Quinone-Based Nitric Oxide Donors for Vascular Therapy
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Solution Overview
Problem
Classical organic nitrates used for treating vascular diseases exhibit nitrate tolerance and side effects such as headache, hypotension, and flush, limiting their clinical use due to decreased vascular sensitivity and short duration of action.
Innovation Solution
Development of nitric oxide donor compounds with a specific chemical structure that provides extended release of NO, reducing nitrate tolerance and side effects, and can be administered through various routes including oral, parenteral, and transdermal methods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If classical organic nitrates are used for treatment, then immediate therapeutic effect is achieved, but nitrate tolerance develops quickly with decreased vascular sensitivity
Solution Approach 1:
The patent segments the nitrate molecule by introducing thiol groups (sulfur-containing amino acids) that can be cleaved off, allowing the nitrate to be released in controlled portions over time. This segmentation prevents complete depletion of active nitrate, thereby reducing tolerance development while maintaining sustained therapeutic effect.
Solution Approach 2:
The patent employs prodrug structures where the active nitrate is masked or combined with other functional groups (such as thiol-containing moieties) that require metabolic activation. This preliminary action allows the compound to be administered in advance in a stable form that then converts to active nitrate in the body, providing extended release and reducing tolerance.
2Reliability
If high doses of nitrates are administered, then therapeutic efficacy is improved, but side effects such as headache, hypotension, and flush increase
Solution Approach 1:
The patent changes the chemical parameters of the nitrate compound by introducing thiol groups and modifying the molecular structure. These parameter changes allow the compound to release nitrate more selectively and sustainably, improving therapeutic efficacy at lower doses while reducing the incidence and severity of side effects such as headache, hypotension, and flush.
3Stability of the object's composition
If nitrate-free periods are included in dosing schedule, then nitrate tolerance is prevented, but rebound vasoconstriction occurs when plasma nitrate falls
Solution Approach 1:
The patent achieves continuous release of nitrate through the specialized molecular structures containing thiol groups. This continuous action maintains plasma nitrate levels within a therapeutic range without requiring nitrate-free intervals, thereby preventing both tolerance development and rebound vasoconstriction. The sustained release ensures that vascular sensitivity is maintained continuously.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The compounds demonstrate improved pharmacological activity with reduced nitrate tolerance and side effects, offering effective treatment for vascular diseases, pulmonary hypertension, and other conditions involving NO deficit, with sustained action and varied administration options.
Implementation Method 1
nitric oxide donor compounds which can produce extended release of NO
Data Source
AI summary
The present invention relates to nitric oxide donor compounds having a quinone based structure, to processes for their preparation and to their use in the treatment of pathological conditions where a deficit of NO plays an important role in their pathogenesis.