Small-Molecule GLP-1R Agonists for Oral Administration
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for easily administered GLP-1 receptor agonists to treat cardiometabolic and associated diseases, as current GLP-1R agonists, such as liraglutide, require subcutaneous injection and have limitations in addressing post-prandial glucose regulation in individuals with Type 2 diabetes.
Innovation Solution
Development of novel GLP-1R agonist compounds, including Formulae (I)-(VIII) and their pharmaceutically acceptable salts, which can be administered orally and exhibit superior pharmacokinetic properties, effectively improving food intake and glucose tolerance in humanized animal models.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If GLP-1R agonists are administered by subcutaneous injection, then therapeutic effect is achieved, but ease of operation deteriorates
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of GLP-1R agonists from peptides to small molecules, which fundamentally changes the pharmacokinetic parameters. This structural transformation enables oral bioavailability while maintaining therapeutic efficacy, resolving the contradiction between reliable therapeutic effect and ease of administration.
Solution Approach 2:
The invention replaces the mechanical injection system with an oral administration system. By substituting the delivery mechanism from subcutaneous injection to oral ingestion, the patent eliminates the need for injection equipment and procedures while achieving comparable or superior therapeutic outcomes through enhanced brain penetration and pharmacokinetic properties.
2Reliability
If peptide-based GLP-1R agonists are used, then glucose-dependent insulin secretion is improved, but ease of manufacture deteriorates
Solution Approach 1:
The patent changes the fundamental parameter of molecular size and structure from large peptides to small molecules. This parameter change simplifies the manufacturing process by enabling standard small molecule synthesis techniques, improving stability during storage and transport, and reducing production costs while preserving the critical glucose-dependent insulin secretion mechanism.
3Ease of operation
If oral GLP-1R agonists are developed, then ease of operation improves, but manufacturing precision deteriorates
Solution Approach 1:
The patent replaces complex peptide synthesis and purification processes with standard small molecule organic synthesis methods. This substitution enables the use of well-established, highly precise manufacturing techniques for small molecules, including automated synthesis robots and advanced chromatography, thereby achieving both ease of oral administration and high manufacturing precision.
Data Source
AI summary
The present application provides compounds that may be used as a glucagon-like peptide-1 receptors (GLP-1R) agonist, or pharmaceutically acceptable salts thereof. Also provided are pharmaceutical compositions containing such compounds, or pharmaceutically acceptable salts thereof. Methods of preparing these compounds and compositions, and methods of using these compounds and compositions to treat or prevent a disease or a condition mediated by GLP-1R, are also provided.