Ted Szczerba | Authors

Regis Technologies, Inc.

Articles

Enantiomeric Separation of Privileged Scaffold Derivatives in Early Drug Discovery Using Chiral SFC

Successful therapeutic intervention often requires chiral medicines because of the intrinsic chirality of protein drug targets, which consist of L-amino acids. Potency, efficacy, and safety can be highly dependent on the precise stereochemical geometry of the molecules. Determining the biological profile of individual enantiomers in the early stages of drug discovery is important for successful optimization towards clinical candidates. Here we demonstrate the benefits of supercritical fluid chromatography (SFC) with three chiral stationary phases exemplified by high frequency resolution of 41 out of 50 chiral derivatives of eight commonly used drug discovery scaffolds including 1,3-thiazoles, 1,3-benzothiazoles, pyranoquinolones, indoles, and leucolines.

Summarization of Screening Hits on Chiral Columns

In new drug development, the number of diverse chiral compounds is increasing and sensitive chiral methods are often needed quickly. Many new CSPs are available on the market making it challenging to select the most important ones for the initial screening stages and expedite method development. The focus of this study is to evaluate high selectivity CSPs and to suggest the best screening method with a limited number of high success rate chiral columns.