Amide CSF-1R Inhibitors With Broader Type III Kinase Coverage
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for novel type III tyrosine kinase receptor inhibitors, particularly CSF-1R inhibitors, to treat diseases such as cancer, autoimmune diseases, and inflammatory diseases, as existing inhibitors like Pexidartinib are limited in their applications.
Innovation Solution
Development of amide compounds of formula (I) and their pharmaceutically acceptable salts, deuterates, solvates, racemic mixtures, enantiomers, and diastereomers, which can inhibit CSF-1R activity in vivo or in vitro, and are used in treating conditions mediated by CSF-1R signaling pathways.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing CSF-1R inhibitors like Pexidartinib are used, then CSF-1R activity is inhibited, but the application scope is limited and therapeutic efficacy is insufficient
Solution Approach 1:
The patent develops compound (I) as a multi-target inhibitor that can inhibit not only CSF-1R but also other type III tyrosine kinase receptors including PDGFRα, PDGFRβ, FLT3, and c-KIT. This multi-functional capability allows the single compound to treat multiple diseases including various cancers, autoimmune diseases, and inflammatory diseases, thereby expanding the application scope while maintaining reliable therapeutic efficacy
Solution Approach 2:
The patent employs structure-activity relationship optimization by modifying the chemical structure of compound (I) with various substituents (R1-R10, X, Y1-Y3, Z1-Z2, L, W parameters) to tune the inhibitory potency and selectivity profile. Through systematic parameter changes in the molecular structure, the compound achieves enhanced therapeutic efficacy across different disease models while maintaining broad applicability
2Adaptability or versatility
If novel amide compounds of formula (I) are developed, then therapeutic efficacy and application scope are improved, but compound structure complexity increases
Solution Approach 1:
The patent divides the complex molecule into distinct functional modules: a core amide structure with separable substituent groups (R1-R10, X, Y1-Y3, Z1-Z2, L, W). This modular segmentation allows systematic optimization of each module's function while maintaining overall structural coherence, enabling the compound to achieve multi-target inhibition capability without excessive complexity
Solution Approach 2:
The patent creates a composite molecular structure combining multiple pharmacophore elements within compound (I) that can interact with different kinase receptors. The composite structure integrates heteroaryl, heterocyclyl, and various substituent groups that work synergistically to achieve broad-spectrum inhibition of type III tyrosine kinase receptors, balancing structural complexity with enhanced functionality
Data Source
AI summary
Provided herein are novel amide compounds of formula (I), pharmaceutical compositions comprising same, methods for preparing same, and uses thereof, wherein the definition of each symbol is as described in the description.