Lew and Kim

Lew and Kim [66] recently synthesized a sulfide isostere of carbocyclic influenza neuraminidase inhibitor 268, moving from trityl protected aziridine 266, in turn prepared from (-)-quinic acid 159 (Scheme 43). Ring opening of 266 with 1-propanethiol promoted by BF3 etherate, followed by acetylation, gave sulfide 267 which was finally hydrogenated to diamine 268, in a good chemical yield. As the authors expected, mercapto-derivative 268 resulted to be a strong inhibitor of... 

Lew, W., Chen, X. and Kim, C.U. (2000) Discovery and development of GS 4104 (oseltamivir) an orally active influenza neuraminidase inhibitor. Current Medicinal Chemistry, 7, 663-672. 

Kim CU, Lew W, Wilhams MA, Liu H, Zhang L, Swaminathan S, Bischofberger N, Chen MS, Mendel DB, Tai CY, Laver WG, Stevens RC (1997) Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity. J Am Chem Soc 119 681-690... 

W. Lew, M. A. Williams, D. B. Mendel, P. A. Escarpe, and C. U. Kim, C3-Thia and C3-carba isosteres of a carbocyclic influenza neuraminidase inhibitor, (3R,4R,5R)-4-acetamido-5-amino-3-propoxy-l-cyclohexene-l-carboxylic acid, Bioorg. Med. Chem. Lett., 7 (1997) 1843-1846. 

Mendel DB, Tai CY, Escarpe PA, Li W, Sidwell RW, Huffman JH, Sweet C, Jakeman KJ, Merson J, Lacy SA, Lew W, Williams M A, Zhang L, Chen MS, Bischofberger N, Kim CU. Oral administration of a prodrug of the influenza virus neuraminidase inhibitor GS 4071 protects mice and ferrets against influenza infection. Antimicrob Agents Chemother 1998 42 640-646. 

Kim, Y.A., Xiao, D., Xiao, H., Powolny, A.A., Lew, K.L, Reilly, M.L., Zeng, Y., Wang, Z., and Singh, S.V, 2007. Mitochondria-mediated apoptosis by diaflyl trisulfide in human prostate cancer cells is associated with generation of reactive oxygen species and regulated by Bax/... 

---