MEDI 96 |
| To enhance anti-HIV efficacy, duration of action, and uptake into infected cells, and resistance profile of 3'-thia-2',3'-dideoxycytidine (1, 3TC, lamivudine), a number of fatty acyl derivatives of 3TC were synthesized and evaluated. Two disubstituted, three 4-amino monosubstituted, and three 5'-O-ester derivatives of 3TC were synthesized. 5'-Hydroxyl group of 3TC was protected in the presence of tert-butyldimethylsilyl chloride to afford 4 that was converted to 4-amino monosubstituted derivatives (8-10). Furthermore, the protection of N4-amino group in 4 in the presence of DMTr-Cl, the deprotection of 5'-O-TBDMS in the presence of TBAF, esterification of 5'-hydroxyl group in the presence of fatty acids, HBTU and NMM, followed by the cleavage of N4-DMTr group with acetic acid afforded 5'-O-fatty acyl derivatives of 3TC (16-18). 3TC was also reacted with fatty acids to give disubstituted derivatives (2 and 3). The N4 or 5'-OH monosubstituted derivatives possessed comparable and, in some cases, better potency than 3TC.
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Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster
Sci-Mix
Division of Medicinal Chemistry |
