Selective PDE10A Inhibitors for Neurological Disorders
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for neurological and psychiatric disorders associated with PDE10A are not efficacious in all patients and often come with unwanted side effects.
Innovation Solution
Development of selective PDE10A enzyme inhibitors, specifically compounds of Formula (I) and (IA), which are administered to inhibit PDE10A in mammals, offering a therapeutic option for these disorders without the typical side effects of current therapies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current PDE10A inhibitors are used to treat neurological and psychiatric disorders, then therapeutic effect is achieved, but unwanted side effects occur
Solution Approach 1:
The patent applies local quality by creating selective PDE10A inhibitors with specific molecular structures (Formula I and IA compounds) that target PDE10A enzyme in specific brain regions (striatum, hippocampus, cortex) while avoiding off-target effects. The selective binding affinity (Kd values) and regional specificity of these compounds enable therapeutic action in particular neurological pathways without the widespread side effects of non-selective inhibitors.
2Duration of action of moving object
If current PDE10A inhibitors are used for long-term treatment, then therapeutic benefit is maintained, but tolerability decreases
Solution Approach 1:
The patent employs parameter changes by optimizing the pharmacological parameters of PDE10A inhibitors through structural modifications of Formula I and IA compounds. These changes result in improved pharmacokinetic properties, including enhanced half-life, reduced metabolism, and optimized binding affinity, which enable long-term treatment while maintaining tolerability and reducing accumulation of harmful effects.
3Adaptability or versatility
If non-selective PDE inhibitors are used, then broad therapeutic coverage is achieved, but specificity and reduced side effects are lost
Solution Approach 1:
The patent applies segmentation by dividing the broad PDE inhibitor class into specific PDE10A-selective compounds (Formula I and IA). This segmentation allows targeted inhibition of PDE10A in specific brain regions (striatum, hippocampus, cortex) while avoiding inhibition of other PDE families that cause side effects. The segmented approach maintains therapeutic coverage for neurological and psychiatric disorders while achieving high specificity.
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 provide effective, long-term treatment for neurological and psychiatric disorders with reduced side effects, addressing the limitations of existing treatments by selectively inhibiting PDE10A.
Implementation Method 1
The present invention provides compounds that are PDE10A enzyme inhibitors, in particular selective PDE10A enzyme inhibitors
Data Source
AI summary
The invention relates to compounds of the formulaor a pharmaceutically acceptable salt thereof, wherein R′, R1 through R7 and Ar are as defined herein. These compounds are useful as inhibitors of phosphodiesterase 10 (PDE10A) which are useful in treating central nervous system diseases such as psychosis and also in treating, for example, obesity, type II diabetes, metabolic syndrome, glucose intolerance, pain and ophthalmic diseases.