Abstract
The syntheses of hydroxyethylsulfonamides, (2S,3R)-tert-butyl N-[4-(N-benzyl-4-R-phenylsulfonamido)-3- hydroxy-1-phenylbutan-2-yl]carbamates and (5) (2S,3R)-2-amino-4-[N-benzyl-4-R-benzenesulfonamido]-3-hydroxy-1- phenylbutane hydrochlorides (6), derived from (2S,3S)-Boc-phenylalanine epoxide, are reported. None of the compounds, containing the Boc group, showed activity against M. tuberculosis ATTC 27294, while compounds 6 did, with the most active compounds having R = p-Cl, p-Br and p-Me. Results indicate that the presence of a free amino group at C2 and the sulphonamide moiety are important for biological activity. The antimycobacterial activity of compounds 6 correlated well with the calculated lipophilicities, but not with the electronic effects of the substituents, R. All compounds 6 were highly cytotoxic against the hepatoma cell lineage Hep G2 A16. The X-ray crystal structure of compound [(6: R = Me).H2O] is also reported. In the propeller-like conformation adopted by the cation, the amino and hydroxy groups have a cis arrangement, and thus are suitably placed to form 5- membered chelates.
Keywords: Antimycobacterial activity, cytotoxicity, hydroxyethylamine derivatives, sulfonamide derivatives, x-ray crystallography.
Medicinal Chemistry
Title:Syntheses and Antimycobacterial Activities of [(2S,3R)-2-(Amino)-4- (Arenesulfonamido)-3-Hydroxy-1-Phenylbutane Derivatives
Volume: 10 Issue: 2
Author(s): Marcele Moreth, Claudia R.B. Gomes, Maria C.S. Lourenco, Rodrigo P. Soares, Marcele N. Rocha, Carlos R. Kaiser, Marcus V.N. de Souza, Solange M.S.V.N. Wardell and James L. Wardell
Affiliation:
Keywords: Antimycobacterial activity, cytotoxicity, hydroxyethylamine derivatives, sulfonamide derivatives, x-ray crystallography.
Abstract: The syntheses of hydroxyethylsulfonamides, (2S,3R)-tert-butyl N-[4-(N-benzyl-4-R-phenylsulfonamido)-3- hydroxy-1-phenylbutan-2-yl]carbamates and (5) (2S,3R)-2-amino-4-[N-benzyl-4-R-benzenesulfonamido]-3-hydroxy-1- phenylbutane hydrochlorides (6), derived from (2S,3S)-Boc-phenylalanine epoxide, are reported. None of the compounds, containing the Boc group, showed activity against M. tuberculosis ATTC 27294, while compounds 6 did, with the most active compounds having R = p-Cl, p-Br and p-Me. Results indicate that the presence of a free amino group at C2 and the sulphonamide moiety are important for biological activity. The antimycobacterial activity of compounds 6 correlated well with the calculated lipophilicities, but not with the electronic effects of the substituents, R. All compounds 6 were highly cytotoxic against the hepatoma cell lineage Hep G2 A16. The X-ray crystal structure of compound [(6: R = Me).H2O] is also reported. In the propeller-like conformation adopted by the cation, the amino and hydroxy groups have a cis arrangement, and thus are suitably placed to form 5- membered chelates.
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Moreth Marcele, Gomes R.B. Claudia, Lourenco C.S. Maria, Soares P. Rodrigo, Rocha N. Marcele, Kaiser R. Carlos, de Souza V.N. Marcus, Wardell M.S.V.N. Solange and Wardell L. James, Syntheses and Antimycobacterial Activities of [(2S,3R)-2-(Amino)-4- (Arenesulfonamido)-3-Hydroxy-1-Phenylbutane Derivatives, Medicinal Chemistry 2014; 10 (2) . https://dx.doi.org/10.2174/15734064113099990003
DOI https://dx.doi.org/10.2174/15734064113099990003 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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