Substituted Amide CCR10 Antagonists for Inflammatory Skin Disease Treatment
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Solution Overview
Problem
Current treatments for inflammatory skin diseases, allergic asthma, and melanoma lack effective inhibitors for CCR10 activity, which plays a crucial role in mediating tissue-specific recruitment of leukocytes to inflammatory sites, leading to inadequate management of these conditions.
Innovation Solution
Development of substituted amides that inhibit CCR10 activity, specifically compounds of formula (I), which can be administered to individuals to treat various diseases and disorders associated with CCR10 activation, including psoriasis, contact sensitivity, allergic dermatitis, systemic sclerosis, cutaneous SLE, and melanoma.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for inflammatory skin diseases are used, then existing therapeutic options are available, but effective inhibition of CCR10 activity is lacking leading to inadequate management
Solution Approach 1:
The patent segments the broad category of inflammatory skin disease treatments into specific CCR10-targeted therapies. By developing compounds that specifically inhibit CCR10 activity rather than using broad-spectrum anti-inflammatory agents, the treatment becomes more precise and effective for conditions mediated by CCR10 pathways.
Solution Approach 2:
The patent changes the therapeutic parameter from general inflammation suppression to specific CCR10 receptor inhibition. The substituted amide compounds modify the biochemical parameter of CCR10 ligand-receptor interaction, providing targeted inhibition that improves treatment effectiveness while reducing off-target effects.
2Object-affected harmful factors
If CCR10 activity is inhibited to reduce leukocyte recruitment, then inflammation and cell recruitment to skin lesions decrease, but new compounds must be developed and tested
Solution Approach 1:
The patent uses substituted amide compounds as intermediary substances that block the interaction between CCR10 and its ligands. These small molecule intermediaries prevent the direct ligand-receptor binding, thereby reducing leukocyte recruitment and inflammation without requiring direct manipulation of the receptor or ligand themselves.
Solution Approach 2:
The patent employs structure-activity relationship (SAR) analysis to systematically modify chemical parameters of the substituted amide compounds. By changing molecular structure parameters (R1-R6 substituents, core structures) and evaluating biological activity, the patent optimizes compounds for both efficacy in inhibiting CCR10-mediated inflammation and feasibility for manufacturing.
Data Source
AI summary
The invention relates to a compound of formula (I): or a tautomer thereof or a pharmaceutically acceptable salt thereof, wherein R1 to R11, W, X, Y, Z, and n are as defined herein. The invention also relates to methods of using the compounds of formula (I) and compositions thereof to treat various diseases and disorders in a patient. The invention also relates to processes for preparing the compounds of formula (I) and intermediates useful in these processes.