Tolbutamide

Structure

• Tolbutamide Chemical Structure – C12H18N2O3S

Synthesis

Synthesis of Tolbutamide

Mode of action

• Tolbutamide reduces blood sugar by inducing the pancreas to produce more insulin and facilitating the body's effective utilisation of that insulin.

Structure-Activity Relationship (SAR) of Tolbutamide

Tolbutamide is a first-generation sulfonylurea drug used in the management of type 2 diabetes mellitus. Its SAR characteristics are:

1. Sulfonylurea Group:

• The core sulfonylurea structure is essential for its hypoglycemic activity.

• The sulfonamide moiety is necessary for binding to the sulfonylurea receptor on pancreatic beta cells, stimulating insulin release.

2. Urea Moiety:

• The urea part of the molecule plays a crucial role in its biological activity.

• The specific positioning and orientation of the urea group are important for the interaction with the sulfonylurea receptor.

3. Alkyl Substituents:

• The presence of alkyl groups, like the butyl group in tolbutamide, affects the drug's potency and pharmacokinetic properties.

• The length and branching of the alkyl chain can influence the drug's absorption, distribution, metabolism, and excretion.

4. Aromatic Ring:

• The para-substitution on the phenyl ring is significant for the activity.

• Alterations in the aromatic ring can lead to changes in the drug's potency and selectivity.

Here is the mind map illustrating the Structure-Activity Relationship (SAR) of Tolbutamide:

Synthesis of Tolbutamide

• The synthesis of Tolbutamide involves a key reaction between a sulfonyl chloride and a butylurea. The simplified chemical reaction can be described as follows:

Synthesis Reaction: 

• C4​H9​N2​O + C7​H7​ClO3​S → C1​2H1​8N2​O3​S

• In this reaction, butylurea (C4H9N2O) reacts with p-toluenesulfonyl chloride (C7H7ClO3S) to form tolbutamide (C12H18N2O3S).This reaction represents the basic synthesis of tolbutamide, highlighting the formation of the sulfonylurea structure.

• In actual industrial synthesis, additional steps for purification and quality control are usually involved.

• The reaction conditions, such as temperature, solvent, and catalysts, can vary depending on the specific process design.

Uses

• Tolbutamide is used to treat type 2 diabetes's high blood sugar levels.