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Tolbutamide

Structure

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

  • Chemical Formula: C₁₆H₂₅N₃O₃S

    Tolbutamide
Structure of Tolbutamide
Structure of Tolbutamide

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⁺ channel.

  • 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

  • Tolbutamide is synthesized through the reaction of 2,4-diethylbenzenesulfonyl chloride with urea, followed by condensation with N,N-dimethylurea.

Synthetic Route Overview:

  • 2,4-Diethylbenzenesulfonyl chloride + Urea → Tolbutamide


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