C-aryl glucoside derivative SGLT inhibitor design
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Solution Overview
Problem
Current antidiabetic drugs have various toxic side effects and are not suitable for long-term treatment, necessitating the development of safer and more effective compounds that target sodium-dependent glucose transporter proteins (SGLTs) to control glucose levels and manage diabetes-related complications.
Innovation Solution
A C-aryl glucoside derivative, specifically compounds of formula (I-a3), is developed as a SGLT inhibitor, which effectively inhibits both SGLT-1 and SGLT-2 proteins, offering a dual action to regulate glucose absorption and reuptake, thereby providing a systemic hypoglycemic effect and treating diabetes-related complications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing antidiabetic drugs (biguanide, sulfonylurea, insulin resistance improving agents, α-glucosidase inhibitors) are used to control blood glucose, then hypoglycemic effect is achieved, but toxic side effects occur
Solution Approach 1:
The patent applies parameter changes by developing a novel C-aryl glucoside derivative with specific chemical structure parameters (formula I) that differs from existing antidiabetic drugs. This structural parameter change results in a compound that inhibits SGLT proteins with an IC50 value of 0.01-10 μM, achieving hypoglycemic effect without the toxic side effects associated with conventional drugs like lactic acidosis, hypoglycemia, edema, heart failure, abdominal pain, and diarrhea
Solution Approach 2:
The patent copies the beneficial function of SGLT protein inhibition (which naturally occurs in the body to regulate glucose transport) and creates a synthetic compound that mimics this physiological mechanism. By designing a compound that specifically targets and inhibits SGLT-1 and SGLT-2 proteins, the invention replicates the body's natural glucose regulation system without introducing the harmful side effects of existing drug classes
2Reliability
If SGLT-2 protein inhibition is enhanced to increase glucose discharge from urine, then hypoglycemic effect is improved, but selectivity between SGLT-1 and SGLT-2 becomes challenging
Solution Approach 1:
The patent applies local quality by designing the C-aryl glucoside derivative with specific substituent patterns at different positions of the molecular structure (R1-R6 in formula I). These localized structural modifications allow the compound to achieve dual inhibition of both SGLT-1 and SGLT-2 proteins with balanced efficacy, rather than exclusively targeting one protein type. The aromatic ring substituents and glucoside moiety work together to provide selective binding to both protein targets
3Duration of action of stationary object
If long-term treatment is required for diabetes management, then sustained glucose control is needed, but existing drugs cause cumulative toxic effects
Solution Approach 1:
The patent applies self-service by creating a compound that leverages the body's own physiological mechanisms for glucose regulation. By inhibiting SGLT proteins, which are naturally involved in glucose transport and reabsorption, the compound works in harmony with bodily functions rather than opposing them. This approach enables long-term treatment (sustained glucose control) without the cumulative toxic effects seen with conventional drugs, as the mechanism is based on modulating natural physiological processes
Data Source
AI summary
The present invention relates to C-aryl glucoside derivative, a preparation method for same, and medical applications thereof. Specifically, the present invention relates to compounds as represented by formula I, and, tautomers, enantiomers, diastereomers, racemates, and pharmaceutically acceptable salts of the compounds, a preparation method for same or a pharmaceutical composition comprising the compounds, and applications thereof as a therapeutic agent and particularly as a sodium-dependent glucose contransporter protein (SGLT) inhibitor.