Ecteinascidin Derivatives with Methoxy and Fluoro Substituents
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current ecteinascidin compounds, despite their potent antitumor properties, face challenges in achieving optimal cytotoxicity, selectivity towards tumors, and reduced systemic toxicity, along with improved pharmacokinetic properties.
Innovation Solution
Development of derivatives with specific substituents such as methoxy, methyl, hydroxy, and fluoro groups, which enhance the therapeutic window and pharmacokinetic properties, including the synthesis of ecteinascidin 736 and related compounds with improved ADME properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ecteinascidin compounds are used for antitumor treatment, then potent antitumor activity is achieved, but systemic toxicity and hepatocyte damage occur
Solution Approach 1:
The patent applies local quality by introducing specific substituents (methoxy, methyl, hydroxy, fluoro groups) at particular positions on the ecteinascidin molecule. These localized modifications enhance antitumor activity while reducing systemic toxicity and hepatocyte damage, allowing different regions of the molecule to have optimized properties for their specific functions.
Solution Approach 2:
The patent employs parameter changes by systematically varying substituent types and positions on the ecteinascidin core structure. This includes changing functional groups (e.g., adding methoxy or fluoro groups) and their locations to optimize the balance between antitumor efficacy and reduction of harmful effects like systemic toxicity and hepatocyte damage.
2Reliability
If ecteinascidin compounds are used for antitumor treatment, then cytotoxicity is achieved, but selectivity towards tumors needs improvement
Solution Approach 1:
The patent applies local quality by introducing specific substituents (methoxy, methyl, hydroxy, fluoro groups) at particular positions on the ecteinascidin molecule. These localized modifications enhance antitumor activity while reducing systemic toxicity and hepatocyte damage, allowing different regions of the molecule to have optimized properties for their specific functions.
Solution Approach 2:
The patent employs parameter changes by systematically varying substituent types and positions on the ecteinascidin core structure. This includes changing functional groups (e.g., adding methoxy or fluoro groups) and their locations to optimize the balance between antitumor efficacy and reduction of harmful effects like systemic toxicity and hepatocyte damage.
3Reliability
If ecteinascidin compounds are used for antitumor treatment, then therapeutic effect is achieved, but pharmacokinetic properties need improvement
Solution Approach 1:
The patent employs parameter changes by systematically varying substituent types and positions on the ecteinascidin core structure. This includes changing functional groups (e.g., adding methoxy or fluoro groups) and their locations to optimize the balance between antitumor efficacy and reduction of harmful effects like systemic toxicity and hepatocyte damage.
Data Source
AI summary
Derivatives of ecteinascidin 736 of general formula (I) wherein the groups R1, R2, R3, R4 and R5 are each independently selected from the group consisting of H, OH, OR′, SH, SR′, SOR′, SO2R′, C(═O)R′, C(═O)OR′, NO2, NH2, NHR′, N(R′)2, NHC(O)R′, CN, halogen, ═O, substituted or unsubstituted C1-C25 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclic; wherein X is independently selected of OR′, CN, (═O), or H; wherein each of the R′ groups is independently selected from the group consisting of H, OH, NO2, NH2, SH, CN, halogen, ═O, C(═O)H, C(═O)CH3, CO2H, substituted or unsubstituted C1-C25 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, substituted or unsubstituted aryl; wherein m is 0, 1 or 2; and wherein n is 0, 1, 2, 3, or 4, and their use as antitumoral agent.