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Isosteric replacements of the carboxylic acid of drug candidate VX-787: Effect of charge on antiviral potency and kinase activity of azaindole-based influenza PB2 inhibitors
- Source :
- Bioorganic & Medicinal Chemistry Letters. 25:1990-1994
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- VX-787 is a first in class, orally bioavailable compound that offers unparalleled potential for the treatment of pandemic and seasonal influenza. As a part of our routine SAR exploration, carboxylic acid isosteres of VX-787 were prepared and tested against influenza A. It was found that the negative charge is important for maintaining potency and selectivity relative to kinase targets. Neutral carboxylic acid replacements generally resulted in compounds that were significantly less potent and less selective relative to the charged species.
- Subjects :
- Indoles
Pyridines
Stereochemistry
Isostere
Carboxylic acid
Clinical Biochemistry
Carboxylic Acids
Pharmaceutical Science
Microbial Sensitivity Tests
Antiviral Agents
Biochemistry
Structure-Activity Relationship
Viral Proteins
Drug Discovery
Potency
Pyrroles
Kinase activity
Protein Kinase Inhibitors
Molecular Biology
chemistry.chemical_classification
Aza Compounds
Dose-Response Relationship, Drug
Molecular Structure
Kinase
Drug candidate
Organic Chemistry
Bioavailability
Pyrimidines
chemistry
Influenza A virus
Molecular Medicine
Selectivity
Subjects
Details
- ISSN :
- 0960894X
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Accession number :
- edsair.doi.dedup.....e5570edbbfde170dfeff5195c9b78ae0