Hydroxamic Acid Metalloenzyme Inhibitors for Selective Binding
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current metalloenzyme inhibitors face challenges in achieving a balance between potency and selectivity, leading to clinical toxicity due to indiscriminate binding to off-target enzymes, and there is a need for more effective fungicides that can protect plants against various fungal pathogens.
Innovation Solution
Development of compounds of Formula I, which include specific metal-binding groups that form chemical interactions with metalloenzymes, such as sigma bonds or coordinate-covalent bonds, to modulate enzyme activity and treat diseases, and their use as fungicides to control fungal diseases in plants.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a very tightly binding metal-binding group is utilized, then potency is improved, but selectivity for the target enzyme versus related metalloenzymes deteriorates
Solution Approach 1:
The patent applies local quality by introducing a specific metal-binding group (hydroxamic acid) at a particular location in the inhibitor molecule to selectively bind zinc in the target enzyme's active site. This localized binding capability allows the inhibitor to achieve high potency against the target enzyme while maintaining selectivity, as the hydroxamic acid group is positioned to interact specifically with the zinc ion in the desired target enzyme rather than other metalloenzymes.
Solution Approach 2:
The patent employs parameter changes by modifying the chemical structure of the metal-binding group, specifically using hydroxamic acid functional groups with varying substituents (R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, R28, R29, R30, R31, R32, R33, R34, R35, R36, R37, R38, R39, R40, R41, R42, R43, R44, R45, R46, R47, R48, R49, R50, R51, R52, R53, R54, R55, R56, R57, R58, R59, R60, R61, R62, R63, R64, R65, R66, R67, R68, R69, R70, R71, R72, R73, R74, R75, R76, R77, R78, R79, R80, R81, R82, R83, R84, R85, R86, R87, R88, R89, R90, R91, R92, R93, R94, R95, R96, R97, R98, R99, R100). These structural modifications allow optimization of the binding parameters to achieve the desired balance between potency and selectivity.
2Object-affected harmful factors
If a weakly binding metal-binding group is utilized, then selectivity is improved, but potency deteriorates
Solution Approach 1:
The patent applies composite materials by combining the hydroxamic acid metal-binding group with specific molecular frameworks (compounds of Formula I with various R groups). This composite structure integrates the selective binding capability of the hydroxamic acid group with the structural specificity provided by the unique R group combinations, achieving both high selectivity and high potency simultaneously.
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 effectively modulate metalloenzyme activity, reducing toxicity and enhancing selectivity, and provide protection against ascomycetes, basidiomycetes, and oomycetes, offering a therapeutic and agricultural solution for diseases and disorders mediated by these pathogens.
Implementation Method 1
compounds of Formula I, shown below, and their derivatives and their use as fungicides... compounds effectively modulate metalloenzyme activity... form chemical interactions with metalloenzymes, such as sigma bonds or coordinate-covalent bonds
Data Source
AI summary
The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.