Peripheral CB1 Receptor Blockers That Avoid CNS Side Effects

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Solution Overview

Problem

Existing CB1 receptor blockers for obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease cause central nervous system (CNS)-mediated side effects, limiting their therapeutic potential.

Innovation Solution

Development of peripherally restricted CB1 receptor antagonists that do not penetrate the blood-brain barrier, utilizing lipophilic compounds with specific properties such as being P-gp substrates and having a brain/plasma ratio below 0.3, and a diphenyl ethylene or diphenyl methylene moiety to block CB1 receptors in peripheral organs without CNS effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If globally acting CB1 receptor blockers are used to treat obesity and metabolic disorders, then therapeutic benefits are achieved in peripheral organs, but CNS-mediated side effects occur

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidCNS side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention segments the distribution of the CB1 receptor blocker by introducing a carrier lipid composition that restricts the compound to peripheral circulation. This segmentation prevents the drug from reaching the CNS while maintaining therapeutic efficacy in peripheral organs through targeted delivery via the carrier system.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The carrier lipid composition acts as an intermediary between the CB1 receptor blocker and the biological system. This intermediary delivers the active compound to peripheral circulation while blocking its access to the CNS, thereby mediating selective peripheral action without central side effects.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If CB1 receptor blockers penetrate the blood-brain barrier, then central CB1 receptors are blocked, but neuropsychiatric side effects occur

Engineering Contradiction:

Improvereceptor blockadeVSAvoidneuropsychiatric side effects

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The invention applies local quality by creating different distribution characteristics for the same drug compound in different body compartments. The carrier lipid composition ensures high concentration in peripheral circulation while maintaining low or zero concentration in the CNS, providing locally differentiated drug action.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The invention adds a dimensional aspect to drug distribution by using the carrier lipid composition to control spatial localization. This dimensional control separates peripheral and central compartments, allowing the drug to act in one dimension (peripheral circulation) while being excluded from another dimension (CNS).

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

Data Source

PatentUS12473270B2CB1R receptor blockers with acyclic backbones

Publication Date: 2025.11.18 YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM LTD

AI summary

The invention generally concerns a novel class of CB 1 receptor binding molecules and uses thereof.