Chemical Properties
White to Off-White Powder
Originator
Almirall (Spain)
Uses
A nonsedating type histamine H1-receptor antagonist. Antihistaminic
Definition
ChEBI: Ebastine is an organic molecular entity.
Manufacturing Process
(a) A mixture of 4-hydroxypiperidine (40.4 g; 0.4 moles), p-tert-butyl-ω-
chlorobutyrophenone (105 g, 0.44 moles), sodium bicarbonate (67.2 g; 0.8
moles) and a crystal of potassium iodide in methyl isobutyl ketone (1 liter)
was boiled under reflux for 24 hours. After cooling, the reaction mixture waswashed with water, dried (Na2SO4) and the solvent removed in vacuum. The
residue was salified with the stoichiometric amount of fumaric acid in a
mixture of acetone and ethanol to give 1-[3-(4-tert-butylbenzoyl)propyl]-4-
hydroxypiperidine fumarate (148 g), melting point 163-165°C. This compound
was converted into the free base, and 1-[3-(4-tert-butylbenzoyl)propyl]-4-
hydroxypiperidine was obtained and recrystallized from a mixture of diethyl
ether and petroleum ether (boiling point 50-70°C). 102 g were obtained (yield
84%), melting point 63-65°C.
(b) A mixture of 1-[3-(tert-butylbenzoyl)propyl]-4-hydroxypiperidine (60.68 g;
0.2 moles) and sodium carbonate (42.4 g; 0.4 moles) in methyl isobutyl
ketone (500 ml) was heated to the boiling point and a solution of
diphenylmethyl bromide (49.42 g; 0.2 moles) in methyl isobutyl ketone (75
ml) was slowly added in 1.5 hours. The resulting mixture was boiled under
reflux for another 12 hours, and then another solution of diphenylmethyl
bromide (24.71 g; 0.1 moles) in methyl isobutyl ketone (50 ml) was added
and the mixture boiled under reflux again for 12 hours. Another solution of
diphenylmethyl bromide in the same quantity was added and after refluxing
for 12 additional hours the reaction mixture was cooled, washed with water,
dried (Na2SO4) and the solvent removed in vacuum.
The residual oil was treated with the stoichiometric amount of fumaric acid in
ethanol and 4-diphenylmethoxy-1-[3-(4-tert-butylbenzoyl)propyl]piperidine
fumarate crystallized. After recrystallisation from ethanol the pure compound
was obtained (88 g; yield 75%), melting point 197-198°C.
Brand name
Kestine (Rhone-Poulenc Rorer);Ebastel.
Therapeutic Function
Antihistaminic, Antiallergic, Calcium entry blocker
General Description
Ebastine is metabolised by cytochrome P450 3A (CYP3A4) to carebastine. It is used to treat allergic rhinitis and chronic idiopathic urticaria.
Biochem/physiol Actions
Ebastine is a non-sedating histamine H1 receptor antagonist, which inhibits allergen-induced bronchospasm in conscious guinea pigs. Unlike other compounds in this category, ebastine does not prolong the QT interval at up to five times the recommended therapeutic dose.
