Heterocyclic Salt Crystal Forms for 15-PGDH Inhibitor Druggability
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Solution Overview
Problem
Existing heterocyclic compounds with 15-PGDH inhibitory activity lack suitable salt forms and solid forms that enhance druggability and other properties.
Innovation Solution
Development of crystal forms and pharmaceutically acceptable salts of heterocyclic compounds, such as those represented by formula I-3A and I-3B, with specific acid and solvent ratios, along with detailed characterization through X-ray powder diffraction, differential scanning calorimetry, and thermogravimetric analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If heterocyclic compounds with 15-PGDH inhibitory activity are developed, then biological activity is achieved, but suitable salt forms and solid forms for improved druggability are lacking
Solution Approach 1:
The patent applies parameter changes by developing multiple salt forms (hydrochloride, phosphate, fumarate, L-tartrate, L-malate, p-toluenesulfonate, methanesulfonate, benzenesulfonate, oxalate) and solvate forms of the heterocyclic compound. Each salt form represents a different chemical parameter variation that improves druggability while maintaining the core biological activity of the parent compound
Solution Approach 2:
The patent creates composite material structures by forming salts between the heterocyclic compound and various acids, as well as creating solvates with different solvents. These composite forms combine the active pharmaceutical ingredient with counterions or solvent molecules to achieve improved physical and chemical properties for drug development
2Ease of manufacture
If crystal forms and salts are developed with specific acid and solvent ratios, then pharmaceutical properties are enhanced, but characterization complexity increases
Solution Approach 1:
The patent performs preliminary characterization actions by establishing detailed X-ray powder diffraction patterns, differential scanning calorimetry curves, and thermogravimetric analysis data for each crystal form and salt before proceeding to drug development. This preliminary characterization prevents future complications by fully understanding the physical and chemical properties of each form
Solution Approach 2:
The patent replaces complex manual characterization processes with standardized instrumental analysis methods including X-ray powder diffraction, differential scanning calorimetry, and thermogravimetric analysis. These instrumental methods provide objective, reproducible data that simplifies the characterization process compared to traditional manual techniques
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The developed crystal forms and salts improve the druggability and stability of the heterocyclic compounds, providing enhanced pharmaceutical properties.
Implementation Method 1
X-ray powder diffraction patterns (XRPD) using Cu-Kα radiation
Implementation Method 2
X-ray powder diffraction patterns (XRPD) using Cu-Kα radiation and expressed by 2θ angles comprising diffraction peaks
Implementation Method 3
differential scanning calorimetry (DSC) curves
Implementation Method 4
thermogravimetric analysis (TGA) curves
Data Source
Figure 1~2
Figure 3~4
Figure 5~6
AI summary
Disclosed in the present invention are a crystal form of a heterocyclic compound, a salt thereof, a crystal form of the salt thereof, and a use. Disclosed in the present invention are a pharmaceutically acceptable salt of a heterocyclic compound or a solvate thereof, wherein the heterocyclic compound is a compound represented by formula I-3A and/or a compound represented by formula I-3B. The crystal form of a heterocyclic compound, the salt thereof, and the crystal form of the salt thereof disclosed in the present invention can be used for drug preparation, and have wide application prospects.