Avermectin Derivatives for SARS-CoV-2 Antiviral Activity
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Solution Overview
Problem
There is an urgent need for compounds with antiviral activity against coronaviruses, particularly SARS-CoV-2, as existing drugs have limited efficacy and safety data, and there is a high risk of severe COVID-19 outcomes.
Innovation Solution
Development of avermectin derivatives represented by a specific general formula (I) with various substituents, which exhibit potent antiviral activity against coronaviruses, including SARS-CoV-2, by targeting the Wnt/β-catenin pathway.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing antiviral compounds (molnupiravir, nirmatrelvir/ritonavir) are used for SARS-CoV-2 treatment, then antiviral activity is achieved, but efficacy and safety data are limited and severe COVID-19 outcomes are not adequately addressed
Solution Approach 1:
The patent modifies the chemical structure of ivermectin by introducing various substituents at positions 2 and 24 of the avermectin core structure, creating derivatives with enhanced antiviral activity. This structural parameter change allows optimization of both efficacy against severe COVID-19 and safety profile while maintaining the parent compound's advantages
2Reliability
If ivermectin is used as an antiviral agent, then antiviral activity against SARS-CoV-2 is demonstrated, but the compound is primarily known for anthelmintic use with limited antiviral validation
Solution Approach 1:
The patent introduces specific substituents at localized positions (2 and 24) of the ivermectin molecule to enhance antiviral properties while preserving the core structure's anthelmintic activity. This localized modification allows the compound to exhibit multiple therapeutic qualities - both antiviral and anthelmintic - thereby validating its adaptability across different therapeutic applications
3Reliability
If new antiviral compounds are developed, then antiviral activity is improved, but development time and resource investment increase
Solution Approach 1:
The patent leverages the existing knowledge and established pharmacological profile of ivermectin as a starting point for derivative development. By building upon this pre-existing compound with known safety and efficacy data, the invention accelerates the development process compared to creating entirely new antiviral agents from scratch, thereby reducing both time and resource investment
Data Source
AI summary
A compound represented by the following general formula (I), or a pharmaceutically acceptable salt thereof: [In the formula (I), n represents an integer of 0 to 2; X represents CH, CF, CCl, N, CHCH=N, CHCH=CH, or CHCH=CF; Y represents O, NH, or a single bond; Z represents a hydroxy group or an oxo group; R1 represents a hydrogen atom, a C1-C6 alkyl group, a 3-to 6-membered cycloalkyl group, a 4- to 8-membered heterocycloalkyl group, a 6- to 10-membered aryl group, a 5- to 10-membered heteroaryl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a group represented by - CO-R2, a group represented by -COO-R2, a group represented by -CONH-R2, or a group represented by - B(OR4)OR5, and these groups may be substituted; and R2, R4, and R5 each represent a hydrogen atom, an alkyl group, etc.].