β-
adrenergic blocking agents have been in use for nearly 40 years. β-blockers have been more thoroughly studied in the past twenty years as they have become commonly prescribed to
heart failure patients. The class of β-blockers has grown considerably and has many
pharmaceutical applications in patients with
heart failure.
Carvedilol has been the most effective beta-blocker in the treatment of the
systolic heart failure.
Carvedilol is a non-selective β- and α-blocker enantiomer with
antioxidant effects that are attributed to its
carbazole moiety.
Carvedilol is taken twice daily because it is extensively metabolized and therefore loses its effectiveness due to a short half-life. Recently a long acting
carvedilol has become available, as
Coreg CR.
Coreg CR is available for once-a-day administration as controlled-release oral capsules containing 10, 20, 40, or 80 mg
carvedilol phosphate. The subject of the current report is to design a new structural analog of
carvedilol that incorporates a protecting group such as a
fluorine atom at position 8 of the
carbazole ring for the purpose of blocking a critical metabolic pathway thus increasing its half life. This will follow discussion regarding current
carvedilol patents. We believe that
carvedilol activity will remain unchanged. The synthesis of 8-Fluoro-1, 2, 3, 9- tetrahydro-4H-carbazol-4-one, a key synthetic intermediate of the designed
carvedilol analog, was carried out and successfully characterized.