Evolution of a thienopyrimidine antitubercular relying on medicinal chemistry and metabolomics insights

  • William R. Jacobs Jr., Shao-Gang Li, Catherine Vilchèze, Sumit Chakraborty, Xin Wang, Hiyun Kim, Monica Anisetti, Sean Ekins, Kyu Y. Rhee, Joel S. Freundlich
  • Tetrahedron Letters, June 2015, Elsevier
  • DOI: 10.1016/j.tetlet.2015.02.129

Optimizing the metabolic stability of an antitubercular

What is it about?

A thienopyrimidine antitubercular was found to be metabolically unstable in mouse liver microsomes in vitro. Steps were taken to modify the molecule that was chemocentric and involved understanding the metabolic fate of the initial hit in vitro.

Why is it important?

Mouse metabolic stability is an important ADME property which can determine whether an antitubercular has in vivo efficacy in the mouse. Therefore modifying the structure to maintain the in vitro activity and improve the metabolic stability is a challenge.

Perspectives

Dr Sean Ekins
Collaborations in Chemistry

This work was partially funded by a project that we are developing open source technologies for, I am therefore keen to see what ADME properties we can predict and whether we can improve our ability to optimize metabolic stability.

Read Publication

http://dx.doi.org/10.1016/j.tetlet.2015.02.129

The following have contributed to this page: Dr Sean Ekins