Guanidine Derivative PPARδ Activator for Transcriptional Activity
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Solution Overview
Problem
Current PPARδ activators do not effectively activate the transcriptional activity of PPARδ, which is crucial for regulating lipid metabolism and improving exercise tolerance.
Innovation Solution
The use of guanidine derivatives or biguanidine derivatives as active ingredients, which bind to the ligand-binding pocket of PPARδ, forming hydrogen bonds with specific amino acid residues, thereby activating the transcriptional activity of PPARδ.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional PPARδ activators (phenoxyacetic acid derivatives) are used, then the basic chemical structure is established, but the transcriptional activity of PPARδ is not effectively activated
Solution Approach 1:
The patent changes the chemical structure parameters of PPARδ activators by introducing guanidine and biguanidine derivatives with specific functional groups (amino groups at positions 1, 3, and 5) to enhance binding effectiveness and transcriptional activity activation, resolving the inadequacy of conventional phenoxyacetic acid derivatives
Solution Approach 2:
The patent applies local quality by positioning specific amino groups at precise locations on the guanidine/biguanidine derivative structures to form targeted hydrogen bonds with PPARδ amino acid residues, thereby locally enhancing the binding interaction and transcriptional activation effectiveness
2Productivity
If PPARδ activators are developed to enhance exercise-induced effects, then exercise endurance is improved, but the mechanism for effective PPARδ activation remains insufficient
Solution Approach 1:
The patent introduces guanidine and biguanidine derivatives as intermediary compounds that mediate between the PPARδ receptor and the desired physiological effect, providing a reliable mechanistic bridge that activates PPARδ transcriptional activity to enhance exercise endurance and metabolic effects
3Adaptability or versatility
If new PPARδ agonist structures are designed, then binding to PPARδ is achieved, but the transcriptional activation ability is not optimized
Solution Approach 1:
The patent creates composite molecular structures by combining guanidine or biguanidine cores with various substituent groups (R1, R2, R3) to produce compounds that simultaneously achieve strong binding capability to PPARδ and optimized transcriptional activation efficiency through the synergistic effect of the composite structure
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 proposed PPARδ activators effectively activate the transcriptional activity of PPARδ, leading to improved exercise tolerance and potential therapeutic benefits for metabolic disorders.
Implementation Method 1
forming hydrogen bonds with specific amino acid residues
Data Source
AI summary
The present invention provides a PPARδ activator containing a novel PPARδ agonist (peroxisome proliferator-activated receptor δ) as an active ingredient, and an exercise tolerance-improving agent containing the same as an active ingredient. The present invention is a PPARδ activator containing a guanidine derivative or a biguanidine derivative as an active ingredient, wherein the PPARδ activator activates transcriptional activity of PPARδ, and the guanidine derivative and the biguanidine derivative are capable of fitting within a PPARδ ligand binding pocket in a state where a guanidino group or a biguanidino group forms a hydrogen bond with amino acid residues corresponding to each of the 413th histidine, 287th histidine, 253rd threonine and the 437th tyrosine of human PPARδ, among amino acid residues constituting an interior surface of the ligand binding pocket; and is an exercise tolerance-improving agent containing the PPARδ activator as an active ingredient.