Description
Lansoprazole is the second proton pump inhibitor approved as an antiulcer agent for the
short term treatment of duodenal ulcer and gastroesophageal reflux disease. Like
omeprazole, lansoprazole is reported to be more efficacious than the H2-antagonists in treating peptic ulcer disease.Other potential uses could be in the treatment of Zollinger-Ellison syndrome.
Chemical Properties
White Crystalline Powder
Originator
Takeda (Japan)
Definition
ChEBI: Lansoprazole is a member of benzimidazoles, a member of pyridines and a sulfoxide. It has a role as an EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor and an anti-ulcer drug.
Manufacturing Process
Preparation of 2-[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methylthio-1Hbenzimidazole:
A mixture of 6.63 g of 2-hydroxymethyl-3-methyl-4-(2,2,2-trifluoroethoxy)
pyridine (30 mmol), 4.5 g of 2-mercaptobenzimidazol (30 mmol) and 8.67 g
of triphenylphosphine (33 mmol) was dissolved in 100 ml of tetrahydrofuran,
5.75 g of diethyl azodicarboxylate (33 mmol) dissolved in 30 ml of
tetrahydrofuran was added dropwise thereto at room temperature, and stirred
for 1 hour. The reaction mixture was concentrated under a reduced pressure,
the resulting residue was combined with 100 ml of ethylacetate, and extracted
twice with 50 ml portions of 1 N HCl. The aqueous layer was then washed
with 50 ml of diethylether; neutralized with 1 N NaOH to adjust the pH to 7.
The resulting precipitates were filtrated, washed with water, and dried, to
obtain 10.06 g of 2-[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methylthio-
1H-benzimidazole as a white solid (yield: 95%), m.p.142-144°C.
4.46 g of 2-[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methylthio-1Hbenzimidazole (12 mmol) and 18.74 mg of tetramethyl-1-piperidinyloxy free
radical (1 mol %, used as a catalyst) were dissolved in 40 ml of
tetrahydrofuran, and combined with 166.76 mg of tetrabutylammonium
chloride (5 mol %) dissolved in 20 ml of distilled water. The resulting mixture
was cooled to 0°C and 13.6 ml of NaOCl (12%, 2.2 equivalent) dissolved in 20
ml of distilled water was added thereto over 2 hours at 0°C, stirred for 10
min, and then for additional 10 min at 20°C. Then, the reaction mixture was
extracted with 40 ml of ethylacetate and the organic layer was washed with
sat. NaHCO3 (30 ml) and then with sat. brine (30 ml), dried over anhydrous
MgSO4, and the solvent was removed therefrom. The resulting crude product
as recrystallized from acetone/hexane, to obtain 3.99 g of 2-[3-methyl-4-
(2,2,2-trifluoroethoxy)-2-pyridyl]methylsulphinyl-1H-benzimidazol
(lansoprazole) as a white-light brown solid (yield: 90%), melting point 164-
165°C (decomposition).
Brand name
Prevacid (TAP);Ogast;Lanzor.
Therapeutic Function
Antiulcer
General Description
Lansoprazole, 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H-benzimidazole(Prevacid), is a white to brownish white, odorless crystallinepowder that is practically insoluble in water.Lansoprazole is a weak base (pyridine N, pKa 3.83.) and aweak acid (benzimidazole N-H, pK 0.62). Like other PPIs,lansoprazole is essentially a prodrug that, in the acidic biophaseof the parietal cell, forms an active metabolite thatirreversibly interacts with the target ATPase of the pump.Lansoprazole must be formulated as encapsulated entericcoatedgranules for oral administration to protect the drugfrom the acidic environment of the stomach.
In the fasting state, about 80% of a dose of lansoprazole(vs. 50% of omeprazole) reaches the systemic circulation,where it is 97% bound to plasma proteins. Thedrug is metabolized in the liver (sulfone and hydroxymetabolites) and excreted in bile and urine, with a plasmahalf-life of about 1.5 hours.
Biological Activity
H + ,K + -ATPase inhibitor (IC 50 = 6.3 μ M) that displays antisecretory and antiulcer activity. Inhibits gastric acid secretion (IC 50 = 0.09 μ M for histamine-induced acid formation) and reduces gastric lesion formation induced by a variety of ulcerative stimuli. Antibacterial against Helicobacter pylori in vitro . Also blocks swelling-dependent chloride channel (ICIswell) in NIH3T3 fibroblasts. More potent than omeprazole (5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole ).
Biochem/physiol Actions
Gastric proton pump inhibitor.
