Entry of human immunodeficiency type 1 virus (HIV-1) into target cells requires both CD

The design, synthesis and anti HIV-1 replication inhibition of 3-(cyclopropylethynyl)-3-hydroxy-indolin-2-ones, analogues of efavirenz (Sustivatrade mark), are described. Different substituted isatins were used to generate final products that contain pharmacophoric features for RT inhibition, such as the oxoindole and cyclopropylethynyl groups. The suitability of the indolin-2-one ring in the planned compounds in replacement to the benzoxazinone ring of efavirenz was proven, since compound 15 presented a greater activity than efavirenz against HIV-1 replication and was not significantly cytotoxic.

The trifluoromethyl group (CF 3 ) is present in commercially available drugs of various therapeutic classes owing to its ability to modify and frequently improve their biological activities. Efavirenz is a trifluoromethylated inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) that shows good results in anti-HIV chemotherapy. With the objective of developing efficient non-nucleoside compounds, we have designed and synthesized some new 3-hydroxy-2-oxo-3-trifluoromethylindole as potential RT inhibitors. We used different substituted isatins as starting materials. The final products contain the group CF 3 , present in Efavirenz, and a pharmacophoric group, oxoindole. We have used molecular docking with HIV-1 RT as a tool to design putative non-nucleoside reverse transcriptase inhibitors (NNRTIs). Based on the calculation results obtained, a series of new 3-hydroxy-2-oxo-3-trifluoromethylindoles were synthesized as a novel class of potential RT inhibitors. The results showed that these compounds are capable of important interactions with the NNRT binding site, which encouraged us

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