Christopher Hulme

Christopher Hulme

Professor, Pharmacology and Toxicology
Professor, BIO5 Institute
Primary Department
Department Affiliations
(520) 626-5322

Work Summary

The Hulme group is focused on small molecule drug design and developing enabling chemical methodologies to expedite the drug discovery process. The development of small molecule inhibitors of kinases is of particular interest.

Research Interest

Christopher Hulme, PhD, focuses on 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. 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 Hulme group.


Hulme, C., Xu, Z., De Moliner, F., Cappelli, A. P., & Hulme, C. -. (2012). Ugi/aldol sequence: expeditious entry to several families of densely substituted nitrogen heterocycles. Angewandte Chemie (International ed. in English), 51(32).
Martinez-Ariza, G., Ayaz, M., Medda, F., & Hulme, C. (2014). Synthesis of diverse nitrogen-enriched heterocyclic scaffolds using a suite of tunable one-pot multicomponent reactions. The Journal of organic chemistry, 79(11), 5153-62.

Five elegant and switchable three-component reactions which enable access to a new series of nitrogen-containing heterocycles are reported. A novel one-step addition of an isocyanide to a hydrazine derived Schiff base affords unique six-membered pyridotriazine scaffolds (A and E). With slight modification of reaction conditions and replacement of the nucleophilic isocyanide moiety with different electrophiles (i.e., isocyanates, isothiocyanates, cyclic anhydrides, and acyl chlorides) five-membered triazolopyridine scaffolds (B, D, F, G) are generated in a single step. Furthermore, the use of phenyl hydrazine enables access to dihydroindazole-carboxamides, devoid of a bridge-head nitrogen (C). All protocols are robust and tolerate a diverse collection of reactants, and as such, it is expected that the new scaffolds and associated chemistry will garner high interest from medicinal chemists involved in either file enhancement or specific target-related drug discovery campaigns.

Hulme, C., Xu, Z., Dietrich, J., Shaw, A. Y., & Hulme, C. -. (2010). Two step syntheses of fused quinoxaline-benzodiazepines and bis-benzodiazepines. Tetrahedron letters, 51(34).

A two-step solution phase synthesis employing a double UDC (Ugi/Deprotect/Cyclize) strategy has been utilized to obtain fused 6,7,6,6-quinoxalinone-benzodiazepines and 6,7,7,6-bis-benzodiazepines. Optimization of the methodology to produce these tetracyclic scaffolds was enabled by microwave irradiation, incorporation of trifluoroethanol as solvent, and the use of the convertible isocyanide, 4-tert-butyl cyclohexen-1-yl isocyanide.

Martinez-Ariza, G., Dietrich, J., Moliner, F. D., & Hulme, C. (2013). A tandem [3+2] cycloaddition-elimination cascade reaction to generate pyrrolo-[3,4-c]pyrrole-1,3-diones. Synlett, 24(14), 1801-1804.


An efficient tandem [3+2] cycloaddition-elimination cascade sequence has been developed enabling assembly of the pharmacologically relevant pyrrolo-[3,4-c]pyrrole-1,3-dione chemotype. The strategy involves simple mixing of readily accessible oxazolin-2-ones and pyrrole-2,5-diones in the presence of base under mild conditions, rendering the title compounds in typically excellent yields. Of note, this route allows for installation of three points of diversity and is ideal for combinatorial applications and parallel synthesis production campaigns. © Georg Thieme Verlag Stuttgart · New York.

Hulme, C., Xu, Z., Shaw, A. Y., Dietrich, J., Cappelli, A. P., Nichol, G., & Hulme, C. -. (2012). Facile, novel two-step syntheses of benzimidazoles, bis-benzimidazoles, and bis-benzimidazole-dihydroquinoxalines. Molecular diversity, 16(1).

Three scaffolds of benzimidazoles, bis-benzimidazoles, and bis-benzimidazole-dihydroquinoxalines were synthesized via Ugi/de-protection/cyclization methodology. Benzimidazole forming ring closure was enabled under microwave irradiation in the presence of 10% TFA/DCE. The methodology demonstrates the utility of 2-(N-Boc-amino)-phenyl-isocyanide for the generation of new molecular diversity.