Synthesis and Structure−Activity Relationships of Conformationally Constrained Histamine H3 Receptor Agonists
| Autor: | Obbe P. Zuiderveld, Roeland C. Vollinga, Ruengwit Kitbunnadaj, Henk Timmerman, Rob Leurs, Anthony L. Spek, Marie-France Deltent, Martin Lutz, Iwan J. P. de Esch, Emile Cavoy, Remko A. Bakker, Wiro M. P. B. Menge |
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| Přispěvatelé: | Medicinal chemistry, Chemistry and Pharmaceutical Sciences, R¿ntgenparticipatieprogramma, Crystal and Structural Chemistry 2, Dep Natuurkunde, Dep Scheikunde |
| Rok vydání: | 2003 |
| Předmět: |
Agonist
Pyrrolidines Stereochemistry medicine.drug_class Histamine Antagonists Molecular Conformation Crystallography X-Ray Ligands Binding Competitive Pyrrolidine Histamine agonist Cell Line Receptors G-Protein-Coupled Histamine Agonists Radioligand Assay Structure-Activity Relationship chemistry.chemical_compound Piperidines SDG 3 - Good Health and Well-being Drug Discovery Cyclic AMP medicine Humans Receptors Histamine H3 Histamine H4 receptor Receptors Histamine H4 Chemistry Imidazoles Stereoisomerism Immepip Receptors Histamine Molecular Medicine Colorimetry Piperidine Histamine H3 receptor Histamine |
| Zdroj: | Kitbunnadaj, R, Zuiderveld, O P, De Esch, I J, Vollinga, R C, Bakker, R A, Lutz, M, Spek, A L, Cavoy, E, Deltent, M F, Menge, W M P B, Timmerman, H & Leurs, R 2003, ' Synthesis and structure-activity relationships of conformationally constrained histamine H(3) receptor agonists ', Journal of Medicinal Chemistry, vol. 46, no. 25, pp. 5445-57 . https://doi.org/10.1021/jm030905y Journal of Medicinal Chemistry, 46(25), 5445-57. American Chemical Society |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | Immepip, a conformationally constrained analogue of the histamine congener imbutamine, shows high affinity and functional activity on the human H(3) receptor. Using histamine and its homologues as prototypes, other rigid analogues containing either a piperidine or pyrrolidine ring in the side chain were synthesized and tested for their activities at the human H(3) receptor and the closely related H(4) receptor. In the series of piperidine containing analogues, immepip was found to be the most potent H(3) receptor agonist, whereas its propylene analogue 13a was identified as a high-affinity neutral antagonist for the human H(3) receptor. Moreover, replacement of the piperidine ring of immepip by a pyrrolidine ring led to a pair of enantiomers that show a distinct stereoselectivity at the human H(3) and H(4) receptor. |
| Databáze: | OpenAIRE |
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