Christopher Hulme

Professor, Pharmacology and Toxicology

Professor, BIO5 Institute

Primary Department

Pharmacology and Toxicology

Department Affiliations

Pharmacology and Toxicology

Contact

(520) 626-5322

hulme@arizona.edu

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.

Publications

Facile and rapid route for the synthesis of novel conformationally constrained norstatine analogs via PADAM-cyclization methodology

Hulme, C., Shaw, A. Y., Medda, F., & Hulme, C. -. (2012). Facile and rapid route for the synthesis of novel conformationally constrained norstatine analogs via PADAM-cyclization methodology. Tetrahedron letters, 53(11).

The following report describes novel methodology for the rapid synthesis of unique conformationally constrained norstatine analogs of potential biological relevance. A PADAM (Passerini reaction - Amine Deprotection - Acyl Migration reaction) sequence is followed by a TFA-mediated microwave-assisted cyclization to generate the final benzimidazole isostere of the norstatine scaffold in moderate to good yields. The applicability of this solution phase methodology to the preparation of a small collection of compounds is discussed.

3-(4-Bromo-phen-yl)-1-butyl-5-[1-(2-chloro-6-methyl-phen-yl)-1H-tetra-zol-5-yl]imidazolidine-2,4-dione

Hulme, C., Hall, G. B., Medda, F., Roberts, S. A., & Hulme, C. -. (2013). 3-(4-Bromo-phen-yl)-1-butyl-5-[1-(2-chloro-6-methyl-phen-yl)-1H-tetra-zol-5-yl]imidazolidine-2,4-dione. Acta crystallographica. Section E, Structure reports online, 69(Pt 7).

In the title mol-ecule, C21H20BrClN6O2, the chloro-substituted benzene ring forms a dihedral angle of 77.84 (7)° with the tetra-zole ring and the bromo-substituted ring forms a dihedral angle of 43.95 (6)° with the imidazole ring. The dihedral angle between the tetra-zole and imidazole rings is 67.42 (8)°. The terminal methyl group of the butyl substituent is disordered over two sets of sites, with refined occupancies 0.67 (3) and 0.33 (3). In the crystal, there is a short Br⋯N contact of 3.183 (2) Å.

Synthesis of (E)-5-methoxy-2-styryl-4-pyrones as potent growth-inhibitory agents against hepatocellular carcinoma cells

Chen, Y., Lu, P., Hulme, C., & Shaw, A. Y. (2014). Synthesis of (E)-5-methoxy-2-styryl-4-pyrones as potent growth-inhibitory agents against hepatocellular carcinoma cells. Journal of Heterocyclic Chemistry, 51(1), 56-61.

Abstract:

The present study a series of (E)-5-methoxy-2-styryl-4H-pyran-4-ones 6a, 6b, 6c, 6d, 6e, 6f, 6g, 6h, 6i, 6j was synthesized and evaluated for growth inhibitory inhibition against carcinoma cells. The growth inhibition study of eight carcinoma cell lines was examined and demonstrated that SKHep cells exhibit significant structure-activity relationship in response to the tested compounds. Among them, 6f showed the most potent activity against SKHep, A549, AGS, and H460 cell lines with GI50 values of 0.17, 8.3, 3.6, 8.0 μM, respectively. © 2013 HeteroCorporation.

New multi-component reaction accessing 3-aminoimidazo[1,2-a]pyridines

Schwerkoske, J., Masquelin, T., Perun, T., & Hulme, C. (2005). New multi-component reaction accessing 3-aminoimidazo[1,2-a]pyridines. Tetrahedron Letters, 46(48), 8355-8357.

Abstract:

The novel one step solution phase synthesis of an array of 3-aminoimidazo[1,2-a]pyridines is reported. Reactions were performed in methanol by mixing a α-amino-pyridine, aldehyde and trimethylsilylcyanide (TMSCN) to give the desired product. Mediated by microwave irradiation and catalyzed by scandium triflate, the methodology represents the first one pot preparation of 3-aminoimidazo[1,2-a]pyridines that avoids the use of an isonitrile and subsequent de-protection strategy. The reaction is an example of a formal three-centre-three-component multi-component reaction.

Facile and rapid route for the synthesis of novel norstatine analogs via PADAM-cyclization methodology

Shaw, A. Y., Medda, F., & Hulme, C. (2012). Facile and rapid route for the synthesis of novel norstatine analogs via PADAM-cyclization methodology. Tetrahedron Letters, 53(11), 1313-1315.

Abstract:

The following report describes novel methodology for the rapid synthesis of unique conformationally constrained norstatine analogs of potential biological relevance. A PADAM (Passerini reaction-Amine Deprotection-Acyl Migration reaction) sequence is followed by a TFA-mediated microwave-assisted cyclization to generate the final benzimidazole isostere of the norstatine scaffold in moderate to good yields. The applicability of this solution phase methodology to the preparation of a small collection of compounds is discussed. © 2012 Elsevier Ltd. All rights reserved.

Christopher Hulme