Selective DDR1 Inhibitor Compound for Fibrosis and Cancer Treatment
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Solution Overview
Problem
Current DDR1 inhibitors lack high selectivity and inhibitory activity, leading to potential side effects such as hypertension and proteinuria, necessitating the development of more targeted therapies for DDR1-related diseases like inflammation, fibrosis, and cancer.
Innovation Solution
A novel compound represented by Formula A or its pharmaceutically acceptable salt, which acts as a selective DDR1 inhibitor, inhibiting the kinase activity with high specificity and efficacy, thereby treating DDR1-related diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current DDR1 inhibitors are used, then DDR1 kinase activity is inhibited, but selectivity is insufficient leading to side effects such as hypertension and proteinuria
Solution Approach 1:
The patent applies local quality by designing a compound with specific structural features (pyridazinone core with particular substituent patterns at defined positions) that confer selective binding to DDR1 kinase domain while sparing other kinase targets. The molecular structure is optimized to interact with unique residues in DDR1's ATP-binding pocket, achieving high selectivity and reducing off-target side effects like hypertension and proteinuria.
Solution Approach 2:
The patent employs parameter changes by systematically varying molecular parameters including substituent types, positions, and stereochemistry around the pyridazinone core to optimize both potency and selectivity. By adjusting these chemical parameters, the compound achieves enhanced binding affinity for DDR1 while maintaining selectivity against other kinases, thereby improving therapeutic index.
2Adaptability or versatility
If non-selective kinase inhibitors are used, then broad kinase activity is suppressed, but specificity for DDR1 is insufficient
Solution Approach 1:
The compound features a pyridazinone core with specifically positioned substituents that create a unique molecular recognition pattern for DDR1. This local structural quality enables selective interaction with DDR1's kinase domain through specific hydrogen bonding, hydrophobic interactions, and steric complementarity, achieving high target specificity while maintaining potent inhibition.
Solution Approach 2:
The patent uses the pyridazinone moiety as an intermediary structure that mediates selective binding to DDR1. This core structure acts as a molecular mediator that bridges the connection between the substituent groups and the DDR1 kinase domain, enabling specific recognition and inhibition through its unique spatial and electronic properties.
Data Source
AI summary
The present invention provides a compound which is the compound represented by Formula A or a pharmaceutically acceptable salt thereof. The present invention further provides a pharmaceutical composition comprising the compound as described above and at least one pharmaceutically acceptable excipient. The present invention further provides the use of the compound as described above in the manufacture of a medicament for the treatment of at least one of inflammation, fibrotic disease and cancer. With the above aspects, the present invention provides a DDR1 inhibitor having both high inhibitory activity and high selectivity, and thus provides a novel solution for the treatment of DDR1-related diseases.