Compound A Salt Forms for Stable, Soluble Kinase Inhibitors

Solution Overview

Problem

Existing pharmaceutical compounds that inhibit Aurora kinases and FLT3 face challenges in achieving desirable physical and chemical stability, solubility, and bioavailability, making them unsuitable for effective clinical use.

Innovation Solution

Development of salts and polymorphic forms of Compound A, including fumarate, mesylate, hydrochloride, and crystalline forms, which enhance solubility, stability, and minimize interaction with cytochrome P450 and hERG channels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing Aurora kinase and FLT3 inhibitor compounds are developed, then dual kinase inhibition activity is achieved, but physical and chemical stability and bioavailability are compromised

Engineering Contradiction:

Improvedual kinase inhibition activityVSAvoidphysical and chemical stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by developing multiple salt forms (fumarate, hydrochloride, mesylate, trifluoroacetate) and polymorphic forms (Forms 1-8 with distinct XRPD patterns) of Compound A. These parameter changes in physical and chemical state resolve the contradiction by maintaining dual kinase inhibition activity while significantly improving physical and chemical stability and bioavailability for clinical use

Inventive Principle:

Principle #35Parameter changes

2Reliability

If existing Aurora kinase and FLT3 inhibitor compounds are developed, then dual kinase inhibition activity is achieved, but aqueous solubility and bioavailability are compromised

Engineering Contradiction:

Improvedual kinase inhibition activityVSAvoidaqueous solubility and bioavailability

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent applies parameter changes by developing multiple salt forms (fumarate, hydrochloride, mesylate, trifluoroacetate) and polymorphic forms (Forms 1-8 with distinct XRPD patterns) of Compound A. These parameter changes in physical and chemical state resolve the contradiction by maintaining dual kinase inhibition activity while significantly improving physical and chemical stability and bioavailability for clinical use

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS12624027B2Salts and polymorphic forms of 6-chloro-7-(4-(4-chlorobenzyl)piperazin-1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

Publication Date: 2026.05.12 ELLIPSES PHARMA LTD

AI summary

The present invention relates to salts and polymorphic forms of Compound A (6-chloro-7-(4-(4-chlorobenzyl)piperazin-1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine), an inhibitor of Aurora kinase and FMS-like tyrosine kinase 3 (FLT3) activity. The present invention also relates to processes for the preparation of the salts and polymorphic forms of the compound, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which Aurora kinase and/or FLT3 activity is implicated.