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Azines and Diazines as Potential Histamine H₃-Receptor Antagonists^†

Katarzyna Kieć-Kononowicz

Department of Chemical Technology of Drugs, Collegium Medicum, Jagiellonian University, ul. Medyczna 9, 30–688 Kraków, Poland

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Xavier Ligneau,

Xavier Ligneau

Unité de Neurobiologie et Pharmacologie, Centre Paul Broca de l'INSERM, 2 ter, rue d'Alésia, 75014 Paris, France

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Holger Stark,

Holger Stark

Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Strasse 2+4, 14195 Berlin, Germany

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Jean-Charles Schwartz,

Jean-Charles Schwartz

Unité de Neurobiologie et Pharmacologie, Centre Paul Broca de l'INSERM, 2 ter, rue d'Alésia, 75014 Paris, France

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Walter Schunack,

Corresponding Author

Walter Schunack

Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Strasse 2+4, 14195 Berlin, Germany

Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Strasse 2+4, 14195 Berlin, GermanySearch for more papers by this author

Katarzyna Kieć-Kononowicz,

Katarzyna Kieć-Kononowicz

Department of Chemical Technology of Drugs, Collegium Medicum, Jagiellonian University, ul. Medyczna 9, 30–688 Kraków, Poland

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Xavier Ligneau,

Xavier Ligneau

Unité de Neurobiologie et Pharmacologie, Centre Paul Broca de l'INSERM, 2 ter, rue d'Alésia, 75014 Paris, France

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Holger Stark,

Holger Stark

Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Strasse 2+4, 14195 Berlin, Germany

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Jean-Charles Schwartz,

Jean-Charles Schwartz

Unité de Neurobiologie et Pharmacologie, Centre Paul Broca de l'INSERM, 2 ter, rue d'Alésia, 75014 Paris, France

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Walter Schunack,

Corresponding Author

Walter Schunack

Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Strasse 2+4, 14195 Berlin, Germany

Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Strasse 2+4, 14195 Berlin, GermanySearch for more papers by this author

First published: 1995

https://doi.org/10.1002/ardp.19953280509

Citations: 13

^†

Presented in part at the 2nd European Congress of Pharmaceutical Sciences, Berlin (Germany), Sept. 29–Oct. 1, 1994.

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Abstract

In search of structure-activity relationships among histamine H₃-receptor antagonists the imidazole ring of known H₃-receptor antagonists was replaced by different heteroaromatic ring systems. Thus, azines and diazines with ether (6–13) and carbamate (15–24) moieties as functional groups were synthesized. The obtained compounds did not show significant H₃-receptor antagonist activity in vitro (rat brain cortex) or in vivo (mice brain). The new compounds were also screened for H₁-receptor antagonist activity on the isolated guinea-pig ileum and for H₂-receptor antagonist activity on the isolated spontaneously beating guinea-pig right atrium. The substances showed only weak antagonistic activity at both histamine receptors, H₁ and H₂.

Abstract

Azine und Diazine als potentielle Histamin-H₃-Rezeptorantagonisten

Im Rahmen von Untersuchungen von Histamin-H₃-Rezeptorantagonisten wurde der Imidazolring bekannter H₃-Rezeptorantagonisten gegen verschiedene heteroaromatische Ringsysteme ausgetauscht. Es wurden Azine und Diazine mit Ether- (6–13) und Urethanstrukturelementen (15–24) als funktionelle Gruppen synthetisiert. Die dargestellten Substanzen zeigten in vitro (Zerebralkortex der Ratte) und in vivo (Mäusehirn) keine bedeutsame H₃-antagonistische Aktivität. Die neuen Verbindungen wurden auch auf H₁-antagonistische Aktivität am Meerschweinchendünndarm und auf H₂-Antagonismus am isolierten, spontan schlagenden rechten Vorhof des Meerschweinchens getestet. Die Substanzen zeigten an H₁- und H₂-Rezeptoren nur schwache antagonistische Aktivität.

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Volume328, Issue5

1995

Pages 445-450

Azines and Diazines as Potential Histamine H₃-Receptor Antagonists^†

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Azines and Diazines as Potential Histamine H₃-Receptor Antagonists^†