Cot Inhibitor Solid Forms with XRPD-Based Form Identification
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Solution Overview
Problem
There is a need to develop solid forms of Cot inhibitor compounds to target the oncogenic and inflammatory pathways mediated by the Cot protein, which is involved in diseases such as rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, diabetes, sepsis, psoriasis, and graft rejection.
Innovation Solution
The development of solid forms of Compound 1, including Freebase Form I, Oxalate Form I, Maleate, and various camsylate forms, characterized by specific XRPD patterns, which can be used in pharmaceutical compositions to treat diseases mediated by Cot.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If solid forms of Cot inhibitor compounds are developed, then therapeutic effectiveness for treating diseases mediated by Cot is improved, but the complexity of characterizing and identifying specific solid forms increases
Solution Approach 1:
The patent applies parameter changes by establishing specific XRPD patterns with defined peak positions (e.g., 10.4, 13.0, and 18.1 degrees 2θ for Freebase Form I) and thermal stability characteristics (DSC onset temperatures, TGA weight loss percentages) to differentiate and characterize multiple solid forms of the Cot inhibitor compound, thereby enabling reliable identification and selection of therapeutically effective forms
Solution Approach 2:
The patent replaces complex physical characterization methods with XRPD (X-ray powder diffraction) and thermal analysis (DSC, TGA) techniques to identify and differentiate solid forms based on their unique diffraction patterns and thermal behavior, simplifying the characterization process while maintaining reliability
2Manufacturing precision
If multiple solid forms with specific XRPD patterns are identified, then manufacturing precision and quality control are improved, but the time required for solid form development increases
Solution Approach 1:
The patent performs preliminary action by pre-characterizing multiple solid forms (Freebase Form I, Oxalate Form I, Maleate, Camsylate Forms I-III) with their specific XRPD patterns and thermal properties during the development phase, establishing reference data that enables rapid quality control and manufacturing precision without requiring extensive additional characterization time later
Solution Approach 2:
The patent uses XRPD patterns as characteristic 'fingerprints' for each solid form, where the specific peak positions and intensities serve as identifiable markers that enable rapid differentiation and quality control, analogous to using color changes for identification
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
These solid forms provide effective treatment options for diseases mediated by Cot, offering therapeutic benefits through specific XRPD patterns and thermal stability characteristics.
Implementation Method 1
XRPD pattern comprising peaks at 10.4, 13.0, and 18.1 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using Cu Kα radiation
Implementation Method 2
XRPD pattern comprising peaks at 10.4, 13.0, and 18.1 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using Cu Kα radiation
Implementation Method 3
DSC curve that comprises an endotherm followed by an exotherm at about 270° C.
Implementation Method 4
TGA curve that comprises a first inflection point at about 80° C. and a second inflection point at about 200° C.
Data Source
AI summary
Disclosed are solid forms of a Cot (cancer Osaka thyroid) inhibitor and corresponding methods of preparation thereof, wherein the Cot inhibitor has the following formula: