Design and synthesis of bioactive 1,2-annulated adamantane derivatives.
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.
Zoidis
Grigoris
G
Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, GR-15771, Athens, Greece.
Tsotinis
Andrew
A
Kolocouris
Nicolas
N
Kelly
John M
JM
Prathalingam
S Radhika
SR
Naesens
Lieve
L
De Clercq
Erik
E
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
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