CDK12/13 Inhibitor Acetamide Derivatives for Selective Kinase Targeting

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Solution Overview

Problem

There is a need for compounds that selectively inhibit CDK12/13 to treat and/or prevent diseases associated with these kinases, as existing inhibitors may have unwanted side effects due to non-selectivity.

Innovation Solution

Substituted N-(pyridin-2-yl)acetamide derivatives are developed to act as selective inhibitors of CDK12/13, targeting the kinases for therapeutic applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing CDK inhibitors are used, then cancer treatment activity is achieved, but unwanted side effects occur due to non-selectivity

Engineering Contradiction:

Improvetreatment efficacyVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by designing CDK inhibitors with specific molecular structures (formula I compounds) that possess unique chemical features tailored to selectively bind to CDK12/13. The substituents and functional groups in the molecular structure are carefully chosen to create high affinity and selectivity for the target kinases, thereby achieving effective treatment with reduced off-target effects and side effects.

Inventive Principle:

Principle #3Local quality

2Object-affected harmful factors

If selective CDK12/13 inhibitors are developed, then side effects are reduced, but compound complexity increases

Engineering Contradiction:

Improveside effectsVSAvoidcompound structure

Core Design Contradiction:

Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent employs segmentation by dividing the molecular structure into distinct functional segments: a core scaffold (pyridin-2-ylacetamide) and variable substituent groups (R1-R6, X1-Y4). This modular approach allows systematic variation of specific regions to optimize selectivity for CDK12/13 while maintaining manageable structural complexity through defined chemical frameworks.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent utilizes parameter changes by systematically varying chemical parameters such as substituent types, positions, and configurations in the molecular structure. By adjusting these parameters within the formula I framework, the compound series achieves high selectivity for CDK12/13 inhibition while maintaining synthesizable complexity levels.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20260000692A1Substituted N-(Pyridin-2-yl)Acetamide Derivatives as CDK12/13 Inhibitors

Publication Date: 2026.01.01 AURIGENE ONCOLOGY LIMITED

AI summary

The present application provides substituted N-(pyridin-2-yl)acetamide derivatives of formula (I)which are therapeutically useful as CDK12/13 inhibitors. These compounds are useful in the treatment and/or prevention of diseases and/or disorders associated with CDK12/13 in a mammal. In addition, the present application provides preparation of the compounds and pharmaceutical compositions comprising at least one of the substituted N-(pyridin-2-yl)acetamide derivatives of formula (I) or a pharmaceutically acceptable salt, an N-oxide or a stereoisomer thereof.