Indole Derivatives Antagonizing PGD2 at CRTH2 Receptors
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Solution Overview
Problem
Current treatments for allergic diseases such as asthma and atopic dermatitis mediated by prostaglandin D2 (PGD2) at the CRTH2 receptor are limited, as existing compounds often have contraindications or different mechanisms of action that are not effective for these conditions.
Innovation Solution
Development of indole derivatives with a carboxylic acid moiety substituted at the indole nitrogen, which act as antagonists to PGD2 at the CRTH2 receptor, providing a novel approach for treating PGD2-mediated inflammatory diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing compounds are used to treat PGD2-mediated allergic diseases, then treatment options are available, but the compounds have contraindications or different mechanisms of action that are not effective
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of indole compounds - specifically substituting the indole nitrogen with a carboxylic acid moiety. This structural parameter change creates compounds with specific CRTH2 antagonist activity that are effective for PGD2-mediated allergic diseases, resolving the contradiction between having available treatment options and achieving effectiveness for these specific conditions
2Object-generated harmful factors
If COX inhibitors are used for anti-inflammatory activity, then inflammation is reduced, but they are contraindicated in asthma and inflammatory bowel disease
Solution Approach 1:
The patent extracts the therapeutic anti-inflammatory effect from the harmful COX inhibition mechanism. By designing compounds that specifically target the CRTH2 receptor pathway involved in PGD2-mediated inflammation, the invention separates the beneficial anti-inflammatory outcome from the harmful effects of COX inhibition, making treatment safe for asthma and IBD patients
Solution Approach 2:
The patent introduces a new intermediary mechanism - CRTH2 receptor antagonism - to mediate the anti-inflammatory effect. Instead of using COX inhibitors that directly block prostaglandin synthesis, the compounds work through the CRTH2 receptor pathway, providing an alternative intermediary that achieves inflammation reduction without the contraindications of COX inhibition
Data Source
AI summary
The present invention provides indole derivatives that antagonize prostaglandin D2, and that can be used to treat inflammatory diseases mediated by prostaglandin D2.