NSAID-EGFR Coupling Compounds via Ester Bonds for Tumor Treatment
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Solution Overview
Problem
Current tumor treatment methods, including surgical removal and chemotherapy, have unsatisfactory therapeutic effects, and while targeted drugs like EGFR inhibitors show promise, some patients are insensitive or develop resistance, highlighting the need for more effective therapies, particularly for lung cancer.
Innovation Solution
Development of coupling compounds formed by connecting NSAID anti-inflammatory and analgesic drugs with EGFR inhibitors through ester bonds, along with their pharmaceutically acceptable salts or stereoisomers, to create new chemical entities with enhanced therapeutic effects for tumor treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional tumor treatment methods (surgical removal and chemotherapy) are used, then treatment coverage is comprehensive, but therapeutic effects are unsatisfactory and toxicity is high
Solution Approach 1:
The patent combines two different therapeutic mechanisms into a single compound: COX-2 inhibition (via NSAID moiety) and EGFR tyrosine kinase inhibition (via gefitinib moiety). This dual-action compound addresses multiple tumor pathways simultaneously, improving therapeutic effect while maintaining selectivity to reduce toxicity compared to conventional chemotherapy
Solution Approach 2:
The invention creates a composite molecular structure by covalently linking an NSAID anti-inflammatory drug molecule with an EGFR inhibitor molecule through a connector group. This composite compound integrates the benefits of both drug classes, achieving enhanced anti-tumor efficacy through multi-target inhibition
2Object-affected harmful factors
If EGFR inhibitors are used for tumor treatment, then selectivity and toxicity are improved, but some patients develop resistance or insensitivity
Solution Approach 1:
The dual-action compound performs multiple therapeutic functions: it inhibits COX-2 enzyme activity (anti-inflammatory and anti-angiogenic effects) and simultaneously blocks EGFR tyrosine kinase activity (anti-proliferative effects). This multi-functionality overcomes resistance to single-target EGFR inhibitors by engaging alternative pathways
Solution Approach 2:
The invention changes the therapeutic parameter from single-target inhibition to multi-target inhibition. By incorporating both COX-2 inhibitory and EGFR inhibitory moieties, the compound expands its mechanism of action, thereby overcoming resistance that develops against monotherapy with EGFR inhibitors alone
3Object-affected harmful factors
If NSAID anti-inflammatory and analgesic drugs are used alone, then anti-inflammatory and analgesic effects are achieved, but anti-tumor efficacy is insufficient
Solution Approach 1:
The patent merges the COX-2 inhibitory NSAID moiety with the EGFR inhibitory gefitinib moiety in a single molecular entity. This combination allows the compound to simultaneously provide anti-inflammatory effects (from the NSAID portion) and potent anti-tumor effects (from both the NSAID and EGFR inhibitor portions), overcoming the limited anti-tumor efficacy of NSAIDs used alone
Data Source
AI summary
The present invention discloses coupling compounds of a structure as shown in Formula I, II or III formed by connecting NSAID anti-inflammatory and analgesic drugs and EGFR inhibitors by ester bonds or pharmaceutically acceptable salts or stereoisomers thereof or prodrug molecules thereof:where R is a NSAID anti-inflammatory and analgesic drug. In the present invention, the coupling compounds obtained by coupling NSAID anti-inflammatory and analgesic drugs with EGFR inhibitors have excellent therapeutic effects of tumors and provide new drugs for clinic treatment options.