Thieno[3,2-d]pyrimidine Derivatives Modulating TLR7 and TLR8
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Solution Overview
Problem
There is a need for novel Toll-Like receptor modulators with preferred selectivity, higher potency, and an improved safety profile compared to existing compounds, particularly for the treatment of viral infections involving TLR7 and TLR8 modulation.
Innovation Solution
Thieno[3,2-d]pyrimidine derivatives are developed, which act as pharmaceutical compounds or pharmaceutical compositions, specifically modulating TLR7 and TLR8, with specific structural variations to enhance selectivity and safety, and are prepared through specific synthetic methods involving intermediates and reaction conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing Toll-Like receptor modulators are used, then viral infections can be treated, but selectivity and safety profile are insufficient
Solution Approach 1:
The patent applies local quality by introducing specific substituent groups at defined positions on the pyrimidine core structure. Different substituents (R1-R6) are strategically placed to target specific TLR subtypes (TLR7, TLR8, TLR9) while avoiding off-target effects, thereby improving selectivity and safety profile simultaneously
Solution Approach 2:
The patent employs parameter changes by systematically varying chemical parameters such as substituent types, positions, and configurations on the pyrimidine scaffold. This allows optimization of binding affinity for desired TLRs while reducing activity against non-target receptors, resolving the contradiction between efficacy and safety
2Reliability
If existing Toll-Like receptor modulators are used, then viral infections can be treated, but potency is insufficient
Solution Approach 1:
The patent introduces specific functional groups at localized positions on the molecule to enhance binding affinity for target TLRs, thereby increasing potency. The localized modification of the pyrimidine core with specific substituents allows selective enhancement of desired interactions without proportionally increasing off-target effects
Solution Approach 2:
The patent constructs composite molecular structures by combining the pyrimidine core with various substituent groups that have complementary functions. This composite approach allows one part of the molecule to provide high affinity binding (potency) while other parts contribute to selective recognition (safety), resolving the contradiction between these two parameters
Data Source
AI summary
This invention relates to thieno[3,2-d]pyrimidines derivatives, processes for their preparation, pharmaceutical compositions, and their use in treating viral infections.