tetano
Editor, Senior Moderator
Bioorg Med Chem. 2015 Jun 18. pii: S0968-0896(15)00524-6. doi: 10.1016/j.bmc.2015.06.030. [Epub ahead of print]
[h=1]Stereoselective synthesis and pharmacological evaluation of [4.3.3]propellan-8-amines as analogs of adamantanamines.[/h] Torres-G?mez H[SUP]1[/SUP], Lehmkuhl K[SUP]1[/SUP], Frehland B[SUP]1[/SUP], Daniliuc C[SUP]2[/SUP], Schepmann D[SUP]1[/SUP], Ehrhardt C[SUP]3[/SUP], W?nsch B[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUB]N[/SUB]2 substitution of diastereomeric mesylates syn-14 and anti-14 with NaN[SUB]3[/SUB]. 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[SUB]i[/SUB]=11μM). 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.
Copyright ? 2015 Elsevier Ltd. All rights reserved.
[h=4]KEYWORDS:[/h] Amantadine; Antiviral activity; NMDA receptor; PCP binding site; Propellanamines; Stereoselective synthesis
PMID: 26145819 [PubMed - as supplied by publisher]
[h=1]Stereoselective synthesis and pharmacological evaluation of [4.3.3]propellan-8-amines as analogs of adamantanamines.[/h] Torres-G?mez H[SUP]1[/SUP], Lehmkuhl K[SUP]1[/SUP], Frehland B[SUP]1[/SUP], Daniliuc C[SUP]2[/SUP], Schepmann D[SUP]1[/SUP], Ehrhardt C[SUP]3[/SUP], W?nsch B[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUB]N[/SUB]2 substitution of diastereomeric mesylates syn-14 and anti-14 with NaN[SUB]3[/SUB]. 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[SUB]i[/SUB]=11μM). 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.
Copyright ? 2015 Elsevier Ltd. All rights reserved.
[h=4]KEYWORDS:[/h] Amantadine; Antiviral activity; NMDA receptor; PCP binding site; Propellanamines; Stereoselective synthesis
PMID: 26145819 [PubMed - as supplied by publisher]