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Updated: Aug 9, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Discovery of novel isothiazole inhibitors of the TrkA kinase: structure-activity relationship, computer modeling,
Blaise Lippa1, Joel Morris, Matthew Corbett
1Pfizer Inc., PGRD Groton, MS-8220-2203 Eastern Point Rd., Groton, CT 06340, USA. blaise.lippa@pfizer.com
Abstract:
The design, synthesis, and biological evaluation of potent inhibitors of the TrkA kinase is presented. A homology model is created to aid in the enhancement of potency and selectivity of isothiazole inhibitors found during a high-throughput screen. Three different syntheses are utilized to make diverse analogs within this series. Aminoheterocycles are found to be good urea surrogates, whereas bicyclic substituents on the C3 thio group were found to be extremely potent TrkA inhibitors in kinase and cell assays.
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