Publications by authors named "R H Troup"
Bioactive compounds generally need to cross membranes to arrive at their site of action. The octanol-water partition coefficient (lipophilicity, logP ) has proven to be an excellent proxy for membrane permeability. In modern drug discovery, logP and bioactivity are optimized simultaneously, for which fluorination is one of the relevant strategies.
View Article and Find Full Text PDFInhibition of Mer and Axl kinases has been implicated as a potential way to improve the efficacy of current immuno-oncology therapeutics by restoring the innate immune response in the tumor microenvironment. Highly selective dual Mer/Axl kinase inhibitors are required to validate this hypothesis. Starting from hits from a DNA-encoded library screen, we optimized an imidazo[1,2-]pyridine series using structure-based compound design to improve potency and reduce lipophilicity, resulting in a highly selective probe compound .
View Article and Find Full Text PDFArticle Synopsis
- The text discusses the significance of lipophilicity in drug development, highlighting how structural modifications, especially through fluorine introduction, can optimize both bioactivity and lipophilicity of orally bioavailable drugs.
- It emphasizes the importance of studying fluorinated compounds' octanol-water partition coefficients to enhance understanding of how fluorine affects lipophilicity, which is crucial for computational modeling.
- The findings reveal that skipped fluorination is more effective in reducing log values compared to single or vicinal fluorination, and also detail the efficient synthesis of these compounds, some of which can be made enantioselective.
Article Synopsis
- The text discusses how fluorination affects the lipophilicity (fat solubility) of different substituents—specifically isopropyl, cyclopropyl, and 3-oxetanyl—at a single carbon atom.
- It compares the results with similar linear chain compounds and examines changes in lipophilicity when extending acyclic precursors to create cyclopropyl compounds.
- Findings show that fluorinating the isopropyl group significantly influences lipophilicity more than fluorinating the cyclopropyl group.
Current strategies for the design of PROTAC linkers: a critical review.
Explor Target Antitumor Ther
October 2020
Article Synopsis
- * The length and composition of the linker are crucial to the effectiveness and properties of PROTACs, with a shift from simple linkers to more complex functional ones promising better therapeutic outcomes.
- * The authors review current linker designs, critique traditional methods, and emphasize the need for improved approaches using computational tools to enhance PROTAC development and address design challenges.