Synthesis and antiviral activity of N-adamantyl-2-amino(or 2-phenoxy)-acylamides

Abstract

New N-adamantyl-2-amino-acylamides(3a–3f) and N-adamantyl-2-phenoxy-acetamides(6a–6d) were designed and synthesized by the modification of the amino group of amantadine 1 and the structures were confirmed by mass spectra(MS) and ¹H NMR spectra. The antiviral potencies of the synthesized compounds were evaluated against the replication of influenza virus A/H₃N₂ subtype in Madin-Darby canine kidney(MDCK) cells. Among the amantadine derivatives, compound 3a had the strongest antiviral potency and showed activity similar to that of amantadine. Interestingly, the bulky and extended lipophilic moieties on the α-position of the carbonyl group resulted in decreases in potency.

Keywords

N-Adamantyl-2-amino(or 2-phenoxy)-acylamide / Antiviral activity / M2 proton channel

References

[1] Peng S X. Progress in Medicinal Chemistry, 2011, Beijing: Chemical Industry Press 150.

[2] Shigeta S, Mori S, Kodama E, Kodama J, Takahashi K, Yamase T. Antiviral Res., 2003, 58(3): 265.

[3] Liu J, Mei W J, Li A X, Tan C P, Shi S, Ji L N. Chem. J. Chinese Universities, 2004, 25(1): 1.

[4] Schnell J R, Chou J J. Nature, 2008, 451: 591.

[5] Stouffer A L, Acharya R, Salom D, Levine A S, Costanzo L D, Soto C S, Tereshko V, Nanda V, Stayrook S, de Grado W F. Nature, 2008, 451: 596.

[6] Lipatov A S, Govorkova E A, Webby R J, Ozaki H, Peiris M, Guan Y, Poon L, Webster R G. J. Virol., 2004, 78: 8951.

[7] Kolocouris N, Foscolos G B, Kolocouris A, Marakos P, Pouli N, Fytas G, Ikeda S, de Clercq E. J. Med. Chem., 1994, 37: 2896.

[8] Kolocouris A, Spearpoint P, Martin S R, Hay A, López-Querol M, Sureda F X, Padalko E, Neyts J, de Clercq E. Bioorg. Med. Chem. Lett., 2008, 18: 6156.

[9] Stamatiou G, Kolocouris A, Kolocouris N, Fytas G, Foscolos G B, Neyts J, de Clercq E. Bioorg. Med. Chem. Lett., 2001, 11: 2137.

[10] Tataridis D, Fytas G, Kolocouris A, Fytas C, Kolocouris N, Foscolos G B, Padalko E, Neyts J, de Clercq E. Bioorg. Med. Chem. Lett., 2007, 17: 692.

[11] Zoidis G, Tsotinis A, Kolocouris N, Kelly J M, Prathalingam S R, Naesens L, de Clercq E. Org. Biomol. Chem., 2008, 6: 3177.

[12] Zoidis G, Kolocouris N, Naesens L, de Clercq E. Bioorg. Med. Chem., 2009, 17: 1534.

[13] Xiu Y J. Study on Syntheses of Natural Peptides Hirsutellide A and Tasiamide, 2004, Tianjin: Tianjin University.

[14] Zhao Y, Yao J S, Dai G, Hu J Q. J. Shandong Inst. Light Ind., 2009, 23(2): 6.

[15] Xie Y, Weng L L. West Chin. J. Pharm. Sci., 2005, 20(4): 310.