Cyclic Dinucleotide Derivatives for Expanded STING Activation

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Solution Overview

Problem

There is a demand for new small molecule STING agonists that can induce type I interferon production for use in vaccines and cancer treatment, as existing cyclic dinucleotides have limitations.

Innovation Solution

Development of compounds of Formula (I) as STING agonists, which include specific substituents and ring formations, to activate the STING pathway and induce interferon production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing cyclic dinucleotides are used as STING agonists, then type I interferon production is induced, but there are limitations in efficacy and versatility

Engineering Contradiction:

ImproveSTING activation efficacyVSAvoidapplication range

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent modifies the chemical structure of cyclic dinucleotides by changing parameters such as ring composition (cyclic GMP vs cyclic AMP), substituent groups (fluorine atoms, sugar moieties), and linkage types to create a series of derivatives with optimized STING activation properties and expanded application scope

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention combines different nucleotide bases (guanosine and adenosine), sugar components (ribose and deoxyribose), and modifying groups (fluorine, phosphate, hydroxyl) to create composite cyclic dinucleotide structures that exhibit enhanced and diversified biological activities

Inventive Principle:

Principle #40Composite materials

2Adaptability or versatility

If cyclic dinucleotides are developed for multiple disease treatments, then versatility is improved, but manufacturing complexity increases

Engineering Contradiction:

Improvedisease treatment rangeVSAvoidsynthesis process complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The synthesis approach is divided into modular steps: preparing cyclic dinucleotide intermediates with protected groups, performing phosphitylation reactions to form phosphoramidites, and final coupling to generate diverse derivatives. This segmented approach allows systematic production of multiple analogs

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent develops a universal synthetic platform using common intermediates (cyclic GMP and cyclic AMP derivatives) and standardized phosphitylation procedures that can be applied to generate multiple STING agonist variants for different disease indications, reducing overall manufacturing complexity

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS12435104B2Cyclic dinucleotides as sting agonists

Publication Date: 2025.10.07 BEONE MEDICINES I GMBH

AI summary

Disclosed herein are cyclic di-nucleotide compounds and derivatives thereof that may be useful as STING agonists, and a pharmaceutical composition comprising the same. Also disclosed herein is the process for synthesis and to uses of such cyclic di-nucleotide compounds in various diseases including cancer, HIV infection and HBV infection.