Amido Compounds Modulating RORγt for Autoimmune Therapy

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Solution Overview

Problem

Current therapies lack effective agents to modulate RORγt activity, which is implicated in various inflammatory and autoimmune diseases, as well as circadian rhythm regulation, leading to unaddressed inflammation and metabolic disorders.

Innovation Solution

Development of specific amido compounds that modulate RORγt activity, administered to mammals to treat diseases related to RORγ or RORγt, including autoimmune disorders and metabolic conditions, through pharmaceutical compositions and methods that target RORγt expression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current therapies are used, then treatment of inflammatory and autoimmune diseases is attempted, but effective modulation of RORγt activity is not achieved

Engineering Contradiction:

Improveeffectiveness of therapyVSAvoidability to modulate RORγt activity

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent employs parameter changes by developing compounds with specific structural parameters (amido group configuration, heterocyclic ring systems, substituent patterns) that optimize RORγt binding affinity and selectivity. The systematic variation of molecular parameters in the compound series enables effective RORγt modulation, directly resolving the contradiction between therapy effectiveness and the ability to modulate RORγt activity.

Inventive Principle:

Principle #35Parameter changes

2Object-affected harmful factors

If RORγt activity is not modulated, then inflammation and metabolic disorders remain unaddressed, but without specific agents, effective treatment cannot be provided

Engineering Contradiction:

Improveinflammation and metabolic disordersVSAvoidavailability of specific therapeutic agents

Core Design Contradiction:

Object-affected harmful factorsVSEase of manufacture

Solution Approach 1:

The patent applies segmentation by dividing the therapeutic approach into specific compound classes with distinct structural features (different heterocyclic cores, amido group variations, substituent patterns). This segmentation allows for targeted development of agents that specifically address RORγt-mediated inflammation and metabolic disorders, making effective treatment achievable through a series of related compounds rather than requiring a single complex agent.

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS10561666B2Amido compounds as RORγt modulators and uses thereof

Publication Date: 2020.02.18 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES

AI summary

Amido compounds are disclosed that have a formula represented by the following:and wherein n1, n2, R1a, R1b, R2, R3, R4, R5, and R6 are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, inflammatory conditions, autoimmune disorders, cancer, and graft-versus-host disease.