Institute for Pharmaceutical Chemistry -
Prof. Dr. Holger Stark

Expertise

Lead structure development and optimization
Medicinal Chemistry of ligands of G-protein coupled receptors (mainly histamine and dopamine receptor subtypes)
Medicinal Chemistry of allosteric modulators of ionotropic receptors (NMDA receptors)
Development of pharmacological tools (ligands with receptor selectivity, radioligands, fluorescent ligands...)
Investigation of structure-activity relationships
Development of enzyme inhibitors, prodrugs etc.
Structural elucidation of compounds
Synthesis of non-peptide target compounds
Binding studies with dopamine receptor subtypes
Medicinal chemistry of sphingolipids and other lipid modulators

Resources and Abilities

Fully equipped synthesis laboratories
High- and low-pressure hydrogenations
High- and low-temperature reactions
Heterocycle synthesis
Microwave synthesis
Chromatography (SC, Flash-SC, Chromatotron, semi-preparative HPLC)
Library of pharmacologically active compounds
Calculations of physicochemical parameters of compounds
1H-NMR, 13C-NMR, 31P-NMR, 19F-NMR, diverse MS-methods, IR, UV, stereochemical purity etc.
Aminergic G-protein coupled receptors (e.g., dopamine (hD1, hD5, hD2, hD3), histamine (hH1, hH3, hH4) and further in the pipeline)
beta-Counter

Publications

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.