Institut für Pharmazeutische Chemie -
Prof. Dr. Holger Stark

Expertise

Leitstrukturentwicklung und -optimierungen unter Berücksichtigung pharmakokinetischer und toxikologischer Aspekte
Medizinische Chemie von Liganden G-Protein-gekoppelter Rezeptoren (Histamin- und Dopaminsubrezeptoren)
Medizinische Chemie von allosterischen Modulatoren ionotroper Rezeptoren (NMDA-Rezeptoren)
Entwicklung von pharmakologischen Tools (rezeptorselektive Liganden, Radioliganden, Fluoreszenzliganden etc.)
Struktur-Wirkungsbeziehungen
Entwicklung von Enzyminhibitoren, Prodrugs etc.
Strukturaufklärung chemischer Verbindungen
Synthese von nicht-peptidischen Zielverbindungen
Bindungsassays an Subtypen von Dopaminrezeptoren
Medizinische Chemie von Sphingolipiden und anderen Lipidmodulatoren

Methoden und Geräte

Voll ausgestattete Syntheselabore
Hoch- und Niederdruckhydrierungen
Tief- und Hochtemperaturreaktionen
Heterozyklensynthesen
Mikrowellen-Synthesen
Chromatographische Reinigungsmethoden (SC, Flash-SC, Chromatotron, semi-präparative HPLC)
Substanzbibliothek pharmakologisch aktiver Verbindungen
Kalkulationen physikochemischer Substanzparameter
1H-NMR, 13C-NMR, 31P-NMR, 19F-NMR, diverse MS-Verfahren, IR, UV, stereochemische Reinheitsbestimmungen etc.
Humane Dopaminrezeptor-Sybtypen (hD1, hD5, hD2, hD3)
Humane Histaminrezeptor-Subtypen (hH1, hH3, hH4)
weitere GPCR-Testungen im Aufbau
beta-Counter

Publikationen

Sasse BC, Mach UR, Leppaenen J, Calmels T, and Stark H: Hybrid Approach for the Design of Highly Affine and Selective Dopamine D3 Receptor Ligands using Privileged Scaffolds of Biogenic Amine GPCR Ligands. Bioorg. Med. Chem 2007; 15: 7258-7273.
Böcker A, Sasse BC, Nietert M, Stark H, Schneider G: GPCR Targeted Library Design: Novel Dopamine D3 Receptor Antagonists. ChemMedChem 2007; 2: 1000-1005.
Ligneau X, Perrin D, Landais L, Camelin JC, Calmels PG, Berrebi-Bertrand I, Lecomte JM, Parmentier R, Anaclet C, Lin JS, Bertaina-Anglade V, Drieu la Rochelle C, d´Aniello F, Rouleau A, Gbahou F, Arrang JM, Ganellin CR, Stark H, Schunack W, Schwartz JC: BF2.649, a Non-Imidazole Inverse Agonist/Antagonist at the Human Histamine H3 Receptor: Preclinical Pharmacology. J Pharmacol Exp Ther 2007; 320: 365-375.
Amon M, Ligneau X, Camelin JC, Berrebi-Bertrand I, Schwartz JC, Stark H: Highly Potent Fluorescence-Tagged Nonimidazole Histamine H3 Receptor Ligands. ChemMedChem 2007; 2: 708-716.
Dijkstra D, Leurs R, Chazot P, Shenton F, Stark H, Werfel T, Gutzmer R: Histamine Downregulates Monocyte CCL2 Production via the Histamine H4 Receptor. J Allergy Clin Immunol 2007; 120: 300-307.
Amon M, Ligneau X, Schwartz JC, Stark H. Fluorescent Non-imidazole Histamine H3 Receptor Ligands with Nanomolar Affinities. Bioorg Med Chem Lett 2006; 16: 1938-1940.
Noeske T, Sasse BC, Stark H, Parsons CG, Weil T, Schneider G: Predicting Compound Selectivity by Self-Organizing Maps: Cross-Activities of Metabotropic Glutamate Receptor Antagonists. ChemMedChem 2006; 1: 1066-1068.
Müllner S, Stark H, Niskanen P, Eigenbrodt E, Mazurek S, Fasold H: From Target to Lead Synthesis. Methods and Principles in Medicinal Chemistry (28) (Proteomics in Drug Research; Ed. M. Hamacher, K. Marcus, K. Stühler, A. van Hall, B. Warscheid, and H. E. Meyer), Ed. R. Mannhold, H. Kubinyi, and G. Folkers, Wiley-VCH Verlag GmbH Co.KGaG 2006;, Weinheim, Germany, 2006, pp. 187-207.(ISBN: 3-527-31226-9).
Grassmann S, Apelt J, Ligneau X, Pertz HH, Arrang JM, Ganellin CR, Schwartz JC, Schunack W, Stark H:. Search for histamine H3 receptor ligands with combined inhibitory potency at histamine N-Methyltransferase: w-piperidinoalkanamine derivatives. Arch Pharm Pharm Med Chem 2004; 337: 533-545.
Gbahou F, Rouleau A, Morisset S, Parmentier R, Crochet S, Lin JS, Ligneau X, Tardivel-Lacombe J, Stark H, Schunack W, Ganellin CR, Schwartz JC, Arrang JM: Protean Agonism at Histamine H3 Receptors in Vitro and in Vivo. Proc Natl Acad Sci U.S.A. 2003; 100: 11086-11091.
Stark H: Recent Advances in Histamine H3/H4 Receptor Ligands. Expert Opin Ther Patents 2003; 13: 851-865.
Hackling A, Ghosh R, Perachon S, Mann A, Höltje HD, Wermuth CG, Schwartz JC, Sippl W, Sokoloff P, Stark H: N-(w-(4-(2-Methoxyphenyl)piperazin-1-yl)alkyl)carboxamides as Dopamine D2 and D3 Receptor Ligands. J Med Chem 2003; 46: 3883-3899.
Graßmann S, Apelt J, Sippl W, Ligneau X, Pertz HH, Zhao YH, Arrang JM, Ganellin CR, Schwartz JC, Schunack W, and H. Stark H: Imidazole Derivatives as a Novel Class of Hybrid Compounds with Inhibitory Histamine N-Methyltransferase Potencies and Histamine hH3 Receptor Affinities. Bioorg Med Chem 2003; 11: 2163-2174.
Mikó T, Ligneau X, Pertz HH, Ganellin CR, Arrang JM, Schwartz JC, Schunack W, Stark H: Novel Nonimidazole Histamine H3 Receptor Antagonists: 1-(4-(Phenoxymethyl)benzyl)piperidines and Related Compounds. J Med Chem 2003; 46: 1523-1530.
Bézard E, Ferry S, Mach U, Stark H, Leriche L, Boraud T, Gross C, Sokoloff P: Attenuation of Levodopa-Induced Dyskinesia by Normalizing Dopamine D3 Receptor Function. Nat Med 2003; 9: 762-767.
Hackling AE, Stark H: Dopamine D3 Receptor Ligands with Antagonist Properties. ChemBioChem 2002; 3: 946-961.
Apelt J, Ligneau X, Pertz HH, Arrang JM, Ganellin CR, Schwartz JC, Schunack W, Stark H: Development of a New Class of Nonimidazole Histamine H3 Receptor Antagonist with Combined Inhibitory Histamine N-Methyltransferase Activity. J Med Chem 2002; 45: 1128-1141.
Weber B, Schlicker E, Sokoloff P, Stark H: Identification of the Dopamine Autoreceptor in the Guinea-Pig Retina as D2 Receptor Using Novel Subtype-Selective Antagonists. Br J Pharmacol 2001; 133: 1243-1248 .
Sasse A, Schunack W, Stark H: Separation of Chiral 4-Substituted Imidazole Derivatives by Cyclodextrin-Modified Capillary Electrophoresis. Biomed Chromatogr 2001; 15: 25-30.
Stark H, Krause M, Rouleau A, Garbarg M, Schwartz JC, Schunack W: Enzyme-Catalyzed Prodrug Approaches for the Histamine H3-Receptor Agonist (R)-alpha-Methylhistamine. Bioorg Med Chem 2001; 9: 191-198.
Morisset S, Rouleau A, Ligneau X, Gbahou F, Tardivel-Lacombe J, Stark H, Schunack W, Ganellin CR, Schwartz JC, Arrang JM: High Constitutive Activity of Native H3 Receptor Regulates Histamine Neurones in Brain. Nature 2000; 408: 860-864.