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

Improved procedure for the solution phase preparation of 1,4- benzodiazepine-2,5-dione libraries via Armstrong's convertible isonitrile and the Ugi reaction

Hulme, C., Peng, J., Tang, S., Burns, C. J., Morize, I., & Labaudiniere, R. (1998). Improved procedure for the solution phase preparation of 1,4- benzodiazepine-2,5-dione libraries via Armstrong's convertible isonitrile and the Ugi reaction. Journal of Organic Chemistry, 63(22), 8021-8023.

2,4-Diphenyl-6-trifluoromethyl-2,3-dihydro-1H,5H-pyrrolo-[3,4-c]pyrrole-1, 3-dione

Roberts, S. A., Martinez-Ariza, G., Dietrich, J., & Hulme, C. (2012). 2,4-Diphenyl-6-trifluoromethyl-2,3-dihydro-1H,5H-pyrrolo-[3,4-c]pyrrole-1, 3-dione. Acta Crystallographica Section E: Structure Reports Online, 68(2), o496-o497.

PMID: 22347098;PMCID: PMC3275242;Abstract:

The asymmetric unit of the title compound, C 19H 11F 3N 2O 2, contains two crystallographically unique mol-ecules which differ in the rotation of a phenyl ring and a -CF3 substituent. The dihedral angles involving the pyrrole ring and the attached phenyl ring are 62.82 (8) and 71.54 (7)° in the two molecules. The difference in the rotation of the CF3 groups with respect to the pyrrolo rings to which they are attached is 23.5(1)°. For one mol-ecule, there is a close contact between an H atom and the centroid of the phenyl ring of an adjacent mol-ecule (2.572 Å). A similar contact is lacking in the second mol-ecule. In the crystal, N - H⋯O inter-actions connect adjacent mol-ecules into a chain normal to (01 ). Crystallographically unique mol-ecules alternate along the hydrogen-bonded chains.

A facile and rapid route toward the synthesis of novel imidazo-tetrazolodiazepinones via post-condensation modifications of the Ugi-azide adduct.

Hulme, C., Medda, F., & Martinez-Ariza, G. (2015). A facile and rapid route toward the synthesis of novel imidazo-tetrazolodiazepinones via post-condensation modifications of the Ugi-azide adduct.. Tetrahedron Letters, 56, 5295-5298.

Construction of functionalized tricyclic dihydropyrazino-quinazolinedione chemotypes via an Ugi/N-acyliminium ion cyclization cascade

Gunawan, S., & Hulme, C. (2013). Construction of functionalized tricyclic dihydropyrazino-quinazolinedione chemotypes via an Ugi/N-acyliminium ion cyclization cascade. Tetrahedron Letters, 54(33), 4467-4470.

Abstract:

Dihydropyrazino-quinazolinedione chemotypes are complex and structurally challenging structures of biological interest, being found in the marine alkaloids such as brevianamide M-N and fumiquinazolines A-C. Herein we report the synthesis of this tricyclic system in three synthetic operations by means of an Ugi multi-component reaction (MCR) followed by a tandem N-acyliminium ion cyclization-intramolecular nucleophilic addition reaction sequence. Additional structural diversification for further library enrichment was also accomplished via sequential N-alkylation and N-acylation/sulfonation. © 2013 Elsevier Ltd. All rights reserved.

Two-step solution-phase synthesis of novel quinoxalinones utilizing a UDC (Ugi/de-Boc/cyclize) strategy

Nixey, T., Tempest, P., & Hulme, C. (2002). Two-step solution-phase synthesis of novel quinoxalinones utilizing a UDC (Ugi/de-Boc/cyclize) strategy. Tetrahedron Letters, 43(9), 1637-1639.

Abstract:

The novel solution-phase synthesis of an array of biologically relevant quinoxalinones in a simple two-step procedure is revealed. Transformations are carried out in excellent yield by condensation of mono-Boc protected ortho-phenylene di-amine, glyoxylic acids and supporting Ugi reagents. Subsequent acid treatment and evaporation affords quinoxalinones in good to excellent yields. © 2002 Elsevier Science Ltd. All rights reserved.

Christopher Hulme