(3Z)-3-(2-[4-(aryl)-1,3-thiazol-2-yl]hydrazin-1-ylidene)-2,3-dihydro-1H-indol-2-one derivatives as dual inhibitors of HIV-1 reverse transcriptase.

Abstract

The HIV-1 Reverse Transcriptase (RT) is a validated and deeply explored biol. target for the treatment of AIDS. However, only drugs targeting the RT-assocd. DNA polymerase (DP) function have been approved for clin. use. We designed and synthesized a new generation of HIV-1 RT inhibitors, based on the (3Z)-3-(2-[4-(aryl)-1,3-thiazol-2-yl]hydrazin-1-ylidene)-2,3-dihydro-1H-indol-2-one scaffold. These compds. are active towards both RT-assocd. functions, DNA polymerase and RNase H. The structure, biol. activity and mode of action of the new derivs. have been investigated. In particular, the nature of the arom. group in the position 4 of the thiazole ring plays a key role in the modulation of the activity towards the two RT-assocd. functions. [on SciFinder(R)]