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

Methoden und Geräte

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

Publikationen

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