title: Discovery, synthesis, and biological evaluation of piperidinol analogs with anti-tuberculosis activity.
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.
authors.affiliation: Department of Pharmaceutical Sciences, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Dianqing
authors.initials: D
authors.lastname: Sun
authors.forename: Michael S
authors.initials: MS
authors.lastname: Scherman
authors.forename: Victoria
authors.initials: V
authors.lastname: Jones
authors.forename: Julian G
authors.initials: JG
authors.lastname: Hurdle
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Woolhiser
authors.forename: Susan E
authors.initials: SE
authors.lastname: Knudson
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Lenaerts
authors.forename: Richard A
authors.initials: RA
authors.lastname: Slayden
authors.forename: Michael R
authors.initials: MR
authors.lastname: McNeil
authors.forename: Richard E
authors.initials: RE
authors.lastname: Lee
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D002522:Chlorocebus aethiops; D055808:Drug Discovery; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000995:Antitubercular Agents; D010880:Piperidines; D054852:Small Molecule Libraries