Selective ROCK Inhibitor Compounds With Lower Cytotoxicity

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Solution Overview

Problem

Current ROCK inhibitors, such as Y-27632 and Fasudil, lack isoform selectivity and exhibit cytotoxicity, solubility issues, and unfavorable pharmacokinetic profiles, limiting their effectiveness in treating ROCK-mediated diseases.

Innovation Solution

Development of novel compounds and pharmaceutical compositions that act as selective ROCK1 or ROCK2 inhibitors, with improved solubility, reduced cytotoxicity, and optimized pharmacokinetic profiles, including specific structural features like various ring systems and functional groups.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current ROCK inhibitors (Y-27632 and Fasudil) are used, then ROCK kinase activity is inhibited, but isoform selectivity is poor and cytotoxicity occurs

Engineering Contradiction:

ImproveROCK inhibition effectivenessVSAvoidcytotoxicity and lack of isoform selectivity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces specific structural modifications at particular positions of the inhibitor molecule to achieve localized interactions with ROCK2 that differ from ROCK1, creating isoform-selective inhibition without broad cytotoxic effects

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent systematically varies chemical parameters such as substituent groups, ring structures, and molecular geometry to optimize the balance between ROCK inhibition potency and selectivity, reducing cytotoxicity while maintaining therapeutic effectiveness

Inventive Principle:

Principle #35Parameter changes

2Reliability

If current ROCK inhibitors are used, then ROCK-mediated disease symptoms are addressed, but solubility issues and unfavorable pharmacokinetic profiles limit effectiveness

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidsolubility and pharmacokinetic properties

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent modifies physicochemical parameters of the inhibitor molecules including polarity, molecular weight, and functional groups to improve aqueous solubility and optimize pharmacokinetic properties such as absorption, distribution, metabolism, and excretion

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs composite molecular structures combining hydrophilic and hydrophobic regions, along with specific functional groups, to achieve both potent ROCK2 inhibition and improved solubility characteristics for better pharmacokinetic profiles

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS20260034140A1Modulators of rho-associated protein kinase

Publication Date: 2026.02.05 REDX PHARMA PLC

AI summary

This invention relates to novel compounds and pharmaceutical compositions comprising. Compounds of the invention useful as modulators of Rho-associated protein kinase (ROCK), for example ROCK1 and/or ROCK2 inhibitors. Methods of treatment employing the compounds are also contemplated by the present invention. The compounds of the invention are useful in treating ROCK mediated diseases.