Solubility-Driven Lead Optimization of PAR4 Antagonists and Prodrug Strategy

O. Scott Halpern published a dataset on figshare in May 2026 detailing lead optimization for PAR4 antagonists. The description outlines structural modifications to improve aqueous solubility, resulting in lead compound 32 and its phosphate ester prodrug 44. The dataset likely contains experimental results comparing the solubility and oral bioavailability of these compounds.

Use Cases

• Analyzing the relationship between structural modifications and aqueous solubility based on the described deannulation and polar functionality introduction.
• Comparing in vivo performance metrics between a parent compound and its prodrug based on the described ex vivo and in vivo platelet aggregation inhibition.
• Evaluating the efficacy of phosphate ester prodrugs for solubility enhancement based on the described >1200-fold solubility improvement.
• Assessing oral exposure and bioavailability trade-offs between parent compounds and prodrugs based on the described 44% relative bioavailability.

Strengths

• The description provides specific, quantitative results, including a >1200-fold solubility improvement for the prodrug.
• It details a clear experimental workflow from lead optimization through in vivo evaluation.
• The dataset is shared under a CC-BY-NC-4.0 license, allowing for non-commercial reuse with attribution.

Limitations

• Column-level documentation is absent; field semantics must be inferred after download.
• Row count is unknown, which may limit suitability assessment.
• The dataset is very small (11.8 KB), indicating limited scope.

Provenance

Source

O. Scott Halpern via figshare

Collection Method

Likely contains experimental data from medicinal chemistry and pharmacology research.

Freshness

Last updated 2026-05-11 15:37:09; freshness should be verified.