Pyrazolopyrimidine CDK2 Inhibitors Efficacy Specificity

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Solution Overview

Problem

There is a need for new compounds and treatments to effectively address diseases and disorders associated with cyclin-dependent kinases (CDKs), as existing inhibitors have limitations in efficacy and specificity.

Innovation Solution

Development of novel pyrazolo[1,5-a]pyrimidine compounds that act as inhibitors of cyclin-dependent kinases, with specific structural formulations that can inhibit CDK2 activity, potentially treating cancers, inflammation, arthritis, and other proliferative diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing CDK inhibitors are used, then CDK inhibition activity is achieved, but efficacy and specificity are insufficient

Engineering Contradiction:

Improveinhibitor efficacyVSAvoidinhibitor specificity

Core Design Contradiction:

ReliabilityVSMeasurement precision

Solution Approach 1:

The patent modifies the chemical structure of pyrazolo[1,5-a]pyrimidine compounds by changing parameters such as substituting hydrogen atoms with various functional groups (fluoro, chloro, bromo, iodo), modifying side chains, and adjusting molecular weight to optimize both efficacy and specificity of CDK inhibition

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates composite molecular structures by combining the pyrazolo[1,5-a]pyrimidine core with various side chains and functional groups to achieve a balance of potent CDK inhibition and selective binding characteristics

Inventive Principle:

Principle #40Composite materials

2Reliability

If new pyrazolo[1,5-a]pyrimidine compounds are developed, then efficacy and specificity are improved, but compound complexity increases

Engineering Contradiction:

Improveinhibitor efficacyVSAvoidcompound structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent divides the molecular structure into distinct segments: a core pyrazolo[1,5-a]pyrimidine scaffold and variable side chains or functional groups, allowing systematic modification of specific regions to optimize properties without redesigning the entire molecule

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention applies local modifications to specific positions on the pyrazolo[1,5-a]pyrimidine core, such as substituting atoms at particular locations or adding functional groups to specific regions, to achieve desired pharmacological properties while maintaining overall structural integrity

Inventive Principle:

Principle #3Local quality

Data Source

PatentEP2069349B1Pyrazolopyrimidines as cyclin dependent kinase inhibitors

Publication Date: 2016.06.15 MERCK SHARP & DOHME CORP

AI summary

In its many embodiments, the present invention provides a class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases (CDKs), methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.