C-Kit Kinase Modulation via Segmented Chemical Structures
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Solution Overview
Problem
There is a need for compounds and methods to modulate receptor protein kinases, particularly c-kit, which are implicated in various pathologic states including neoplastic pathology, carcinogenesis, and tumor growth, as existing treatments are inadequate.
Innovation Solution
The disclosure provides compounds of specific formulas, including (I′), (I), (II), (III), and (IV), and their pharmaceutically acceptable salts, solvates, and isomers, which are used to modulate protein kinases, specifically c-kit protein kinases, for treating diseases mediated by these enzymes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing treatments are used for c-kit mediated diseases, then treatment options are limited, but therapeutic effectiveness is inadequate
Solution Approach 1:
The patent employs parameter changes by developing a series of chemical compounds with varying molecular structures (formulas I, II, III, IV and their variants) to optimize c-kit inhibition. The compounds feature different substituents (R1-R6, L1-L3, G groups) and ring systems that are systematically modified to improve therapeutic effectiveness while maintaining selectivity for c-kit kinase modulation.
2Measurement precision
If compounds are designed to selectively target c-kit kinase, then specificity is improved, but compound complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the kinase inhibitor compound into distinct functional modules: a core heterocyclic ring system (formula I core structure), substituent groups (R1-R6 at specific positions), linker regions (L1-L3), and terminal groups (G). This modular structure allows for systematic optimization of c-kit selectivity while managing molecular complexity through defined structural elements.
Solution Approach 2:
The patent implements local quality by placing specific functional groups and substituents at predetermined positions within the molecular structure. The R1-R6 groups, L1-L3 linkers, and G terminal groups are strategically positioned to maximize interaction with specific residues in the c-kit kinase binding pocket, thereby enhancing selectivity without requiring uniform complexity throughout the entire molecule.
Data Source
AI summary
Compounds active on c-kit protein kinases or mutant c-kit protein kinases having any mutations are described, as well as methods of making and using such compounds to treat diseases and conditions associated with aberrant activity of the c-kit protein kinases and/or mutant c-kit protein kinases.