Ulf Madsen

1983: Graduated (Cand.pharm.) from The Royal Danish School of Pharmacy.
1988: Ph.D. (Lic.pharm.) from The Royal Danish School of Pharmacy.

1987: Visiting scientist at Dept. of Pharmacology, University of Sydney, Australia.
1990: Visiting scientist at Inst. of Organic Chemistry, Syntex Research, CA, U.S.A.
1992: Friedrich-Merz Foundation Guest-Professor at Inst. of Pharmaceutical Chemistry, Johan Wolfgang Goethe-Universität, Frankfurt am Main, Germany.

1984-1987: Research scholarship from The Royal Danish School of Pharmacy
1987-1993: Research scholarships from The Lundbeck Foundation (at PHARMA)
1994-: Associate professor (Lektor), Dept. of Medicinal Chemistry, PHARMA
1996-2002: Head of Department, Dept. of Medicinal Chemistry, PHARMA
2005-2008: Head of Department, Dept. of Medicinal Chemistry, PHARMA
2008-2011: Associate Dean, PHARMA
2012-: School Director, School of Pharmaceutical Sciences

• Supervisor of 12 ph.d.-students (11 graduated and 1 presently enrolled)
• Supervisor of more than 25 graduate-project students
• 2003 – 2005: Chairman of the Ph.D. Study board (Ph.D.-Studienævnet, PHARMA)
• 2003 – 2005: Chairman of the Research grant board (Stipendieudvalget, PHARMA)
• 2005 – 2007: Director of the Drug Research Academy (DRA) at PHARMA
• 2003 – 2012: Member of The Danish Commitee on Scientific Dishonesty (Health Sciences)
• Member of the editorial board of ChemMedChem
• Referee at 5 international scientific journals
• Author of 115 scientific papers, co-editor of a textbook (three editions) and co-inventor on two patents

Neuromedicinal chemistry. The PhD obtained 1988 covered medicinal chemistry aspects within the area of excitatory amino acids. This involved design and synthesis of heterocyclic glutamate analogues, conformational studies by high resolution NMR techniques and computer based molecular modelling studies. On this background further medicinal chemistry studies has been carried out primarily on glutamate receptors.

Following a research visit at University of Sydney an in vitro electrophysiological model (the rat cortical slice model) was established at PHARMA. This model has been used extensively in the structure-activity studies performed. In addition to receptorbinding and electrophysiological studies on native receptors the pharmacological characterization has been supplemented with assays based on recombinant receptors.

The research has led to the development of highly potent and specific agonists for different receptor subtypes, and development of new antagonists, functional partial agonists and enhancers of excitatory activity, the three latter exampels representing possible therapeutic strategies in the areas of neurodenerative and neuropsychiatric disorders. The research is part of the focus area ”Structure Based Drug Research” at PHARMA, and includes strong collaboration with computational chemistry and molecular pharmacology groups.

U.Madsen, H.Bräuner-Osborne, J.R.Greenwood, T.N.Johansen, P.Krogsgaard- Larsen, T.Liljefors, M.Nielsen and B.Frølund, GABA and Glutamate receptor ligands and their therapeutic potential in CNS disorders, in S.C.Gad (ed.) Drug Discovery Handbook, Wiley, Hoboken, 2005, p. 797-907.

U.Madsen, D.S.Pickering, B.Nielsen and H.Bräuner-Osborne, 4-Alkylated homoibotenic acid (HIBO) analogues: versatile pharmacological agents with diverse selectivity profiles towards metabotropic and ionotropic glutamate receptor subtypes, Neuropharmacology, 2005, 49 (2005) 114-119.

J.Andersen, U.Madsen, F.Björkling and X. Liang, Rapid synthesis of aryl azides from aryl halides under mild conditions, Synlett (2005) 2209-2213.

B.Frølund, J.R.Greenwood, M.H.Holm, J.Egebjerg, U.Madsen, B.Nielsen, H.Bräuner-Osborne, T.B.Stensbøl and P.Krogsgaard-Larsen, Tetrazolyl isoxazole amino acids as ionotropic glutamate receptor antagonists: synthesis, modelling and molecular pharmacology, Bioorg. Med. Chem. 13 (2005) 5391-5398.

P.Conti, M.De Amici, G.Grazioso, G.Roda, A.Pinto, K.B.Hansen, B.Nielsen, U.Madsen, H.Bräuner-Osborne, J.Egebjerg, V.Vestri, D.E.Pellegrini-Giampietro, P.Sibille, F.A.Acher and C.De Micheli, Synthesis, binding affinity at glutamic acid receptors, neuroprotective effects, and molecular modelling investigation of novel dihydroisoxazole amino acids, J. Med. Chem. 48 (2005) 6315-6325.

C.G.Jørgensen, R.P.Clausen, K.B.Hansen, H.Bräuner-Osborne, B.Nielsen, B.Metzler, J.Kehler and U.Madsen, Synthesis and pharmacology of glutamate receptor ligands: new isothiazole analogues of ibotenic acid, Org. Biomol. Chem. 5 (2007) 463-471.

P.Conti, M.De Amici, G.Roda, A.Pinto, L.Tamborini, U.Madsen, B.Nielsen, H.Bräuner-Osborne and C.De Micheli, Synthesis and pharmacological characterization at glutamate receptors of erythro- and threo-tricholomic acid and homologues thereof, Tetrahedron 63 (2007) 2249-2256.

C.G.Jørgensen, H.Bräuner-Osborne, B.Nielsen, J.Kehler, R.P.Clausen, P.Krogsgaard-Larsen and U.Madsen, Novel 5-substituted 1-pyrazolol analogues of ibotenic acid: Synthesis and pharmacology at glutamate receptors, Bioorg. Med. Chem. 15 (2007) 3524-3538.

P.Conti, A.Caligiuri, A.Pinto, G.Roda, L.Tamborini, B.Nielsen, U.Madsen, K.Frydenvang, A.Colombo and C.De Micheli, Synthesis and pharmacological evaluation of novel conformationally constrained homologues of glutamic acid, Eur. J. Med. Chem. 42 (2007) 1059-1068.

H.Hald, P.Naur, D.S.Pickering, D.Sprogøe, U.Madsen, D.B.Timmermann, P.K.Ahring, T.Liljefors, A.Schousboe, J.Egebjerg, M.Gajhede and J.S.Kastrup, Partial agonism and antagonism of the ionotropic glutamate receptor iGluR5, J. Biol. Chem. 282 (2007) 25726-25736.

B.H.Kaae, K.Harpsøe, J.S.Kastrup, A.Contreras Sanz, D.S.Pickering, B.Metzler, R.P.Clausen, M.Gajhede, P.Sauerberg, T.Liljefors and U.Madsen, Structural proof of a dimeric positive modulator bridging two identical AMPA receptor-binding sites, Chemistry & Biology 14 (2007) 1294-1303.

A.Pinto, P.Conti, M.De Amici, L.Tamborini, U.Madsen, B.Nielsen, T.Christesen, H.Bräuner-Osborne and C.De Micheli, Synthesis and pharmacological characterization at glutamate receptors of the four enantiopure isomers of tricholomic acid, J. Med. Chem. 51 (2008) 2311-2315.

P.Krogsgaard-Larsen, K.Strømgaard and U.Madsen (eds.), Textbook of Drug Design and Discovery, 4. ed., CRC Press, Boca Raton, 2009.

P.Conti, A.Pinto, L. Tamborini, U.Madsen, B.Nielsen, H.Bräuner- Osborne, K.B.Hansen, E.Landucci, D.E.Pellegrini-Giampietro, G.De Sarro, E.D.Di Paola and C.De Micheli. Novel 3-carboxy- and 3- phosphonopyrazoline amino acids as potent and selective NMDA receptor antagonists: Design, synthesis, and pharmacological characterization, ChemMedChem 5 (2010) 1465-75.

J.Pøhlsgaard, K.Frydenvang, U.Madsen and J.S.Kastrup. Lessons from more than 80 structures of the GluA2 ligand-binding domain in complex with agonists, antagonists and allosteric modulators, Neuropharmacology 60 (2011) 135-150.

A.Pinto, P.Conti, G.Grazioso, L.Tamborini, U.Madsen, B.Nielsen and C.De Micheli, Synthesis of new isoxazoline-based amino acids and investigation of their affinity and selectivity profile at ionotropic glutamate receptors, Eur. J. Med. Chem. 46 (2011) 787-793