Beta-lactamase Inhibitor Compounds for Resistant Bacterial Infections
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current beta-lactamase inhibitors are insufficient against the increasing diversity of beta-lactamases, particularly Class C and D enzymes, and lack an oral bioavailability form, limiting their use against resistant bacterial infections, especially in outpatient settings.
Innovation Solution
Development of orally available beta-lactamase inhibitors, represented by compounds of specific formulas (I, II, III, IV, V), which are effective against Class A, C, and D beta-lactamases, allowing for broad-spectrum inhibition and administration in both intravenous and oral forms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If currently available beta-lactamase inhibitors (clavulanic acid, tazobactam, sulbactam) are used, then activity against certain Class A enzymes is achieved, but utility is severely limited due to inability to counter diverse beta-lactamases including Class C and D enzymes
Solution Approach 1:
The patent develops beta-lactamase inhibitor compounds that function universally across multiple enzyme classes. The compounds are designed to inhibit Class A, Class C, and Class D beta-lactamases simultaneously, making a single agent effective against diverse resistant bacterial strains that previously required multiple different inhibitors.
Solution Approach 2:
The patent modifies the chemical structure of beta-lactamase inhibitors by incorporating specific substituents (R1-R6 groups) and stereochemical configurations to change the molecular parameters. These structural changes enable the compounds to bind to and inhibit multiple classes of beta-lactamases that have different active site geometries and mechanisms.
2Reliability
If intravenous beta-lactamase inhibitors are used in hospital settings, then effective treatment of resistant infections is achieved, but patient discharge is delayed and healthcare costs increase due to required hospital admission
Solution Approach 1:
The patent develops oral formulations of beta-lactamase inhibitors by modifying pharmacokinetic parameters such as bioavailability, absorption rate, and metabolic stability. The oral compounds maintain therapeutic effectiveness while enabling outpatient administration, allowing patients to be discharged earlier from hospital settings.
Solution Approach 2:
The patent creates oral bioavailable compounds that serve as intermediaries between intravenous treatment and complete discharge. These oral formulations allow patients to continue effective beta-lactamase inhibition therapy at home, bridging the gap between hospital-based IV treatment and community-based oral maintenance therapy.
3Adaptability or versatility
If broad-spectrum beta-lactamase inhibition is achieved through multiple compounds, then coverage of all beta-lactamase classes is improved, but device complexity and formulation requirements increase
Solution Approach 1:
The patent achieves broad-spectrum coverage through a single multi-functional compound design rather than requiring multiple separate formulations. The chemical structure incorporates features that enable simultaneous inhibition of Class A, C, and D beta-lactamases, simplifying the therapeutic regimen to a single oral agent.
Solution Approach 2:
The patent combines multiple inhibitory activities into a single molecular entity. By merging the ability to bind to different classes of beta-lactamase enzymes within one compound structure, the patent eliminates the need for complex multi-drug formulations or sequential therapy regimens.
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
These compounds provide effective beta-lactamase inhibition across multiple classes, enabling treatment of resistant bacterial infections in both hospital and outpatient settings, facilitating earlier discharge and reducing healthcare costs by allowing oral administration after initial intravenous treatment.
Implementation Method 1
Beta-lactamases are enzymes that are produced by some bacteria that ring open the beta-lactam portion of a beta-lactam antibiotic and thereby deactivate it. These compounds provide effective beta-lactamase inhibition across multiple classes
Data Source
AI summary
The present invention is directed to compounds which are beta-lactamase inhibitors. The compounds and their pharmaceutically acceptable salts are useful in combination with beta- lactam antibiotics, for the treatment of bacterial infections, including infections caused by drug resistant organisms, including multi-drug resistant organisms. The present invention includes compounds according to Formula (I): or a pharmaceutically acceptable salt thereof, wherein the values of R1, R2, R3, R4, R5 and R6 are described herein.