Polycyclic Amide Derivative CDK9 Inhibitor Selectivity

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Solution Overview

Problem

Current CDK9 inhibitors exhibit uncertainty in terms of efficacy, safety, and selectivity, necessitating the development of new selective CDK9 inhibitors with improved properties.

Innovation Solution

A polycyclic amide derivative is developed, represented by specific structural formulas, which serves as a CDK9 inhibitor with enhanced kinase inhibitory activity, safety, and selectivity, and is prepared through various synthetic steps involving protection, Suzuki reactions, and condensation reactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing CDK9 inhibitors are used, then CDK9 inhibition is achieved, but efficacy and selectivity are uncertain

Engineering Contradiction:

ImproveCDK9 inhibition efficacyVSAvoidinhibitor selectivity

Core Design Contradiction:

ReliabilityVSManufacturing precision

Solution Approach 1:

The patent modifies molecular parameters of CDK9 inhibitors by changing the core structure from traditional flavones, pyrimidines, or pyridines to a polycyclic amide derivative with specific substituents (R1-R6 groups). This structural parameter change enhances both the reliability of CDK9 inhibition and the selectivity against other kinases, resolving the uncertainty in efficacy and selectivity of existing inhibitors.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite molecular structure combining polycyclic amide core with various functional groups (halogen, alkyl, alkoxy, heterocyclic substituents). This composite approach allows optimization of both inhibitory efficacy and selectivity by combining different structural elements that contribute to target binding affinity and specificity.

Inventive Principle:

Principle #40Composite materials

2Reliability

If CDK9 inhibition is enhanced, then anti-tumor efficacy is improved, but safety may be compromised

Engineering Contradiction:

Improveanti-tumor efficacyVSAvoiddrug safety

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces specific local structural features (R1-R6 substituents) on the polycyclic amide core that are optimized for target engagement while minimizing off-target effects. The localized modification of specific positions on the molecule allows enhancement of anti-tumor efficacy through improved CDK9 binding while maintaining safety by avoiding interactions with other biological targets.

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20230192703A1Polycyclic amide derivative as CDK9 inhibitor, preparation method therefor and use thereof

Publication Date: 2023.06.22 SUZHOU ALPHAMA BIOTECHNOLOGY CO LTD

AI summary

The present disclosure belongs to the technical field of polycyclic amide derivatives, in particular to a polycyclic amide derivative as a CDK9 inhibitor, a preparation method therefor and use thereof. The polycyclic amide derivative exhibits an excellent CDK9 kinase inhibitory activity, and can be used for preparing a medicine for treating cancers, wherein the cancers are especially hematological cancers, including acute myeloid leukemia, multiple myeloma, chronic lymphocytic leukemia, follicular lymphoma and solid tumors including breast cancer, prostate cancer, ovarian cancer, hepatocellular cancer, pancreatic cancer, renal cancer, gastric cancer, colorectal cancer, lung cancer, and the like.