Substituted Diaminocyclohexane Compounds for Selective NPY Y4 Receptor Modulation
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Solution Overview
Problem
Current therapies for obesity and related conditions, such as type 2 diabetes, are poorly effective and often associated with side effects, highlighting a need for targeted treatments that specifically modulate the NPY Y4 receptor to control appetite, food intake, and energy expenditure without cardiovascular risks.
Innovation Solution
Development of substituted diaminocyclohexane compounds that act as agonists, partial agonists, or modulators of the NPY Y4 receptor, which can be used in pharmaceutical compositions to treat obesity and related conditions, including diabetes, by selectively targeting the Y4 receptor over Y1 and Y2 receptors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies for obesity are used, then weight reduction may be achieved, but cardiovascular side effects occur and effectiveness is poor
Solution Approach 1:
The patent applies local quality by designing compounds with specific molecular structures (substituted diaminocyclohexane core with particular R groups) that confer selective affinity for the Y4 receptor subtype. This structural specificity ensures the drug acts locally on the target receptor without affecting other receptor subtypes, thereby achieving effective obesity treatment without cardiovascular side effects associated with non-selective therapies
Solution Approach 2:
The patent employs parameter changes by systematically varying molecular parameters (substituents R1-R6 on the diaminocyclohexane structure) to optimize the balance between Y4 receptor affinity and cardiovascular safety. By adjusting these chemical parameters, the compounds achieve subnanomolar affinity for Y4 receptors while maintaining safety profiles superior to existing obesity therapies
2Ease of operation
If NPY Y4 receptor modulation is implemented, then appetite and food intake are controlled, but selectivity over Y1 and Y2 receptors must be maintained to avoid side effects
Solution Approach 1:
The patent applies segmentation by dividing the NPY receptor family into distinct subtypes (Y1, Y2, Y4, Y5) and designing compounds that selectively target only the Y4 subtype. The segmented approach involves creating molecules with specific structural features that match only the Y4 receptor binding site, thereby achieving appetite control through Y4 modulation while avoiding off-target effects on Y1 and Y2 receptors
Solution Approach 2:
The patent uses the substituted diaminocyclohexane compound as an intermediary molecule that mediates selective Y4 receptor activation. This intermediary has been specifically designed with molecular features that facilitate preferential binding to Y4 receptors, acting as a bridge between the administered drug and the desired physiological effect while excluding interaction with other receptor subtypes
Data Source
AI summary
The present invention provides compounds of Formula (I):or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are agonists, partial agonists and modulators of the NPY Y4 receptor and may be used for the treatment and prophylaxis of various diseases and conditions.