Synthesis of 2-(2-adamantyl)piperidines and structure anti-influenza virusA 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 bi ological activity. This dramatic reduction in biological activity may be at tributed to the different conformational properties between N-H and N-alkyl piperidines, as deduced from the combination of computational chemistry an d NMR spectroscopy. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.