- Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors
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New analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were synthesized and evaluated for their in vitro activities against HIV-1 in MT-4 cell cultures. Chemical diversity was introduced in 4 of the six positions of the core and the influence of each substituent was studied. This library was built on the basis of a rational diversity analysis with the objective of maximizing diversity and thus, the activity range with a minimum number of synthesized compounds. Among them, 2{1,2,3,1} and 2{1,2,3,4} exhibited the most potent anti-HIV-1 activities (EC50 = 0.015 μg/mL; 0.046 μM, SI >1667) and (EC50 = 0.025 μg/mL; 0.086 μM, SI >1000), respectively, which were about 71-fold and 38-fold more active than the reference compound HEPT (EC50 = 1.01 μg/mL; 3.27 μM, SI >25).
- Puig-De-La-Bellacasa, Raimon,Gimenez, Laura,Pettersson, Sofia,Pascual, Rosalia,Gonzalo, Encarna,Este, Jose A.,Clotet, Bonaventura,Borrell, Jose I.,Teixido, Jordi
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experimental part
p. 159 - 174
(2012/09/05)
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- Synthesis and Antiviral Activity of Deoxy Analogs of 1--6-(phenylthio)thymine (HEPT) as Potent and Selective Anti-HIV-1 Agents
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The effect of substitution in the acyclic structure of 1--6-(phenylthio)thymine (HEPT) on anti-HIV-1 activity was investigated by synthesizing a series of deoxy analogs and related compounds.Preparation of 1-(2-alkyloxyethoxy)met
- Tanaka, Hiromichi,Takashima, Hideaki,Ubasawa, Masaru,Sekiya, Kouichi,Nitta, Issei,et al.
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p. 4713 - 4719
(2007/10/02)
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