Biaryl Amide CRTh2 Modulator Stereochemistry
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Solution Overview
Problem
Current compounds targeting the CRTh2 receptor for treating respiratory disorders, such as asthma and COPD, have limitations in potency and metabolic stability, which affect their therapeutic efficacy and duration of action.
Innovation Solution
A bi-aryl amide compound with high CRTh2 potency and a long half-life, specifically in the form of the (S) enantiomer, is developed, which can be used as a pharmaceutical compound or in combination with other therapeutic agents to treat various inflammatory and respiratory conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If amide based compounds are used to target CRTh2 receptor, then CRTh2 activity is achieved, but potency and metabolic stability are limited
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure from conventional amide-based compounds to a bi-aryl amide with specific stereochemical configuration ((S)-enantiomer). This structural parameter change results in improved metabolic stability and prolonged half-life while maintaining CRTh2 potency, directly resolving the contradiction between achieving receptor activity and ensuring metabolic stability.
2Reliability
If amide based compounds are used to target CRTh2 receptor, then CRTh2 activity is achieved, but metabolic turn over rate is high
Solution Approach 1:
The invention changes the chemical parameters by introducing a bi-aryl amide structure with specific stereochemistry ((S)-configuration) and molecular weight optimization. These parameter modifications reduce the metabolic turnover rate by improving resistance to enzymatic degradation, thereby maintaining CRTh2 potency while reducing metabolic loss.
3Reliability
If existing CRTh2 compounds are used, then therapeutic effect is achieved, but therapeutic efficacy and duration of action are insufficient
Solution Approach 1:
The patent optimizes molecular parameters including molecular weight, lipophilicity, and stereochemical configuration to achieve improved pharmacokinetic properties. The (S)-enantiomer configuration and bi-aryl amide structure provide enhanced metabolic stability, extending the duration of action while preserving therapeutic efficacy at the CRTh2 receptor.
Data Source
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AI summary
The present invention relates to amide compounds useful as pharmaceuticals for treating respiratory disorders such as asthma, rhinitis and COPD.