Tegoprazan is a novel potassium-competitive acid blocker (P-CAB) developed for the treatment of acid-related gastrointestinal disorders, including gastroesophageal reflux disease (GERD) and peptic ulcers. Chemically, it is a substituted pyrrole derivative designed to selectively inhibit the gastric H+/K+-ATPase enzyme in parietal cells, thereby reducing gastric acid secretion. The development of tegoprazan reflects efforts to improve upon the limitations of traditional proton pump inhibitors (PPIs), such as delayed onset of action and variability due to CYP2C19-mediated metabolism.
The discovery of tegoprazan involved structure-based drug design to identify compounds capable of reversibly binding to the potassium-binding site of the H+/K+-ATPase. This competitive mechanism allows tegoprazan to inhibit acid secretion more rapidly than conventional PPIs, providing faster symptom relief in patients with acid-related disorders. Preclinical studies demonstrated potent acid suppression, high selectivity for gastric proton pumps, and favorable pharmacokinetic properties, including good oral bioavailability and a relatively long half-life suitable for once-daily dosing.
Tegoprazan’s clinical pharmacology is characterized by rapid onset of action, sustained acid suppression, and minimal influence from CYP2C19 polymorphisms. Unlike PPIs, which require activation in acidic conditions, tegoprazan is active immediately upon absorption, allowing effective acid inhibition from the first dose. Its pharmacokinetics show peak plasma concentrations within 1–2 hours after oral administration and a half-life that supports once-daily or twice-daily dosing, depending on clinical indication.
In clinical applications, tegoprazan has been evaluated in patients with erosive esophagitis, non-erosive reflux disease, and Helicobacter pylori-associated gastritis. Randomized controlled trials reported rapid symptom relief, high rates of mucosal healing, and favorable tolerability compared with PPIs. The most commonly observed adverse events were mild gastrointestinal disturbances, headache, and transient increases in liver enzymes, all of which were manageable under clinical supervision. Tegoprazan has also been studied in combination with antibiotics for H. pylori eradication therapy, demonstrating enhanced efficacy due to its potent acid suppression.
The synthesis of tegoprazan involves multistep organic reactions to construct the substituted pyrrole core and introduce the functional groups required for selective binding to the potassium site of H+/K+-ATPase. The final compound is isolated as a stable crystalline solid suitable for formulation into oral tablets or capsules. Its chemical stability and solubility support consistent dosing and long-term storage, facilitating pharmaceutical development.
Tegoprazan represents a significant advancement in acid-suppressive therapy, offering rapid, potent, and sustained inhibition of gastric acid secretion with improved pharmacokinetic predictability. Its clinical efficacy, favorable safety profile, and convenience of dosing make it a promising alternative to conventional PPIs for the management of acid-related gastrointestinal disorders. Ongoing research continues to explore additional indications and long-term safety, reflecting its potential as a versatile therapeutic agent in gastroenterology.
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![CAS # 942195-55-3, Tegoprazan, 7-[[(4S)-5,7-difluoro-3,4-dihydro-2H-chromen-4-yl]oxy]-N,N,2-trimethyl-3H-benzimidazole-5-carboxamide](/structures/942195-55-3.gif)
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