title: The 4-aminopiperidine series has limited anti-tubercular and anti-staphylococcus aureus activity.
abstract: BACKGROUND
  Tuberculosis (TB) caused by Mycobacterium tuberculosis is the leading cause of death from a bacterial infection. The 4-aminopiperidine (PIP) series has been reported as having anti-bacterial activity against M. tuberculosis. We explored this series for its potential to inhibit aerobic growth of M. tuberculosis. We examined substitution at the N-1 position and C-4 position of the piperidine and modifications of the piperidine moiety systematically to delineate structure-activity relationships influencing potency. Compounds were tested for growth-inhibitory activity against virulent M. tuberculosis. A selected set of compounds were also tested for its activity against Staphylococcus aureus.
  
  
  RESULTS
  The compound with a norbornenylmethyl substituent at the N-1 position and N-benzyl-N-phenethylamine at the C-4 position of the piperidine (1) was the only active compound with a minimum inhibitory concentration (MIC) of 10 μM against M. tuberculosis. Compounds were not active against S. aureus.
  
  
  CONCLUSIONS
  We were unable to derive any other analogs with MIC < 20 μM against M. tuberculosis. Therefore we conclude that the lack of activity is a liability in this series precluding it from further development.
authors.affiliation: TB Discovery Research, Infectious Disease Research Institute, 1616 Eastlake Avenue E, Seattle, WA, 98102, USA. Susantha.Chandrasekera@idri.org.
authors.forename: N Susantha
authors.initials: NS
authors.lastname: Chandrasekera
authors.affiliation: TB Discovery Research, Infectious Disease Research Institute, 1616 Eastlake Avenue E, Seattle, WA, 98102, USA. toreyalling@gmail.com.
authors.forename: Torey
authors.initials: T
authors.lastname: Alling
authors.affiliation: TB Discovery Research, Infectious Disease Research Institute, 1616 Eastlake Avenue E, Seattle, WA, 98102, USA. mabailey@seagen.com.|Current address: Seattle Genetics, Bothell, USA. mabailey@seagen.com.
authors.forename: Mai
authors.initials: M
authors.lastname: Bailey
authors.affiliation: TB Discovery Research, Infectious Disease Research Institute, 1616 Eastlake Avenue E, Seattle, WA, 98102, USA. Aaron.Korkegian@idri.org.
authors.forename: Aaron
authors.initials: A
authors.lastname: Korkegian
authors.affiliation: TB Discovery Research, Infectious Disease Research Institute, 1616 Eastlake Avenue E, Seattle, WA, 98102, USA. James.Ahn@idri.org.
authors.forename: James
authors.initials: J
authors.lastname: Ahn
authors.affiliation: TB Discovery Research, Infectious Disease Research Institute, 1616 Eastlake Avenue E, Seattle, WA, 98102, USA. Yulia.Ovechkina@idri.org.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Ovechkina
authors.affiliation: TB Discovery Research, Infectious Disease Research Institute, 1616 Eastlake Avenue E, Seattle, WA, 98102, USA. Joshua.Odingo@idri.org.
authors.forename: Joshua
authors.initials: J
authors.lastname: Odingo
authors.affiliation: TB Discovery Research, Infectious Disease Research Institute, 1616 Eastlake Avenue E, Seattle, WA, 98102, USA. Tanya.Parish@idri.org.
authors.forename: Tanya
authors.initials: T
authors.lastname: Parish
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000502:physiology; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: C481395:4-aminopiperidine; D000995:Antitubercular Agents; D010880:Piperidines