Research Advancements on Fluorinated and Non-Fluorinated 4- Phenyl(thio)ureido-Substituted 2,2-Dimethylchromans Acting as Inhibitors of Insulin Release and Smooth Muscle Relaxants-Reference-Cited by-同舟云学术

Research Advancements on Fluorinated and Non-Fluorinated 4- Phenyl(thio)ureido-Substituted 2,2-Dimethylchromans Acting as Inhibitors of Insulin Release and Smooth Muscle Relaxants

Published:2022-08 Issue:8 Volume:18 Page:884-894
ISSN:1573-4064
Container-title:Medicinal Chemistry
language:en
Short-container-title:MC

Author:

Pirotte Bernard¹^ORCID,Florence Xavier¹²,Goffin Eric¹,Leleux Fabienne²,Lebrun Philippe³

Affiliation:

1. Laboratoire de Chimie Pharmaceutique, Center for Interdisciplinary Research on Medicines (CIRM), Université de Liège, Quartier Hôpital, Avenue Hippocrate 15, B-4000 Liège, Belgium

2. Laboratoire de Physiologie et Pharmacologie, Université Libre de Bruxelles, Faculté de Médecine, 808 Route de Lennik, B-1070 Bruxelles, Belgium

3. Laboratoire de Physiologie et Pharmacologie, Université Libre de Bruxelles, Faculté de Médecine, 808 Route de Lennik, B-1070 Bruxelles, Belgium

Abstract

Aims: The present study aimed at characterizing the impact of the presence or absence of fluorine atoms on the phenyl and benzopyran rings of 4-phenyl(thio)ureido-substituted 2,2- dimethylchromans on their ability to inhibit insulin release from pancreatic β-cells or to relax vascular smooth muscle cells. Methods: Most compounds were found to inhibit insulin secretion and to provoke a marked myorelaxant activity. Results: The lack of a fluorine or chlorine atom at the 6-position of the 2,2-dimethylchroman core structure reduced the inhibitory activity on the pancreatic endocrine tissue. One of the most active compounds on both tissues, compound 11h (BPDZ 678), was selected for further pharmacological investigations. Conclusion: The biological data suggested that 11h mainly expressed the profile of a KATP channel opener on pancreatic β-cells, although a calcium entry blockade effect was also observed. On vascular smooth muscle cells, 11h behaved as a calcium entry blocker.

Publisher

Bentham Science Publishers Ltd.

Subject

Drug Discovery

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