PKC Inhibitor Compounds Modulating Enzymatic Activity

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Solution Overview

Problem

Current treatments for diseases mediated by protein kinase C (PKC) activity lack effective inhibitors, which are crucial for managing various disorders sustained through PKC activity.

Innovation Solution

Development of specific compounds represented by chemical structures that act as PKC inhibitors, including pharmaceutical compositions and methods for their preparation, targeting various PKC isozymes to modulate their activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for PKC-mediated diseases are used, then existing therapeutic options are available, but effective PKC inhibition is lacking

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidPKC inhibition capability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent develops novel chemical compounds with specific molecular structures (formulas I, II, III, IV, V, VI) that are designed to bind to and inhibit PKC enzymes. By changing the chemical parameters and structural characteristics of the inhibitors, the patent achieves effective PKC inhibition where previous treatments failed, directly addressing the lack of therapeutic effectiveness in current treatments

Inventive Principle:
Principle #35Parameter changes

2Reliability

If specific PKC inhibitor compounds are developed, then effective PKC inhibition is achieved, but complexity of compound structure increases

Engineering Contradiction:
ImprovePKC inhibition efficacyVSAvoidmolecular structure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent presents multiple series of compounds (formulas I through VI) with progressively refined structures. Each formula represents a segmented approach to inhibitor design, building upon previous structures by modifying specific molecular regions. This segmentation allows for systematic optimization of inhibition efficacy while managing structural complexity through modular design

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces specific substituent groups (R1-R20) at localized positions within the molecular structures. By optimizing the chemical properties at specific local regions rather than uniformly modifying the entire molecule, the patent achieves enhanced PKC inhibition while controlling overall molecular complexity. The local quality principle allows targeted modification of key interaction regions

Inventive Principle:
Principle #3Local quality

Data Source

PatentUS10005777B2Protein kinase C inhibitors and uses thereof
Publication Date: 2018.06.26 RIGEL PHARMACEUTICALS INC

AI summary

This disclosure concerns compounds which are useful as inhibitors of protein kinase C (PKC) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC. This disclosure also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.