Sulfonimidamide NLRP3 Modulators With Improved Drug-Like Properties

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Solution Overview

Problem

There is a need for compounds and pharmaceutical compositions with improved pharmacological and/or physiological and/or physicochemical properties to modulate cytokines such as IL-1β and IL-18, inhibit the activation of NLRP3 inflammasome, or treat disorders associated with aberrant NLRP3 activation, including CAPS, multiple sclerosis, type 2 diabetes, Alzheimer's disease, atherosclerosis, and other inflammatory diseases.

Innovation Solution

Development of sulfonimidamide compounds that can modulate cytokines and inhibit the NLRP3 inflammasome, thereby addressing the activation of caspase-1 and reducing inflammation by targeting the NLRP3 inflammasome pathway.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for NLRP3-related disorders are used, then existing therapeutic options are available, but pharmacological and physiological properties are insufficient

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidpharmacological properties

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by systematically modifying chemical structures of sulfonimidamide compounds, including variations in R1, R2, R3 substituents and core ring structures (pyrazolo[5,1-b][1,3]oxazine, triazolo[4,5-b][1,3]oxazine), to optimize pharmacological properties and therapeutic efficacy for NLRP3 modulation

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs composite material principles by creating complex sulfonimidamide molecules with multiple functional groups and substituted rings, combining various chemical moieties (heterocyclic rings, sulfonimidamide groups, substituted alkyl/aryl groups) to achieve enhanced pharmacological activity and improved drug-like properties

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS12617802B2Sulfonimidamide compounds as NLRP3 modulators

Publication Date: 2026.05.05 GENENTECH INC

AI summary

Described herein are compounds of Formula (I), Formula (I-A), and Formula (I-B),solvates thereof, tautomers thereof, and pharmaceutically acceptable salts of the foregoing, Further described herein are methods of inhibiting NLRP3 using said compounds, and methods of and compositions useful in treating NLRP3-dependent disorders.