Polymorphic AHR Inhibitor Forms for Solubility and Stability
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Solution Overview
Problem
There is an unmet need to develop inhibitors of the aryl hydrocarbon receptor (AHR) to treat diseases and conditions associated with its activation, particularly those involving aldehyde toxicity and immune suppression.
Innovation Solution
Development of polymorphic forms and salt forms of small molecule therapeutics, such as compound A, which act as AHR inhibitors, providing improved aqueous solubility, stability, and ease of formulation, including crystalline and amorphous forms, and specific X-ray powder diffraction patterns.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional small molecule therapeutics are developed as AHR inhibitors, then therapeutic effectiveness is achieved, but aqueous solubility and stability are insufficient
Solution Approach 1:
The patent applies polymorphic form transformation to change the physical state parameters of the compound, transitioning from conventional forms to specific polymorphic forms (Form A, Form B, Form C) with optimized crystal structures that enhance aqueous solubility and stability while maintaining AHR inhibitory activity
Solution Approach 2:
The patent utilizes phase transition phenomena to convert the compound between different polymorphic forms and amorphous states, leveraging controlled crystallization and amorphous formulation to achieve desired solubility and stability characteristics for therapeutic applications
2Ease of manufacture
If polymorphic forms are developed to improve solubility and stability, then formulation ease is enhanced, but manufacturing complexity increases
Solution Approach 1:
The patent segments the formulation development into distinct polymorphic forms (Form A, Form B, Form C) and amorphous variants, allowing selective optimization of specific forms for different therapeutic needs while maintaining a unified compound identity, thereby simplifying regulatory and manufacturing processes
Data Source
AI summary
The present invention provides freebase and salt forms, and compositions and methods thereof, useful for treating various conditions in which the aryl hydrocarbon receptor (AHR) is implicated, by the administration of small molecule therapeutics which act as inhibitors of AHR.