C-17 Oleanolic Acid Derivatives for Inflammation Resolution
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Solution Overview
Problem
Current anti-inflammatory and antioxidant therapies are inadequate for chronic inflammation and oxidative stress, with existing drugs having side effects, limited efficacy, and failing to address both conditions simultaneously.
Innovation Solution
Development of oleanolic acid derivatives with specific modifications at the C-17 position, providing compounds with potent antioxidant and anti-inflammatory properties to modulate cellular signaling pathways and reduce inflammation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If COX-2 inhibitors are used to reduce inflammation, then inflammation symptoms are reduced, but full resolution of inflammation is interfered with and chronic inflammation may persist
Solution Approach 1:
The patent combines COX-2 inhibition with selective cyclopentenone prostaglandin (PGJ2) production by using oleanolic acid derivatives that possess dual enzymatic activity. This allows simultaneous reduction of harmful inflammatory mediators (COX-2 products) and promotion of beneficial resolution mediators (PGJ2), resolving the contradiction between suppressing inflammation symptoms and enabling full resolution.
Solution Approach 2:
The oleanolic acid derivatives act as intermediary compounds that modulate multiple enzymatic pathways. These compounds serve as mediators between COX-2 inhibition and PGJ2 production, enabling coordinated control of both inflammatory and resolution pathways without requiring separate drug mechanisms.
2Object-affected harmful factors
If corticosteroids are used for anti-inflammatory treatment, then inflammation is suppressed, but many undesirable side effects occur and chronic use is not suitable
Solution Approach 1:
The patent changes the chemical parameters of anti-inflammatory therapy by using oleanolic acid derivatives with specific molecular structures (formula I) that enable selective enzymatic modulation. This structural parameter change allows the compounds to achieve anti-inflammatory effects through a different mechanism than corticosteroids, avoiding the harmful side effects while maintaining therapeutic efficacy.
3Reliability
If protein-based drugs such as anti-TNF monoclonal antibodies are used, then certain autoimmune diseases are treated effectively, but administration by injection is required and severe side effects may occur
Solution Approach 1:
The patent replaces the mechanical injection system required for protein-based drugs with a small molecule chemical therapy system. The oleanolic acid derivatives can be administered orally or by other non-invasive routes, eliminating the need for injections while maintaining therapeutic effectiveness through direct enzymatic modulation of inflammatory pathways.
4Object-affected harmful factors
If existing anti-inflammatory drugs are used, then inflammation is addressed, but antioxidant properties are lacking and oxidative stress is not reduced
Solution Approach 1:
The oleanolic acid derivatives exhibit multi-functionality by simultaneously providing anti-inflammatory and antioxidant activities. The compounds can modulate multiple enzymatic pathways including COX-2, iNOS, and Nrf2, enabling them to address both inflammation and oxidative stress with a single agent, thereby achieving universal therapeutic coverage.
Data Source
AI summary
This invention provides, but is not limited to, novel oleanolic acid derivatives having the formula:wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds, methods and intermediates useful for making the compounds, and methods of using the compounds and compositions.