Sigma Receptor Ligands for Selective Therapeutic Targeting

Solution Overview

Problem

Current treatments for Alzheimer's disease, ALS, cancer, substance abuse, and related conditions lack effective therapeutics, particularly sigma receptor subtype-selective ligands.

Innovation Solution

Development of specific compounds with defined chemical structures that can act as pharmaceutical agents, including sigma 1 and sigma 2 receptor agonists/antagonists, for treating various diseases such as cancer, neurodegenerative disorders, ethanol withdrawal, anxiety, depression, and neuropathic pain.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If existing sigma receptor ligands are used, then some therapeutic effect is achieved, but lack of subtype selectivity limits treatment effectiveness

Engineering Contradiction:

Improvereceptor subtype selectivityVSAvoidtherapeutic effectiveness

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent applies local quality by designing compounds with specific structural features that selectively interact with particular sigma receptor subtypes (sigma-1 or sigma-2). The chemical structures incorporate specific substituents and stereochemical configurations that create differential binding affinity for different receptor subtypes, enabling subtype-selective therapeutic effects rather than non-specific activity.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent utilizes parameter changes by systematically varying chemical parameters such as substituent types, molecular weight, and stereochemical configuration to optimize receptor binding characteristics. These parameter modifications enable fine-tuning of selectivity for specific sigma receptor subtypes while maintaining or enhancing therapeutic efficacy.

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If non-selective sigma receptor ligands are used, then broader receptor activity is achieved, but increased off-target effects and reduced safety

Engineering Contradiction:

Improvereceptor activity breadthVSAvoidoff-target effects

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by designing compounds with specific structural features that selectively interact with particular sigma receptor subtypes (sigma-1 or sigma-2). The chemical structures incorporate specific substituents and stereochemical configurations that create differential binding affinity for different receptor subtypes, enabling subtype-selective therapeutic effects rather than non-specific activity.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent converts the potential harm of non-selective binding into benefit by using stereochemical specificity and structural precision to achieve selective binding. The careful design of chiral centers and substituent patterns ensures that the compound binds preferentially to the desired receptor subtype, transforming what could be non-specific activity into targeted therapeutic action with reduced off-target effects.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS10954217B2Sigma receptor binders

Publication Date: 2021.03.23 BOARD OF RGT THE UNIV OF TEXAS SYST

AI summary

Provided herein, inter alia, are compounds and methods of treating diseases including cancer, neurological disease, alcohol withdrawal, depression and anxiety, and neuropathic pain.