title: Design and synthesis of bioactive 1,2-annulated adamantane derivatives.
abstract: Adamantanopyrrolidines 8, 9 and 10, adamantanopyrrolidines 16 and 18, adamantanoxazolone 20, adamantanopyrazolone 23, adamantanopyrazolothione 24 and adamantanocyclopentanamine 32 were synthesized and tested for anti-influenza A virus and trypanocidal activity. The stereoelectronic requirements for optimal antiviral and trypanocidal potency were investigated. Pyrrolidine 16 proved to be the most active of the compounds tested against influenza A virus, being 4-fold more active than amantadine, equipotent to rimantadine and 19-fold more potent than ribavirin. Oxazolone 20 showed significant trypanocidal activity against bloodstream forms of the African trypanosome, Trypanosoma brucei, being approximately 3 times more potent than rimantadine and almost 50-fold more active than amantadine.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, GR-15771, Athens, Greece.
authors.forename: Grigoris
authors.initials: G
authors.lastname: Zoidis
authors.forename: Andrew
authors.initials: A
authors.lastname: Tsotinis
authors.forename: Nicolas
authors.initials: N
authors.lastname: Kolocouris
authors.forename: John M
authors.initials: JM
authors.lastname: Kelly
authors.forename: S Radhika
authors.initials: SR
authors.lastname: Prathalingam
authors.forename: Lieve
authors.initials: L
authors.lastname: Naesens
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000547:Amantadine / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D015195:Drug Design; D053122:Influenza A Virus, H3N2 Subtype / Q000472:pathogenicity; D009976:Orthomyxoviridae Infections / Q000188:drug therapy; D012254:Ribavirin / Q000627:therapeutic use; D012299:Rimantadine / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D013552:Swine; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects; D014353:Trypanosomiasis, African / Q000188:drug therapy; D014763:Viral Matrix Proteins / Q000378:metabolism; D000086082:Viroporin Proteins
chemical_list: D000547:Amantadine; D000998:Antiviral Agents; D012254:Ribavirin; D012299:Rimantadine; D014344:Trypanocidal Agents; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins