Selective CCR2 Antagonists for Inflammatory Disease Treatment
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Solution Overview
Problem
Current CCR2 antagonists lack selectivity for CCR2 over CCR5, which can lead to off-target effects and reduced efficacy in treating inflammatory and immune-related diseases such as asthma, COPD, and atherosclerotic diseases.
Innovation Solution
Development of novel compounds that selectively bind to CCR2 with minimal activity on CCR5, specifically designed to modulate chemokine receptors and reduce macrophage-induced inflammation, thereby treating inflammatory, respiratory, neurologic, and cardiovascular diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing CCR2 antagonists are used to block monocyte CCR2, then inflammation is reduced, but off-target effects occur due to lack of selectivity over CCR5
Solution Approach 1:
The patent modifies molecular parameters of the antagonist compounds by changing specific substituents at defined positions in the chemical structure. This allows optimization of binding affinity for CCR2 while minimizing binding to CCR5, thereby achieving selectivity without off-target effects.
Solution Approach 2:
The invention introduces specific functional groups and substituents at particular locations within the molecule to create local chemical properties that favor CCR2 binding. This localized modification enables selective interaction with CCR2 while avoiding CCR5, resolving the selectivity issue.
2Adaptability or versatility
If non-selective CCR2/CCR5 antagonists are used, then broader receptor coverage is achieved, but efficacy is reduced due to off-target effects
Solution Approach 1:
By systematically varying chemical parameters such as substituent types and positions, the patent creates a series of compounds with optimized CCR2 affinity and selective binding characteristics, maintaining efficacy while improving selectivity.
Data Source
AI summary
The present invention relates to novel and selective antagonists for CCR2 (CC chemokine receptor 2) and their use for providing medicaments for treating conditions and diseases, especially pulmonary diseases like asthma and COPD as well as pain. Claimed are compounds of formula (I), wherein G and E are independently selected from among C-H or N; wherein A is a group selected from among wherein R6 is a group of the structure -L1-R13, wherein L1 is selected from among -NH-, and -N(C1-C4-alkyl)-, and wherein R13 is selected from among -C5-C6-heterocyclyl comprising 1 or 2 hetero atoms selected from among N, and 0, and wherein R13 is optionally substituted; The other variables are as defined in the claims