Macrocyclic Purine Derivatives Modulate TLRs
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Solution Overview
Problem
There is a need for novel Toll-Like receptor modulators with preferred selectivity, higher potency, higher metabolic stability, and an improved safety profile for the treatment of viral infections and immune or inflammatory disorders, as existing compounds lack these characteristics.
Innovation Solution
Development of macrocyclic purine derivatives that modulate Toll-Like Receptors (TLRs), specifically compounds of formula (I) and their pharmaceutically acceptable salts, which are designed to enhance TLR modulation with improved pharmacokinetic properties and safety.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing Toll-Like receptor modulators are used, then viral infections and immune disorders can be treated, but the compounds lack preferred selectivity, have lower potency, have lower metabolic stability, and have an inferior safety profile
Solution Approach 1:
The patent modifies the chemical structure of purine derivatives by changing parameters such as introducing macrocyclic rings, adjusting substituent groups (R1-R6, X, Y, Z), and modifying physical-chemical properties to achieve improved selectivity for TLR7/8 while enhancing metabolic stability and safety profile compared to prior art compounds
Solution Approach 2:
The invention creates composite molecular structures by combining purine cores with macrocyclic rings and various substituent groups to form novel macrocyclic purine derivatives that exhibit enhanced pharmacological properties including improved selectivity, potency, and metabolic stability
2Reliability
If existing Toll-Like receptor modulators are used, then viral infections and immune disorders can be treated, but the compounds have lower potency
Solution Approach 1:
The patent enhances potency by modifying the chemical parameters of the purine derivatives, including the introduction of macrocyclic structures and optimization of substituent groups, which increases the binding affinity and biological activity at TLR7/8 receptors
3Stability of the object's composition
If existing Toll-Like receptor modulators are used, then viral infections and immune disorders can be treated, but the compounds have lower metabolic stability
Solution Approach 1:
The invention improves metabolic stability by altering the chemical structure parameters of the purine derivatives, particularly through macrocyclic ring formation and substituent modification, which reduces metabolic degradation and increases half-life while maintaining safety
Data Source
AI summary
This invention relates macrocyclic purine derivatives, processes for their preparation, pharmaceutical compositions, and their use in treating viral infections.