Synthesis and <i>in vitro</i> study of novel borneol derivatives as potent inhibitors of the influenza A virus.
Sokolova AS, Yarovaya OI, Semenova MD, Shtro AA, Orshanskaya IR, Zarubaev VV, Salakhutdinov NF.
Herein, we present the design and synthesis of a series of novel heterocyclic derivatives of (-)-borneol and (-)-isoborneol as potent inhibitors of the influenza A virus. All compounds were tested for their toxicity against MDCK cells and for virus-inhibiting activity against the influenza virus A/Puerto Rico/8/34 (H1N1). Compounds <b>7</b>, <b>16</b> and <b>26</b> containing a morpholine fragment exhibited the highest efficiency as agents inhibiting the replication of the influenza virus A(H1N1) with selectivity indices of 82, 45 and 65, correspondingly. Derivatives <b>9</b> (SI = 23) and <b>18</b> (SI = 25) containing a 1-methylpiperazine motif showed moderate antiviral activity. Structure-activity analysis of this new series of borneol derivatives revealed that a 1,7,7-trimethylbicyclo[2.2.1]heptan scaffold is required for the antiviral activity.