Modified Cyclic Dinucleoside STING Agonists for Immune Activation

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Solution Overview

Problem

Current treatments for inflammatory conditions, infectious diseases, and cancers lack effective modulation of the STING pathway, which is crucial for activating immune responses and inducing type I interferon production.

Innovation Solution

Development of compounds of Formula (I), (II), and (III), or their pharmaceutically acceptable salts, which act as STING agonists, inducing a STING-dependent type I interferon production and immune response activation when administered, thereby modulating the immune system to treat various diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments are used for inflammatory conditions, infectious diseases, and cancers, then existing therapeutic approaches are maintained, but effective modulation of the STING pathway is lacking

Engineering Contradiction:

Improveeffectiveness of treatmentVSAvoidmodulation of STING pathway

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent modifies the chemical structure of cyclic dinucleoside compounds by changing parameters such as sugar ring substitutions, base modifications, and stereochemistry to create analogs that effectively modulate the STING pathway, thereby improving treatment effectiveness for inflammatory conditions, infectious diseases, and cancers

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention divides the cyclic dinucleoside structure into modular components (sugar rings, phosphate bridges, nitrogenous bases) that can be independently modified and optimized to achieve specific STING pathway modulation while maintaining overall therapeutic effectiveness

Inventive Principle:

Principle #1Segmentation

2Reliability

If STING pathway modulation is achieved through new compounds, then immune response activation is improved, but the complexity of the treatment increases

Engineering Contradiction:

Improveimmune response activationVSAvoidcompound structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent introduces specific localized modifications at particular positions of the cyclic dinucleoside structure (such as 2'-O-methyl substitutions or specific base modifications) that enable STING pathway activation while minimizing overall structural complexity and maintaining pharmacological efficacy

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS11787833B2Modified cyclic dinucleoside compounds as sting modulators

Publication Date: 2023.10.17 ALIGOS THERAPEUTICS INC

AI summary

Provided herein are compounds of Formula (I), Formula (II) and/or Formula (III), or pharmaceutically acceptable salts of any of the foregoing, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), Formula (II) and/or Formula (III), or a pharmaceutically acceptable salt of any of the foregoing.