(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

European Journal of Medicinal Chemistry
Rita MeledduElias Maccioni

Abstract

The HIV-1 Reverse Transcriptase (RT) is a validated and deeply explored biological target for the treatment of AIDS. However, only drugs targeting the RT-associated DNA polymerase (DP) function have been approved for clinical use. We designed and synthesised 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 compounds are active towards both RT-associated functions, DNA polymerase and ribonuclease H. The structure, biological activity and mode of action of the new derivatives have been investigated. In particular, the nature of the aromatic group in the position 4 of the thiazole ring plays a key role in the modulation of the activity towards the two RT-associated functions.

References

Oct 1, 1974·Canadian Journal of Biochemistry·B R Glick, L J Brubacher
Apr 6, 2004·Biochemical and Biophysical Research Communications·Julie Qi HangKlaus Klumpp
Oct 14, 2005·Journal of Medicinal Chemistry·Richard Morphy, Zoran Rankovic
May 27, 2006·Current Pharmaceutical Design·Klaus Klumpp, Tara Mirzadegan
Jun 22, 2006·Mini Reviews in Medicinal Chemistry·Enzo Tramontano
Jun 14, 2008·The Journal of Infectious Diseases·Martin S Hirsch
Jun 19, 2009·Medicinal Chemistry·Kharlamova TatyanaTramontano Enzo
Sep 15, 2009·Current Medicinal Chemistry·Peng ZhanErik De Clercq
Sep 30, 2009·Journal of Medicinal Chemistry·Youcef Mehellou, Erik De Clercq
Sep 23, 2010·Current Medicinal Chemistry·E Tramontano, R Di Santo
Apr 6, 2011·Antimicrobial Agents and Chemotherapy·Eric B LansdonThorsten A Kirschberg
Oct 25, 2012·Current Pharmaceutical Design·Simona DistintoEnzo Tramontano
May 11, 2013·Journal of Medicinal Chemistry·Steven J TaylorHidenori Takahashi
Oct 8, 2013·European Journal of Medicinal Chemistry·Parameshwar MakamTharanikkarasu Kannan
Oct 24, 2013·European Journal of Medicinal Chemistry·Variam Ullas JeankumarDharmarajan Sriram
Nov 23, 2013·Future Medicinal Chemistry·Angela CoronaStuart F J Le Grice
Aug 11, 2011·ACS Medicinal Chemistry Letters·Stefano CrosignaniAndré Chollet
Aug 6, 2014·Antimicrobial Agents and Chemotherapy·Angela CoronaEnzo Tramontano

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Citations

Oct 22, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Rita MeledduElias Maccioni
Oct 25, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Claudia MelisElias Maccioni
Feb 18, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Adriana GrozavDaniela Hanganu
Dec 20, 2016·Chembiochem : a European Journal of Chemical Biology·Riccardo MartiniMaurizio Botta
Oct 27, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Serena MassariOriana Tabarrini
Mar 19, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Angela CoronaEnzo Tramontano
May 1, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Wagdy M EldehnaMohamed I Attia
Sep 25, 2019·Antiviral Research·Enzo TramontanoLuis Menéndez-Arias
Apr 12, 2021·Bioorganic & Medicinal Chemistry Letters·Vijai Kumar Reddy TangadanchuCheng-He Zhou
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rita MeledduElias Maccioni

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