Phenyl-Alkyl Piperazines for TNF-Alpha Modulation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current phenyl-alkyl-piperazines with TNF-α modulating activity lack specificity due to variations in the R1 group and absence of the CH2CH2R3 group, limiting their effectiveness in modulating TNF-alpha levels, particularly in inflammatory conditions.
Innovation Solution
Development of novel phenyl-alkyl-piperazines of formula (I) with specific structural modifications, including R1 and R2 groups as hydrogen, halogen, alkyl, or perfluoroalkyl, and R3 as alkyl, which can exist as enantiomers, diastereoisomers, or their mixtures, and as bases or addition salts, to enhance TNF-alpha modulation activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If phenyl-alkyl-piperazines with varied R1 groups are used, then structural diversity is improved, but TNF-alpha modulating specificity deteriorates
Solution Approach 1:
The patent applies local quality by specifying particular substitutions at defined positions (R1 at position 3 or 4 of phenyl ring, R2 at position 4 of piperazine) while maintaining consistency in the core phenyl-alkyl-piperazine scaffold. This localized variation approach achieves structural diversity where needed while preserving the specific TNF-alpha modulating activity required for therapeutic effectiveness.
2Device complexity
If the CH2CH2R3 group is absent from the molecule, then molecular simplicity is improved, but TNF-alpha modulation effectiveness deteriorates
Solution Approach 1:
The patent applies parameter changes by systematically varying the R3 alkyl group (C1-C6 alkyl including methyl, ethyl, propyl, butyl, pentyl, hexyl and their branched isomers) attached to the ethyl chain at position 1 of the piperazine ring. This parameter optimization allows the molecule to achieve effective TNF-alpha modulation while maintaining reasonable structural simplicity for pharmaceutical development.
3Manufacturing precision
If R1 and R2 groups are limited to specific options, then manufacturing precision is improved, but molecular adaptability deteriorates
Solution Approach 1:
The patent applies segmentation by dividing the molecule into distinct functional segments: the phenyl ring segment (with controlled R1 substitutions at positions 3 or 4), the ethyl linker segment, and the piperazine segment (with R2 and R3 substitutions). This segmentation allows each part to be optimized independently for manufacturing precision while the combination provides the necessary molecular adaptability for TNF-alpha modulation.
Data Source
AI summary
The present invention relates to novel phenyl-alkyl piperazines having a modulating activity of TNF, to the pharmaceutical compositions containing same, and to a method for the preparation thereof.