Discovery, synthesis, and biological evaluation of piperidinol analogs with anti-tuberculosis activity. Academic Article uri icon

abstract

  • Direct anti-tuberculosis screening of commercially available compound libraries identified a novel piperidinol with interesting anti-tuberculosis activity and drug like characteristics. To generate a structure activity relationship about this hit a 22 member optimization library was generated using parallel synthesis. Products of this library 1-((R)-3-(4-chlorophenoxy)-2-hydroxypropyl)-4-(4-chloro-3-(trifluoromethyl) phenyl)piperidin-4-ol and 1-((S)-3-(4-(trifluoromethyl) phenoxy)-2-hydroxypropyl)-4-(4-chloro-3-(trifluoromethyl) phenyl) piperidin-4-ol demonstrated good anti-tuberculosis activity. Unfortunately, side effects were observed upon in vivo anti-tuberculosis testing of these compounds precluding their further advancement, which may be in part due to the secondary pharmacology associated with the aryl piperidinol core.

published proceedings

  • Bioorg Med Chem

author list (cited authors)

  • Sun, D., Scherman, M. S., Jones, V., Hurdle, J. G., Woolhiser, L. K., Knudson, S. E., ... Lee, R. E.

citation count

  • 20

complete list of authors

  • Sun, Dianqing||Scherman, Michael S||Jones, Victoria||Hurdle, Julian G||Woolhiser, Lisa K||Knudson, Susan E||Lenaerts, Anne J||Slayden, Richard A||McNeil, Michael R||Lee, Richard E

publication date

  • January 2009