Naphthyridine Compounds for c-Met and VEGFR-2 Inhibition
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Solution Overview
Problem
Current naphthyridine compounds, particularly 1,6-naphthyridines-1(2H)-ketones, have limited therapeutic potential as protein kinase inhibitors, and there is a need for compounds with enhanced kinase inhibiting activity and efficacy against diseases such as tumors, as they show inferior performance compared to other structural types like quinazoline derivatives.
Innovation Solution
Development of new naphthyridine compounds with specific structural modifications, including variations in the quinolyl ring substituents, to enhance their inhibitory activity on c-Met and VEGFR-2, leading to improved anti-tumor activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If 1,6-naphthyridines-1(2H)-ketones are used as protein kinase inhibitors, then they can inhibit c-Met and VEGFR-2 activity, but their therapeutic potential and inhibitory activity are limited compared to other structural types
Solution Approach 1:
The patent applies parameter changes by systematically modifying the chemical structure of 1,6-naphthyridines-1(2H)-ketones, specifically varying substituents at positions R1, R2, R3, R4, R5, and R6 in Formula (I). These structural parameter changes include introducing different aromatic groups, heterocyclic groups, and substituent patterns to optimize binding affinity to c-Met and VEGFR-2 kinases, thereby enhancing inhibitory activity and therapeutic potential while maintaining the core naphthyridine scaffold.
2Reliability
If quinazoline derivatives are used instead of naphthyridine compounds, then kinase inhibiting activity is enhanced, but the desired structural type (naphthyridine) is not achieved
Solution Approach 1:
The patent applies local quality by making specific localized modifications to the naphthyridine core structure through substituted patterns at defined positions (R1-R6). This allows the molecule to achieve localized interactions with kinase active sites similar to quinazoline derivatives, while maintaining the overall naphthyridine structural identity. The selective substitution pattern enables optimized binding to c-Met and VEGFR-2 without requiring a complete structural switch to quinazoline.
Data Source
Figure 1
AI summary
This invention involves the field of biomedicine, and reveals naphthyridine compounds, medical combinations and use thereof. The naphthyridine compounds has the structure as shown by Formula (I), or its stereoisomers, geometric isomers, tautomers, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or their prodrugs. The naphthyridine compounds of this invention has anti-tumor efficacy significantly superior to that of prior art. Moreover, the naphthyridine compounds of this invention can treat diseases mediated by protein kinases.