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Updated: May 27, 2026

Measuring Biomolecular DSC Profiles with Thermolabile Ligands to Rapidly Characterize Folding and Binding Interactions
Published on: November 21, 2017
Kinetic and mechanistic insight into the thermodynamic degradation of saxagliptin
G Scott Jones1, Scott A Savage, Sabrina Ivy
1Chemical Development, Bristol-Myers Squibb Company, One Squibb Drive, New Brunswick, New Jersey 08903, USA. scott.jones@bms.com
Abstract:
The dipeptidyl peptidase-IV inhibitor saxagliptin (Onglyza) can undergo a thermodynamically favored cyclization to form the corresponding cyclic amidine. The kinetics and mechanism of this conversion were examined to develop a commercial synthesis that afforded saxagliptin with only trace levels of this key byproduct. Important findings of this work are the identification of a profound solvent effect and the determination of an autocatalytic pathway. Both of these phenomena result from transition structures involving proton transfer.
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