Pyrazolone Derivatives for Heart Failure Nitroxyl Donation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current nitroxyl donors for therapeutic use face challenges due to metastability, limiting their development for oral administration, and there is a need for compounds with improved solid state stability and safety profiles for treating heart failure.
Innovation Solution
Development of pyrazolone derivative compounds and their pharmaceutical compositions that can donate nitroxyl, offering enhanced stability and suitability for oral administration while maintaining a safe profile for treating heart failure.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nitroxyl donors are developed for parenteral administration, then therapeutic efficacy is improved, but solid state stability deteriorates
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of nitroxyl donors through substitution patterns on the phenyl ring and variations in the R groups. These structural parameter changes enhance solid state stability while preserving nitroxyl donation capability, resolving the contradiction between therapeutic efficacy and solid state stability
Solution Approach 2:
The patent develops composite molecular structures combining pyrazolone core with various substituted phenyl groups and heterocyclic moieties. These composite structures achieve both adequate solubility for bioavailability and improved solid state stability, overcoming the limitation of conventional nitroxyl donors
2Stability of the object's composition
If nitroxyl donors are designed for oral administration, then solid state stability is improved, but bioavailability may deteriorate
Solution Approach 1:
The patent modifies molecular parameters including introducing polar substituents (halo, alkoxy, hydroxyl groups) and heterocyclic moieties that enhance both solid state stability and aqueous solubility. These parameter changes ensure adequate bioavailability while maintaining improved solid state properties for oral formulation
Solution Approach 2:
The patent creates analogues of existing nitroxyl donors with modified molecular structures that copy the essential nitroxyl donation function while improving physicochemical properties. The substituted pyrazolone derivatives replicate the therapeutic mechanism with enhanced stability and solubility profiles
3Productivity
If conventional nitroxyl donors are used, then nitroxyl donation capability is achieved, but safety profile deteriorates due to metastability
Solution Approach 1:
The patent applies beforehand cushioning by designing nitroxyl donors with pre-stabilized molecular structures that prevent premature decomposition. The substituted pyrazolone framework provides structural reinforcement that cushions against metastability, preventing harmful decomposition products while maintaining nitroxyl donation capability
Solution Approach 2:
The patent employs nitroxyl donors designed as stable prodrugs that decompose only when needed for therapeutic effect. The improved stability allows oral administration with controlled release, making the compound effectively 'disposable' after delivering its nitroxyl payload, thereby improving safety by eliminating persistent unstable species
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 pyrazolone derivative compounds provide improved solid state stability and safety, enabling effective nitroxyl donation for treating heart failure through oral administration, addressing the limitations of existing nitroxyl donors.
Implementation Method 1
nitroxyl for therapeutic use is typically generated in situ from donor compounds
Data Source
AI summary
The disclosed subject matter provides pyrazolone derivative compounds, pharmaceutical compositions comprising such compounds, kits comprising such compounds, and methods of using such compounds or pharmaceutical compositions. In particular, the disclosed subject matter provides methods of using such compounds or pharmaceutical compositions for treating heart failure.