Alpha V Beta 6 Integrin Inhibitors Oral Bioavailability

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Solution Overview

Problem

Current αVβ6 and αVβ1 integrin inhibitors have shown limited therapeutic success in treating conditions such as platelet disorders, atherosclerosis, cancer, osteoporosis, fibrosis, and autoimmune diseases, highlighting a need for effective orally deliverable inhibitors that can modulate these integrins.

Innovation Solution

Development of compounds of Formula (I) and its derivatives, including pharmaceutically acceptable salts, hydrates, and solvates, which are designed to inhibit αVβ6 and αVβ1 integrins, thereby preventing or treating various medical disorders by administering therapeutically effective amounts to patients.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing αVβ6 and αVβ1 integrin inhibitors are used, then some therapeutic effect is achieved, but therapeutic success has been elusive and limitations remain

Engineering Contradiction:

Improvetherapeutic successVSAvoidoral deliverability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by modifying the chemical structure of integrin inhibitors to achieve oral bioavailability. Specifically, the compounds of Formula (I) are designed with molecular weight between 200-800 Da, logP between 1-6, and appropriate hydrogen bond donors/acceptors to satisfy oral drug-likeness criteria while maintaining integrin inhibition activity.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent segments the integrin inhibitor molecules into distinct functional regions: an RGD motif for integrin binding, a hydrophobic core for membrane permeation, and polar groups for solubility. This segmentation allows optimization of each region's properties to achieve both therapeutic efficacy and oral deliverability.

Inventive Principle:

Principle #1Segmentation

2Adaptability or versatility

If αVβ6 and αVβ1 integrins are inhibited, then conditions like platelet disorders, atherosclerosis, cancer, osteoporosis, fibrosis, and autoimmune diseases can be treated, but existing inhibitors have shown limited success

Engineering Contradiction:

Improvedisease treatment capabilityVSAvoidtherapeutic efficacy

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent develops universal integrin inhibitors that can treat multiple diseases by targeting the common αVβ6 and αVβ1 integrin pathway. The compounds of Formula (I) are designed to inhibit both αVβ6 and αVβ1 integrins, providing multi-disease applicability for conditions including platelet disorders, atherosclerosis, cancer, osteoporosis, fibrosis, and autoimmune diseases.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent uses the RGD (Arginine-Glycine-Aspartic acid) motif as an intermediary that mediates binding between the inhibitor compounds and the integrin receptors. This RGD sequence serves as a universal recognition element that enables the compounds to effectively inhibit both αVβ6 and αVβ1 integrins across different disease contexts.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20240208968A1Alpha v beta 6 and alpha v beta 1 integrin inhibitors and uses thereof

Publication Date: 2024.06.27 DICE MOLECULES SV INC

AI summary

Provided herein are alpha V beta 6 and alpha V beta 1 integrin inhibitors, methods of making such alpha V beta 6 and alpha V beta 1 integrin inhibitors, pharmaceutical compositions of alpha V beta 6 and alpha V beta 1 integrin inhibitors, and methods of treating and/or preventing various medical disorders in a subject by administering to the subject in need thereof alpha V beta 6 and alpha V beta 1 integrin inhibitors.