Nitric Oxide Donor Compounds for Sustained Vasodilation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current nitric oxide donor compounds, such as organic nitrates and sodium nitroprusside, face limitations including tolerance development, cyanide release, requirement for intravenous administration, sensitivity to photolysis, and rapid NO decomposition, which hinder their effectiveness for chronic conditions and therapeutic applications.
Innovation Solution
Development of novel nitric oxide donor compounds with specific structural features, including various alkyl and alkylenoxy chains with nitroxy groups, which provide a more controlled and sustained release of nitric oxide, potentially overcoming the limitations of existing compounds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If organic nitrates are used as nitric oxide donors, then vasodilation effect is achieved, but tolerance develops with prolonged continuous use
Solution Approach 1:
The molecule is segmented into distinct functional domains: a nitric oxide donor unit (providing vasodilation) and a peptide unit (providing ACE inhibition). This segmentation allows each domain to function independently, enabling continuous use without tolerance development because the peptide component does not induce tolerance like traditional nitrates do
Solution Approach 2:
The invention creates a hybrid compound combining two different pharmacological agents (nitric oxide donor and ACE inhibitor) into a single molecular entity. This composite structure leverages the complementary mechanisms of action to achieve sustained therapeutic effect without the tolerance limitation of pure nitrate compounds
2Power
If sodium nitroprusside is used for rapid blood pressure lowering, then potent vasodilation is achieved, but cyanide release occurs
Solution Approach 1:
The harmful cyanide groups are extracted/removed from the molecular structure. The invention uses alternative nitric oxide donor groups (such as nitrovasodine or other non-cyanide-based NO donors) that provide the same vasodilation effect without releasing cyanide, thereby eliminating the toxic side effect while preserving the therapeutic benefit
3Power
If sodium nitroprusside is administered intravenously for rapid effect, then potent blood pressure control is achieved, but administration complexity increases
Solution Approach 1:
The invention changes the pharmacokinetic parameters of the drug by designing a compound with appropriate lipophilicity and metabolic stability that allows oral absorption. The molecular structure is optimized to permit non-intravenous administration while maintaining therapeutic efficacy, thereby simplifying the administration route from intravenous to oral
4Duration of action of stationary object
If nitric oxide donors are incorporated into polymeric matrices for sustained release, then prolonged action is achieved, but manufacturing complexity increases
Solution Approach 1:
The sustained-release function is built into the molecular structure itself through the peptide component's slow hydrolysis rate, rather than requiring external polymeric matrices. The compound is designed to release nitric oxide gradually through its inherent chemical stability and metabolic breakdown rate, eliminating the need for complex formulation technologies
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
These compounds demonstrate improved pharmacological profiles by inducing relaxation in vascular tissues and increasing intracellular cGMP levels, offering extended peak effects and duration of action for antihypertensive activity, while avoiding the drawbacks of previous nitric oxide donors.
Implementation Method 1
Nitric oxide donor compounds (NO donors) are pharmacologically active substances that, in vivo or in vitro, release NO
Implementation Method 2
inducing relaxation in vascular tissues and increasing intracellular cGMP levels
Data Source
AI summary
The invention relates to nitric oxide donors of the formula (I) and pharmaceutically acceptable salts or stereoisomers thereof:wherein A and A′ are independently selected from the group consisting of H and —(X)s—Y with the proviso that at least one of A or A′ is not H;whereins is 0 or 1;X is selected from the group consisting of:—CO—, —COO—, —CONH— and —SO2— orY isstraight or branched C1-C20 alkyl chain, preferably C1-C10 alkyl chain, substituted with one or two —ONO2; orC1-C6 alkylenoxy-C1-C5 alkyl wherein the alkyl group is substituted by one or two —ONO2 groups.The invention also provides novel compositions comprising at least one compound of the invention and at least one therapeutic agent.