Piperidine-Substituted Indole CCR-3 Modulators
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Solution Overview
Problem
Current agents for modulating chemokine receptors, particularly CCR-3, often have significant side effects and are not adequately effective in treating inflammatory, infectious, and immunoregulatory disorders such as asthma and autoimmune pathologies.
Innovation Solution
Development of novel piperidine-substituted indole compounds that act as modulators of CCR-3 receptors with reduced side effects, specifically designed to inhibit or promote chemokine receptor activity for therapeutic benefits.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current agents for modulating chemokine receptors are used, then chemokine receptor activity is modulated, but significant side effects occur
Solution Approach 1:
The patent modifies the chemical structure of existing chemokine receptor modulators by changing molecular parameters - specifically incorporating piperidine rings substituted at the 4-position with propane-thiol chains of varying lengths and configurations. This structural parameter change results in compounds that maintain therapeutic effectiveness while reducing side effects, as demonstrated by the patent's claim of improved safety profile.
Solution Approach 2:
The invention creates composite molecular structures by combining piperidine core with substituted propane-thiol side chains. This composite approach allows the molecule to integrate multiple functional features - the piperidine provides binding affinity while the variable propane-thiol chains modulate receptor interaction, achieving a balance between efficacy and reduced toxicity.
2Productivity
If current agents for modulating chemokine receptors are used, then chemokine receptor activity is modulated, but adequate effectiveness is not achieved
Solution Approach 1:
The patent systematically varies molecular parameters including the length of propane-thiol chains (1-3 carbons), the position of substitution on the piperidine ring, and the configuration of chiral centers. These parameter changes optimize the compound's binding affinity and receptor modulation capability, achieving adequate therapeutic effectiveness.
3Object-affected harmful factors
If novel piperidine-substituted indole compounds are developed, then side effects are reduced, but compound complexity increases
Solution Approach 1:
The patent divides the molecular structure into distinct functional segments: a piperidine core unit, variable propane-thiol side chains, and optional indole substituents. This segmentation allows systematic variation of specific portions (the side chains) while maintaining a stable core structure, thereby reducing side effects through controlled structural modification rather than complete redesign.
Solution Approach 2:
The invention applies local modification to specific regions of the molecule - substituting the piperidine 4-position with propane-thiol chains of specific lengths and configurations. This localized change affects the molecular interaction with chemokine receptors in a controlled manner, reducing side effects without requiring complete redesign of the entire molecular structure.
Data Source
AI summary
One object of the present invention are novel substituted piperidyl-propane-thiols of the formula (1), wherein R1, R2, R3 and D are defined as below. Another object of the present invention is to provide agonists or antagonists of CCR-3, or pharmaceutically acceptable salts thereof, more particularly to provide pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt thereof.