Irreversible Btk Inhibitor Covalent Bonding
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Solution Overview
Problem
Current treatments for diseases involving Bruton's tyrosine kinase (Btk) lack effective inhibitors that can selectively and irreversibly target Btk, leading to inadequate control of B-cell-related disorders and cancers.
Innovation Solution
Development of specific compounds that selectively and irreversibly inhibit Btk by forming a covalent bond with a cysteine residue, offering therapeutic benefits for B-cell proliferative diseases and cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for Btk-related diseases, then treatment is provided, but effective and selective irreversible inhibition of Btk is not achieved
Solution Approach 1:
The patent modifies the chemical structure of Btk inhibitors by introducing specific substituents (R1-R6) and aromatic/heteroaromatic groups (Ar) to enhance binding affinity and selectivity for Btk, achieving irreversible inhibition through covalent bonding while maintaining therapeutic effectiveness
Solution Approach 2:
The invention introduces specific functional groups and substitution patterns at particular positions on the molecular structure to create localized interactions with Btk's active site, enabling selective and irreversible inhibition without affecting other kinases
2Reliability
If selective irreversible Btk inhibitors are developed, then Btk activity is effectively inhibited, but compound structure complexity increases
Solution Approach 1:
The inhibitor molecule is divided into distinct functional segments: a core aromatic/heteroaromatic ring system (Ar), substituent groups (R1-R6) for selectivity, and a warhead group for irreversible binding, allowing systematic optimization of each segment's contribution to potency and selectivity
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The compounds demonstrate potent inhibition of Btk activity with high selectivity and irreversibility, effectively treating B-cell-related disorders and cancers with improved efficacy compared to existing treatments.
Implementation Method 1
Development of specific compounds that selectively and irreversibly inhibit Btk by forming a covalent bond with a cysteine residue
Data Source
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AI summary
The present invention provides a Bruton's tyrosine kinase inhibitor, which is a compound represented by formula (I) or a pharmaceutically acceptable salt, solvate, ester, acid, metabolite or prodrug thereof. The present invention also provides a pharmaceutical composition comprising the compound. The present invention also provides a method and use of using the Bruton's tyrosine kinase inhibitor to inhibit the tyrosine kinase activity or treat diseases, disorders or symptoms benefiting from the inhibition of the Bruton's tyrosine kinase (Btk) activity.