Nitrooxy Bis(nitrooxy) Derivatives for Sustained Nitric Oxide Release
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for hypertension and related cardiovascular and renal disorders often fail to provide sustained and controlled delivery of angiotensin II receptor antagonists, leading to inadequate nitric oxide release and suboptimal therapeutic effects.
Innovation Solution
Development of angiotensin II receptor antagonist bis(nitrooxy) derivatives, specifically 2-butyl-4-chloro-1-[(2'-(1-H-tetrazol-5-yl)biphenyl-4-yl)methyl]-imidazole-5-carboxylate bis(nitrooxy) compounds, which offer enhanced nitric oxide release and improved vessel relaxation, formulated for controlled and sustained delivery through various pharmaceutical forms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional angiotensin II receptor antagonists are used, then hypertension treatment is provided, but sustained and controlled delivery is insufficient leading to suboptimal therapeutic effects
Solution Approach 1:
The patent modifies the chemical structure of angiotensin II receptor antagonists by introducing nitrooxy groups at specific positions (e.g., 5-position of imidazole ring, 3-position of phenoxy group). These structural parameter changes enable the compounds to serve dual functions: maintaining angiotensin II receptor blocking activity while gaining nitric oxide releasing capability, thereby achieving sustained vasodilation and improved therapeutic reliability
Solution Approach 2:
The invention creates composite functional molecules that combine two pharmacological activities in one structure: angiotensin II receptor antagonism and nitric oxide donation. The nitrooxy-functionalized compounds act as hybrid agents that simultaneously block the renin-angiotensin system and provide nitric oxide-mediated vasodilation, enhancing overall therapeutic effect for hypertension and cardiovascular conditions
2Quantity of substance
If conventional angiotensin II receptor antagonists are used, then blood pressure control is achieved, but nitric oxide release is inadequate
Solution Approach 1:
The patent systematically varies the position and number of nitrooxy groups on the angiotensin II receptor antagonist scaffold. By changing these molecular parameters, the compounds achieve different nitric oxide release rates and potencies while maintaining acceptable receptor binding affinity, thus optimizing nitric oxide quantity without excessive structural complexity
Solution Approach 2:
The nitrooxy groups serve as intermediary functional elements that mediate nitric oxide release from the angiotensin II receptor antagonist scaffold. These groups act as nitric oxide donors that can transfer nitric oxide to biological systems, bridging the gap between the pharmacological agent and the desired vasodilatory effect
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 significantly increased nitric oxide levels and improved vessel relaxation, providing effective treatment for hypertension and associated conditions by enhancing nitric oxide release and bioavailability.
Implementation Method 1
enhanced nitric oxide release and improved vessel relaxation
Implementation Method 2
improved vessel relaxation, providing effective treatment for hypertension
Data Source
AI summary
A compound having the structure (Formula I), wherein R is an angiotensin receptor antagonist active group, Y is -Y1-Y2-Y3-Y4-Y5.; Y1 is C(R1R2); R1 is selected from the group consisting of hydrogen and C1-4 alkyl; R2 is selected from the group consisting of hydrogen, C1-4 alkyl, and -0C(0)C1-4 alkyl; Y2 is O or CH2; Y3 is C(O) or CH2; Y4 is O or CH2; Y5 is -(CH2) 1-2-(X)0-1-(CH2)0-1- or is absent; X is -O- or -CR3R4-; and R3 and R4 are independently selected from the group consisting of hydrogen and C1-C4 alkyl; or a pharmaceutically acceptable salt or hydrate thereof, which is useful for treating hypertension.