Immunomodulating Azalides for Non-Antibacterial Inflammation Control
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Solution Overview
Problem
There is an unmet need for non-antibacterial, anti-inflammatory and immune-modulating agents to control or prevent inflammatory and immune responses in animals, particularly in bovine respiratory disease (BRD), which are not associated with the antibacterial effects of traditional macrolides, and to reduce the risk of antibiotic resistance.
Innovation Solution
Development of 13-membered macrolide ring compounds, known as azalides, which are in equilibrium with 15-membered macrolide ring structures, that possess anti-inflammatory and immune-modulating properties without antibacterial activity, used in compositions to treat or prevent inflammatory and immunological diseases in animals.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional macrolide antibiotics are used to treat respiratory diseases, then antibacterial effects are achieved, but immune-modulating activity is insufficient and antibiotic resistance develops
Solution Approach 1:
The patent extracts and isolates the immune-modulating properties from the antibacterial properties of traditional macrolides. By modifying the chemical structure to create azalides with enhanced immune-modulating activity and reduced or eliminated antibacterial effects, the invention separates the desired therapeutic effect (immune modulation) from the harmful effect (antibiotic resistance selection pressure).
Solution Approach 2:
The patent applies parameter changes by modifying the chemical structure parameters of macrolide compounds. Specifically, it alters the lactone ring size (13-membered vs 15-membered), sugar substitution patterns, and hydroxyl group configurations to transform the compound properties from primarily antibacterial to primarily immune-modulating, thereby achieving the desired therapeutic effect without contributing to antibiotic resistance.
2Reliability
If macrolide antibiotics are used to control inflammatory responses, then some immune-modulating benefits are achieved, but antibacterial activity persists which drives resistance
Solution Approach 1:
The patent converts the harmful selection pressure for antibiotic resistance into a beneficial outcome by designing compounds that deliberately lack significant antibacterial activity. The modified azalide structures provide immune-modulating benefits while eliminating the harmful side effect of driving antibiotic resistance, effectively turning the limitation into an advantage.
3Reliability
If current macrolides are used at higher dosages to enhance immune-modulating activity, then therapeutic effect increases, but side effects and antibiotic pressure increase
Solution Approach 1:
The patent achieves enhanced immune-modulating activity at lower dosages through strategic parameter changes in the molecular structure. By optimizing the lactone ring size to 13-members, adjusting sugar substitutions, and modifying hydroxyl group positions, the compounds achieve superior immune-modulating potency with improved safety profiles, avoiding the side effects associated with high-dose traditional macrolide therapy.
Data Source
AI summary
Defined herein are immunomodulating Formula (1) compounds, wherein R, R0, R1, R2and W are as defined herein, stereoisomers thereof, and pharmaceutically acceptable salts thereof; and compositions comprising said compounds. The invention also includes methods for treating or preventing an inflammatory and/or immunological disease or disorder in an animal by administering a therapeutically effective amount of a Formula (1) compound, stereoisomer thereof, or pharmaceutically acceptable salt thereof; or use of said Formula (1) compound to prepare a medicament for treating or preventing an inflammatory and/or immunological disease or disorder in an animal.