个人简介

Abbott Labs New Faculty Award, 2007

研究领域

Organic/Chemical Biology/Synthesis/Synthetic Methods Development

Organic and Medicinal Chemistry The Hulme group located at BIO5 Oro Valley Drug Discovery Center (www.bio5orovalley.org) and 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. Projects are highly collaborative in nature, and students are exposed to the full array of design hurdles involved in progressing molecules along the value chain to clinical evaluation.

近期论文

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De Molinera F, Hulme C (2012) A Van Leusen deprotection-cyclization strategy as a fast entry into two imidazoquinoxaline families. Tetrahedron Lett., 53:5787-5790. Smith B, Medda F, Gokhale V, Dunckley T, Hulme C (2012) Recent advances in the design, synthesis, and biological evaluation of selective DYRK1A inhibitors: a new avenue for a disease modifying treatment of Alzheimer's? ACS Chem. Neurosci. DOI: 10.1021/cn300094k. Medda F, Hulme C (2012) A facile and rapid route for the synthesis of novel 1,5-substituted tetrazole hydantoins and thiohydantoins via a TMSN3-Ugi/RNCX cyclization. Tetrahedron Lett., 53:5593-5596. Chen YH, Lu PJ, Hulme C, Shaw AY (2012) Synthesis of kojic acid-derived copper-chelating apoptosis inducing agents. Med. Chem. Res. DOI 10.1007/s00044-012-0094-y. Xu Z, De Moliner F, Cappelli A, Hulme C (2012) Ugi/Aldol sequence: expeditious entry to several families of densely substituted nitrogen heterocycles. Angew. Chem. Int. Ed. Engl., 51:8037-8040. Sells E, Medda F, Chang H, Gokhale V, Hulme C, Meuillet EJ (2012) Abstract 2834: Discovery of a novel class of prostaglandin e2 synthesis inhibitors with anti-tumor activity in colorectal cancer. Cancer Res., 72:1. Xu Z, Shaw AY, Nichol GS, Cappelli AP, Hulme C (2012) Applications of ortho-phenylisonitrile and ortho-N-Boc aniline for the two-step preparation of novel bis-heterocyclic chemotypes. Mol. Divers., 16:607-612. Gunawan S, Keck K, Laetsch A, Hulme C (2012) Synthesis of peptidomimetics, d- and e-lactam tetrazoles. Mol. Divers., 16:601-606. Ayaz, M, De Moliner F, Dietrich J, Hulme C (2012) Applications of isocyanides in IMCRs for the rapid generation of molecular diversity. In "Isocyanide Chemistry"; Nenajdenko, V. Ed. Wiley-VCH: Weinheim, Germany; pp. 335-384. Xu Z, Ayaz M, Cappelli A, Hulme C (2012) A general one-pot, two-step protocol accessing a range of novel polycyclic heterocycles with high skeletal diversity. ACS Comb. Sci., 14:460-464. [Congrats also on getting the cover!] Shaw AY, Denning CR, Hulme C (2012) Selenium dioxide-mediated synthesis of a-ketoamides from arylglyoxals and secondary amines. Tetrahedron Lett., 53:4151-4153. Xu Z, Shaw AY, Dietrich J, Cappelli AP, Nichol G, Hulme C (2012) Facile, novel two-step syntheses of benzimidazoles, bis-benzimidazoles, and bis-benzimidazole-dihydroquinoxalines. Mol. Divers., 16:73-79. Gunawan S, Ayaz M, De Moliner F, Frett B, Kaiser C, Patrick N, Xu Z, Hulme C (2012) Synthesis of tetrazolo-fused benzodiazepines and benzodiazepinones by a two-step protocol using an Ugi-azide reaction for initial diversity generation. Tetrahedron, 68:5606-5611. Smith B, Chang HH, Medda F, Gokhale V, Dietrich J, Davis A, Meuillet EJ, Hulme C (2012) Synthesis and biological activity of 2-aminothiazoles as novel inhibitors of PGE2 production in cells. Bioorg. Med. Chem. Lett., 22:3567-3570. Shaw AY, McLaren JA, Nichol GS, Hulme C (2012) Hydrazine-mediated cyclization of Ugi products to synthesize novel 3-hydroxypyrazoles. Tetrahedron Lett., 53:2592-2594. Shaw AY, Xu Z, Hulme C (2012) Ugi/Robinson-Gabriel reactions directed toward the synthesis of 2,4,5-trisubstituted oxazoles. Tetrahedron Lett., 53:1998-2000. Shaw AY, Medda F, Hulme C (2012) Facile and rapid route for the synthesis of novel norstatine analogs via PADAM-cyclization methodology. Tetrahedron Lett., 53:1313-1315. De Moliner F, Hulme C (2012) Straightforward assembly of phenylimidazoquinoxalines via a one-pot two-step MCR process. Organic Lett., 14:1354-1357. Gunawan S, Petit J, Hulme C (2012) Concise one-pot preparation of unique bis-pyrrolidinone tetrazoles. ACS Comb. Sci., 14:160-163. Gunawan S, Nichol G, Hulme C (2012) Concise route to a series of novel 3-(tetrazol-5-yl)quinoxalin-2(1H)-ones. Tetrahedron Lett., 53:1664-1667. Roberts SA, Martinez-Ariza G, Dietrich J, Hulme C (2012) 2,4-Diphenyl-6-trifluoro-methyl-2,3-dihydro-1H,5H-pyrrolo-[3,4-c]pyrrole-1,3-dione. Acta Crystallogr. Sec. E: Struct. Rep. Online:E68.2:o496-o497. Ayaz M, Dietrich J, Hulme C (2011) A novel route to synthesize libraries of quinoxalines via Petasis methodology in two synthetic operations. Tetrahedron Lett., 52:4821-4823. Dömling A, Hulme C (2011) Editorial in "Special issue on Mini-MCR issue and SCS-09 - Second International Symposium on Combinatorial Sciences in Biology, Chemistry, Catalysts and Materials." Mol. Divers., 15:1-2. Gunawan S, Nichol GS, Chappeta S, Dietrich J, Hulme C (2011) Concise preparation of novel tricyclic chemotypes: fused hydantoin-benzodiazepines. Tetrahedron Lett., 51:4689-4692. Xu ZG, Dietrich J, Shaw AY, Hulme C (2010) Two-step syntheses of fused quinoxaline-benzodiazepines and bis-benzodiazepines. Tetrahedron Lett., 51:4566-4569. Dietrich J, Hulme C, Hurley LH (2010) The design, synthesis, and evaluation of 8 hybrid DFG-out allosteric kinase inhibitors: a structural analysis of the binding interactions of Gleevec®, Nexavar®, and BIRB-796. Bioorg. Med. Chem., 18:5738-5748. Dietrich J, Kaiser C, Meurice N, Hulme C (2010) Concise two-step solution phase syntheses of four novel dihydroquinazoline scaffolds. Tetrahedron Lett., 51:3951-3955. Meurice N, Wang L, Lipinski CA, Yang ZB, Hulme C, Loftus JC (2010) Structural conservation in band 4.1, ezrin, radixin, moesin (FERM) domains as a guide to identify inhibitors of the proline-rich tyrosine kinase 2. J. Med. Chem., 53:669-677. Hulme C, Chappeta S, Dietrich J (2009) A simple, cheap alternative to designer convertible isonitriles' expedited with microwaves. Tetrahedron Lett., 50:4054-4057. Hulme C, Dietrich J (2009) Emerging molecular diversity from the intra-molecular Ugi reaction: iterative efficiency in medicinal chemistry. Mol. Divers., 13:195-207. Hulme C, Chappeta S, Griffith C, Lee YS, Dietrich J (2009) An efficient solution phase synthesis of triazadibenzoazulenones: 'designer isonitrile free' methodology enabled by microwaves. Tetrahedron Lett., 50:1939-1942. Hulme C, Lee YS (2008) Emerging approaches for the syntheses of bicyclic imidazo[1,2-x]-heterocycles. Mol. Divers., 12:1-15. Hulme C, Maggiora GM (2008) Molecular diversity: from small to large, emerging to enabling. Curr. Opin. Chem. Biol., 12:257-259. Umkehrer M, Ross G, Jager N, Burdack C, Kolb J, Hu H, Alvini-Gaston M, Hulme C (2007) Expeditious synthesis of imidazo[1,2-c]pyrimidines via a [4+1]-cycloaddition. Tetrahedron Lett., 48:2213-2216. Masquelin T, Bui H, Brickley B, Stephenson G, Schwerkoske J, Hulme C (2006) Sequential Ugi/Strecker reactions via microwave assisted organic synthesis: novel 3-center-4-component and 3-center-5-component multi-component reactions. Tetrahedron Lett., 47:2989-2991. Ma V, Bannon AW, Baumgartner J, Hale C, Hsieh F, Hulme C, Rorrer K, Salon J, Van Staden C, Tempest P (2006) Solid-phase synthesis and structure-activity relationships of novel biarylethers as melanin-concentrating hormone receptor-1 antagonists. Bioorg. Med. Chem. Lett., 16:5066-5072. Salamant W, Hulme C (2006) Unique one step, multicomponent a,β,β-oxidations of carbamates with Willgerodt-like hypervalent iodine reagents - an example of triple C-H bond activation. Tetrahedron Lett., 47:605-609.