Dimethylaminoethanol Salt GLP-1 Agonist Crystallinity
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current GLP-1 receptor agonists face challenges in achieving desired crystallinity, solubility, and thermal behavior, as well as formulation, storage, and delivery issues, which affect their efficacy in treating diabetes and related conditions.
Innovation Solution
A novel dimethylaminoethanol (deanol) salt of compound Cpd. No. 76, referred to as deanol-RP-101, is developed, which exhibits improved crystallinity, solubility, and thermal behavior, and is used to create a crystalline form that can be characterized by XRPD and has purity levels exceeding 95% by weight, facilitating its use in pharmaceutical compositions and methods for activating the GLP-1 receptor.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional GLP-1 receptor agonists are used, then therapeutic activity is achieved, but desired crystallinity, solubility, and thermal behavior are not obtained
Solution Approach 1:
The patent applies parameter changes by converting the compound from its free acid form to a dimethylaminoethanol salt form. This chemical parameter change fundamentally alters the physical properties including crystallinity, solubility, and thermal behavior, while preserving the therapeutic GLP-1 receptor agonist activity. The salt formation transforms the molecular structure's interaction with solvents and heat, resolving the contradiction between maintaining therapeutic activity and achieving desired physical stability.
Solution Approach 2:
The invention creates a composite material system by forming a salt between the GLP-1 receptor agonist compound and dimethylaminoethanol. This composite approach combines two different chemical entities to produce a new material with superior and balanced properties - the therapeutic activity of the original compound plus the improved crystallinity, solubility, and thermal behavior contributed by the salt formation with dimethylaminoethanol.
2Ease of manufacture
If improved crystallinity and solubility are achieved through salt formation, then formulation and storage are facilitated, but compound complexity increases
Solution Approach 1:
The dimethylaminoethanol acts as an intermediary substance that mediates between the active pharmaceutical ingredient (GLP-1 receptor agonist) and the final formulation requirements. By introducing this intermediate salt-forming agent, the patent simplifies the overall formulation process and storage conditions, even though it adds a step in the synthesis process. The intermediary enables better manufacturability and storage without significantly complicating the final drug product.
Data Source
Figure 1A~1B
Figure 1C
Figure 2A~2B
AI summary
Crystalline 2-hydroxy-N,N-dimethylethanaminium 1 -(2-(5-(tert-butyl) -thiophene-2-carboxamido)-3-(4-(5-(4'-ethyl-[1,1'-bi(cyclohexan)]-3- en-4-yl)pyrimidin-2-yl)phenyl)propanoyl)azetidine-3-carboxylate salt, and methods related to synthesis and therapeutic use of the same.