Thioaryl Derivatives as GPR120 Agonists for Diabetes Treatment
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Solution Overview
Problem
Current antidiabetic drugs for type 2 diabetes have limitations such as side effects, inadequate efficacy, and mechanisms that primarily target single organs, failing to effectively control blood glucose levels and improve insulin resistance.
Innovation Solution
Development of novel thioaryl derivatives as GPR120 agonists that promote GLP-1 secretion in the gastrointestinal tract, improving insulin resistance and anti-inflammatory actions, which can be used in pharmaceutical compositions to treat diabetes, its complications, obesity, non-alcoholic fatty liver, steatohepatitis, and osteoporosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antidiabetic drugs (sulfonylureas, metformins, glitazones) are used to control blood glucose, then blood glucose levels can be controlled, but side effects occur such as pancreatic function decrease, hypoglycemia, gastroenteric disorders, renal toxicity, weight gain, and heart failure
Solution Approach 1:
The patent divides the therapeutic approach into multiple mechanisms of action. Instead of relying on a single drug targeting one organ, the composition uses multiple compounds that collectively affect multiple target organs (liver, pancreas, muscle, gastrointestinal tract) through different mechanisms, thereby distributing and reducing the harmful effects associated with single-target drugs
Solution Approach 2:
The patent creates a multi-functional pharmaceutical composition where the compound of Formula 1 and co-administered antidiabetic drugs work together to achieve multiple therapeutic effects: blood glucose control, insulin resistance improvement, anti-inflammatory action, and weight management, thereby reducing the need for multiple separate medications and their associated side effects
2Object-generated harmful factors
If incretin-related drugs (DPPIV inhibitors, Exenatide) are used to solve problems of traditional antidiabetics, then side effects such as increase of glucagon production, decrease of β-cell function, hypoglycemia, and weight gain can be addressed, but DPPIV inhibitors have marginal effect and skin toxicity, while Exenatide requires injection administration
Solution Approach 1:
The patent develops an oral pharmaceutical composition that provides sustained therapeutic effect through the synergistic combination of the compound of Formula 1 and co-administered drugs, eliminating the need for repeated injections required by Exenatide while maintaining effective blood glucose control and avoiding the marginal effects and skin toxicity of DPPIV inhibitors
3Adaptability or versatility
If most antidiabetic drugs target a single organ (liver, pancreas, or muscle) to control blood glucose, then a specific mechanism of action can be achieved, but the expected effect is hardly accomplished and side effects occur
Solution Approach 1:
The patent segments the therapeutic approach by having the compound of Formula 1 and co-administered drugs target different organs and mechanisms separately, which then work together synergistically to achieve comprehensive blood glucose control and improved insulin resistance without the limitations of single-organ targeting
Solution Approach 2:
The patent merges multiple drugs with different mechanisms of action into a single pharmaceutical composition, where the compound of Formula 1 enhances incretin hormone secretion while co-administered drugs provide additional mechanisms (such as metformin's glucolysis prevention or sulfonylurea's insulin secretion), creating a synergistic effect that improves overall therapeutic efficacy
Data Source
AI summary
The present invention relates to thioaryl derivatives of Formula 1 as defined in the specification, a method for preparing the same, a pharmaceutical composition comprising the same and use thereof. The thioaryl derivatives of Formula 1 according to the present invention promote GLP-1 formation in the gastrointestinal tract and improve insulin resistance in macrophages, pancreas cells, etc. due to anti-inflammatory action, and can accordingly be effectively used for preventing or treating diabetes, complications of diabetes, inflammation, obesity, non-alcoholic fatty liver, steatohepatitis or osteoporosis.