Purine Derivative Immunomodulators for Selective Interferon Induction
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Solution Overview
Problem
Current strategies for inducing type I interferons and modulating the immune response are limited by the lack of understanding of molecular targets for small molecule purine-like compounds, and existing treatments for allergic diseases, infectious diseases, and cancer have adverse effects and limited efficacy.
Innovation Solution
Development of specific compounds, such as those of formula (I) and (I'), which act as potent immunomodulators by selectively inducing human interferon alpha with enhanced potency and specificity, potentially used in treating allergic diseases, infectious diseases, and cancer, as well as serving as vaccine adjuvants.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing treatments for allergic diseases, infectious diseases, and cancer are used, then therapeutic effects are achieved, but adverse effects and limited efficacy occur
Solution Approach 1:
The patent modifies the chemical structure of purine-like compounds by changing parameters such as substituent groups at positions 2, 6, and 9 of the purine ring, as well as the basic moiety attached. These structural parameter changes result in compounds with improved selectivity for TLR7 and enhanced IFNα induction while reducing off-target effects and adverse reactions
Solution Approach 2:
The invention introduces specific functional groups at particular positions of the purine molecule (e.g., amino group at position 6, heterocyclic groups at position 9) to create localized interactions with TLR7. This local optimization of molecular structure enhances binding specificity and therapeutic selectivity, reducing systemic adverse effects
2Reliability
If small molecule purine-like compounds are used to induce type I interferons, then immune response modulation is achieved, but the molecular targets and mechanisms are not well understood
Solution Approach 1:
The patent employs structure-activity relationship (SAR) analysis where the effects of various structural modifications on TLR7 binding and IFNα induction are systematically measured and fed back into the design process. This iterative feedback loop has helped identify the molecular mechanisms and targets of these purine-like compounds
3Measurement precision
If compounds with high potency for IFNα induction are developed, then selectivity and potency are improved, but compound structure complexity increases
Solution Approach 1:
The purine molecule is divided into functional segments: the purine core structure and substituent groups at positions 2, 6, and 9. Each segment is optimized independently for its specific function (e.g., position 9 for TLR7 binding, position 6 for solubility and selectivity), allowing high potency without excessive overall complexity
Data Source
AI summary
Compounds of formula (I) wherein R1 is C1-6alkylamino, or C1-6alkoxy; R2 is a group having the structure (II): n is an integer having a value of 1 to 6; Het is a 6-membered saturated heterocycle containing one nitrogen atom wherein Het is attached to the -(CH2)n- moiety at any carbon atom of the heterocycle; R3 is hydrogen, C1-8alkyl, or C3-7cycloalkylC0-6alkyl; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.