Salt-Type GLP-1 Receptor Agonist Crystals for Oral Stability

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current GLP-1 receptor agonists for treating type II diabetes are primarily administered via injection, limiting patient compliance and necessitating the development of oral small molecule alternatives with improved solubility and stability for effective treatment of diabetes and related disorders.

Innovation Solution

Development of a small molecule GLP-1 receptor agonist (Compound I) in the form of pharmaceutically acceptable salts, particularly tromethamine salts like Compound Z, and their crystalline forms (e.g., Crystal Forms A, P, C, V, W) to enhance solubility, stability, and bioavailability, facilitating oral administration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If GLP-1 receptor agonists are administered via injection, then therapeutic efficacy is achieved, but patient compliance deteriorates

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidpatient compliance

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent changes the molecular parameters of GLP-1 receptor agonists by developing small molecule compounds with specific chemical structures (e.g., Compound I with molecular weight 626.65, containing specific heterocyclic rings and functional groups) that differ fundamentally from peptide-based injectable agonists, enabling oral administration while maintaining therapeutic efficacy

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent utilizes phase transition principles by developing crystalline forms (Crystal Forms A, P, C, V, W) of the small molecule agonists, transitioning from amorphous or soluble forms to stable crystalline structures that enhance oral bioavailability and gastrointestinal stability while maintaining therapeutic activity

Inventive Principle:

Principle #36Phase transitions

2Ease of operation

If oral small molecule GLP-1 receptor agonists are developed, then patient compliance improves, but solubility and stability deteriorate

Engineering Contradiction:

Improvepatient complianceVSAvoidsolubility and stability

Core Design Contradiction:

Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent optimizes molecular parameters including molecular weight (626.65), logP value, and structural features (specific heterocyclic arrangements, fluorine substitution at position 4) to achieve the optimal balance between oral bioavailability, gastrointestinal stability, and solubility properties

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent develops composite crystalline forms combining the small molecule agonist with specific counterions (e.g., tromethamine salt, Compound Z with molecular formula C37H47FN4O8) to create stable, soluble, and bioavailable oral formulations that overcome the limitations of pure compound forms

Inventive Principle:

Principle #40Composite materials

Data Source

PatentEP4635951A1Salt-type GLP-1 receptor agonist, crystal form thereof, preparation method therefor, pharmaceutical composition thereof, and use thereof

Publication Date: 2025.10.22 HANGZHOU ZHONGMEI HUADONG PHARMACEUTICAL CO LTD

Figure 1
Figure 2
Figure 3

AI summary

Disclosed are a salt-type GLP-1 receptor agonist, a crystal form thereof, a preparation method therefor, a pharmaceutical composition thereof, and the use thereof. Specifically, the GLP-1 receptor agonist is (S)-2-((4-(6-((2-fluoro-4-(oxetane-3-yl)benzyl)oxy)pyridin-2-yl)piperidin-1-yl)methyl)-1-(oxetane-2-ylmethyl)-1H-benzo[d]imidazole-6-carboxylic acid.