Fused Cyclic Compounds for GPR40 Agonist Activity and Stability
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Solution Overview
Problem
Current pharmaceutical compositions for modulating GPR40 receptor function lack compounds with superior agonist activity, stability, and low toxicity, which are essential for effective prophylaxis or treatment of diabetes and related diseases.
Innovation Solution
Development of a pharmaceutical composition comprising specific fused cyclic compounds, such as those represented by the formula (I), which include a benzene ring and a 5- to 7-membered ring, combined with dipeptidyl peptidase IV inhibitors, insulin preparations, or other antidiabetic agents, to enhance GPR40 receptor agonist activity and improve pharmacokinetic properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional GPR40 receptor agonists are used, then some GPR40 receptor activity is achieved, but the agonist activity, stability, and safety profile are insufficient
Solution Approach 1:
The patent applies parameter changes by systematically varying the chemical structure parameters of the compounds, specifically using a fused cyclic core structure (formula I) with variable substituents R1-R6 at different positions and configurations. This structural parameter optimization enables achieving superior GPR40 agonist activity while maintaining low toxicity and improved stability compared to conventional compounds.
Solution Approach 2:
The patent employs composite material principles by creating compounds with a fused cyclic core structure combined with various aromatic rings and substituent groups. The composite nature of these molecules, integrating multiple functional groups (formula I structure), results in enhanced pharmacological properties including superior agonist activity and improved safety profile.
2Stability of the object's composition
If conventional GPR40 agonists are used, then some therapeutic effect is achieved, but the stability and pharmacokinetic properties are insufficient
Solution Approach 1:
The patent optimizes stability and pharmacokinetic properties by changing the chemical structure parameters of the compounds. The fused cyclic structure (formula I) with specific aromatic ring combinations and substituent patterns provides enhanced metabolic stability and improved blood sustainability, addressing the insufficient stability and duration of action of conventional agonists.
Data Source
AI summary
The present invention provides a pharmaceutical composition comprising a compound represented by the formula (I): wherein each symbol is as defined in the description, or a salt thereof, in combination with a dipeptidyl peptidase IV inhibitor, an insulin preparation, a PPAR function modulator, an α-glucosidase inhibitor, a biguanide, a sulfonylurea, mitiglinide or calcium salt hydrate thereof or nateglinide.