Imidazo-pyrazine Derivatives as Soluble Guanylate Cyclase Activators
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Solution Overview
Problem
Current treatments for cardiovascular diseases and related disorders, such as hypertension and heart failure, often rely on nitrate-based compounds that develop tolerance and require higher dosages, while alternative soluble guanylate cyclase stimulators, like hormones and natural compounds, exhibit weak effects on cyclic guanosine monophosphate (cGMP) production.
Innovation Solution
Development of specific compounds, represented by structural Formula I, which strongly activate soluble guanylate cyclase, thereby modulating cGMP levels to treat and prevent diseases associated with disturbed cGMP balances.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nitrate-based compounds are used to treat cardiovascular diseases, then therapeutic effect is achieved, but tolerance develops and higher dosages are required
Solution Approach 1:
The patent changes the chemical structure from traditional nitrate compounds to imidazo-pyrazine derivatives with specific substitution patterns (R1-R10 groups), fundamentally altering the molecular parameters to achieve sGC activation without nitrate tolerance. This structural parameter change enables sustained therapeutic effect without the tolerance phenomenon that plagues nitrate-based treatments.
Solution Approach 2:
The imidazo-pyrazine compounds act as intermediary substances that directly activate soluble guanylate cyclase without requiring metabolic conversion to nitric oxide. This intermediary mechanism bypasses the tolerance pathway associated with nitrate metabolism, providing a new route for achieving vasodilation and therapeutic effects.
2Adaptability or versatility
If hormones and natural compounds are used as soluble guanylate cyclase stimulators, then alternative treatment is provided, but effects on cGMP production are weak
Solution Approach 1:
The patent introduces specific local structural features at defined positions (R1-R10 substituents) on the imidazo-pyrazine core to optimize binding affinity and activity at the soluble guanylate cyclase active site. These localized structural modifications enhance the compound's ability to stimulate cGMP production, transforming weak natural compounds into potent therapeutic agents with specific molecular interactions.
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 effectively stimulate soluble guanylate cyclase, providing a therapeutic option for cardiovascular diseases and other disorders by enhancing cGMP production without the limitations of tolerance development and dosage increase seen with nitrate-based treatments.
Implementation Method 1
compounds which activate soluble guanylate cyclase and are valuable pharmaceutically active compounds... capable of modulating the body's production of cyclic guanosine monophosphate ('cGMP')
Data Source
AI summary
A compound of Formula II or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate ("cGMP") and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula II, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of Formula II or a pharmaceutically acceptable salt thereof.