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

 

>

Staff:

  • Pharmacist Moritz Schübler (NMDA receptor ligands)
  • Dipl. Chemist Yvonne von Coburg (dopamin and histamin receptor ligands)
  • Pharmacist Britta Sasse (pharmacological test systems)
  • Pharmacist Tim Kottke (pharmacological test systems)
  • Dipl. Chemist Michael Amon (histamine receptor ligands)
  • Pharmacist Oliver Saur (dopamine receptor ligands)

>

ZAFES-Coordinator:

 

 

 

INSTITUTES AND
MEDICAL CENTERS

 
 

RHEUMATOLOGY

 
 

GASTROENTEROLOGY - HEPATOLOGY

 
 

PAEDIATRIC HAEMATOL., ONCOL. & HAEMOSTASEOLOGY

 
 

NEURORADIOLOGY

 
 

CLINICAL PHARMACOLOGY

 
 

GENERAL PHARMACOLOGY &
TOXICOLOGY

 
 

IMMUNE PHARMACOLOGY

 
 

INTERDISCIPLINARY PHARMACOLOGY

 
 

PHARMACEUTICAL TECHNOLOGY

 

PHARMACEUTICAL CHEMISTRY

 

PROF. KARAS
PROF. SCHUBERT-ZSILAVECZ
PROF. STARK
PROF. STEINHILBER

 

 

 

 

 

PHARMACEUTICAL
BIOLOGY

 
 

GEORG SPEYER HAUS

 
 

ORGANIC CHEMISTRY &
CHEMICAL BIOLOGY

 
 

NEUROLOGY

 
 

ANESTHESIOLOGY, INTENSIVE CARE AND
PAIN CONTROL

 
 

OBSTETRICS AND GYNECOLOGY

 
 

DEPARTMENT OF DERMATOLOGY & VENEROLOGY

 
 

CARDIOVASCULAR PHYSIOLOGY

 
 

PEDIATRIC PNEUMOLOGY, ALLERGY AND CYSTIC FIBROSIS

MEDICAL VIROLOGY

ECOLOGY, EVOLUTION AND DIVERSITY, DEPARTMENT AQUATIC ECOTOXICOLOGY

 
 

ORAL, CRANIO-
MAXILLOFACIAL AND
FACIAL PLASTIC SURGERY

 
 

GENERAL AND VASCULAR SURGERY

 
 

CLINICAL NEUROANATOMY

 

GENERAL PEDIATRICS

HAEMATOLOGY, ONCOLOGY

DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY