Tegoprazan is a modern potassium-competitive acid blocker (P-CAB) used for the treatment of acid-related gastrointestinal disorders. It is a selective and reversible inhibitor of the gastric H⁺/K⁺-ATPase proton pump and suppresses gastric acid secretion without requiring conversion to an active form in an acidic environment. Tegoprazan is also known by the development code CJ-12420 and is marketed in South Korea as K-CAB.
Tegoprazan has the molecular formula C20H19F2N3O3, molecular weight 387.4 g/mol, and CAS No. 942195-55-3. FDA's Global Substance Registration System identifies tegoprazan under UNII W017G7IF4S.
Tegoprazan is a single-enantiomer small-molecule API produced in the S-form. The active substance has one chiral center, and regulatory assessment information indicates that the R-enantiomer is controlled as an impurity.
The API is characterized as a white to light-yellow or pink crystalline powder. It is practically insoluble in water and more soluble in organic solvents such as methanol and ethanol.
Tegoprazan belongs to the benzimidazole-derived P-CAB class. Its IUPAC name is 7-[[(4S)-5,7-difluoro-3,4-dihydro-2H-chromen-4-yl]oxy]-N,N,2-trimethyl-3H-benzimidazole-5-carboxamide. PubChem reports an exact mass of 387.13944780 Da, XLogP3-AA of approximately 3.2, one hydrogen-bond donor, six hydrogen-bond acceptors and a topological polar surface area of 67.5 Ų.
Tegoprazan is a weak base with a reported pKa of approximately 5.1–5.2. Its aqueous solubility is strongly dependent on pH. Published pharmaceutical research reports approximately 0.7 mg/mL at pH 3.0 and 0.02 mg/mL at pH 6.8.
Tegoprazan competitively inhibits potassium binding at the gastric proton pump. By interacting directly with the H⁺/K⁺-ATPase, it reduces the final step of gastric acid secretion. Unlike conventional proton-pump inhibitors, tegoprazan does not require acid-mediated activation.
Its reversible P-CAB mechanism provides rapid suppression of gastric acid secretion and sustained elevation of intragastric pH. This pharmacological profile makes tegoprazan suitable for acid-related gastrointestinal disorders.
Tegoprazan API is used in the development and manufacture of pharmaceutical products for acid-related gastrointestinal conditions, including:
Tegoprazan is commercially marketed in tablet formulations, including 50 mg and 100 mg strengths in certain markets.
Tegoprazan drug substance is subject to a comprehensive quality-control strategy. Regulatory assessment information identifies testing for visual description, IR and HPLC identification, differential scanning calorimetry, heavy metals, palladium, enantiomeric purity, related substances, water content, residue on ignition, HPLC assay and residual solvents by GC.
Because tegoprazan is a chiral API, control of the R-enantiomer is particularly important. One regulatory assessment reports an R-isomer criterion of NMT 0.1%.
Tegoprazan API manufacturing requires controlled chemical synthesis followed by purification and crystallization. The manufacturing process should maintain control over stereochemical purity, related substances, residual solvents, inorganic residues and water content.
The API's polymorphic and solid-state characteristics are also important. Regulatory characterization includes DSC and XRD testing to evaluate the crystalline form.
Tegoprazan demonstrates pronounced pH-dependent solubility. Published data report:
The higher value of 223 mg/mL at pH 1 reported in some literature is a predicted value, not an experimentally established API release specification, so it should not be used as a CMS specification.
Tegoprazan API should be packed in suitable pharmaceutical-grade, well-closed containers that protect the material from moisture, heat and excessive light. Regulatory stability information indicates stability under controlled storage conditions, including evaluation at 25°C.
Pharmaceutical-grade Tegoprazan API may be supplied with:
Tegoprazan is a technically demanding pharmaceutical API because its quality profile includes stereochemical purity, related substances, residual solvents, water, inorganic impurities and solid-state characteristics. A suitable manufacturing program should therefore employ validated chromatographic, spectroscopic and solid-state analytical methods.
Particular attention should be given to the S-enantiomeric form and control of the R-enantiomer. Regulatory assessment identifies the R-isomer as a controlled impurity with a criterion of NMT 0.1%.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | ≥99.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| pH (1% Solution) | 6.8 |
| Individual Impurity | NMT 0.1% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |