Ulf Madsen

CV

Address          Department of Drug Design and Pharmacology

School of Pharmaceutical Sciences

(former Faculty of Pharmaceutical Sciences (PHARMA)/

Danish University of Pharmaceutical Sciences/

Royal Danish School of Pharmacy)

University of Copenhagen

Universitetsparken 2, DK-2100 Copenhagen

EDUCATION:

Graduated (Cand.pharm.) from The Royal Danish School of Pharmacy             1983

Ph.D. (Lic.pharm.) from The Royal Danish School of Pharmacy                         1988

INTERNATIONAL EXPERIENCE:

Visiting scientist at Dept. of Pharmacology, University of Sydney, Australia     1987           

Visiting scientist at Inst. of Organic Chemistry, Syntex Research, CA, U.S.A.   1990  

Friedrich-Merz Foundation Guest-Professor at Inst. of Pharmaceutical

Chemistry, Johan Wolfgang Goethe-Universität, Frankfurt am Main, Germany    1992

EMPLOYMENTS:

Research scholarship from The Royal Danish School of Pharmacy      1984 – 1987           

Research scholarships from The Lundbeck Foundation (at PHARMA)  1987 – 1993              

Associate professor (Lektor), Dept. of Medicinal Chemistry, PHARMA  1994 –        

Head of Department, Dept. of Medicinal Chemistry, PHARMA              1996 ­­– 2002         

Head of Department, Dept. of Medicinal Chemistry, PHARMA              2005 –  2008

Associate Dean, PHARMA                                                                 2008 –  2011

School Director, School of Pharmaceutical Sciences, SUND                  2012 -

OTHER PROFESSIONAL ACTIVITIES:

Supervisor of 12 ph.d.-students (all graduated)

Supervisor of more than 25 graduate-project students

Chairman of the PhD Study board (Ph.d.-Studienævnet, PHARMA)         2003 – 2005

Chairman of the Research grant board (Stipendieudvalget, PHARMA)     2003 – 2005

Director of the Drug Research Academy (DRA) at PHARMA                    2005 – 2007

Member of The Danish Commitee on Scientific Dishonesty                     2003 – 2012

Author of more than 100 scientific papers, co-editor of a textbook (four editions) and

co-inventor on two patents.

GRANTS:

EU, BIO2-CT93-0243                                         DKK 1.286.000                1993 – 1996

(co-applicant P.Krogsgaard-Larsen)

Graduate School of Drug Research,               DKK 1.300.000                2000 – 2003

PhD. grant, industry partner: Neurosearch

DRA, PhD grant, industry partner: Lundbeck       DKK 1.400.000                2002 – 2006

Danish Research Agency, Scholar stipend        DKK 162.000                   2004

DRA, Post.doc. grant                                         DKK 1.000.000                2004 – 2005

DRA, PhD grant, industry part: Novo Nordisk       DKK 1.400.000                2004 – 2007

The Carlsberg Foundation, Secretary Assist.     DKK 1.620.000                2003-2011

Danish Agency for Science, Technology and Innovation, grants for DRA:

3 international PhD scholarships                          DKK 5.102.496               2007 – 2009

8 Co-financed PhD scholarships                           DKK 4.080.000               2007 – 2009

Operating costs (Kvalitetsfremmemidler)              DKK 10.000.000             2007 – 2011

Publications 1986 - 2006:

1.         U.Madsen, K.Schaumburg, L.Brehm, D.R.Curtis and P.Krogsgaard-Larsen, Ibotenic acid analogues. Synthesis and biological testing of two bicyclic 3-isoxazolol amino acids, Acta Chem. Scand. B40 (1986) 92-97.

2.         P.Krogsgaard-Larsen, L.Nielsen, U.Madsen and E.Ø.Nielsen, GABA and glutamic acid agonists of pharmacological interest, in L.L.Iversen and E.Goodman (eds.) Fast and Slow Chemical Signalling in the Nervous System, Oxford Science Publ., 1986, p. 75-88.

3.         E.Ø.Nielsen, U.Madsen , K.Schaumburg, L.Brehm and P.Krogsgaard-Larsen, Studies on receptor-active conformations of excitatory amino acid agonists and antagonists, Eur. J. Med. Chem. - Chim. Ther. 21 (1986) 433-437.

4.         P.Krogsgaard-Larsen, U.Madsen, B.Nielsen, J.J.Hansen, E.Ø.Nielsen, L.Brehm and D.R.Curtis, Molecular pharmacology of excitatory amino acid receptors: Conformational and stereochemical requirements, in M.J.Rand and C.Raper (eds.) Pharmacology, Elsevier Science Publ., Amsterdam, 1987, p. 113-116.

5.         U.Madsen, L.Brehm and P.Krogsgaard-Larsen, Excitatory amino acids. Improved synthesis of ibotenic acid and X-ray analysis of an unexpected reaction product, (RS)-N-[2-(3-benzyloxyisoxazol-5-yl)-1 phenylethyl]-3-oxobutyramide, J. Chem. Soc., Perkin Trans. I (1988) 359-364.

6.         U.Madsen, K.Schaumburg, L.Brehm, F.S.Jørgensen and P.Krogsgaard-Larsen, Relationship between structure, conformational mobility and biological activity of amino acid neurotransmitter analogs, in J.W.Jaroszewski, K.Schaumburg and H.Kofod (eds.) NMR Spectroscopy in Drug Research, Munksgaard, Copenhagen, 1988, p. 57-71.

7.         P.Krogsgaard-Larsen, A.Hedegaard, L.Nielsen, B.Nielsen, U.Madsen, L.Brehm, E.Falch, H.Hjeds and J.J.Hansen, Medicinal chemical and pharmacological focus on GABA and glutamic acid receptors in neurodegenerative disorders, in H.van der Goot, G.Domány, L.Pallos and H.Timmerman (eds.) Trends in Medicinal Chemistry ´88, Elsevier Sciense Publ., Amsterdam, 1989, p. 429-452.

8.         I.T.Christensen, A.Reinhardt, B.Nielsen, B.Ebert, U.Madsen, E.Ø.Nielsen, L.Brehm and P.Krogsgaard Larsen, Excitatory amino acid agonists and partial agonists, Drug Des. Del. 5 (1989) 57-71.

9.         J.J.Hansen, U.Madsen, E.Ø.Nielsen, B.Nielsen, L.Brehm and P.Krogsgaard-Larsen, Isoxazole amino acids as glutamic acid receptor agonists: Conformational and stereochemical aspects, in A.Makriyannis (ed.) New Methods in Drug Research, Vol. 3, Prous Science Publ., Barcelona, 1989, p. 73-101.

10.        U.Madsen, L.Brehm, K.Schaumburg, F.S.Jørgensen and P.Krogsgaard-Larsen, Relationship between structure, conformational flexibility and biological activity of agonists and antagonists at the N-methyl D-aspartic acid subtype of excitatory amino acid receptors, J. Med. Chem. 33 (1990) 374-380.

11.        U.Madsen, E.Ø.Nielsen, D.R.Curtis, D.T.Beattie and P.Krogsgaard-Larsen, Synthesis and single cell pharmacology of potential heterocyclic bioisosteres of the excitatory amino acid antagonist glutamic acid diethyl ester, Acta Chem Scand. 44 (1990) 96-102.

12.        P.Krogsgaard-Larsen, U.Madsen, L.Brehm, I.T.Christensen, B.Nielsen, A.Reinhardt, B.Ebert and J.J.Hansen, Structural, stereochemical and conformational requirements for activation and blockade of central glutamic acid receptors, in M.Simonyi (ed.) Problems and Wonders of Chiral Molecules, Akadémiai Kiadó, Budapest, 1990, p. 205-223.

13.        L.Brehm, I.T.Christensen, B.Nielsen, A.Reinhardt, B.Ebert, U.Madsen, F.S.Jørgensen, J.J.Hansen and P.Krogsgaard-Larsen, Structural and stereochemical requirements for interactions with subtypes of central excitatory amino acid receptors, in B.Jensen, F.S.Jørgensen and H.Kofod (eds.) Frontiers in Drug Research, Munksgaard, Copenhagen, 1990, p. 92-105.

14.        U.Madsen, J.W.Ferkany, B.E.Jones, B.Ebert, T.N.Johansen, T.Holm and P.Krogsgaard-Larsen, NMDA receptor agonists derived from ibotenic acid. Preparation, neuroexcitation and neurotoxicity, Eur. J. Pharmacol. - Mol. Pharmacol. Sect. 189 (1990) 381-391.

15.        P.Krogsgaard-Larsen, J.W.Ferkany, E.Ø.Nielsen, U.Madsen, B.Ebert, J.S.Johansen, N.H.Diemer, T.Bruhn, D.T.Beattie and D.R.Curtis, Novel class of amino acid antagonists at non-N-Methyl-D aspartic acid excitatory amino acid receptors. Synthesis, in vitro and in vivo pharmacology and neuroprotection, J. Med. Chem. 34 (1991) 123-130.

16.        B.Ebert, U.Madsen, T.N.Johansen and P.Krogsgaard-Larsen, NMDA receptor agonists: Relationships between structure and biological activity, Adv. Exp. Med. Biol. 287 (1991) 483-487.

17.        T.M.Lund, U.Madsen, B.Ebert, F.S.Jørgensen and P.Krogsgaard-Larsen, Conformational and pharmacological characterization of 4-AHCP, a bicyclic homologue of the excitatory amino acid receptor agonist AMPA, Med. Chem. Res. 1 (1991) 136-141.

18.        P.Krogsgaard-Larsen, B.Ebert, T.N.Johansen, J.W.Ferkany and U.Madsen, Novel N-methyl-D-aspartate (NMDA) agonists and non-NMDA antagonists, in B.S.Meldrum, F.Moroni, R.P.Simon and J.H.Woods (eds.) Excitatory Amino Acids, Raven Press, New York, 1991, p. 433-441.

19.        L.Brehm, U.Madsen, J.S.Johansen and P.Krogsgaard-Larsen, Chemistry of 3-oxygenated isoxazoles. Formation and X-ray analysis of ethyl (RS)- 6-tert-butyl-5-methyl-4-oxo-2,3-dihydro-4H-1,3-oxazine-2 carboxylate, an isoxazol-3(2H)-one rearrangement product, J. Chem. Soc., Perkin Trans. I (1991) 2009 2013.

20.        U.Madsen and E.H.F.Wong, Heterocyclic excitatory amino acids. Synthesis and biological activity of novel analogues of AMPA, J. Med. Chem. 35 (1992) 107-111.

21.        B.Ebert, U.Madsen, T.M.Lund, T.Holm and P.Krogsgaard-Larsen, Molecular pharmacology of cortical and spinal AMPA receptors, Mol. Neuropharmacol. 2 (1992) 47-49.

22.        P.Krogsgaard-Larsen, U.Madsen, B.Ebert and J.J.Hansen, Excitatory amino acid receptors: Multiplicity and ligand specificity of receptor subtypes, in P.Krogsgaard-Larsen and J.J.Hansen (eds.) Excitatory Amino Acid Receptors. Design of Agonists and Antagonists, Horwood, Chichester, 1992, p. 34-55.

23.        B.Ebert, T.M.Lund, U.Madsen, L.Brehm and P.Krogsgaard-Larsen, Subtype-selective excitatory amino acid receptor agonists and antagonists derived from ibotenic acid, in P.Krogsgaard-Larsen, S.B.Christensen and H.Kofod (eds.) New Leads and Targets in Drug Research, Munksgaard, Copenhagen, 1992, p. 340-351.

24.        P.Krogsgaard-Larsen, B.Ebert, U.Madsen and L.Brehm, Excitatory amino acid receptors: Multiplicity and ligand specificity of the NMDA and AMPA receptor subtypes, in P.Angeli, U.Gulini and W.Quaglia (eds.) Trends in Receptor Research, Elsevier Science Publ., Amsterdam, 1992, p. 209-229.

25.        U.Madsen, B.Ebert, P.Krogsgaard-Larsen and E.H.F.Wong, Synthesis and pharmacology of (RS)-2 amino-3-(3-hydroxy-5-trifluoromethyl-4-isoxazolyl)propionic acid, a potent AMPA receptor agonist, Eur. J. Med. Chem. 27 (1992) 479-484.

26.        I.T.Christensen, B.Ebert, U.Madsen, B.Nielsen, L.Brehm and P.Krogsgaard-Larsen, Excitatory amino acid receptor ligands. Synthesis and biological activity of 3-isoxazolol amino acids structurally related to homoibotenic acid, J. Med. Chem. 35 (1992) 3512-3519.

27.        P.Krogsgaard-Larsen, P.Wahl, A.Schousboe, U.Madsen and J.J.Hansen, Excitatory amino acid research in Alzheimer´s disease: Enhancement and blockade of receptor functions, Biochem. Soc. Trans. 21 (1993) 102-106.

28.        U.Madsen, B.Ebert, J.J.Hansen and P.Krogsgaard-Larsen, The non-depolarizing D-form of bromohomoibotenic acid enhances depolarizations evoked by the L-form or quisqualate, Eur. J. Pharmacol. 230 (1993) 383-386.

29.        B.Nielsen, H.Fisker, B.Ebert, U.Madsen, D.R.Curtis, P.Krogsgaard-Larsen and J.J.Hansen, Enzymatic resolution of AMPA by use of a-chymotrypsin, Bioorg. Med. Chem. Lett. 3 (1993) 107-114.

30.        U.Madsen, L.Andresen, G.A.Poulsen, T.B.Rasmussen, B.Ebert, P.Krogsgaard-Larsen and L.Brehm, Excitatory amino acid receptor antagonists: Synthesis and pharmacology og 3-(carboxymethoxy) isoxazoles derived from AMPA, Bioorg. Med. Chem. Lett. 3 (1993) 1649-1654.

31.        U.Madsen, B.Frølund, T.M.Lund, B.Ebert and P.Krogsgaard-Larsen, Design, synthesis and pharmacology of model compounds for indirect elucidation of the topography of AMPA receptor sites, Eur. J. Med. Chem. 28 (1993) 791-800.

32.        B.Ebert, U.Madsen, T.M.Lund, S.M.Lenz and P.Krogsgaard-Larsen, Molecular pharmacology of the AMPA agonist, (S)-2-amino-3-(3-hydroxy-5-phenyl-4-isoxazolyl)propionic acid [(S)-APPA] and the AMPA antagonists, (R)-APPA, Neurochem. Int. 24 (1994) 507-515.

33.        U.Madsen, B.Ebert and P.Krogsgaard-Larsen, Modulation of AMPA receptor function in relation to glutamatergic abnormalities in Alzheimer’s disease, Biomed. & Pharmacother. 48 (1994) 305-311.

34.        T.N.Johansen, K.Frydenvang, B.Ebert, P.Krogsgaard-Larsen and U.Madsen, Synthesis and structure activity                  studies on acidic amino acids and related diacids as NMDA receptor ligands, J. Med. Chem. 37 (1994) 3252-3262.

35.        B. Ebert, K.K.Søby, U.Madsen and P.Krogsgaard-Larsen, Glutamic acid receptors in schizophrenia and Alzheimer´s disease: Functional partial agonism and receptor modulation as potential therapeutic approaches, in R.Fog, J.Gerlach and R.Hemmingsen (eds.) Schizophrenia, Munksgaard, Copenhagen, 1995, p. 379-395.

36.        F.Bischoff, T.N.Johansen, B.Ebert, P.Krogsgaard-Larsen and U.Madsen, Excitatory amino acid receptor ligands: Asymmetric synthesis, absolute stereochemistry, and pharmacology of (R)- and (S) homoibotenic acid, Bioorg. Med. Chem. 3 (1995) 553-558.

37.        J.Arnt, C. Sánchez, S.M.Lenz, U.Madsen and P.Krogsgaard-Larsen, Differentiation of in vivo effects of AMPA and NMDA receptor ligands using drug discrimination methods and convulsant/anticonvulsant activity, Eur. J. Pharmacol. 285 (1995) 289-297.

38.        P.Krogsgaard-Larsen, B.Ebert, T.N.Johansen, F.Bischoff and U.Madsen, Excitatory amino acid agonists, partial agonists, antagonists and modulators: Design and therapeutic prospects, in H.Wheal and A.Thomson (eds.) Excitatory Amino Acids and Synaptic Transmission, 2. ed., Academic Press, London, 1995, p. 41-59.

39.        K.Frydenvang, T.N.Johansen, B.Ebert, U.Madsen and P.Krogsgaard-Larsen, Conformational analysis of new structural analogues of a selective NMDA receptor agonist, in F.Sanz, J.Giraldo and F.Manaut (eds.) QSAR and Molecular Modelling: Concepts, Prous Sci. Publ., Barcelona, 1995, p. 332-334.

40.        U.Madsen, K.Frydenvang, B.Ebert, T.N.Johansen, L.Brehm and P.Krogsgaard-Larsen, N-Methyl-D aspartic acid receptor agonists: Resolution, absolute stereochemistry, and pharmacology of the enantiomers of 2-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid, J. Med. Chem. 39 (1996) 183 190.

41.        U.Madsen, B.Bang-Andersen, L.Brehm, I.T.Christensen, B.Ebert, I.T.S.Kristoffersen, Y.Lang and P.Krogsgaard-Larsen, Synthesis and pharmacology of highly selective carboxy and phosphono isoxazole amino acid AMPA receptor antagonists, J. Med. Chem. 39 (1996) 1682-1691.

42.        U.Madsen, Excitatory amino acid receptors, in P.Krogsgaard-Larsen, T.Liljefors and U.Madsen (eds.) A Textbook of Drug Design and Development, 2. ed., Harwood Acad. Publ., Amsterdam, 1996, p. 235-253.

43.        P.Krogsgaard-Larsen, B.Ebert, T.M.Lund, H.Bräuner-Osborne, F.A.Sløk, T.N.Johansen, L.Brehm and U.Madsen, Design of excitatory amino acid receptor agonists, partial agonists and antagonists: ibotenic acid as a key lead structure, Eur. J. Med. Chem. 31 (1996) 515-537.

44.        P.Wahl, U.Madsen, T.Banke, P.Krogsgaard-Larsen and A.Schousboe, Different characteristics of AMPA receptor agonists acting at AMPA receptors expressed in Xenopus oocytes, Eur. J. Pharmacol. 308 (1996) 211-218.

45.        T.N.Johansen, V.Balasubramanian, U.Madsen, J.W.Ferkany and P.Krogsgaard-Larsen, Synthesis of tritiated (RS)-2-amino-2-(3-hydroxy-5-methylisoxazol-4-yl)acetic acid (AMAA). A potent and selective NMDA agonist, J. Labelled Compd. Radiopharm. 38 (1996) 915-922.

46.        B.Ebert, U.Madsen, K.K.Søby and P.Krogsgaard-Larsen, Functional partial agonism at ionotropic excitatory amino acid receptors, Neurochem. Int. 29 (1996) 309-316.

47.        B.Ebert, U.Madsen and P.Krogsgaard-Larsen, Glutamic acid and GABAA receptors as potential drug targets in schizophrenia and Alzheimer’s disease, Medizinische Forschung 9 (1996) 75-96.

48.        U.Madsen, F.A.Sløk, T.N.Johansen, B.Ebert and P.Krogsgaard-Larsen, Design and development of isoxazole amino acids as ligands for ionotropic excitatory amino acid receptors, Current Topics in Medicinal Chemistry 2 (1997) 1-14.

49.        F.A.Sløk, B.Ebert, Y.Lang, P.Krogsgaard-Larsen, S.M.Lenz and U.Madsen, Excitatory amino-acid receptor agonists. Synthesis and pharmacology of analogues of 2-amino-3-(3-hydroxy-5 methylisoxazol-4-yl)propionic acid, Eur. J. Med. Chem. 32 (1997) 329-338.

50.        H.Bräuner-Osborne, U.Madsen, E.Mikiciuk-Olasik and K.Curry, New analogues of ACPD with selective activity for group II metabotropic glutamate receptors, Eur. J. Pharmacol. 332 (1997) 327 331.

51.        T.N.Johansen, K.Frydenvang, B.Ebert, U.Madsen and P.Krogsgaard-Larsen, Excitatory amino acid receptor antagonists: Resolution, absolute stereochemistry, and pharmacology of (S)- and (R)-2-amino 2-(5-tert-butyl-3-hydroxyisoxazol-4-yl)acetic acid (ATAA), Chirality 9 (1997) 529-536.

52.        H.Ahmadian, B.Nielsen, H.Bräuner-Osborne, T.N.Johansen, T.B.Stensbøl, F.A.Sløk, N.Sekiyama, S.Nakanishi, P.Krogsgaard-Larsen and U.Madsen, (S)-Homo-AMPA, a specific agonist at the mGlu6 subtype of metabotropic glutamic acid receptors, J. Med. Chem. 40 (1997) 3700-3705.

53.        P.Wahl, C.Anker, S.F.Traynelis, J.Egebjerg, J.S.Rasmussen, P.Krogsgaard-Larsen and U.Madsen, Antagonist properties of a phosphono isoxazole amino acid at Glutamate R1-4 (R,S)-2-amino-3-(3 hydroxy-5-methyl-4-isoxazolyl)propionic acid receptor subtypes, Mol. Pharmacol. 53 (1998) 590-596.

54.        T.N.Johansen, B.Ebert, H.Bräuner-Osborne, M.Didriksen, I.T.Christensen, K.K.Søby, U.Madsen, P.Krogsgaard-Larsen and L.Brehm, Excitatory amino acid receptor ligands: Resolution, absolute stereochemistry, and enantiopharmacology of 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid, J. Med. Chem. 41 (1998) 930-939.

55.        U.Madsen, M.A.Dumpis, H.Bräuner-Osborne and L.B.Piotrovsky, Synthesis and pharmacology of N alkylated derivatives of the excitotoxin ibotenic acid, Bioorg. Med. Chem. Lett. 8 (1998) 1563-1568.

56.        D.Zimmermann, P.Krogsgaard-Larsen, J.-D.Ehrhardt, U.Madsen and Y.L.Janin, Unambiguous synthesis of 1-methyl-3-hydroxypyrazoles, Tetrahedron 54 (1998) 9393-9400.

57.        P.Conti, M.De Amici, G.De Sarro, T.B.Stensbøl, H.Bräuner-Osborne, U.Madsen and C.De Micheli, Synthesis and pharmacology of a new AMPA-kainate receptor agonist with potent convulsant activity, J. Med. Chem. 41 (1998) 3759-3762.

58.        W.-M.Dai, B.Ebert, U.Madsen and J.D.C.Lambert, Studies of the antagonist actions of (RS)-2-amino 3-[5-tert-butyl-3-phosphonomethoxy)-4-isoxazolyl]propionic acid (ATPO) on non-NMDA receptors in cultured rat neurones, Br. J. Pharmacol. 125 (1998) 1517-1528.

59.        P.Wahl, A.Frandsen, U.Madsen, A.Schousboe and P.Krogsgaard-Larsen, Pharmacology and toxicology of ATOA, an AMPA receptor antagonist and a partial agonist at GluR5 receptors, Neuropharmacology 37 (1998) 1205-1210.

60.        T.B.Stensbøl, F.A.Sløk, J.Trometer, S.Hurt, B.Ebert, C.Kjøller, J.Egebjerg, U.Madsen, N.H.Diemer and P.Krogsgaard-Larsen, Characterization of a new AMPA receptor radioligand, [3H]2-amino-3-(3 carboxy-5-methyl-4-isoxazolyl)propionic acid, Eur. J. Pharmacol. 373 (1999) 251-262.

61.        P.Conti, M.De Amici, G.De Sarro, M.Rizzo, T.B.Stensbøl, H.Bräuner-Osborne, U.Madsen, L.Toma and C.De Micheli, Synthesis and enantiopharmacology of new AMPA-kainate receptor agonists, J. Med. Chem. 42 (1999) 4099-4107.

62.        T.B.Stensbøl, L.Borre, T.N.Johansen, J.Egebjerg, U.Madsen, B.Ebert and P.Krogsgaard-Larsen, Resolution, absolute stereochemistry and molecular pharmacology of the enantiomers of ATPA, Eur. J. Pharmacol. 380 (1999) 153-162.

63.        E.H.Møller, J.Egebjerg, L.Brehm, T.B.Stensbøl, T.N.Johansen, U.Madsen and P.Krogsgaard-Larsen, Resolution, absolute stereochemistry and enantiopharmacology of the GluR1-4 and GluR5 antagonist 2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl]propionic acid, Chirality 11 (1999) 752 759.

64.        D.Zimmermann, Y.L.Janin, L.Brehm, H.Bräuner-Osborne, B.Ebert, T.N.Johansen, U.Madsen and P. Krogsgaard-Larsen, 3-Pyrazolone analogues of the 3-isoxazolol metabotropic excitatory amino acid receptor agonist homo-AMPA. Synthesis and pharmacological testing, Eur. J. Med. Chem. 34 (1999) 967-976.

65.        U.Madsen, F.A.Sløk, T.B.Stensbøl, H.Bräuner-Osborne, H.-C.H.Lützhøft, M.V.Poulsen, L.Eriksen and P.Krogsgaard-Larsen, Ionotropic excitatory amino acid receptor ligands. Synthesis and pharmacology of a new amino acid AMPA antagonist, Eur. J. Med. Chem. 35 (2000) 69-76.

66.        H.Bräuner-Osborne, J.Egebjerg, E.Ø.Nielsen, U.Madsen and P.Krogsgaard-Larsen, Ligands for glutamate receptors: Design and therapeutic prospects, J. Med. Chem. 43 (2000) 2609-2645.

67.        T.Coquelle, J.K.Christensen, T.G.Banke, U.Madsen, A.Schousboe and D.S.Pickering, Agonist discrimination between AMPA receptor subtypes, Neuroreport 11 (2000) 2643-2648.

68.        B.Bang-Andersen, H.Ahmadian, S.M.Lenz, T.B.Stensbøl, U.Madsen, K.P.Bøgesø and P.Krogsgaard Larsen, Structural determinants of AMPA agonist activity in analogues of 2-amino-3-(3-carboxy-5 methyl-4-isoxazolyl)propionic acid: Synthesis and pharmacology, J. Med. Chem. 43 (2000) 4910 4918.

69.        L.Bunch, P.-O.Norrby, K.Frydenvang, P.Krogsgaard-Larsen and U.Madsen, Unpresedented migration of N-alkoxycarbonyl groups in protected pyroglutaminol, Org. Lett. 3 (2001) 433-435.

70.        U.S.Sørensen, E.Falch, T.B.Stensbøl, J.W.Jaroszewski, U.Madsen and P.Krogsgaard-Larsen, Structural determinants for AMPA agonist activity of aryl or heteroaryl substituted AMPA analogues. Synthesis and pharmacology, Arch. Pharm. Pharm. Med. Chem. 334 (2001) 62-68.

71.        U.Madsen, H.Bräuner-Osborne, K.Frydenvang, L.Hvene, T.N.Johansen, B.Nielsen, C.Sánchez, T.B.Stensbøl, F.Bischoff and P.Krogsgaard-Larsen, Synthesis and pharmacology of 3-isoxazolol amino acids as selective antagonists at group I metabotropic glutamic acid receptors, J. Med. Chem. 44 (2001) 1051-1059.

72.        L.Bunch, T.H.Johansen, H.Bräuner-Osborne, T.B.Stensbøl, T.N.Johansen, P.Krogsgaard-Larsen and U.Madsen, Synthesis and receptor binding affinity of new selective GluR5 ligands, Bioorg. Med. Chem. 9 (2001) 875-879.

73.        F.A.Sløk, H.Bräuner-Osborne, T.B.Stensbøl, T.N.Johansen, B.Ebert, M.Mortensen, B.Nielsen, U.Madsen, L.Brehm, E.Falch and P.Krogsgaard-Larsen, Structural and stereochemical requirements for activation and blockade of excitatory amino acid receptors, in M.M.Campbell and I.S.Blagbrough (eds.) Medicinal Chemistry into the Millennium, Royal Society of Chemistry, Cambridge, 2001, p. 52-64.

74.        U.Madsen, T.B.Stensbøl and P.Krogsgaard-Larsen, Inhibitors of AMPA and kainate receptors, Curr. Med. Chem. 8 (2001) 1291-1301.

75.        T.N.Johansen, T.B.Stensbøl, B.Nielsen, S.B.Vogensen, K.Frydenvang, F.A.Sløk, H.Bräuner-Osborne, U.Madsen and P.Krogsgaard-Larsen, Resolution, configurational assignment, and enantiopharmacology at glutamate receptors of 2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA) and demethyl-ACPA, Chirality 13 (2001) 523-532.

76.        U.Madsen, T.N.Johansen, T.B.Stensbøl and P.Krogsgaard-Larsen, Pharmacology of AMPA/kainate receptors, in  J.Egebjerg, A.Schousboe and P.Krogsgaard-Larsen (eds.) Glutamate and GABA Receptors and Transporters, Taylor and Francis Books Ltd., London, 2001, p. 99-118.

77.        L.Bunch, P.Krogsgaard-Larsen and U.Madsen, Mixed cyano-Gilman cuprates – Advances in conjugate addition to a,b-unsaturated pyroglutaminol, Synthesis (2002) 31-33.

78.            T.B.Stensbøl, P.Uhlmann, S.Morel, B.L.Eriksen, J.Felding, H.Kromann, M.B.Hermit, J.R.Greenwood, H.Bräuner-Osborne, U.Madsen, F.Junager, P.Krogsgaard-Larsen, M.Begtrup and P.Vedsø, Novel 1-hydroxyazole bioisosteres of glutamic acid. Synthesis, protolytic properties, and pharmacology, J. Med. Chem. 45 (2002) 19-31.

79.            H.Kromann, F.A.Sløk, T.B.Stensbøl, H.Bräuner-Osborne, U.Madsen and P.Krogsgaard-Larsen, Selective antagonists at group I metabotropic receptors: Synthesis and molecular pharmacology of 4-aryl-3-isoxazolol amino acids, J. Med. Chem. 45 (2002) 988-991.

80.            L.Bunch, P. Krogsgaard-Larsen and U.Madsen, Regioselective lithiation and functionalization of 3-(benzyloxy)isothiazole: Application to the synthesis of thioibotenic acid, J. Org. Chem. 67 (2002) 2375-2377.

81.            M.Guldbrandt, T.N.Johansen, K.Frydenvang, H.Bräuner-Osborne, T.B.Stensbøl, B.Nielsen, R.Karla, F.Santi, P.Krogsgaard-Larsen and U.Madsen, Glutamate receptor ligands: Synthesis, stereochemistry, and enantiopharmacology og methylated 2-aminoadipic acid analogs, Chirality 14 (2002) 351-363.

82.            T.N.Johansen, Y.L.Janin, B.Nielsen, K.Frydenvang, H.Bräuner-Osborne, T.B.Stensbøl, S.B.Vogensen, U.Madsen and P.Krogsgaard-Larsen, 2-Amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid: Resolution, absolute stereochemistry and enantiopharmacology at glutamate receptors, Bioorg. Med. Chem. 10 (2002) 2259-2266.

83.            T.B.Stensbøl, U.Madsen and P.Krogsgaard-Larsen, The AMPA receptor binding site: Focus on agonists and competitive antagonists, Curr. Pharm. Design 8 (2002) 857-872.

84.            P.Conti, M.De Amici, H.Bräuner-Osborne, U.Madsen, L.Toma and C.De Micheli, Synthesis and pharmacology of 3-hydroxy-D²-isoxazoline-cyclopentane analogues of glutamic acid, Il Farmaco 57 (2002) 889-895.

85.            U.Madsen, Excitatory and inhibitory amino acid receptor ligands, in P.Krogsgaard-Larsen, T.Liljefors and U.Madsen (eds.) A Textbook of Drug Design and Discovery, 3. ed., Taylor and Francis Books Ltd., London, 2002, p. 232-271.

86.            P.Conti, M.De Amici, G.Roda, G.Vistoli, T.B.Stensbøl, H.Bräuner-Osborne, U.Madsen, L.Toma and C.De Micheli, Design of novel conformationally restricted analogues of glutamic acid, Tetrahedron 59 (2003) 1443-1452.

87.        L.Bunch, T.Liljefors, J.R.Greenwood, K.Frydenvang, H.Bräuner-Osborne, P.Krogsgaard-Larsen and U.Madsen, Rational design, synthesis, and pharmacological evaluation of 2-azanorbornane-3-exo,5-endo-dicarboxylic acid: A novel conformationally restricted glutamic acid analogue, J. Org. Chem. 68 (2003) 1489-1495.

88.        T.N.Johansen, J.R.Greenwood, K.Frydenvang, U.Madsen and P.Krogsgaard-Larsen, Stereostructure-activity studies on agonists at the AMPA and kainate subtypes of ionotropic glutamate receptors, Chirality 15 (2003) 167-179.

89.        E.J.Bjerrum, A.S.Kristensen, D.S.Pickering, J.R.Greenwood, B.Nielsen, T.Liljefors, A.Schousboe, H.Bräuner-Osborne and U.Madsen, Design, synthesis, and pharmacology of a highly subtype-selective GluR1/2 agonist, (RS)-2-amino-3-(4-chloro-3-hydroxy-5-isoxazolyl)propionic acid (Cl-HIBO), J. Med. Chem. 46 (2003) 2246-2249.

90.        P.Conti, M.De Amici, S.J.di Ventimiglia, T.B.Stensbøl, U.Madsen, H.Bräuner-Osborne, E.Russo, G.De Sarro, G.Bruno and C.De Micheli, Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids, J. Med. Chem. 46 (2003) 3102-3108.

91.        J.Valgeirsson, J.K.Christensen, A.S.Kristensen, D.S.Pickering, B.Nielsen, C.H.Fischer, H.Bräuner-Osborne, E.Ø.Nielsen, P.Krogsgaard-Larsen and U.Madsen, Synthesis and in vitro pharmacology at AMPA and kainate preferring glutamate receptors of 4-heteroarylmethylidene glutamate analogues, Bioorg. Med. Chem. 11 (2003) 4341-4349.

92.        P.Conti, M.De Amici, G.Grazioso, G.Roda, T.B.Stensbøl, H.Bräuner-Osborne, U.Madsen, L.Toma and C.De Micheli, Design of cyclopentaisoxazoline amino acids as conformationally constrained agonists at glutamate receptors, Eur. J. Org. Chem. (2003) 4455-4461.

93.        J.Valgeirsson, E.Ø.Nielsen, D.Peters, T.Varming, C.Mathiesen, A.S.Kristensen and U.Madsen, 2-Arylureidobenzoic acids: Selective noncompetitive antagonists for the homomeric kainate receptor subtype GluR5, J. Med. Chem. 46 (2003) 5834-5843.

94.        M.B.Hermit, J.R.Greenwood, B.Nielsen, L.Bunch, C.G.Jørgensen, H.T.Vestergaard, T.B.Stensbøl, C.Sanchez, P.Krogsgaard-Larsen, U.Madsen and H.Bräuner-Osborne, Ibotenic acid and thioibotenic acid: a remarkable difference in activity at group III metabotropic glutamate receptors, Eur. J. Pharmacol. 486 (2004) 241-250.

95.        H.T.Vestergaard, S.B.Vogensen, U.Madsen and B.Ebert, Analogues of homoibotenic acid show potent and selective activity following sensitisation by quisqualic acid, Eur. J. Pharmacol. 488 (2004) 101-109.

96.        P.Conti, M.De Amici, G.Grazioso, G.Roda, F.F.B.Negra, B.Nielsen, T.B.Stensbøl, U.Madsen, H.Bräuner-Osborne, K.Frydenvang, G.De Sarro, L.Toma and C.De Micheli, Design, synthesis and pharmacological characterization of novel, potent NMDA receptor antagonists, J. Med. Chem. 47 (2004) 6740-6748.

97.        J.Valgeirsson, E.Ø.Nielsen, D.Peters, C.Mathiesen, A.S.Kristensen and U.Madsen, Bioisosteric modifications of 2-arylureidobenzoic acids: Selective noncompetitive antagonists for the homomeric kainate receptor subtype GluR5, J. Med. Chem. 47 (2004) 6948-6957.

98.        U.Meyer, P.Bisel, H.Bräuner-Osborne, U.Madsen, G.Höfner, K.T.Wanner and A.W.Frahm, Rigid nonproteinogenic cyclic amino acids as ligands for glutamate receptor: trans-tris(homoglutamic) acids, Chirality 17 (2005) 99-107.

99.        P.Conti, G.Grazioso, S.J.di Ventimiglia, A.Pinto, G.Roda, U.Madsen, H.Bräuner-Osborne, B.Nielsen, C.Costagli and A.Galli, Synthesis of novel N¹-substituted bicyclic pyrazole amino acids and evaluation of their interaction with glutamate receptors, Chemistry and Biodiversity 2 (2005) 748-757.

100.      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.

101.      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.

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

103.      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.

104.      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.

Kort præsentation

Skoleleder og formand for Uddannelsesrådet på School of Pharmaceutical Sciences.

Extensive research experience with design and synthesis of glutamate receptor ligands. Selective ligands for ionotropic as well as metabotropic glutamate receptors have been developed for structure-activity studies of the different receptor classes, and the work has afforded a number of important pharmacological tools. Compounds with antagonist activities have shown neuroprotective properties in animal models and are consequently leads for potential therapeutic candidates. Projects involving structure-based drug design have resulted in the development of important pharmacological agents with high subtype selectivity. The work generally involves synthesis of heterocyclic compounds, use of bioisosteric principles and molecular pharmacology on native as well as recombinant receptors. See also CV.