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Christopher Hulme, Department of Chemistry, The University of Arizona
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Christopher Hulme


Associate Professor of Organic and Medicinal Chemistry
hulme@pharmacy.arizona.edu
Skaggs Pharmacy Building 414
Phone: (520) 626-5322
Fax: (520) 626 2466

Honors


  • Abbott Labs New Faculty Award, 2007

Education and Appointments


  • B.S. 1989, Hertford College, University of Oxford
  • Ph.D. 1992, Hertford College, University of Oxford
  • Postdoctoral Fellow 1992-1994, University of Texas, Austin
  • Research Fellow 1994-1999, RPR, Collegeville PA
  • Head HTMC 1999-2004, Amgen, Thousand Oaks, CA

Research Interests


  • Organic
  • Biological
  • Pharmacology and Toxicology
  • Synthesis and Synthetic Methodology

Research Summary

Organic and Medicinal Chemistry

The focus of the Hulme group is small molecule drug design and developing enabling chemical methodologies to expedite the drug discovery process. Target families of particular current interest for the group are kinases, protein-protein interactions and emerging DNA receptors for indications in oncology. Such efforts are highly collaborative in nature and students will be exposed to the full array of design hurdles involved in progressing molecules along the value chain to clinical evaluation. These efforts will be aided by the group’s interest in both microwave assisted organic synthesis (MAOS) and flow chemistry. Both technologies enable ‘High-throughput Medicinal Chemistry’ (HTMC) and will be supported by similar High-throughput Purification capabilities.

The group also has a long standing interest in the development of new reactions that produce biologically relevant molecules in an efficient manner. Front loading screening collections with molecules possessing high ‘iterative efficiency potential’ is critical for expediting the drug discovery process. Compounds derived from multi-component reactions (MCRs) demonstrate such potential and thus their discovery and applications are of high interest. An added facet of MCR chemistry is ‘High Exploratory Efficiency’. Since the completion of the human genome project, coupled with tremendous advances in systems biology and cell imaging methods, a plethora of proteins with unknown physiological function have appeared. This ‘Knowledge Gap’ is a result of a growing need for new small molecule probes, positioned in new regions of diversity space. The discovery of such tools that perturb cellular systems is of high value to the scientific community and may be facilitated by rapid forays into MCR space that can produce a multitude of novel scaffolds with appropriate decoration for evaluation with a variety of different screening paradigms.

Novel hypervalent iodine mediated C-H activation methodologies is also an active area of interest. Probing the scope of the transformation below and investigating applications toward the synthesis of new peptidomimetics will be an additional pursuit in the group.



Selected Publications

    Selected Publications

  • Editorial: 2008 Themed Issue of Molecular Diversity. C. Hulme and G. Maggiora, Curr. Op. Chem. Biol. 2008, in preparation.

  • The Historical Development of the Intramolecular Ugi Reaction: The Bi-functional Approach (BIFA). C. Hulme Mini Reviews in Organic Chemistry, 2007, in preparation.

  • Syntheses and Therapeutic Applications of Bicyclic Imidazo[1,2-x]-heterocycles. C. Hulme Molecular Diversity, 2007, in press.

  • [1,2-c] Pyrimidines via [4+1]-cycloaddition Michael Umkehrer , Günther Ross, Nadine Jäger, Maria Alvim-Gaston, Hong Hu and C. Hulme Tetrahedron Lett., 2007, 48(12), 2213-2216.

  • Facile Access to a Range of Heterocyclic Chemo-types via a Novel Combination of Flow Hydrogenation and Microwave Incubation Processes. A. Godfrey, T. Masquelin and C. Hulme. Abstracts of Papers, 233rd ACS National Meeting, Chicago, IL, United States, March 25-29, 2007, ORGN-207.

  • Novel, potent inhibitors of Polo-like Kinase (Plk-1). Adrian Smith, Tom Nixey and Christopher Hulme. Abstracts of Papers, 231st ACS National Meeting, Atlanta, GA, United States, March 26- 30, 2006, MEDI-277.

  • A Novel 3-Centre-5-Component Reaction – Interesting Analogous Strecker-Strecker reactions. John Schwerkoske, Thierry Masquelin, Tom Perun, Gregory Stephenson and Christopher Hulme Tetrahedron Lett, 2006, 47, 2989-2981.

  • Unique a, b, b – Oxidations of Carbamates with ‘Willgerodt-like’ Hypervalent Iodine Reagents. Walter Salamant and Christopher Hulme Tetrahedron Lett, 2006, 47, 605-609.

  • Solid Phase Derived Library of Potent Melanin-Concentrating Hormone 1 Receptor Antagonists Vu Ma, Paul Tempest, Tony Bannon, John Salon, Carlo Van Staden, Michelle McElvain, Gondi Kumar, Clarence Hale, James Baumgartner, Thomas Nixey, Randall Hungate and Christopher Hulme Bioorganic & Medicinal Chemistry Letters, 2006, 16, 5066-5072.

  • New Multi-component Reaction accessing 3-Amino-imidazo[1,2-a]pyridines John Schwerkoske, Thierry Masquelin, Tom Perrun and Christopher Hulme Tetrahedron Lett, 2005, 46, 8355-8357.

  • Applications of MCRs in Medicinal Chemistry C. Hulme ‘Multi-Component Reactions’ Chapter 11. Ed. H. Bienayme & J. Zhu, Wiley, 2005.

  • Vanilloid receptor ligands and their use in treatments. Hulme, Christopher; Ncube, Mghele Vellah; Norman, Mark H.; Ognyanov, Vassil I.; Pettus, Liping H.; Wang, Xianghong; Zhu, Jiawang. U.S. Pat. Appl. Publ. US 20050165046 A1 20050728 AN 2005:672886, 2005.

  • Vanilloid receptor ligands and their use in treatments. Hulme, Christopher; Ncube, Mghele Vellah; Norman, Mark H.; Ognyanov, Vassil I.; Pettus, Liping H.; Wang, Xianghong; Zhu, Jiawang. U.S. Pat. Appl. Publ., US 20050165049 A1 20050728 AN 2005:672887, 2005.

  • Melanin concentrating hormone receptor antagonists. Tempest, P.; Hulme, C.; Ma, V. PCT Int. Appl. 2005, 319 pp. WO 2005019240 A2 20050303.

  • Melanin concentrating hormone receptor antagonists. Hulme, Christopher; Tempest, Paul; Ma, Vu; Nixey, Thomas; Balow, Guity. PCT Int. Appl., 2005, 260 pp. WO 2005019167 A2 20050303

  • Novel Benzoxazepinone Inhibitors of c-Jun N-terminal kinase 3 (JNK3) and utility as Stroke Therapeutics: SAR and Ligand co-crystallization studies. Vu Ma, Paul Tempest, Liping Pettus, Janan Jona, Charles Henley, Gary Zajic, Weiya Wang, Mark Michaels, Rob Kurzeja, Andrew Tasker, Randall Hungate and Christopher Hulme. Abstracts of Papers, 227th ACS National Meeting, Anaheim, CA, United States, March 28- April 1, 2004, MEDI-043.

  • Preparation of (aryloxy)pyrimidine and (aryloxy)pyridazine as vanilloid receptor ligands. C. Hulme et al. PCT Int. Appl. WO 2004014871, 2004.

  • Library Generation via Post Condensation Modifications of Isocyanide Based Multi-Component Reactions C. Hulme, H. Bienayme, T. Nixey, B. Chenera, W. Jones, P. Tempest and Adrian Smith Methods in Enzymology, 2003, Special Edition on Combinatorial Chemistry, Book Chapter.

  • Multi-component Reactions: Emerging Chemistry in Drug Discovery. C. Hulme and V. Gore Current Medicinal Chemistry, 2003, 10, 151.

  • MCC/SNAr1 Methodology II: Novel three-step solution phase access to libraries of benzodiazepines. P. Tempest, L. Pettus, V. Gore and C. Hulme Tetrahedron Lett. 2003, 44, 1947.

  • One-pot Microwave driven Preparation of Pyrazoloquinazolinone Libraries T. Vasquez, T. Nixey, V. Gore, M. Bartberger, Yax Sun and C. Hulme Molecular Diversity. 2003, 7, 161-164.

  • Rapid Assembly of Molecular Diversity via exploitation of Isocyanide based Multi-Component Reactions. C. Hulme and T. Nixey Current Opinion in Drug Discovery Today, 2003, 6, 921-929.

  • One-pot Solution Phase preparation of fused Azepine-tetrazoles. T. Nixey, M. Kelly and C. Hulme Tetrahedron Lett. 2002, 43, 3681.

  • Two step solution phase synthesis of novel Quinoxalinones utilizing a UDC (Ugi/De-BOC/Cyclize) Strategy. T. Nixey, P. Tempest, and C. Hulme Tetrahedron Lett. 2002, 43, 1637.

  • A three step synthesis of tetrazole derived Norstatine isosteres using the TMSN3 modified Passerini reaction. T. Nixey and C. Hulme Tetrahedron Lett. 2002, 43, 6833.

  • Parallel Preparation of Amides using Polystyrene Bound TFP Esters: New Approaches to Automation W. Jones, D. Overland, L. Poppe, J. Cardenas, M. Pate and C. Hulme Lab. Automation, 2002, Palm Springs, T002.

  • Knowledge based approaches in the Design and Selection of Compound Libraries for Drug Discovery. V. N. Viswanadhan, C. Balan, C. Hulme, J. C. Cheetham and Y. Sun Current Opinion in Drug Discovery and Development, 2002, 5, 400.

  • MCC/SNAr1 Methodology I: Novel access to a range of Heterocyclic Cores P. Tempest, V. Ma, M. Kelly, W. Jones and C. Hulme Tetrahedron Lett. 2001, 42, 4963.

  • Novel two step solution phase protocol to Benzimidazoles via a UDC strategy. P. Tempest, M. Kelly and C. Hulme Tetrahedron Lett. 2001, 42, 4959.

  • Synthetic Organic Chemistry Advances (S. Stinson Ed.) T. Nixey, P. Tempest, V. Ma and C. Hulme Chemical & Engineering News, 2001, September 10th, 31.

  • Novel Applications of Wang bound a-amino acids for the synthesis of Benzodiazepines and Ketopiperazines via a UDC Strategy. C. Hulme, L. Ma and R. Labaudiniere Tetrahedron Lett. 2000, 41, 1509.

  • Novel Applications of Convertible Isonitriles for the synthesis of g-lactams via a UDC strategy. C. Hulme, L. Ma, J. Romano, MP. Cherrier, J. Salvino, G. Morton and R. Labaudiniere Tetrahedron Lett. 2000, 41, 1889.

  • Maximizing synthetic efficiency: multi-component transformations lead the way. H. Bienayme, C. Hulme, G. Oddon, and P. Schmitt Chem. Eur. J., 2000, 6, 3321.

  • Novel Applications of CO2/MeOH for the Synthesis of Hydantoins and Cyclic Ureas via the Ugi Reaction. C. Hulme, L. Ma, J. Romano, G. Morton, S-Y Tang, M-P Cherrier, S. Choi, and R. Labaudiniere Tetrahedron Lett. 2000, 41, 1883.

  • Remarkable One-pot Solution Phase preparation of fused Tetrazole-ketopiperazines. T. Nixey, M. Kelly and C. Hulme Tetrahedron Lett. 2000, 41, 8729.

  • A new 4-point Pharmacophore Method for Molecular Similarity and Diversity and its Application to the Design of Combinatorial Libraries containing Privileged Substructures J. S. Mason, I. Morize, P. R. Menard, D. L. Cheney, R. Labaudiniere and C. Hulme J. Med. Chem., 1999, 42, 3251.

  • Novel Applications of Ethyl Glyoxalate in Secondary Reactions for the Solution Phase Synthesis of Benzodiazepines, Ketopiperazines and Diketopiperazines utilizing a UDC Strategy. C.Hulme and M.P. Cherrier, Tetrahedron Lett., 1999, 40, 5295.

  • Remarkable 3-step-1-pot Solution Phase Synthesis of Imidazolines via a UDC Strategy C. Hulme, M. Morrissette and Liang Ma Tetrahedron Lett. 1999, 40, 7925.

  • Preparation of N-acyl-2-aminoacetamides and cyclization products thereof. C. Hulme, G. Morton, J.M. Salvino, R.F. Labaudiniere, H.J. Mason, M.M. Morrissette, L. Ma, M-P Cherrier. PCT Int. Appl. 1999, WO 9938844 A1.

  • Quaternary Substituted PDE4 Inhibitors I: Novel Series of Oxindoles C. Hulme, G. Poli, Fu-chih Huang, J. Souness and S. W. Djuric Bioorg. Med. Chem. Lett, 1998, 8, 175-178.

  • Quaternary Substituted PDE4 Inhibitors II: Novel Series of g-lactams C. Hulme, K. Moriarty, Fu-chih Huang, J. Souness and S. W. Djuric. Bioorg. Med. Chem. Lett, 1998, 8, 399.

  • The Solution Phase Synthesis of Diketopiperazine Libraries: Novel Application of Armstrong's Convertible Isonitrile C. Hulme, M. Morrissette, F.Volz and C.Burns Tetrahedron Lett., 1998, 39, 1113.

  • New Indazole Derivatives as Phosphodiesterase Type IV Inhibitors C.Hulme Exp. Opin. Ther. Patents, 1998, 8(5): 1-4.

  • Improved Procedure for the Solution Phase Synthesis of 1,4-Benzodiazepines-2,5-dione Libraries via the Ugi reaction and Armstrong's Convertible Isonitrile C. Hulme, S. Tang, C. Burns and R. Labaudiniere J. Org. Chem., 1998, 63, 8021.

  • Solution Phase Synthesis of Ketopiperazine Libraries Utilizing the Ugi/De-BOC/Cyclization (UDC) Strategy C. Hulme, J. Peng, P. Menard, B. Louridas, V.N. Kumar and P. Krolikowski Tetrahedron Lett., 1998, 39, 3635.

  • The Synthesis and Biological Evaluation of a Novel Series of Indole PDEIV Inhibitors C. Hulme, R. Mathew, K. Moriarty, John Souness, Paul Cox, Joanne Uhl, and Stevan W. Djuric Bioorg. Med. Chem. Lett, 1998, 8, 1867.

  • Orally Active Indole N-Oxide PDEIV Inhibitors C. Hulme, R. Mathew, K. Moriarty, John Souness, Joanne Uhl, Fu-chih Huang, and Stevan W. Djuric Bioorg. Med. Chem. Lett, 1998, 8, 3053.

  • Solid Phase Synthesis of 1,4-Benzo-diazepine-2,5-diones, Diketopiperazines and Ketopiperazines Utilizing the Ugi/De-BOC/Cyclization (UDC) Strategy C. Hulme, J. Peng, G. Morton, J. Salvino and R. Labaudiniere Tetrahedron Lett., 1998, 39, 7227.

  • Inhibitors of Tyrosine Kinases Involved In Inflammation and Autoimmune Disease. M.R. Myers, W. Hei and C. Hulme Curr. Pharm. Design, 1997, 3, 463-492.

  • Synthesis and Analysis of Leu-enkephalin analogues containing reverse turn peptidomimetics T. D. W. Claridge, C. Hulme, V. Lee, R. Kelly, I. Nash and C. J. Schofield, Bioorg. Med. Chem. Lett, 1996, 6, 485-490.

  • Hypervalent Iodine Chemistry: New Oxidation Reactions Using the PhIO/TMSN3 Reagent Combination. Direct alpha and beta Azido functionalisation of Triisopropylsilyl (TIPS) enol ethers. P. D. Magnus, J. Lacour, P.A. Evans, M. B. Roe and C. Hulme J. Am. Chem. Soc., 1996, 118, 3406-3418.

  • The structure of a stable new organotellurium azide: bis-azidodiphenyltellurium (IV) oxide P. D. Magnus, M. B. Roe, V. Lynch and C. Hulme J. Chem. Soc., Chem. Commun., 1995, (16), 1609-1610.

  • New trialkyl enol ether chemistry: direct 1,2-bis-azidonation of triisopropylsilyl enol ethers: an azido-radical addition process promoted by TEMPO P. D. Magnus, C. Hulme and M. B. Roe J. Chem. Commun., 1995, (2), 263-265.

  • Comments on the use of chromophoric circular dichroism assay for the identification of beta-turns in peptides J. E. Baldwin, T. D. W. Claridge, C. Hulme, A. Rodger and C. J. Schofield Int.J. Pept. Protein Res., 1994, 43(2), 180-3

  • Alpha-azidonation of Amides, Carbamates, and Ureas with the iodosylbenzene/trimethylsilyl azide reagent combination: N-Acyliminium ion precursors P. D. Magnus, C. Hulme and Wolfgang Weber J. Am. Chem. Soc., 1994, 116(10), 4501-2

  • Oxidation of L-Proline methyl ester derivatives with the iodosylbenzene\trimethylsilylazide reagent combination P. D. Magnus and C. Hulme Tetrahedron Lett., 1994, 35(44), 8097-8100

  • Synthesis of a bicyclic -lactam dipeptide analog J. E. Baldwin, C. Hulme, A. J. Edwards, K. E. B. Parkes and C. J. Schofield Tetrahedron Lett., 1993, 34, 1665-8

  • Synthesis of potential beta-turn bicyclic dipeptide mimetics J. E. Baldwin, C. Hulme and C. J. Schofield J. Chem. Soc., Chem. Commun., 1993, 11, 935-6

  • Syntheses of cis- and trans-pyrrolidine-2,5-dicarboxylic acids J. E. Baldwin, C. Hulme and C. J. Schofield J. Chem. Res. (S), 1992, 173