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
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
Angina Pectoris: Prevents and treats anginal attacks by reducing myocardial oxygen demand.
Heart Failure: Manages symptoms by decreasing cardiac preload and afterload.
Hypertension: Utilized in hypertensive emergencies as part of combination therapy.
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