Non-steroidal Glucocorticoid Receptor Modulators for Selective Anti-inflammatory Therapy
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current glucocorticoid therapies are limited by significant side effects such as diabetes, osteoporosis, and glaucoma, and there is a need for compounds that can modulate glucocorticoid receptor (GR) activity to treat inflammatory and metabolic disorders without these side effects, as well as compounds that can either antagonize or induce GR activity to address associated diseases.
Innovation Solution
Development of new non-steroidal compounds that act as GR modulators, including agonists and antagonists, which can be administered to patients to treat GR-associated diseases by modulating GR activity, thereby addressing inflammatory, immune, and metabolic disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional glucocorticoid therapies are used to treat inflammatory and immune disorders, then anti-inflammatory activity is achieved, but significant side effects occur including diabetes, osteoporosis, and glaucoma
Solution Approach 1:
The patent applies segmentation by separating the anti-inflammatory transrepression function from the metabolic transactivation function of the glucocorticoid receptor. Non-steroidal compounds are designed to selectively modulate GR transrepression activity while avoiding transactivation, thereby achieving anti-inflammatory effects without the metabolic side effects associated with traditional glucocorticoid therapies
Solution Approach 2:
The invention implements local quality by creating compounds with selective pharmacological properties that affect specific biological targets differently. The non-steroidal GR modulators exhibit local quality by selectively interacting with the glucocorticoid receptor to produce beneficial anti-inflammatory effects in inflammatory tissues while avoiding harmful metabolic effects in other organ systems
2Reliability
If glucocorticoid receptor transactivation activity is enhanced to treat metabolic disorders, then therapeutic benefit is achieved, but adverse metabolic effects occur
Solution Approach 1:
The patent applies the taking out principle by extracting and isolating the desirable transrepression function from the glucocorticoid receptor system while leaving the problematic transactivation function untouched. Non-steroidal compounds are designed to specifically engage GR transrepression pathways that suppress inflammatory gene expression without activating transactivation pathways that regulate metabolism, thereby separating therapeutic benefit from adverse effects
Data Source
AI summary
Novel non-steroidal compounds are provided which are glucocorticoid receptor modulators which are useful in treating diseases requiring glucocorticoid receptor agonist or antagonist therapy such as obesity, diabetes, inflammatory and immune disorders, and have the structurewhere A, B, and R1-R6 are defined herein.