Isosorbide Dinitrite

Structure of Isosorbide Dinitrite

• Isosorbide dinitrate is an organic nitrate derived from isosorbide, featuring two nitrate groups esterified to the hydroxyl groups of the isosorbide moiety.

• Chemical Formula: C₆H₈N₂O₆

Structure of Isosorbide Dinitrite

Mode of Action

• Nitric Oxide Release: Metabolizes to release NO, leading to vasodilation.

• Vasodilation: Primarily dilates veins (preload reduction) and arteries (afterload reduction), decreasing cardiac workload.

• Coronary Artery Dilation: Enhances blood flow to the myocardium, alleviating ischemia.

Uses

1. Angina Pectoris: Prevents and treats anginal attacks by reducing myocardial oxygen demand.

2. Heart Failure: Manages symptoms by decreasing cardiac preload and afterload.

3. Hypertension: Utilized in hypertensive emergencies as part of combination therapy.

4. Raynaud’s Phenomenon: Off-label use to promote blood flow in affected extremities.

Structure-Activity Relationship (SAR)

• Nitrate Ester Groups: Crucial for NO release; their presence and position determine the potency and duration of action.

• Isosorbide Backbone: Provides rigidity, facilitating proper orientation for enzyme-mediated NO release.

• Hydroxyl Substituents: Influence solubility, bioavailability, and metabolic stability.

Synthesis

• Isosorbide dinitrate is synthesized by nitrating isosorbide with nitric acid in the presence of a catalyst.

Synthetic Route:

• Starting Material: Isosorbide.

• Nitration Reaction: React isosorbide with nitric acid under controlled conditions to introduce nitrate groups.

• Purification: Isolate isosorbide dinitrate through crystallization and filtration.

Reaction Scheme:

Isosorbide + 2 HNO₃ → Isosorbide dinitrate + 2 H₂O