Synthetic Organic Chemist
Resume:
JULIUS JARET MATASI, PhD. Chemistry
** ****** ****, ******** ********, NJ 08852
********@*****.***
SUMMARY OF QUALIFICATIONS:
A motivated results-oriented synthetic organic chemist with over 10 years research experience working as a medicinal chemist in drug discovery at a pharmaceutical company. Extensive technical and hands on experience in the design and synthesis of novel drugs, multistep organic synthesis, lead identification, optimization and scale up of compounds for in vivo and safety studies, optimization of pharmacokinetic properties, structure-activity relationships, intellectual property search and analysis, writing disclosures and drafting of patents, presentation at meetings and publication of papers and patents. Significant interaction with biologists, efficient mentoring of associates and a record of advancing projects.
RESEARCH EXPERIENCE:
Principal Scientist
Merck Research Laboratories November 2009-Present
• Identified potent and selective compounds using a structure-based drug design for a lead identification kinase receptor program with potential for advancement to lead optimization in a pain program.
• Novel and potent compounds were identified for the Nav1.7 program to speed up entry to the lead optimization program from lead identification.
Principal Scientist
Schering-Plough Research Institute April 2002-November 2009
• Lead optimization of P2X7 antagonists resulting in novel compounds with in vivo efficacy in the rat MIA, CCI and SNL models of pain and as leading recommendation candidates for the clinical trials
• Led chemistry effort on the P2X7 program in meetings, updates and collaboration with AMRI scientists to advance the project and readily addressed the issues that were encountered
• Led the effort for the development of potent mGLUR1 antagonists for the treatment of chronic pain and SAR effort that provided the successful completion of the project, also developed CB2 agonists for pain management
• Associates were hired and motivated to be high performing members of a fully collaborative group and allowed to become independent with little guidance through difficult synthetic and biological issues.
Associate Principal Scientist
Schering-Plough Research Institute April 1999- April 2002
• Discovered and led the chemistry for the synthesis of novel truncated biaryls as back-up to Preladent, a promising A2a antagonist drug for treatment of Parkinson’s disease currently in clinical trials.
• Developed imidazole analogs as possible back-up for the A2a program.
Senior Research Scientist
Schering-Plough Research Institute October 1996- April 1999
• Explored the SAR of potent spiropiperidines at the Nociceptin Receptor (NOP1) for the treatment of pain, cough and anxiety for advancement to the clinical trials as back-up.
Post-Doctoral Fellow
State University of New York, Buffalo, NY and Wake Forest University, NC. September 1992-October 1996
• Developed an asymmetric synthesis of tropanes using a chiral auxiliary or a chiral rhodium (II) catalyst towards novel conformational constrained tropanes, a novel rearrangement leading to 7-azabicyclo [4.2.0] octadienes.
ADDITIONAL SKILLS
NMR, FT-IR, UV/VS, LC-MS, HPLC, microwave reactions, parallel synthesis, purification techniques, Microsoft word, Microsoft Excel, Microsoft PowerPoint, ChemWindows, ISIS, SciFinder, ELN
EDUCATION: University of Maryland, College Park, MD: Doctor of philosophy in chemistry
Thesis: The intramolecular reaction of cyclopropylcarbene-chromium complexes with alkynes. Efforts directed towards the synthesis of Prostacyclin PGI1.
University of Nairobi, Nairobi, Kenya: Master of Science and Bachelor of Science
SCHOLARSHIPS AND AWARDS:
Schering-Plough Shining Performance for cross-functional activities
DAAD Scholarship for MSc studies
PUBLICATIONS:
1.Brumfield, Stephanie; Matasi, Julius J.; Tulshian, Deen; Czarnecki, Michael; Greenlee, William; Garlisi, Charles G.; Qiu, Hongchen; Devito, Kristine; Chen, Shu-Cheng; Sun, Youngliang; Bertorelli, Rosalia; Geiss, William; Le, Van-Duc; Martin, Gregory S.; Vellekoop, Samuel A.; Haber, James; Allard, Melissa L. Synthesis and SAR development of novel P2X7 receptor antagonists for the treatment of pain: Part 2. Bioorganic & Medicinal Chemistry Letters (2011), 21(24), 7287-7290.
2.Matasi, Julius J.; Brumfield, Stephanie; Tulshian, Deen; Czarnecki, Michael; Greenlee, William; Garlisi, Charles G.; Qiu, Hongchen; Devito, Kristine; Chen, Shu-Cheng; Sun, Youngliang; Bertorelli, Rosalia; Geiss, William; Le, Van-Duc; Martin, Gregory S.; Vellekoop, Samuel A.; Haber, James; Allard, Melissa L. Synthesis and SAR development of novel P2X7 receptor antagonists for the treatment of pain: Part 1. Bioorganic & Medicinal Chemistry Letters (2011), 21(12), 3805-3808.
3.Yang, Shu-Wei; Smotryski, Jennifer; Matasi, Julius; Ho, Ginny; Tulshian, Deen; Greenlee, William J.; Brusa, Rossella; Beltramo, Massimiliano; Cox, Kathleen. Structure-activity relationships of 2,4-diphenyl-1H-imidazole analogs as CB2 receptor agonists for the treatment of chronic pain. Bioorganic & Medicinal Chemistry Letters (2011), 21(1), 182-185.
4.Caldwell, John P.; Matasi, Julius J.; Fernandez, Xiomara; McLeod, Robbie L.; Zhang, Hongtao; Fawzi, Ahmad; Tulshian, Deen B. Synthesis and structure-activity relationships of N-substituted spiropiperidines as nociceptin receptor ligands: Part 2. Bioorganic & Medicinal Chemistry Letters (2009), 19(4), 1164-1167.
5.Varty, Geoffrey B.; Lu, Sherry X.; Morgan, Cynthia A.; Cohen-Williams, Mary E.; Hodgson, Robert A.; Smith-Torhan, April; Zhang, Hongtao; Fawzi, Ahmad B.; Graziano, Michael P.; Ho, Ginny D.; Matasi, Julius; Tulshian, Deen; Coffin, Vicki L.; Carey, Galen J. The anxiolytic-like effects of the novel, orally active nociceptin opioid receptor agonist 8-[bis(2-methylphenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol (SCH 221510). Journal of Pharmacology and Experimental Therapeutics (2008), 326(2), 672-682.
6. Matasi, J. J.; Caldwell, J.; Tulshian, D.; Zhang, H.; Torhan, S. A.; Fawzi, A. Synthesis and structure-activity relationships of N-substituted spiropiperidines as nociceptin receptor ligands: Part 1. Biorg. Med. Chem. Lett.. 2007, 17, 2281-2284.
7. Silverman, L. S.; Matasi, J. J.; Caldwell, J.; Kiselgof, E. J.; Tulshian, D.; Greenlee, W.; Arik, L.; Foster, C.; Bertorelli, R.; Monopoli, A.; Ongini, E. 3H-[1,2,4]-Triazolo[5,1-1]purin-5-amine derivatives as adenosine A2a antagonists. Biorg. Med. Chem. Lett.. 2007, 17(6), 1659-1662.
8. Matasi, J. J.; Caldwell, J.; Hao, J.; Tulshian, D.; Neustadt, B.; Arik, L.; Foster, C.; Lachowicz, J. The discovery and synthesis of novel adenosine A2a Receptor Antagonists. Biorg. Med. Chem.Lett. 2005, 15(5), 1333-1336.
9. Matasi, J. J.; Caldwell, J.; Zhang, H.; Tulshian, D.; Fawzi, A.; Cohen-Williams, M. E.; Varty, G. B. 2-(2-Furanyl)-7-phenyl[1,2,4]triazolo[1,5-c]pyrimidin-5-amine analogs: Highly potent, orally active, adenosine A2A antagonists. Part 1. Biorg. Med. Chem.Lett. 2005, 15(16), 3670-3674.
10. Matasi, J. J.; Caldwell, J.; Zhang, H.; Tulshian, D.; Fawzi, A.; Cohen-Williams, M. E.; Varty, G. B. 2-(2-Furanyl)-7-phenyl[1,2,4]triazolo[1,5-c]pyrimidin-5-amine analogs: The successful reduction of hERG activity. Biorg. Med. Chem.Lett. 2005, 15(16), 3675-3678.
11. Corboz, M. R.; Rivelli, M. A.; Egan, R. W.; Tulshian, D.; Matasi, J. J.; Fawzi, A. B.; Benbow, L.; Smith-Torhan, A.; Zhang, H.; and Hey, J. A. Nociceptin inhibits capsaicin-induced bronchoconstriction in isolated guinea pig lung. Eur. J. Pharm. 402, 2000, 171-179.
12. Churchill, M. R.; Churchill, D. G.; Matasi, J. J.; Davies, H. M. L. Absolute configuration of C27H41NO8Si, the diasteroselective product of the rhodium(II) octanoate catalyzed decomposition of a chiral vinyldiazomethane in the presenceof 2-acetylpyrrole: A structural study rendered difficult by disorder of a “heavy” atom. J. Chemical crystallography. 1999, 29(9), 1061-1066.
13. Matasi, J. J.; Yan, J.; Herndon, J. W. Intramolecular coupling of conjugated enynes with Cyclopropylcarbene-Chromium Complexes; A complex reaction pathway. Inorganica Chemica Acta 1999, 296(1), 273-277.
14. Yan, J.; Zhu, J.; Matasi, J. J.; and Herndon, J. W., Relative Asymmetric Induction in the Intramolecular Reaction between Alkynes and Cyclopropylcarbene-Chromium Complexes: Stereocontrolled Synthesis of Five-Membered Rings Fused to Oxygen Heterocycles. J. Org. Chem. 1999, 64, 1291-1301.
15. Davies, H. M. L.; Hodges, L. M.; Matasi, J. J.; Hansen, T.; Stafford, D.G. Effects of carbenoid structure on the reactivity of rhodium-stabilized carbenoids. Tetrahedron Lett. 1998, 39(25), 4417-4420.
16. Davies, H. M. L.; Matasi, J. J.; Hodges, L. M.; Huby, N. J. S.; Thornley, C.; Kong, N.; Houser, J. H., Enantioselective Synthesis of Functionalized Tropanes by Rhodium (II) Carboxylate-Catalyzed Decomposition of Vinyldiazomethanes in the Presence of Pyrroles. J. Org. Chem. 1997, 62, 1095.
17. Porrino, L. J.; Miller, M.; Hedgecock, A. A.; Thornley, C.; Matasi, J. J.; Davies, H. M. L. Local cerebral metabolic effects of novel cocaine analog WF-31: comparisons to fluoxetine. Synapse (NEW YORK) 1997, 27(1), 26-35.
18. Hernby, S. E.; Lucki, I.; Gatto, G.; Singh, A.; Thornley, C.; Matasi, J. J.; Kong, N.; Smith, J. E.; Davies, H. M. L.; Dworkin, S. Potential antidepressant effects of novel tropane compounds, selective for serotonin or dopamine transporters. J. Pharm. and Experintal Therapautics 1997, 282(2), 727-733.
19. Daunais, J. B.; Hart, S. L.; Hedgecock-Rowe, A.; Thornley, C.; Matasi, J. J.; Davies, H. M. L.; Porrino, L. J. Alterations in behavior and opioid gene expression induced by the novel tropane analog WF-31. Molecular Brain Research 1997, 50(1, 2), 293-304.
20. Davies, H. M. L.; Matasi, J. J.; and Ahmed, G. Divergent Pathways in the Intramolecular Reactions Between Rhodium-Stabilized Vinylcarbenoids and Pyrroles: Construction of Fused Tropanes and 7-Azabicyclo [4.2.0] octadienes. .J. Org. Chem. 1996, 61, 2305.
21. Davies, H. M. L.; Kuhn, L. A.; Thornley, C.; Matasi, J. J.; Sexton, T.; and Childers, S. R. Synthesis of 3b-Aryl-8-azabicyclo[3.2.1]octanes with High Binding Affinities and Selectivities for the Serotonin Transporter Site. J. Med. Chem. 1996, 39, 2554.
22. Davies, H. M. L.; Matasi, J. J.; and Thornley, C. Control of Carbenoid Reactivity Through Neighboring Group Participation. Tetrahedron Lett. 1995,36,7205.
23. Davies, H. M. L and Matasi, J. J., Synthesis of 7-azabicyclo [4.2.0] octadienes by Rhodium (II) Catalyzed reaction of diazomethanes and pyrroles. Tetrahedron Lett. 1994, 35, 5209-5212.
24. Herndon, J. W.; Tumer, S. U.; Matasi, J. J.; McMullen, L. A.; and Schnatter, W. F. K. Cyclopropylcarbene-Chromium Complexes: Versatile Reagents for the Synthesis of Five-Membered Rings. Advances in Metal-Organic Chemistry, JAI Press, L. S. Liebeskind Ed., 1994, 3, 51-95.
25. Davies, H. M. L.; Saikali, E.; Huby, N. J. S.; Gilliatt, V. J.; Matasi, J. J.; Sexton, T. and Childers, S. R., Synthesis of Novel 2-Substituted Cocaine Analogs and Their Binding Affinities at Dopamine and Serotonin Transport Sites in Rat Striatum and Frontal Cortex. J. Med. Chem. 1994, 37, 1262-1268.
26. Herndon, J. W.; Zora, M.; Patel, P. P.; Chatterjee, G.; Matasi, J. J.; and Tumer, S. U. Preparation of Seven-Member Rings by the Reaction of Cyclopropylcarbene-Tungsten and Molybdenum Complexes with Alkynes. Tetrahedron, 49, 1993, 5507-5530.
27. Herndon, J. W. and Matasi, J. J., Reduction of Vinylogous Esters. Tetrahedron Lett. 1992, 33, 5725-5728.
28. Herndon, J. W.; Chatterjee, G.; Patel, P. P.; Matasi, J. J.; Tumer, S. U.; Harp, J. J. and Reid, M., Cyclopropylcarbene-Tungsten Complexes + Alkynes: a [4+2+1] Cycloaddition route for the Construction of Seven-Member Rings. J. Am. Chem. Soc. 1991, 113, 7808.
29. Herndon, J. W.; Tumer, S. U.; McMullen, L. A.; Matasi, J. J.; Schnatter, W. F. K. and Daitch, C. E., Reactions of Cyclopropylcarbene-Chromium Complexes. Comm. Inorg. Chem. 1990, 10, 1-24.
30. Herndon, J. W.; and Matasi, J. J., Synthesis of Cyclopentane-Fused Oxygen Heterocycles from the Intramolecular Reaction of Alkynes with Cyclopropylcarbene-Chromium Complexes. J. Org. Chem. 1990, 55, 786-788.
PATENTS:
1. Tulshian, Deen; Matasi, Julius J.; Czarniecki, Michael F.; Brumfield, Stephanie Nicole. Preparation of dihydroimidazopurinone derivatives for use as analgesic or anti-inflammatory agents. PCT Int. Appl. (2011), 82pp.
2. Tulshian, Deen; Geiss, William B.; Martin, Gregory S.; Le, Van-Duc; Haber, James C., Jr.; Matasi, Julius J.; Czarniecki, Michael F.; Cooke, Stephanie Nicole. Preparation of polycyclic guanine derivatives for use as analgesics. PCT Int. Appl. (2008), 111pp. CODEN: PIXXD2 WO 200-***-**** A2 20081231
3. Matasi, J. J.; Tulshian, D.; Burnett, D.; Wu, W-L.; Korakas, P.; Silverman, L.; Sasikumar, T.; Qiang, L.; Domalski, M.S. Preparation of tricyclic compounds as mGLUR1 antagonists, US Pat. Appl. Publ. 2006 (US 200-***-**** A1, WO 200-***-****)
4. Matasi, J. J.; Caldwell, J.; Silverman, L. S.; Tulshian, D.; and Neustadt, B. R. “ Preparation of triazolopyrimidinamines as adenosine A2a Receptor Antagonists” PCT Int. Appl. 2003 (WO 200-***-**** A2).
5. Tulshian, D.; Silverman, L. S.; Matasi, J. J.; Caldwell, J.; and Kiselgof, E. J. “Preparation of imidazo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as adenosine A2a Receptor Antagonists” PCT Int. Appl. 2003 (WO 200-***-**** A1).
6. Tulshian, D.; Ho, G. H.; Silverman, L. S.; Matasi, J. J.; Bercovici, A.; McLeod, R. L.; Hey, J.A.; Chapman, R. W.; and Cuss, F. M., “ Piperidine derivatives as high affinity ligands for Nociceptin receptor”. US 6,262,066, Jul. 17, 2001.
7. Tulshian, D.; Ho, G. H.; Silverman, L. S.; Matasi, J. J.; Bercovici, A.; McLeod, R. L.; Hey, J.A.; and Cuss, F. M., “ Preparation of substituted piperidines as nociceptin receptor ORL-1 agonists for treating cough”. PCT Int. Appl. 2001.
PRESENTATION
1. Matasi, J. J. and Herndon, J. W., ACS Meeting, “A Synthetic Approach to Prostacyclins Using Chromium-Carbene Complexes”. ACS Meeting, Washington, DC, Aug. 1990.
2. Matasi, J. J., Davies, H. M. L., and Thornley, C., “General Synthesis of Functionalized Tropanes by the Intermolecular Reactions of Rhodium-Stabilized Vinylcarbenoids and Pyrroles”, ACS Meeting, Chicago, IL, Aug. 1995.
3. Caldwell, J.; Matasi, J. J.; Tulshian, D.; Fawzi, A.; Isaac, L. K.; Arik, L.; Foster, C.; Lachowicz, J.; Zhang, H. Synthesis and biological evaluation of adenosine A2a receptor antagonists” 228th ACS meeting, Philadelphia, PA. August 2004.
4. Silverman, L.; Caldwell, J.; Greenlee, W.; Kiselgof, E.; Matasi, J. J.; Tulshian, D.; Arik, L.; Foster, C. Design, synthesis, and biological evaluation of novel adenosine A2a receptor antagonists” 230th ACS meeting, Washington, DC. August 2005.
5. Caldwell, J.; Matasi, J. J.; Tulshian, D.; Zhang, H.; Torhan, S. A.; Fawzi, A. Synthesis and structure-activity relationships of N-substituted spiropiperidines as nociceptin receptor ligands: Part 1” 232nd ACS Meeting, San Francisco, CA. Sept.2006.
6. Caldwell, J.; Matasi, J. J.; Tulshian, D.; Zhang, H.; Torhan, S. A.; Fawzi, A. Synthesis and structure-activity relationships of N-substituted spiropiperidines as nociceptin receptor ligands: Part 2” 232nd ACS Meeting, San Francisco, CA. Sept.2006.
7. Matasi, J. J.; Caldwell, J.; Tulshian, D.; Zhang, H.; Torhan, S. A.; Fawzi, A. Synthesis and structure-activity relationships of N-substituted spiropiperidines as nociceptin receptor ligands: Part 3” 232nd ACS Meeting, San Francisco, CA. Sept.2006.
8. Ho, G.; Bercovici, A.; Caldwell, J.; Matasi, J. J.; Fawzi, A.; Tulshian, D.; Zhang, H.; Torhan, S. A.; Synthesis and structure-activity relationships of 4-hydroxy-4-phenyl-and spiropiperidines as nociceptin ligands: 232nd ACS Meeting, San Francisco, CA. Sept.2006.
9. Julius Matasi, Stephanie Cooke, Peter Korakas, Lisa Silverman, Deen Tulshian, Duane Bernett, A. Reggiani, A. Veltri, R. Bertorelli, P. Downey, S. Fredduzzi, E. Nicolussi, G. Lozza, A. Forlani, R. Petro, V. Liporati, G. Tarozzo, S. Foglia. The SAR and Discovery of Orally Active Tricyclic mGLUR1 Antagonists for the Treatment of Chronic Pain: ACS Meeting, Boston, MA. Sept. 2007
10. Stephanie Cooke, Julius Matasi, Peter Korakas, Lisa Silverman, Deen Tulshian, Duane Bernett, A. Reggiani, A. Veltri, R. Bertorelli, P. Downey, S. Fredduzzi, E. Nicolussi, G. Lozza, A. Forlani, R. Petro, V. Liporati, G. Tarozzo, S. Foglia. Synthesis and SAR Development of Novel mGLUR1 Receptor Antagonists for the Treatment of Chronic Pain. ACS Meeting, Boston, MA, Sept. 2007.
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