Small-Molecule GLP-1 Receptor Agonists for Stable Administration

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Solution Overview

Problem

There is a need for safe, stable, and easy-to-administer therapeutic options targeting the GLP-1 receptor for treating metabolic diseases such as type 2 diabetes, as current treatments are primarily peptide-based and limited in number.

Innovation Solution

Development of GLP-1 receptor modulator compounds represented by Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), and their sub-formulas, which can be used to agonize the GLP-1 receptor activity, formulated into pharmaceutical compositions for treatment and diagnosis of metabolic diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If peptide-based GLP-1 receptor drugs are used, then therapeutic efficacy is achieved, but administration complexity and stability issues arise

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidadministration ease

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent transforms the chemical structure from peptide-based to small molecule compounds (Formulas I-XVIII, XXV-XXVII, XXX, XXXI, XXXIX, XL-XLVII), changing the fundamental parameters of molecular weight, solubility, and metabolic stability. This enables oral administration while maintaining GLP-1 receptor agonist activity, resolving the contradiction between efficacy and administration ease

Inventive Principle:

Principle #35Parameter changes

2Reliability

If peptide-based GLP-1 receptor drugs are used, then therapeutic effects are achieved, but storage and handling stability deteriorate

Engineering Contradiction:

Improvetherapeutic effectsVSAvoidstorage stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The invention changes the chemical composition from peptides to small molecules with enhanced metabolic stability. The small molecule compounds (Formulas I-XVIII, XXV-XXVII, XXX, XXXI, XXXIX, XL-XLVII) exhibit improved resistance to enzymatic degradation and better storage stability compared to peptide-based drugs, while maintaining therapeutic effects

Inventive Principle:

Principle #35Parameter changes

3Adaptability or versatility

If more GLP-1 receptor drugs are developed, then treatment options increase, but development complexity increases

Engineering Contradiction:

Improvetreatment optionsVSAvoiddevelopment complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent presents multiple distinct chemical series (Formulas I-XVIII, XXV-XXVII, XXX, XXXI, XXXIX, XL-XLVII) with different structural motifs and substitution patterns. This segmented approach to drug design allows for systematic optimization of pharmacological properties while maintaining a manageable development framework

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention employs systematic variation of chemical parameters (substituents R1-R6, linkers L1-L5, ring structures) to generate diverse GLP-1 receptor agonists. This parameter-based design strategy enables efficient exploration of chemical space and optimization of therapeutic properties without proportionally increasing development complexity

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS12459929B2GPCR receptor agonists, pharmaceutical compositions comprising the same, and methods for their use

Publication Date: 2025.11.04 CARMOT THERAPEUTICS INC

AI summary

Provided herein are GLP-1 receptor modulator compounds, pharmaceutical compositions, methods of their preparation, and methods of their use in treatment, and/or diagnosis.