Pteridine Derivatives Modulating RORγ for Autoimmune Disorders
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Solution Overview
Problem
Current treatments for autoimmune and allergic disorders lack effective inhibitors of RORγ with desirable metabolic stability for achieving therapeutic levels.
Innovation Solution
Development of a novel class of heteroaromatic compounds with specific structural features that exhibit potent inhibitory activity against RORγ, designed to possess metabolic stability and acceptable pharmacokinetic properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If compounds are designed to inhibit RORγ for treating autoimmune disorders, then therapeutic efficacy is improved, but metabolic stability deteriorates leading to poor pharmacokinetic properties
Solution Approach 1:
The patent applies parameter changes by systematically modifying chemical structure parameters of pteridine derivatives. Specific substitutions at defined positions (R1-R6, W) are optimized to achieve the desired balance between RORγ inhibitory activity and metabolic stability, transforming the molecular properties to resolve the contradiction between efficacy and stability
Solution Approach 2:
The invention creates composite molecular structures by combining pteridine core with various heteroaromatic substituents and side chains. This composite approach allows integration of multiple functional elements that collectively provide both potent RORγ inhibition and improved metabolic stability, achieving therapeutic efficacy with acceptable pharmacokinetic properties
2Reliability
If compounds are designed to achieve potent RORγ inhibition, then therapeutic benefit is improved, but metabolic stability deteriorates preventing achievement of therapeutic levels
Solution Approach 1:
The patent modifies chemical parameters including molecular weight, lipophilicity, and metabolic susceptibility through strategic substituent selection. These parameter changes enable compounds to maintain potent RORγ inhibition while improving metabolic stability, thereby achieving sufficient therapeutic concentrations in vivo
Solution Approach 2:
The invention addresses the short-living nature of metabolically unstable compounds by designing structures with improved metabolic half-lives. Through optimized molecular architecture, the compounds achieve prolonged circulation and sustained therapeutic levels, effectively extending their functional lifetime in the body
Data Source
AI summary
The present invention encompasses compounds of formula (I) wherein the variables are defined herein which are suitable for the modulation of RORγ and the treatment of diseases related to the modulation of RORγ. The present invention also encompasses processes of making compounds of formula (I) and pharmaceutical preparations containing them.