Nitroglycerin

Structure

• Nitroglycerin Chemical Structure – C3H5N3O9

Structure-Activity Relationship (SAR) of Nitroglycerin

• Nitroglycerin, also known as glyceryl trinitrate, is a potent vasodilator used primarily for the treatment of heart conditions like angina pectoris.

The SAR characteristics of nitroglycerin include:

1.  Nitrate Esters:

• The presence of three nitrate ester groups in nitroglycerin is crucial for its vasodilating activity.

• These groups are responsible for the release of nitric oxide (NO), a potent vasodilator, upon metabolism.

2.  Glycerol Backbone:

• The glycerol backbone provides the structure onto which the nitrate groups are attached.

• The three-dimensional conformation of the molecule, dictated by this backbone, is important for the correct positioning of the nitrate groups for metabolic conversion.

3.  Metabolism to NO:

• The bioactivation of nitroglycerin, which involves the conversion to NO, is essential for its pharmacological effect.

• The ease with which nitroglycerin releases NO in the body is a key aspect of its effectiveness as a vasodilator.

4.  Lipophilicity:

• The lipophilicity of nitroglycerin facilitates its absorption and transport within the body, allowing it to reach its sites of action effectively.
  

Synthesis of Nitroglycerin

• The chemical synthesis of nitroglycerin is typically carried out via the nitration of glycerol.

The reaction is as follows:

1. Nitration Reaction:

• C3​H5​(OH)3 ​+ 3HNO3 ​→ C3​H5​(NO3​)3 ​+ 3H2​O 

• In this reaction, glycerol (C3H5(OH)3) is treated with nitric acid (HNO3), producing nitroglycerin (glyceryl trinitrate, C3H5(NO3)3) and water.

• This reaction is an example of nitration, where a nitro group (NO2) is introduced into an organic molecule.

• In the case of nitroglycerin, the nitration must be controlled carefully due to the high reactivity and explosive nature of the product.

• The process typically requires a mixture of concentrated nitric and sulfuric acids, the latter acting as a dehydrating agent to drive the reaction forward.

• The manufacturing of nitroglycerin needs to be carried out with extreme caution due to the explosive characteristics of the compound.

Mode of action

• When guanylate cyclase is activated by Nitroglycerin, it produces free radical nitric oxide (NO), which raises the level of cyclic GMP in smooth muscle and other tissues. It causes blood arteries to dilate (vasodilator), which lowers blood pressure.

Uses

• This commonly used to treat angina attacks in patients with coronary artery disease (narrowing of the blood vessels that supply blood to the heart).