Heterocyclylamide IRAK4 Solid Forms for Pharmaceutical Stability

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Solution Overview

Problem

Existing IRAK4 inhibitors have not been effectively explored for the treatment of respiratory diseases such as asthma and COPD, and there is a need for stable solid forms of N-(Imidazo[1,2-b]pyridazin-3-yl)-6-methoxy-2-((1r,4r)-4-(N-methylacetamido)cyclohexyl)-2H-indazole-5-carboxamide suitable for pharmaceutical development.

Innovation Solution

Development of novel polymorph, salt, and solvate forms of N-(Imidazo[1,2-b]pyridazin-3-yl)-6-methoxy-2-((1r,4r)-4-(N-methylacetamido)cyclohexyl)-2H-indazole-5-carboxamide, including crystalline forms A, B, C, and oxalate salt, with specific X-ray diffraction patterns, to enhance stability and suitability for pharmaceutical use.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing IRAK4 inhibitors are used for treatment, then anti-inflammatory effect is achieved, but stability and suitability for pharmaceutical development are insufficient

Engineering Contradiction:

ImprovestabilityVSAvoidsuitability for pharmaceutical development

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by developing multiple solid forms (polymorphs, salts, solvates) of the IRAK4 inhibitor compound. Each solid form has different physical and chemical parameters such as crystalline structure, solubility, and stability characteristics. This allows optimization of the compound's properties for pharmaceutical development while maintaining its biological activity.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent utilizes phase transitions by creating different crystalline forms and solid states of the compound. The development of polymorphic forms involves controlled phase transitions from amorphous to crystalline states, and the formation of salts and solvates represents phase transitions that enhance stability and pharmaceutical suitability.

Inventive Principle:

Principle #36Phase transitions

2Stability of the object's composition

If novel solid forms are developed, then chemical and physical stability is enhanced, but manufacturing complexity increases

Engineering Contradiction:

Improvechemical and physical stabilityVSAvoidmanufacturing complexity

Core Design Contradiction:

Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by pre-developing and characterizing multiple stable solid forms of the compound before pharmaceutical formulation. The crystalline forms, salts, and solvates are prepared and characterized in advance to ensure stability, which simplifies subsequent manufacturing processes by eliminating the need for complex stability control measures.

Inventive Principle:

Principle #10Preliminary action

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 novel solid forms provide enhanced chemical and physical stability, enabling effective storage and handling, and are suitable for the development of medicaments for respiratory diseases and inflammatory/autoimmune disorders.

Implementation Method 1

with specific X-ray diffraction patterns

Methodology Applied

Scientific EffectX-ray diffraction: X-Ray

Data Source

PatentUS20250326757A1Solid forms of heterocyclylamides as IRAK4 inhibitors

Publication Date: 2025.10.23 ASTRAZENECA AB

AI summary

The present specification relates to novel physical forms of a indazole-5-carboxamide derivative, as well as solvate and salt forms of the same compound. A process for the preparation of the compound and uses of the new physical forms are also provided.