Borolone Compounds Metabolic Stability Boronic Acids
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Solution Overview
Problem
Boronic acids have poor metabolic stability, leading to their limited clinical implementation due to degradation pathways such as protodeboronation and oxidative deboronation, which affects their use as therapeutics.
Innovation Solution
Development of borolone compounds and their pharmaceutically acceptable salts, which exhibit superior metabolic stability compared to boronic acids and borole counterparts, by forming stable cyclic esters and resisting oxidation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If boronic acids are used as therapeutics, then they can bind covalently to proteins and carbohydrates, but they exhibit poor metabolic stability due to degradation pathways
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of boronic acids through oxidation to form boronic esters. This structural transformation changes the chemical properties of the compound, converting it from a state susceptible to degradation (boronic acid) to a state with enhanced metabolic stability (boronic ester), thereby resolving the contradiction between therapeutic utility and metabolic stability
Solution Approach 2:
The invention creates composite molecular structures by forming cyclic esters that incorporate both the boronic acid moiety and a diol component within a single molecular framework. This composite structure provides the benefits of boronic acid binding while the cyclic ester configuration confers resistance to degradation, simultaneously achieving both therapeutic function and metabolic stability
2Stability of the object's composition
If boronic acids are used in aqueous solutions, then they can form cyclic esters with diols, but they undergo oxidative deboronation leading to loss of reactivity
Solution Approach 1:
The patent converts the harmful oxidative deboronation process into a beneficial feature by designing compounds where oxidation leads to the formation of stable boronic esters rather than degradation. The oxidation that would normally destroy the C-B bond instead facilitates the formation of a more stable cyclic ester structure, transforming a degradation pathway into a stabilization mechanism
Solution Approach 2:
The invention applies preliminary anti-action by pre-forming the cyclic ester structure that is resistant to oxidative deboronation. By anticipating the oxidative environment in aqueous solutions, the molecular design incorporates the protective cyclic ester configuration before exposure to oxidizing conditions, preventing the harmful degradation that would occur with conventional boronic acids
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 borolone compounds demonstrate enhanced metabolic stability, effectively addressing the degradation issues of boronic acids, thereby potentially increasing their utility as therapeutics for various conditions including infections, dermatitis, inflammatory-related diseases, high blood pressure, and cancer.
Implementation Method 1
The electronic properties of boronic acids also impart a unique ability to bind covalently, yet reversibly, to proteins and carbohydrates
Implementation Method 2
oxidative deboronation, in which a C—B bond is replaced with a C—O bond. Protodeboronation generally requires an extreme pH, high temperature, or a metal catalyst, conditions that are not relevant physiologically. In contrast, the primary metabolite of boronic acids in vivo is the oxidative deboronation product, an alcohol, with reactivity that can be replicated in vitro by using reactive oxygen species or P450 enzymes
Data Source
AI summary
Provided herein are boron-containing compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat diseases or disorders.