Measurement of atropisomer racemization kinetics using segmented flow technology

Area of Science:

• Medicinal Chemistry
• Chemical Kinetics
• Drug Discovery

Background:

• Stable atropisomers present challenges in drug discovery due to potential variations in biological activity, pharmacokinetics, and toxicity.
• Understanding atropisomer interconversion kinetics is vital for making informed decisions in drug development.

Purpose of the Study:

• To develop and validate a novel method for rapidly measuring atropisomer racemization kinetics.
• To utilize segmented flow technology for efficient acquisition of kinetic data.

Main Methods:

• Development of a new method employing segmented flow technology for kinetic measurements.
• Comparison of data obtained via segmented flow with traditional thermal methods.
• Application to the atropo isomerization of AMPA antagonist CP-465021.

Main Results:

• The segmented flow method demonstrated speed, accuracy, and required minimal sample amounts.
• The technique proved to be safe and semiautomated.
• Validation was achieved by comparing results with traditional thermal methods.

Conclusions:

• Segmented flow technology offers an efficient approach for determining atropisomer activation parameters.
• This method facilitates informed decision-making in drug discovery concerning chiral compounds.
• The developed technique supports the experimental probing of atropisomer interconversion kinetics.