Quinoline Kinase Ligands for CDK-2 Inhibition

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Solution Overview

Problem

Current CDK inhibitors for treating diseases such as cancer and inflammation are limited in effectiveness, with few molecules progressing to human clinical trials, highlighting a need for more potent and diverse CDK inhibitors.

Innovation Solution

Development of novel quinoline compounds with aryl amido moieties that act as cyclin-dependent kinase (CDK) inhibitors, specifically targeting CDK-2, to modulate disease symptoms in humans and animals, including those for cancer, inflammation, and neurodegenerative diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current CDK inhibitors are used for treating diseases such as cancer and inflammation, then disease treatment is achieved, but effectiveness is limited and few molecules progress to human clinical trials

Engineering Contradiction:

Improveeffectiveness of CDK inhibitorsVSAvoiddiversity of CDK inhibitors

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by systematically varying key molecular parameters including the quinoline core structure, aryl amido moiety configurations, and substituent patterns (R1-R6 groups) to generate a diverse library of CDK inhibitors with improved effectiveness and clinical trial progression potential

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs composite materials by combining the quinoline core structure with aryl amido moieties and various substituent groups to create composite molecular structures that exhibit enhanced CDK inhibition activity and broader therapeutic applicability across multiple disease indications

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS7511063B2High affinity quinoline-based kinase ligands

Publication Date: 2009.03.31 MERCK SHARP & DOHME LLC

AI summary

Quinoline-based inhibitors of cyclin dependent kinase 2, compositions including the inhibitors, and methods of using the inhibitors and inhibitor compositions are described. The inhibitors and compositions including them are useful for treating disease or disease symptoms. The invention also provides for methods of making CDK-2 inhibitor compounds, methods of inhibiting CDK-2, and methods for treating disease or disease symptoms.