Synthesis of 2-(2-adamantyl)piperidines and structure anti-influenza virus A activity relationship study using a combination of NMR spectroscopy and molecular modeling.
The 2-(2-adamantyl)piperidines 13 and 15a-c were synthesized and evaluated for anti-influenza virus A and B activity. The parent N-H compound 13 was 3-4 times more active than amantadine and rimantadine against H2N2 influenza A. N-alkylation of 13 resulted in derivatives 15a-c that were devoid of biological activity. This dramatic reduction in biological activity may be attributed to the different conformational properties between N-H and N-alkyl piperidines, as deduced from the combination of computational chemistry and NMR spectroscopy.
Kolocouris
A
A
National Hellenic Research Foundation, Institute of Organic and Pharmaceutical Chemistry, Athens, Greece.
Tataridis
D
D
Fytas
G
G
Mavromoustakos
T
T
Foscolos
G B
GB
Kolocouris
N
N
De Clercq
E
E
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D004285:Dogs; D009980:Influenza A virus / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000998:Antiviral Agents; D010880:Piperidines