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Design and Synthesis of Cysteine Protease Inhibitors †

Department de Química Inorgànica i Orgànica, Universitat Jaume I, 12071 Castelló, Spain
Presented at the 1st Molecules Medicinal Chemistry Symposium, Barcelona, Spain, 8 September 2017.
Proceedings 2017, 1(6), 672;
Published: 18 October 2017
We have been preparing new dipeptidyl inhibitors against parasitic cysteine proteases cruzain (related to Chagas disease) and rhodesain (related to Sleeping Sickness disease), and against human cathepsins. Inhibitors display new warheads embedded into a dipeptidic framework. Dipeptidyl epoxyesters [1] and Dipeptidyl enoates [2] are highly potent irreversible inhibitors of cruzain and rhodesain. We also prepared an oxidized version of well-known Vinylsulfones (Epoxysulfones [3]) as inhibitors of human cathepsins. Recently, we have reported the synthesis of Dipeptidyl nitroalkenes [4] as a new type of highly potent covalent reversible inhibitors of cysteine proteases exhibiting certain selectivity for the parasitic cysteine proteases rhodesain and cruzain.


The author thanks Generalitat Valenciana (AICO/2016/32) for financial support.

Conflicts of Interest

The author declares no conflict of interest.


  1. González, F.V.; Izquierdo, J.; Rodríguez, S.; McKerrow, J.H.; Hansell, E. Dipeptidyl α,β-Epoxyesters as Potent Irreversible Inhibitors of the Cysteine Proteases Rhodesain and Cruzain. Bioorg. Med. Chem. Lett. 2007, 17, 6697–6700. [Google Scholar] [CrossRef] [PubMed]
  2. Royo, S.; Rodríguez, S.; Schirmeister, T.; Kesselring, J.; Kaiser, M.; González, F.V. Dipeptidyl Enoates as Potent Rhodesain Inhibitors that display a Dual Mode of Action. Chem. Med. Chem. 2015, 10, 1484–1487. [Google Scholar] [CrossRef] [PubMed]
  3. Latorre, A.; Rodríguez, S.; González, F.V.; Florea, B.I.; Overkleeft, H.S. Synthetic Studies on the Preparation of Alanyl Epoxysulfones as Cathepsin Cysteine Protease Electrophilic Traps. J. Org. Chem. 2015, 80, 7752–7756. [Google Scholar] [CrossRef] [PubMed]
  4. Latorre, A.; Schirmeister, T.; Kesselring, J.; Jung, S.; Johé, P.; Hellmich, U.A.; Heilos, A.; Engels, B.; Krauth-Siegel, R.L.; Dirdjaja, N.; et al. Dipeptidyl Nitroalkenes as Potent Reversible Inhibitors of Cysteine Proteases Rhodesain and Cruzain. ACS Chem. Med. Lett. 2016, 12, 1073–1076. [Google Scholar] [CrossRef] [PubMed]
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MDPI and ACS Style

Gonzalez, F.V. Design and Synthesis of Cysteine Protease Inhibitors. Proceedings 2017, 1, 672.

AMA Style

Gonzalez FV. Design and Synthesis of Cysteine Protease Inhibitors. Proceedings. 2017; 1(6):672.

Chicago/Turabian Style

Gonzalez, Florenci V. 2017. "Design and Synthesis of Cysteine Protease Inhibitors" Proceedings 1, no. 6: 672.

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