title: Synthesis of Adamantane Aminoethers with Antitubercular Potential.
abstract: BACKGROUND
  Intrigued by the fact that aminoadamantane derivatives, bearing the active 1,2-ethylenediamine moiety, are promising antitubercular agents, we report herein the synthesis and the antitubercular evaluation of N,N'-substituded-4,4'-[adamantane-2,2-diyl]bis(phe-noxyalkylamines) 1a-g, N,N'-substituded-4,4'-[adamantane-1,3-diyl]bis(phenoxyalkylamines) 2a-f, N,N'- substituded-[4-(1-adamantyl)phenoxy]alkylamines 3a-d and N,N'-substituded-[4-(2-adamantyl)- phenoxy]alkylamines 4a,b.
  
  
  METHODS
  A substituted diarylmethane moiety was introduced on the adamantane skeleton of the new derivatives. The synthesis of the above compounds involved the nucleophilic attack of the corresponding phenoxide, to the appropriate aminoalkylchloride hydrochloride under heating.
  
  
  RESULTS
  The double substituted adamantane derivatives with an aminoether side chain exhibit significant activity against Mycobacterium tuberculosis.
  
  
  CONCLUSIONS
  The length and the nature of the amino end of the side chain influence the antitubercular activity. The double phenolic substitution of the adamantane scaffold and the aminoether side chain with a three-methylene spacer between the phenoxy group and the nitrogen atom present the better results. (analogues 1f,g and 2e,f). These findings merit further investigation aiming at the design of more potent adamantane antituberculars, bearing a number of different substituents on the diarylmethane pharmacophore, which will also be translocated to other posititions on the adamantane ring.
authors.affiliation: School of Health Sciences, Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 157 84 Athens. Greece.
authors.forename: Angeliki-Sofia
authors.initials: AS
authors.lastname: Foscolos
authors.affiliation: Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimioupoli- Zografou, 157 84 Athens. Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papanastasiou
authors.affiliation: School of Health Sciences, Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 157 84 Athens. Greece.
authors.forename: Andrew
authors.initials: A
authors.lastname: Tsotinis
authors.affiliation: School of Health Sciences, Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 157 84 Athens. Greece.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Kolocouris
authors.affiliation: School of Health Sciences, Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 157 84 Athens. Greece.
authors.forename: George B
authors.initials: GB
authors.lastname: Foscolos
authors.affiliation: Global Health Institute, Ecole Polytechnique Federale de Lausanne, Station 19, 1015 Lausanne. Switzerland.
authors.forename: Anthony
authors.initials: A
authors.lastname: Vocat
authors.affiliation: Global Health Institute, Ecole Polytechnique Federale de Lausanne, Station 19, 1015 Lausanne. Switzerland.
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Cole
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D000588:Amines / Q000138:chemical synthesis / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D004977:Ethambutol / Q000494:pharmacology; D008956:Models, Chemical; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D012293:Rifampin / Q000494:pharmacology
chemical_list: D000588:Amines; D000995:Antitubercular Agents; D004977:Ethambutol; D000218:Adamantane; D012293:Rifampin
keywords: (Adamantane-2; (adamantane-1; 2-diyl) substitution; 3-diyl) substitution; Tuberculosis (TB); aminoethers; antitubercular activity; antitubercular chemotherapy