PPARδ Agonist Compounds for Metabolic Stability
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Solution Overview
Problem
There is a need for novel compounds that effectively and reliably activate peroxisome proliferator-activated receptor delta (PPARδ) in vitro and in vivo, with improved pharmacokinetic properties and metabolic stability, to treat PPARδ-related diseases such as mitochondrial, muscular, demyelinating, vascular, and metabolic disorders.
Innovation Solution
Development of specific compounds, including those of Formula (I), which are PPARδ agonists, designed to modulate PPARδ activity, and their use in pharmaceutical compositions for treating PPARδ-related diseases, with structures that include various substituents and functional groups to enhance activity and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing PPARδ activating compounds are used, then PPARδ activity is increased, but pharmacokinetic properties and metabolic stability are insufficient
Solution Approach 1:
The patent applies parameter changes by systematically modifying molecular parameters of PPARδ agonists, including substituent types (halogen, alkyl, alkoxy, cyano groups), ring structures (phenylene, pyridinylene, N-oxide pyridinylene), and positional arrangements to optimize both PPARδ activity and metabolic stability. The general formula (I) framework allows for controlled variation of R1, R2, R3, R4, Ar, Ring A, Z, W, and L parameters to achieve compounds with improved pharmacokinetic properties while maintaining reliable PPARδ activation.
2Ease of manufacture
If compound structure is simplified for easier synthesis, then manufacturing ease is improved, but PPARδ activating effectiveness may be reduced
Solution Approach 1:
The patent applies segmentation by dividing the PPARδ agonist molecule into distinct functional segments represented by R1, R2, R3, R4, Ar, Ring A, Z, W, and L in formula (I). Each segment can be independently selected and optimized, allowing for modular synthesis approaches where complex structures are built from simpler, well-characterized building blocks, thus balancing manufacturing ease with biological effectiveness.
Data Source
AI summary
Provided herein are compounds of formula (I) useful for the treatment of PPAR-delta related diseases (e.g. mitochondrial diseases, muscular diseases, vascular diseases, demyelinating diseases and metabolic diseases).