2005, 5, 913-918.

13. Shipe, W. D.; Barrow, J. C.; Yang, Z.-Q. et. al “Design, synthesis, and evaluation of a novel 4- aminomethyl-4-fluoropiperidine as a T-type Ca2+ channel antagonist.” J. Med. Chem. 2008, 51, 3692-3695.

14. Barrow, J. C.; Stauffer, S. R.; Rittle, K. E.; Ngo, P. L.; Yang, Z.-Q. et. al. “Discovery and X-ray Crystallographic Analysis of a Spiropiperidine Iminohydantoin Inhibitor of beta-Secretase” J. Med. Chem. 2008, 51, 6259-6262.

15. Yang, Z.-Q.; Barrow, J. C.; Shipe, W. D. et. al. “Discovery of 1,4-Substituted Piperidines as Potent and Selective Inhibitors of T-Type Calcium Channels.” J. Med. Chem. 2008, 51, 6471-6477. 16. Uebele, V.N.; Gotter, A. L.; Nuss, C. E.; Kraus, R. L.; Doran, S. M.; Garson, S. L. Reiss, D. R.; Li, Y. X.; Barrow, J. C.; Reger, T. S.; Yang, Z.-Q. et. al. “Antagonism of T-type calcium channels inhibits high- fat diet-induced weight gain in mice.” J. Clin. Investi. 2009, 119, 1659-1667. 17. Courtney, A. H.; Puffer, E. B.; Pontrello, J. K.; Yang, Z.-Q.; Kiessling, L. L. “Sialylated multivalent antigens engage CD22 in trans and inhibit B cell activation.” Proc. Nat. Acad Sci. U. S. A. 2009, 106 2500-2505.

18. Uebele, V. N.; Nuss, C. E.; Fox, S. V.; Garson, S. L.; Cristescu, R.; Doran, S. M.; Kraus, R. L.; Santarelli, V. P.; Li, Y.; Barrow, J. C.; Yang, Z.-Q. et. al. “Positive Allosteric Interaction of Structurally Diverse T-Type Calcium Channel Antagonists.” Cell Biochem. Biophys. 2009, 55, 81–93. 19. Barrow, J.C., Rittle, K.E., Reger, T.S., Yang, Z.Q., Bondiskey, P., McGaughey, G.B., Bock, M.G., Hartman, G.D., Tang, C., Ballard, J.E., Kuo, Y., Prueksaritanont, T., Nuss, C.E., Doran, S.M., Fox, S.V., Garson, S.L., Kraus, R.L., Li, Y., Marino, M.J., Kuzmick, Graufelds V., Uebele, V.N., Renger, J.J. Discovery of 4,4-Disubstituted Quinazolin-2-ones as T-Type Calcium Channel Antagonists. ACS Med. Chem. Lett. 2010, 1, 75.

20. Schlegel, K.A.S., Yang, Z.Q., Reger, T.S., Shu, Y., Cube, R., Rittle, K.E., Bondiskey, P., Bock, M.G., Hartman, G.D., Tang, C., Ballard, J., Kuo, Y., Prueksaritanont, T., Nuss, C.E., Doran, S.M., Fox, S.V., Garson, S.L., Kraus, R.L., Li, Y., Uebele, V.N., Renger, J.J., Barrow, J.C. Discovery and Expanded SAR of 4,4-Disubstituted Quinazolin-2-ones as Potent T-type Calcium Channel Antagonists. Bioorg. Med. Chem. Lett. 2010, 20, 5147-5152.

21. Kraus, R.L., Li, Y., Gregan, Y., Gotter, A.L., Uebele,V.N., Fox, S.V., Doran, S.M., Barrow, J.C., Yang, Z.Q., Reger, T.S., Koblan, K.S., Renger, J.J. In Vitro Characterization of T-type Calcium Channel Antagonist TTA-A2 and In Vivo Effects on Arousal in Mice. Journal of Pharmacology and Experimental Therapeutics 2010, 335, 409-417.

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22. Yang, Z.-Q, et. al. Short-Acting T-Type Calcium Channel Antagonists Significantly Modify Sleep Architecture in Rodents. ACS Med. Chem. Lett. 2010, 1, 75-77. 23. Reger, T. S.; Yang, Z.-Q. et. al. Pyridyl amides as potent inhibitors of T-type calcium channels. Bioorg. Med. Chem. Lett. 2011, 21, 1692-1696.

24. Yang, Z.-Q.; Shu, Y.; Ma, L.; Wittmann, M.; Ray, W. J.; Seager, M. A.; Koeplinger, K. A.; Thompson, Charles D.; Hartman, George D.; Bilodeau, Mark T.; Kuduk, Scott D. Discovery of Naphthyl-Fused 5- Membered Lactams as a New Class of M1 Positive Allosteric Modulators. ACS Med. Chem. Lett., 2014, 5, 604–608.

PATENTS

1. Danishefsky, S. J.; Yang, Z.-Q.; Geng, X.; Chou, T.-C.; Rosen, N. “Preparation of aigialomycin D, radicicol and monocillin I and their macrocyclic analogs for use in pharmaceutical compositions as antitumor agents.” PCT Int. Appl. (2005), WO 200******* A1 20050707. 2. Barrow, J. C.; Coburn, C. A.; Egbertson, M. S.; McGaughey, G. B.; McWherter, M. A.; Neilson, L.; Selnick, H. G.; Stauffer, S. R.; Yang, Z.-Q. et al. “Preparation of spiropiperidine compounds as β- secretase inhibitors for the treatment of Alzheimer's disease” PCT Int. Appl. (2006), WO 200******* A2 20060427.

3. Barrow, J. C.; Cube, R. V.; Ngo, P. L.; Rittle, K. E.; Yang, Z.-Q; Young, Steven, D. “Preparation of quinazolinones as T-type calcium channel antagonists.” PCT Int. Appl. (2006), 72pp. WO 200******* A2 20060921.

4. Barrow, J. C.; Lindsley, C. W.; Shipe, W. D.; Yang, Z.-Q.; Wisnoski, D. “Preparation of 4- fluoropiperidine derivatives as T-type calcium antagonists.” PCT Int. Appl. (2007), 89 pp. WO 200******* A2 20070104.

5. Barrow, J. C.; Lindsley, C. W.; Shipe, W. D.; Yang, Z.-Q. “Preparation of 3-fluoropiperidine compounds as T-type calcium channel antagonists. “ PCT Int. Appl. (2007), 50 pp. WO 200******* A2 20070104.

6. Barrow, J. C.; Bieber, K. S.; Cube, R. V.; Mattern, M. C.; Reger, T. S.; Shu, Y; Yang, Z.-Q. “Pyridyl amide derivatives, processes for preparing them, pharmaceutical compositions containing them, and their use as T-type calcium channel antagonists.” PCT Int. Appl. (2007), 117 pp. WO 200******* A2 20071025.

7. Barrow, J. C.; Yang, Z.-Q. “Quinazolinone T-type calcium channel antagonists.“ PCT Int. Appl.

(2009), WO 200******* A1 20090115.

8. Barrow, J. C.; Yang, Z.-Q. “Preparation of pyrazinyl amide T-type calcium channel antagonists.” PCT Int. Appl. (2009), WO 200******* A1 20090430.

9. Barrow, J. C.; Coleman, P. J.; Reger, T. S.; Schlegel, K. S.; Shu, Y; Yang, Z.-Q. “Preparation of N- pyridinylethyl phenylacetamides as T-type calcium channel antagonists.” PCT Int. Appl. (2009), 72pp. WO 200******* A1 20090430.

10. Barrow, J. C.; Reger, T. S.; Shu, Y.; Yang, Z.-Q. “Preparation of heterocycle amides as T-type calcium channel antagonists.” PCT Int. Appl. (2009), WO 200******* A1 20090430. 11. Barrow, J. C.; Yang, Z.-Q. “Pyrazinyl phenyl amides as T-type calcium channel antagonists.” PCT Int. Appl. (2011), WO 201******* A1 20110224.

12. Schlegel, K.-A.; Shu, Y.; Yang, Z.-Q.; Barrow, J. “Heterocycle amides as T-type calcium channel antagonists and their preparation and use for the treatment of diseases.” PCT Int. Appl. (2011), WO 201******* A1 20110505.

13. Yang, Z.-Q. Nantermet, P. G.; Kreatsoulas, C.; Moore, K. P.; Shalen, E. F. “Preparation of oxazole derivatives useful as modulators of FAAH.” PCT Int. Appl. (2011), WO 201******* A1 20111027. 14. Nantermet, P. G.; Yang, Z.-Q.; Kreatsoulas, C.; Walji, A. M.; Zhu, H. “Oxazole derivatives as FAAH modulators and their preparation and use for the treatment of FAAH-mediated diseases.” PCT Int. Appl. (2011), WO 201******* A1 20111027.

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15. Kuduk, S.D.; Di Marco, C.N.; Yang, Z.-Q. “Quinolizidinone M1 receptor positive allosteric modulators.” WO 201******* A1 20121122.

16. Kuduk, S. D.; Schlegel, K.; Yang, Z.-Q. “Quinoline-amide derivatives as M1 receptor positive allosteric modulators and their preparation, pharmaceutical compositions and use in the treatment of diseases.” PCT Int. Appl. (2011), WO 201******* A1 20110714. 17. Kuduk, S. D.; Beshore, D. C.; Yang, Z.; Shu, Y. “Fused isoindolone M1 receptor positive allosteric modulators and their preparation and use for the treatment of M1-mediated diseases.” PCT Int. Appl. (2012), WO 201******* A1 20120105.

18. Kuduk, S. D.; Beshore, D. C.; Yang, Z.-Q.; Shu, Y.; Pitts, D. “Preparation of benzoisoindolylmethyllactam derivatives and analogs for use as M1 receptor positive allosteric modulators.” PCT Int. Appl. (2012), WO 201******* A1 20121122. 19. Kuduk, S. D.; Dimarco, C. N.; Yang, Z.-Q. “N-linked quinolineamide M1 receptor positive allosteric modulators”. PCT Int. Appl. (2012), WO 201******* A1 20121122. 20. Yang, Z.; Zhang, F.; Dong, G.; Knowles, S. L.; Maletic, M.” 7A-amide substituted 6,6-difluoro bicyclic himbacine derivatives” PCT Int. Appl. (2015), WO 201******* A1 20150226. 21. Yang, Z.; Dong, G.; Maletic, M. “7A-Heterocycle substituted-6, 6-Difluoro bicyclic himbacine derivatives” PCT Int. Appl. (2015), WO 201******* A1 20150226. 22. Campbell, B. T.; Dong, G.; Garfunkle, J.; Kim, A.; Ornoski, O.; Parker, D., Jr.; Raghavan, S.; Xu, L.; Yang, Z. “Preparation of imidazopyrazine derivatives useful as soluble guanylate cyclase activators” PCT Int. Appl. (2015), WO 201******* A1 20151210. 23. Stamford, A. W.; Cai, S.; Duan, X.; Cao, J.; Yang, Z.-Q.; Maletic, M. “Preparation and use of cyclic sulfonamide derivatives as PAR-1 receptor antagonists” PCT Int. Appl. (2016), WO 201******* A1 20160421.

24. Stamford, A. W.; Yang, Z.-Q.; Maletic, M.; Cai, S.; Duan, X.; Cao, J. “Preparation and use of cyclic sulfonamide derivatives as PAR-1 receptor antagonists” PCT Int. Appl. (2016), WO 201******* A1 20160421.

25. Berger, R.; Dong, G.; Raghavan, S.; Yang, Z. “Preparation of triazolo-pyrazinyl derivatives useful as soluble guanylate cyclase activators” PCT Int. Appl. (2016), WO 201******* A1 20160526. PRESENTATIONS

1. Synthesis of Sulfated Lewis x Glycolipids for L-Selectin (poster). 36th National Organic Chemistry Symposium, Madison, WI, June 1999.

2. Total Synthesis of Polymeric 6-Sulfo Sialyl Lewis X as a Multivalent Ligand for L-Selectin

(poster). 220th ACS National Meeting, Washington, DC, August 2000. 3. 1, 4-Piperidines as AlphaI1I Calcium Antagonists Significantly Modify Sleep Architecture in vivo.

(Invited talk) Chemistry Council Medicinal Chemistry Conference, La Sapiniere, Val David, Quebec, Canada, June18-22, 2005

3. Discovery of 1,4-Piperidines as Selective and Potent T-type Calcium Channel Antagonists.

(Invited talk) 224th National ACS Meeting, Boston, MA, August 19, 2007. 4. Selective and Potent T-Type Calcium Channel Antagonists Significantly Improve Sleep Architecture in Rodents and Nonhuman Primates (Invited talk). 238th National ACS Meeting, Washington, DC, August 16-20, 2009.

5. Short acting T-Type Calcium Channel Antagonists Significantly Modify Sleep Architecture in Rodents (invited talk). BIT’s 1st Annual International Conference of Medchem, Beijing, May 18-20, 2010.

6. Discovery of Heterocycle Amides as Selective and Potent T-Type Calcium Channel Antagonists

(poster). Gordon Conference Heterocyclic Compounds, June 26 - July 1, 2011, Salve Regina University, Newport, RI.

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7. Discovery of Potent and Soluble FAAH Inhibitors for Treatment of Pain (poster). Gordon Conference Heterocyclic Compounds, June 21 – June 26, 2015, Salve Regina University, Newport, RI.

8. Discovery of Thrombin Receptor Antagonists for QD Dosing (poster). Gordon Conference Medicinal Chemistry, August 07 – August 12, 2016, Colby Sawyer University, New London, NH.



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