Boron-Containing Small Molecules for Selective ROCK Kinase Inhibition
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Solution Overview
Problem
Current ROCK inhibitors have limitations in therapeutic applications due to their effects on smooth muscle contraction and inflammation, which can lead to adverse outcomes in conditions like asthma, and there is a need for compounds that can effectively target ROCK kinases for various therapeutic areas such as glaucoma, pulmonary hypertension, and wound healing.
Innovation Solution
Development of specific compounds that inhibit ROCK kinases, which are designed to target the kinase's hinge region, thereby modulating its activity and reducing unwanted side effects on smooth muscle contraction and inflammation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ROCK inhibitors are used to treat conditions like glaucoma and pulmonary hypertension, then therapeutic benefits are achieved, but adverse effects on smooth muscle contraction and inflammation occur
Solution Approach 1:
The patent applies local quality by designing inhibitors that specifically target the ROCK kinase hinge region with selective binding characteristics. The compounds are structurally optimized to interact preferentially with the hinge region of ROCK kinases, creating localized selective inhibition that spares other protein interactions. This selective local action reduces off-target effects on smooth muscle contraction and inflammation while maintaining therapeutic efficacy in conditions like glaucoma and pulmonary hypertension.
2Reliability
If ROCK inhibitors are designed to target the kinase hinge region, then selectivity and reduced side effects are achieved, but compound design complexity increases
Solution Approach 1:
The patent employs parameter changes by systematically modifying molecular parameters of the inhibitor compounds to optimize hinge region binding. Specific structural parameters such as the boron-containing group configuration, substituent patterns, and molecular geometry are adjusted to enhance selectivity for the ROCK kinase hinge region. This parameter optimization approach achieves improved selectivity and reduced side effects while managing design complexity through structured molecular modification rather than random screening.
Data Source
AI summary
This invention provides novel compounds of the following formula and pharmaceutical compositions containing such compounds.