Institute for pharmaceutical chemistry -
Prof. Dr. Holger Stark

Profile

The group of Prof. Dr. Stark has expert knowledge in Medicinal Chemistry. The primary interest is synthesis and analytical characterization as well as functional testing of drugs. Pharmacological and toxicological aspects are considered in the development of the compound structures in order to optimize the drug profile in an early stage. The functional testing includes several in vitro test systems mainly for drugs acting in the central nervous system.

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

Resources and Abilities

Fully equipped synthesis laboratories
High- and low-pressure hydrogenations
High- and low-temperature reactions
Heterocycle synthesis
Chromatography (SC, Flash-SC, Chromatotron, semi-preparative HPLC)
Library of pharmacologically active compounds
Calculations of physicochemical parameters of compounds
1H-NMR, 13C-NMR, diverse MS-methods, IR, UV, stereochemical purity etc.
Human dopamine receptor sybtypes (hD1, hD5, hD2, hD3)
Human histamine receptor subtypes (hH1, hH3, hH4 in development)
beta-Counter

Publications

J. Apelt, S. Grassmann, X. Ligneau, H. H. Pertz, C. R. Ganellin, J.-M. Arrang, J.-C. Schwartz, W. Schunack, H. Stark. Search for histamine H3 receptor antagonists with combined inhibitory potency an Nt-methyltranserase: ether derivatives. Pharmazie 2005, 60, 97-106
S. Grassmann, J. Apelt, X. Ligneau, H. H. Pertz, J.-M. Arrang, C. R. Ganellin, J.-C. Schwartz, W. Schunack, H. Stark. 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.
F. Gbahou, A. Rouleau, S. Morisset, R. Parmentier, S. Crochet, J.-S. Lin, X. Ligneau, J. Tardivel-Lacombe, H. Stark, W. Schunack, C. R. Ganellin, J.-C. Schwartz, and J.-M. Arrang. Protean Agonism at Histamine H3 Receptors in Vitro and in Vivo. Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 11086-11091
H. Stark. Recent Advances in Histamine H3/H4 Receptor Ligands. Expert Opin. Ther. Patents 2003, 13(6), 851-865
A. Hackling, R. Ghosh, S. Perachon, A. Mann, H.-D. Höltje, C. G. Wermuth, J.-C. Schwartz, W. Sippl, P. Sokoloff, and H. Stark. N-(w-(4-(2-Methoxyphenyl)piperazin-1-yl)alkyl)carboxamides as Dopamine D2 and D3 Receptor Ligands. J. Med. Chem. 2003, 46, 3883-3899
S. Graßmann, J. Apelt, W. Sippl, X. Ligneau, H. H. Pertz, Y. H. Zhao, J.-M. Arrang, C. R. Ganellin, J.-C. Schwartz, W. Schunack, and H. Stark. 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(10), 2163-2174
T. Mikó, X. Ligneau, H. H. Pertz, C. R. Ganellin, J.-M. Arrang, J.-C. Schwartz, W. Schunack, and H. Stark. Novel Nonimidazole Histamine H3 Receptor Antagonists: 1-(4-(Phenoxymethyl)benzyl)piperidines and Related Compounds. J. Med. Chem. 2003, 46, 1523-1530
E. Bézard, S. Ferry, U. Mach, H. Stark, L. Leriche, T. Boraud, C. Gross, and P. Sokoloff. Attenuation of Levodopa-Induced Dyskinesia by Normalizing Dopamine D3 Receptor Function. Nat. Med. 2003, 9(6), 762-767
A. E. Hackling and H. Stark. Dopamine D3 Receptor Ligands with Antagonist Properties. ChemBioChem. 2002, 3, 946-961
J. Apelt, X. Ligneau, H. H. Pertz, J.-M. Arrang, C. R. Ganellin, J.-C. Schwartz, W. Schunack, and H. Stark. 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
B. Weber, E. Schlicker, P. Sokoloff, and H. Stark. 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
A. Sasse, W. Schunack, and H. Stark. Separation of Chiral 4-Substituted Imidazole Derivatives by Cyclodextrin-Modified Capillary Electrophoresis. Biomed. Chromatogr. 2001, 15, 25-30
H. Stark, M. Krause, A. Rouleau, M. Garbarg, J.-C. Schwartz, and W. Schunack. Enzyme-Catalyzed Prodrug Approaches for the Histamine H3-Receptor Agonist (R)-a-Methylhistamine. Bioorg. Med. Chem. 2001, 9, 191-198
S. Morisset, A. Rouleau, X. Ligneau, F. Gbahou, J. Tardivel-Lacombe, H. Stark, W. Schunack, C. R. Ganellin, J.-C. Schwartz, and J.-M. Arrang. High Constitutive Activity of Native H3 Receptor Regulates Histamine Neurones in Brain. Nature (London) 2000, 408, 860-864