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Medicinal Chemistry

Author(s): Bernard Pirotte*, Xavier Florence, Eric Goffin, Fabienne Leleux and Philippe Lebrun

DOI: 10.2174/1573406418666220221145500

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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

Page: [884 - 894] Pages: 11

  • * (Excluding Mailing and Handling)

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.

Keywords: 2, 2-Dimethylchromans, potassium channel openers, calcium channel blockers, insulin secretion, smooth muscle contractile activity, fluorine atoms impact.

Graphical Abstract

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