Medicinal Chemistry
Key staff: Dr John Spencer
Drug discovery is a costly exercise with a high attrition rate. Our research focuses on improving reactions that are important to medicinal chemistry e.g. accelerating reactions or simplifying purification processes such that many molecules (a “library”) can be synthesised over a shorter period of time. “Atom economical” reactions, where fewer synthetic steps are required, are being employed to modify biologically relevant molecules.
A number of these projects are in conjunction with Greenwich colleagues as well as external groups including Strathclyde University, Porto Alegre University (Brazil), ULP Strasbourg (France), Ecole Nat. Sup., Paris (France), Beatson Cancer Institute (Scotland). We have also received funding from Novartis, Avexa and the Royal Society of Chemistry.
X-ray crystallography also plays a fundamental role in our structural studies and we collaborate with groups from Heidelberg, Southampton (EPSRC unit) and London Metropolitan University.
Recent projects
- Synthesis & catalytic evaluation of palladacycles.
- Heck, Suzuki and C-H activations.
- Bioactive metal containing anticancer agents.
- Microwave assisted organic synthesis.
- Solid state studies of medicinally important molecules.
Highlighted research
www.organic-chemistry.org/Highlights/2007/15OctoberB.html
http://in-cities.com/papers/Spencer_Dupont.html
Publications
Low, C.M.R., McDonald, I. M., Pether, M.J., Spencer, J., Tisselli, P., Wright, P.T. Pyrimidine Derivatives: Patent WO 2008 009963, James Black Foundation.
McDonald, I.M., Spencer, J., Buck, I.M., Dunstone, D.J., Linney, I.D., Tisselli, P. , Hull, R.A.D., Austin, C., Harper, E.A., Sykes, D., Griffin, E. and Shaxted, M. (2007). Benzotriazeponone derivatives. Patent WO 2007 135350, James Black Foundation.
McDonald, I.M. et al. (2007) Discovery and characterization of novel, potent, non-peptide parathyroid hormone-1 receptor antagonists. J. Med. Chem. 50, 4789.
McDonald, I.M., Black, J.W. et al. (2007) Optimisation of 1,3,4-benzotriazepine-based CCK2 antagonists to obtain potent, orally-active inhibitors of gastrin-mediated gastric acid secretion. J. Med. Chem. 50, 3101.
Spencer, J., Chowdhry, B.Z., Mallett, A.I.,Rahman, R.P.,Adatia, T.,Bashall, A.,Rominger, F. (2008) C-H activations on a 1H- 1,4-benzodiazepin-2(3H)-one template. Tetrahedron, 64, 6082.
Spencer, J., McDonald, I.M., Gaffen, J., Griffin, E., Harper, E.A., Linney, I.D., Roberts, S.P., Shaxted, M.E., Bashall, A., Adatia, T. (2008) Achiral, selective CCK2 receptor antagonists based on a 1,3,5-benzotriazepine-2,4-dione template. Bioorg. Med. Chem., 16, 2974.
Spencer, J., Nazira, A., Patel, H., Rathnam, R.P., Verma, J. (2007) Molybdenum hexacarbonyl & DBU reduction of nitro compounds under microwave irradiation. Synlett, 2557.