Tolbutamide

Tolbutamide is a first-generation sulfonylurea antidiabetic drug that lowers blood sugar by stimulating insulin release from the pancreas.

Structure of Tolbutamide

• Tolbutamide is a first-generation sulfonylurea with a benzene ring substituted with a sulfonylurea moiety and butyl side chains.
• Chemical Formula: C₁₆H₂₅N₃O₃S

Mode of Action

• ATP-Sensitive K⁺ Channel Blockade: Inhibits K⁺ channels on pancreatic beta cells, leading to cell membrane depolarization.
• Calcium Influx: Depolarization opens voltage-dependent calcium channels, increasing intracellular calcium.
• Insulin Secretion: Elevated calcium stimulates insulin granule exocytosis, enhancing insulin release.

Uses

• Type 2 Diabetes Mellitus: Improves glycemic control by increasing insulin secretion.
• Gestational Diabetes: Used cautiously under medical supervision to manage blood glucose levels.

Structure-Activity Relationship (SAR)

• Sulfonylurea Moiety: Essential for binding to the SUR1 (sulfonylurea receptor 1) subunit of the K⁺
• Alkyl Side Chains: Longer butyl chains enhance lipophilicity and binding affinity.
• Benzene Substitution: Substituents on the benzene ring can affect potency and duration of action.

Synthesis of Tolbutamide

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