Voglibose
[CAS 83480-29-9]

Identification

• Classification: API >> Hormone and endocrine-regulating drugs >> Pancreatic hormones and other blood sugar regulating drugs
• Name: Voglibose
• Synonyms: 5-(1,3-Dihydroxypropan-2-ylamino)-1-(hydroxymethyl)cyclohexane-1,2,3,4-tetrol
• Molecular Formula: C₁₀H₂₁NO₇
• Molecular Weight: 267.13
• CAS Registry Number: 83480-29-9
• SMILES: C1[C@@H]([C@@H]([C@H]([C@@H]([C@]1(CO)O)O)O)O)NC(CO)CO

Properties

• Density: 1.6$+/-$0.1 g/cm³ Calc.^*
• Melting point: 162-163 $degree$C (Expl.)
• Boiling point: 601.9$+/-$55.0 $degree$C 760 mmHg (Calc.)^*
• Flash point: 274.1$+/-$22.1 $degree$C (Calc.)^*
• Solubility: DMSO 70 mg/mL, Water 70 mg/mL (Expl.)
• Index of refraction: 1.636 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P305+P351+P338

Discovery and Applications

Voglibose is an orally active antidiabetic drug belonging to the class of α-glucosidase inhibitors. It is used primarily in the management of type 2 diabetes mellitus to reduce postprandial (after-meal) blood glucose spikes by slowing carbohydrate digestion in the small intestine.

α-Glucosidases are enzymes located on the brush border of the intestinal epithelium. They catalyze the final step in carbohydrate digestion by breaking down oligosaccharides and disaccharides into absorbable monosaccharides such as glucose. By inhibiting these enzymes, voglibose delays carbohydrate breakdown and glucose absorption, resulting in a flatter and delayed postprandial glucose curve.

Structurally, voglibose is a pseudo-sugar aminocyclitol, meaning it resembles a monosaccharide but contains a nitrogen atom in place of a ring oxygen and lacks a true glycosidic structure. Its multiple hydroxyl groups and amino functionality allow it to closely mimic the transition state of carbohydrate substrates during enzymatic hydrolysis. This structural mimicry is a key reason for its high binding affinity to α-glucosidase active sites.

The molecule is highly polar and hydrophilic due to the presence of several hydroxyl groups and a protonatable amino group. This results in poor gastrointestinal absorption, which is actually beneficial for its mechanism of action, since voglibose is intended to act locally within the intestinal lumen rather than systemically. Minimal systemic absorption reduces the risk of systemic side effects.

Voglibose functions as a competitive inhibitor of α-glucosidase enzymes such as sucrase, maltase, and isomaltase. By competing with dietary carbohydrates for binding to these enzymes, it reduces enzymatic breakdown and slows glucose release. This mechanism helps blunt postprandial hyperglycemia without directly stimulating insulin secretion.

Unlike insulin secretagogues or insulin sensitizers, voglibose does not directly affect insulin levels or insulin sensitivity. Instead, it targets carbohydrate digestion at an early stage, making it particularly useful in combination therapy with other antidiabetic agents such as metformin or sulfonylureas.

From a structural perspective, voglibose is closely related to natural sugar mimetics and aminocyclitol compounds such as valiolamine. These compounds share a carbohydrate-like framework that enables them to interact effectively with glycosidase enzymes.

The stereochemistry of voglibose is critical for its biological activity. The spatial arrangement of hydroxyl groups allows it to fit precisely into the enzyme’s active site, mimicking the transition state of glycosidic bond hydrolysis. Even minor stereochemical changes can significantly reduce inhibitory potency.

Pharmacokinetically, voglibose remains largely within the gastrointestinal tract and is excreted unchanged. Its lack of significant metabolism and systemic exposure contributes to a favorable safety profile. The most common side effects are gastrointestinal in nature, including flatulence, abdominal discomfort, and diarrhea, which result from increased fermentation of unabsorbed carbohydrates in the colon.

Overall, voglibose is a carbohydrate-mimicking α-glucosidase inhibitor that acts locally in the intestine to delay glucose absorption. Its significance lies in its ability to control postprandial hyperglycemia through enzyme inhibition without systemic endocrine effects, making it an important component in the management of type 2 diabetes mellitus.

References

2026. Flavan-3-ol- and phenolic acid–rich Beldi sweet and bitter almond oils as natural enzyme inhibitors: Chemical profiling and in silico mechanistic insights. Journal of Food Measurement and Characterization.
DOI: 10.1007/s11694-025-04005-y

2026. Molecular docking, synthesis, and antiglycation activity of novel polyhydroxy-containing pyrrolidine derivatives. Journal of the Iranian Chemical Society.
DOI: 10.1007/s13738-026-03387-0

2026. Advancement in peptide-based therapeutics for the treatment of type 2 diabetes mellitus: current progress and future prospects. Molecular Diversity.
DOI: 10.1007/s11030-025-11455-5