Urea Compounds Inhibit PD-1/PD-L1 Interaction
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Solution Overview
Problem
Current immune checkpoint inhibitors targeting the PD-1/PD-L1 signaling pathway, primarily antibodies, face challenges such as adverse side effects and long half-lives leading to continuous target inhibition, necessitating the development of small molecule inhibitors for safer and more effective cancer treatment.
Innovation Solution
Development of urea compounds that can block the PD-1/PD-L1 signaling pathway, including derivatives, pharmaceutical acceptable salts, stereoisomers, and prodrugs, which can be administered orally and are designed to target and inhibit the interaction between PD-1 and PD-L1, offering a safer therapeutic window for treating various cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibody drugs are used to block PD-1/PD-L1 signaling pathway, then immune checkpoint inhibition effect is achieved, but side effects increase and therapeutic safety decreases
Solution Approach 1:
The patent changes the molecular parameter from large antibody molecules to small molecule compounds, fundamentally altering the drug's physical and chemical properties. This parameter change enables oral administration and reduces immunogenicity, thereby improving therapeutic safety and reducing side effects while maintaining PD-1/PD-L1 pathway inhibition efficacy
2Reliability
If conventional antibody drugs are used, then PD-1/PD-L1 interaction is blocked, but half-life is prolonged leading to continuous target inhibition
Solution Approach 1:
The patent changes the molecular size and structure parameter from antibody to small molecule, which fundamentally alters the pharmacokinetic profile. Small molecules have shorter half-lives compared to antibodies, enabling more controlled and reversible target inhibition, thus improving the reliability of target inhibition control
3Ease of operation
If conventional antibody drugs are used, then immune checkpoint inhibition is achieved, but administration complexity increases due to injection requirement
Solution Approach 1:
The patent changes the molecular parameter from large antibody to small molecule, which enables oral administration through the gastrointestinal tract. This parameter change eliminates the need for injection and complex administration procedures, significantly improving ease of operation and patient compliance
4Reliability
If conventional antibody drugs are used, then PD-1/PD-L1 pathway is inhibited, but treatment cost increases
Solution Approach 1:
The patent employs small molecule compounds that are cheaper to manufacture and administer compared to expensive antibody drugs. Although small molecules may have shorter half-lives requiring more frequent dosing, the overall treatment cost is reduced due to lower drug acquisition costs and simplified administration, while maintaining clinical efficacy
Data Source
AI summary
The present invention relates to a urea compound and a preparation method and an application thereof. The structure of the present compound is represented by formula (I), the definition of each variable in the formula being as described in the description. The compound can block interaction between the PD-1/PD-L1 signalling pathways. The compound of the present invention can be used for treating or preventing diseases related to the signalling pathways, such as cancer, autoimmune disease, chronic infectious disease, and other diseases.