5-Substituted Indazole Kinase Inhibitors for Multi-Target Therapy
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Solution Overview
Problem
Current methods lack a single agent capable of effectively targeting specific sets of kinases or kinase pathways, necessitating the development of compounds that can inhibit multiple kinases simultaneously to achieve clinical efficacy in treating various diseases.
Innovation Solution
The development of 5-substituted indazole compounds that inhibit kinases such as GSK-3, ROCK, JAK2, and Cdc7, among others, offering selective inhibition and therapeutic potential for diseases like Alzheimer's, cancer, and inflammatory disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If multiple kinase pathways are targeted simultaneously, then therapeutic efficacy is improved, but device complexity increases
Solution Approach 1:
The 5-substituted indazole compound is designed to perform multiple functions by simultaneously inhibiting multiple kinase pathways including GSK-3, ROCK, JAK2, and Cdc7. This multi-functional inhibitor approach allows a single compound to target multiple disease-relevant pathways, improving therapeutic efficacy while avoiding the need for multiple separate drugs
Solution Approach 2:
The patent combines multiple kinase inhibition activities into a single molecular structure. By merging the inhibitory functions against different kinases into one compound, the treatment regimen is simplified and the compound can address the complexity of kinase pathways through integrated multi-target inhibition
2Measurement precision
If selective kinase inhibition is achieved, then therapeutic precision is improved, but manufacturing precision requirements increase
Solution Approach 1:
The indazole compound employs local quality variations through specific substituent groups at different positions on the molecular structure. These localized chemical features (substituents at positions 1, 2, 3, 4, or 5 of the indazole ring) provide selective interactions with specific kinase binding sites, enabling precise targeting of desired kinases while sparing others
Data Source
AI summary
The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts,wherein A, R1, R2, R3 and m, are defined in the description. The present invention relates also to methods of making said compounds, and compositions containing said compounds which are useful for inhibiting kinases such as Glycogen Synthase kinase 3 (GSK-3), Rho kinase (ROCK), Janus Kinases (JAK), Cdc7, AKT, PAK4, PLK, CK2, KDR, MK2, JNK1, aurora, pim 1 and nek 2.