期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 23, 期 15, 页码 4277-4285出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2015.06.030
关键词
NMDA receptor; PCP binding site; Antiviral activity; Amantadine; Propellanamines; Stereoselective synthesis
资金
- NRW Graduate School of Chemistry
- Government of the State Nordrhein-Westfalen
- Westfalische Wilhelms-Universitat Munster, Germany
Amantadine (1) exerts its anti-Parkinson effects by inhibition of the NMDA associated cation channel and its antiviral activity by inhibition of the M2 protein channel of influenza A viruses. Herein the synthesis, NMDA receptor affinity and anti-influenza activity of analogous propellanamines 3 are reported. The key steps in the synthesis of the diastereomeric propellanamines syn-3 and anti-3 are diastereoselective reduction of the ketone 7 with L-Selectride to give anti-11, Mitsunobu inversion of the alcohol anti-13 into syn-13, and S(N)2 substitution of diastereomeric mesylates syn-14 and anti-14 with NaN3. The affinity of the propellanamines syn-3 and anti-3 to the PCP binding site of the NMDA receptor is similar to that of amantadine (K-i = 11 mu M). However, both propellanamines syn-3 and anti-3 do not exhibit activity against influenza A viruses. Compared to amantadine (1), the structurally related propellanamines syn-3 and anti-3 retain the NMDA antagonistic activity but loose the antiviral activity. (C) 2015 Elsevier Ltd. All rights reserved.
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