Synthesis of diphenoxyadamantane alkylamines with pharmacological interest

Markos-Orestis Georgiadis; Violeta Kourbeli; Vaya Ioannidou; Evangelos Karakitsios; Ioannis Papanastasiou; Andrew Tsotinis; Dimitri Komiotis; Anthony Vocat; Stewart T Cole; Martin C Taylor; John M Kelly

doi:10.1016/j.bmcl.2019.04.010

Synthesis of diphenoxyadamantane alkylamines with pharmacological interest

Bioorg Med Chem Lett. 2019 Jun 1;29(11):1278-1281. doi: 10.1016/j.bmcl.2019.04.010. Epub 2019 Apr 6.

Affiliations

¹ School of Health Sciences, Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 157 84 Athens, Greece.
² School of Health Sciences, Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 157 84 Athens, Greece. Electronic address: papanastasiou@pharm.uoa.gr.
³ Department of Biochemistry and Biotechnology, Laboratory of Bioorganic Chemistry, University of Thessaly, 41221 Larissa, Greece.
⁴ Global Health Institute, École Polytechnique Fédérale de Lausanne, Station 19, 1015 Lausanne, Switzerland.
⁵ Global Health Institute, École Polytechnique Fédérale de Lausanne, Station 19, 1015 Lausanne, Switzerland; Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris Cedex 15, France.
⁶ Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1 E7HT, UK.

PMID: 30981579
DOI: 10.1016/j.bmcl.2019.04.010

Abstract

In this work, the synthesis and the pharmacological evaluation of diphenoxyadamantane alkylamines Ia-f and IIa-f is described. The new diphenoxy-substituted adamantanes share structural features present in trypanocidal and antitubercular agents. 1-Methylpiperazine derivative Ia is the most potent against T. brucei compound, whilst its hexylamine congener IIf exhibits a significant antimycobacterial activity.

Keywords: Aminoalkane side chain; Antimycobacterial activity; Diphenoxyadamantane; Substituted piperazine; Trypanocidal activity.

MeSH terms

Adamantane / analogs & derivatives
Adamantane / chemistry
Adamantane / pharmacology*
Amines / chemical synthesis
Amines / chemistry
Amines / pharmacology*
Antitubercular Agents / chemical synthesis
Antitubercular Agents / chemistry
Antitubercular Agents / pharmacology*
Dose-Response Relationship, Drug
Molecular Structure
Mycobacterium tuberculosis / drug effects*
Parasitic Sensitivity Tests
Structure-Activity Relationship
Trypanocidal Agents / chemical synthesis
Trypanocidal Agents / chemistry
Trypanocidal Agents / pharmacology*
Trypanosoma brucei brucei / drug effects*

Substances

Amines
Antitubercular Agents
Trypanocidal Agents
Adamantane