Research overview

Medicinal Chemistry is a multi-disciplinary field of study that utilizes synthetic organic chemistry in conjunction with developments in biochemistry, computational chemistry, molecular biology, and pharmacology to advance drug discovery.

In our laboratory problems at the chemistry-life sciences interface are addressed. A large part of our work concentrates on the development of small molecule modulators of new (i.e., yet unexplored) targets. These modulators can be both enabling chemical tools to interrogate biology or therapeutically useful compounds. From a chemical point of view, much of our work is centred on the chemical synthesis of novel nucleoside and sphingolipid analogues.

Our research interest also includes carbohydrate, phosphonate and bioconjugate chemistry. Several of the running projects deal with the design of new lead structures for the treatment of infectious diseases with unmet medical needs (e.g. malaria and TB).

Research topics

Scientific awards

Dr. Fabain Hulpia wins UGent Katritzky award for organic synthesis (Blankenberge, Belgium 2019) and poster price at the VIII EFMC-ASMC 2019 Medicinal Chemistry Symposium (Athens, Greece 2019)

Jakob Buton wins best multimedia poster award at the IX meeting of the Paul Ehrlich Euro-PhD Network 2019, Catanzaro, Italy

Dr. Thomas Verbrugghen is the 2014 laureate of the Janssen R&D prize. This prize is  awarded biannually for the best PhD thesis in Flanders in the field of Medicinal Chemistry of the last two years.

J&JRD prize for medicinal chemistry for Mathias Trappeniers for best thesis in the Medicinal Chemistry area at a Flemish institution during the November 09-October 11 period (€ 1000; 2012).

Thomas Verbrugghen and Nora Pauwels win the awards for best oral and poster presentation in the section Medicinal Chemistry and Pharmacy on the 10th Flemish Youth Conference of Chemistry (VJC10) in Blankenberge (1-2 March, 2010)

Matthias Trappeniers wins travel scholarship for 5th International Symposium on CD1/NKT Cells (100,000 JPY, 2009)

Prize of the of the Royal Belgian Academy of Medicine (5th division; 2003 – 2005) for SVC for his contribution on the “Structure-Aided design of inhibitors of Mycobacterium tuberculosis thymidylate kinase” (€ 2500; 2005)

KVCV-award (Royal Flemish Chemical Society) for oral presentation of Ineke Van Daele on young-KVCV conference (VJC8, 2006)

J&JRD prize for medicinal chemistry for Veerle Vanheusden for best thesis in the Medicinal Chemistry area at a Flemish institution during the November 03-October 05 period (€ 1000; 2005).

KVCV-award (Royal Flemish Chemical Society) for oral presentation of Philippe Van Rompaey on young-KVCV conference (VJC7, 2004)

Young Faculty Poster Award at the XVI International Roundtable of the IS3NA in Minneapolis for SVC with credits to Ineke and Veerle ($ 500; 2004).

KVCV-award (Royal Flemish Chemical Society) for oral presentation of Steven De Jonghe on young-KVCV conference (19??)

SVC is Laureate of a NATO postdoctoral research fellowship (225.000 BEF, 1996)

KVCV-award (Royal Flemish Chemical Society) for oral presentation of SVC on young-KVCV conference (VJC2, 1994)

Inhibitors of the non-mevalonate pathway

A mevalonate independent pathway of isoprenoid biosynthesis, the so-called DOXP pathway, has been discovered recently and validated as new drug target. Most bacteria, but also P. falciparum, seem to use this pathway to produce isoprenoids. In a joint project we are aiming to develop inhibitors of selected enzymes of the DOXP pathway as new antimalarial or antibacterial agents. Initially, we focused on DOXP reducto-isomerase (DR). Starting from the structure of fosmidomycin, an interesting lead inhibitor of this enzyme, we have synthesized several analogues that exhibit comparable or even improved inhibitory activity, both on the enzyme level as in vitro on P. falciparum.

project 3

Currently, we are also designing inhibitors for two enzymes that catalyze the last two steps of the DOXP patway, i.e., GcpE and LytB. Since these enzymes contain oxygen-sensitive iron-sulphur clusters, a screening assay under anaerobic conditions had to be developed by our partner in Giessen.
Inhibitors can be anticipated to display activity against a variety of bacterial and protozoan pathogens.

Superposition of a home-made conformationally restricted fosmidomycin analogue (in gold) with fosmidomycin (in grey) in its enzyme-bond conformation. The purple ball represents a Mg-ion.

Researchers: René Chofor, Charlotte Courtens

Collaborators: Prof. T. Alwyn Jones & Prof. Sherry L. Mowbray

M. tuberculosis thymidylate kinase inhibitors


In search for better TB drugs we  have synthesized a number of promising inhibitors of M. tuberculosis thymidine monophosphate (thymidylate) kinase (TMPKmt), an attractive target for blocking mycobacterial DNA synthesis. The 3D structure of this enzyme proved a valuable tool for inhibitor design. Unfortunately, translating these inhibitors into leads with in vitro antimycobacterial activity was not obvious.

Recently, two series of thymidine analogues that were originally designed as TMPKmt inhibitors, were evaluated for their inhibitory activity against a panel of other nucleoside kinases (TK-1, TK-2, HSV-1 and VZV TK). Several substituted 3’-thiourea derivatives of β-dThd proved highly inhibitory to and exquisitely selective for human mitochondrial TK-2 (IC50: 0.15-3.1 µM) compared to the other enzymes. In fact, TK-2 was inhibited at concentrations at least 3 orders of magnitude lower than those required to inhibit cytosolic TK-1. These analogues showed competitive inhibition of TK-2 when dThd was used as the variable substrate, but uncompetitive inhibition of the enzyme in the presence of variable concentrations of ATP, which suggests specific binding of the inhibitor to an enzyme–ATP complex. These kinetic properties against TK-2 could be accounted for by molecular modeling results showing that two hydrogen bonds can be formed between the thiourea nitrogens and the oxygens of the γ-phosphate of the co-substrate ATP.


Proposed binding mode of a 3’-thiourea derivative of β-thymidine (C atoms in white)  in the active site of human TK-2 (pink ribbon).

Human mitochondrial TK-2 catalyses the phosphorylation of pyrimidine deoxynucleosides to the corresponding deoyxnucleoside 5’-monophosphate analogues.  In resting cells TK-2 is the most important thymidine phosphorylating enzyme. TK-2  is suggested to play a key role in the mitochondrial salvage pathway in which nucleotides are provided for mtDNA synthesis. Since long-term treatment with antiviral nucleoside analogues such as AZT and FIAU has been associated with severe mitochondrial toxicity, it is assumed that TK-2 is involved in their toxicity. In this respect, TK-2 inhibitors could be valuable tools to unravel the role of TK-2 in mitochondrial dNTP pools and homeostasis and may also help to clarify the contribution of TK-2 activity to mitochondrial toxicity of certain antivirals.

In addition, a striking close correlation was found between the inhibitory activities of the test compounds against TK-2 and Mycobacterium tuberculosis thymidylate kinase that is strongly indicative of close structural and/or functional similarities between both enzymes in relation to their mode of interaction with these nucleoside analogue inhibitors.

Currently, we are constructing new thymidine analogues to optimize TK-2 inhibition, to further explore the SAR for TK-2 inhibition and to validate the homology models of TK-2.

Researchers: Charlotte Courtens
TK-2: Jan Balzarini (Rega Institute, Leuven),
Federico Gago (Universidad de Alcalá, Madrid, Spain), Anna Karlsson (The Karolinska Institute, Huddinge, Sweden)
Hélène Munier-Lehmann (Institut Pasteur, Paris), Mathy Froeyen (Rega Institute, Leuven)

P2Y2 receptor ligands


The P2 nucleotide receptors are subdivided into a subfamily of ligand-gated ion channels (P2X receptors) activated by ATP and a family of GPCRs that consists of at least eight members including the P2Y2 receptor which is expressed in epithelial cells, smooth-muscle cells, endothelial cells, leukocytes, osteoblast and cardiomyocytes. P2Y2 receptors were found to be implicated in a variety of pathophysiological states such as lung diseases, cancer progression as well as vascular, inflammatory and immune diseases. Agonists could be interesting for the symptomatic treatment of cystic fibrosis and dry eye syndrome. The natural ligand UTP, as well as most reported analogs, are liable to enzymatic degradation at the surface of the air-ways. This results in a relative short time of action when these molecules are administered by inhalation.

Recently, we synthesized a UTP analogue (MRS2698) that combines a 2’-amino and a 2-thio modification. These modifications synergized to enhance potency and selectivity (EC50 of 8 nM and 300-fold selectivity for P2Y2 versus P2Y4).


We’ re engaged to discover new P2Y2 receptor agonists with a high affinity and selectivity but also with an increased metabolic stability.


Collaborators: Ken Jacobson (Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, NIH, Bethesda, MD)

MTX conjugates for identification of new targets using MASPIT


The number of therapeutic targets that the modern pharmacopoeia acts on is surprisingly small (ca. 500) and only a small fraction of the recently approved drugs interferes with new target families.

This project aims to explore MASPIT, a 3-hybrid variant developed in the Cytokine Receptor Laboratory (CRL), for the identification of novel intracellular therapeutic targets.

In MASPIT a dihydrofolate reductase fusion protein forms a high affinity binding site for the methotrexate (MTX) part of a MTX–“bait” conjugate, allowing to present a “bait” compound to the intracellular environment. A “bait”–“prey” interaction activates the JAK2-STAT3 signalization and can be easily detected via a reporter protein (e.g., luciferase), whose expression is controlled by a STAT3-responsive promoter.



Overview of the MASPIT system

Our role in this project involves the synthesis of versatile MTX building blocks which will be used for the construction of MTX–“bait” conjugates of a series of therapeutically interesting small molecules.

Identification of new intracellular targets may feed new target-based drug discovery projects.

ResearcherDr. Martijn Risseeuw

Collaborators: Prof. Jan Tavernier, Dr. Sam Lievens (Cytokine Receptor Laboratory, UGent)




alpha-Galactosylceramide analogues

The processing and presentation of lipid antigens by antigen presenting cells (APC) is important for defense against infection, tumor immunosurveillance and autoimmunity. During the past years the use of glycolipids as immunostimulating agents has become increasingly important. When presented by the major histocompatibility complex (MHC) class I-like molecule CD1d, certain glycolipids are recognized by the semi-invariant T cell receptors (TCR) of natural killer T (NKT) cells. The prototypical antigen for NKT cells is a-galactosylceramide (a-GalCer), which was obtained by structural optimization of agelasphins (a-linked glycosphingolipids isolated from a marine sponge). Upon recognition of the CD1d-a-GalCer bimolecular complex by their TCR, NKT cells are activated, resulting in the rapid release of T helper 1 (Th1) and T helper 2 (Th2) cytokines.  As both Th1 and Th2 cytokines influence the outcome of different immune responses, disruption of the carefully controlled Th1/Th2 balance can lead to disease induction and progression.


While certain autoimmune diseases are characteristic of hyporesponsiveness to Th2 and overactivation of pathogenic Th1 cells, the opposite is true for many types of cancer that have a predominant Th2 response. Hence, a-GalCer analogues that induce a biased Th1/Th2 response are highly awaited.

Most of the known a-GalCer analogues able to induce polarized cytokine responses are characterized by modifications of the phytosphingosine or fatty acyl chains, expected to alter the affinity for CD1d.

Recently, we identified a series of 6’-derivatized a-GalCer analogues with an intact phytoceramide moiety, which are capable of skewing the cytokine release profile to Th1 and possess a comparable ability to induce INF-γ secretion as a-GalCer. In contrast to modifications of other Gal OH-groups, these analogues clearly retain antigenic activity.


Synthetic efforts to further expand the structure–activity relationship (SAR) and to improve our understanding of the structural requirements for optimal and skewed natural killer T-cell activation are ongoing, while collaborations are established to explore the potential of our analogues to treat malignant diseases.

Researcher: Joren Guillaume, Jonas Janssens

Collaborators: Sandrine Aspeslagh, Dirk Elewaut (Dept. of Internal Medicine, UGent),
Dr. Bruno Linclau (School of Chemistry, University of Southampton)

Portfolio of hits


This N-(3’-deoxythymidin-3’-yl)-1-substituted-1H-tetrazol-5-arylamine with a 5-(2-bromovinyl) substituent is the most potent and selective mithondrial thymidine kinase (TK-2) inhibitor reported so far (IC50 = 14 nM; Org. Biomol. Chem. 2011, 9, 892-901)


NU-α-GalCer, a Th1 biasing NKT cell agonist that occupies an extra binding pocket in mCD1d through induced fit (J. Am. Chem. Soc. 2008, 130, 16468-16469; EMBO J. 2011, 30, 2294-2305)


This α-thymidine derivative, featuring a 5’-(3-trifluoromethyl-4-chlorophenyl)-
thiourea moiety, was the first M. tuberculosis TMPK inhibitor (Ki of 0.6 µM) showing good inhibitory activity on growing M. bovis and M. tuberculosis, thereby promoting mycobacterial TMPK as an attractive target for inhibitor design (J. Med. Chem. 2007, 50, 5281-5292)


2’-Amino-2’-deoxy-2-thioUTP, most potent and selective P2Y2 agonist reported so far (J. Med. Chem. 2007, 50, 1166-1176)


α-Dichlorophenyl analogue of fosmidomycin that exhibits significantly improved in vitro antimalarial activity than fosmidomycin (Bioorg. Med. Chem. Lett. 2006, 16, 1888-1891)


Hypermodified adenosine analogue with potent (Ki = 1.8 nM) fully agonistic A3AR activity and high A3/A1 selectivity (J. Med. Chem. 2006, 49, 7373-7383)


Traditional approaches to treat diseases typically utilize a chemical agent to modulate the activity of (a) selected protein(s), e.g. enzyme inhibitors. A different approach utilizing Proteolysis Targeting Chimeras (PROTACs) was developed by the group of Craig Crews at Yale university.[1-2] This involves the active and specific lowering of the cellular abundance of proteins resulting in a reduction of their harmful activities. To achieve this, it employs the cellular Ubiquitin-Proteasome-System, which has been shown to degrade proteins that have been (poly)ubiquitinated.[3]






Figure 1: Mechanism of PROTAC mediated protein degradation.

Selective forced Ubiquitination of the offending proteins is achieved by the application of PROTACs: heterodimeric ligands built up from an E3-ligase ligand, a ligand for the target protein and a linker moiety connecting the two ligands. A PROTAC will thus induce the formation of a ternary complex  with an E3-ligase and the target protein, thereby inducing (by proximity) (poly)ubiquitination of the target protein. This polyubiquitin tag acts as a signal for degradation of the protein by the proteasome after which the PROTAC is released again in the cytosol. Here it can act in successive cycles of trimerization and ubiquitination. PROTACs can thus be considered catalytic in nature.


















Table 1: PROTAC toolkit reagents

In our research, we utilize PROTACs as tools in the fields of oncology and immunology. To enable expedient PROTAC synthesis we have designed and synthesized a toolkit of general purpose PROTACs reagents that combine the E3-ligase ligand and the linker moiety in one molecule. The terminal end of the linker moiety comes pre-equipped with an azide moiety. With these reagents in hand, it only requires a ligand for the target protein equipped with a terminal alkyne and a simple CuAAC reaction[4] to prepare a sizable pool or PROTACs in a minimal amount of time. Reagents with ligands for several E3-ligases, including Cereblon, VHL and MDM2, have been prepared. [5-9]






Figure 2: PROTAC synthesis based on the toolkit reagent and a target ligand equipped with a terminal alkyne.



[1]          Sakamoto K.M.; Kim K.B.; Kumagai, A.; Mercurio, F.; Crews, C.M.; Deshaies, R.J. Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box
              complex for ubiquitination and degradation Proc. Natl. Acad. Sci. U.S.A. 2001, 98(15), 8554-8559

[2]          Schapira M.; Calabrese, M.F.; Bullock, A.N.; Crews C.M. Targeted protein degradation: expanding the toolbox Nat. Rev. Drug Discov. 2019, 18(12), 949-963.

[3] (accessed April 2020)

[4]          Rostovtsev, V.V.; Green, L.G.; Fokin, V.V.; Sharpless, K.B. A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective Ligation of Azides and
               Terminal Alkynes. Angew. Chem. Int. Ed. 2002, 41(14), 2596-2599.

[5]          Lohbeck, J. and Miller A.K. Practical synthesis of a phthalimide-based Cereblon ligand to enable PROTAC development.
               Bioorg. Med. Chem. Lett. 2016, 26(21), 5260-5262.

[6]          Galdeano, C.; Gadd, M.S.; Soares, P.; Scaffidi, S.; Van Molle, I.; Birced, I.; Hewitt, S.; Dias, D.M.; Ciulli, A. Structure-guided design and optimization of small
               molecules targeting the protein-protein interaction between the von Hippel-Lindau (VHL) E3 ubiquitin ligase and the hypoxia inducible factor (HIF) alpha
               subunit with in vitro nanomolar affinities. J. Med. Chem. 2014, 57(20), 8657-63.

[7]          Raina, K.; Lu, J.; Qian, Y.; Altieri, M.; Gordon, D.; Rossi, A.M.; Wang, J.; Chen, X.; Dong, H.; Siu, K.; Winkler, J.D.; Crew, A.P.; Crews, C.M.; Coleman, K.G. PROTAC-induced
               BET protein degradation as a therapy for castration-resistant prostate cancer. Proc. Natl. Acad. Sci. U.S.A. 2016, 113(26), 7124-7129.

[8]          Schneekloth, A.R.; Pucheault, M.; Tae, H.S.; Crews, C.M. Targeted intracellular protein degradation induced by a small molecule: En route to chemical
               proteomics. Bioorg. Med. Chem. Lett. 2008, 18(22):5904-5908

[9]          Rimmler, G.; Alker, A.; Bosco, M.; Diodone, R.; Fishlock, D.; Hildbrand, S.; Kuhn, B.; Moessner, C.; Peters, C.; Rege, P.D.; Schantz, M. Practical Synthesis of MDM2
               Antagonist RG7388. Part 2: Development of the Cu(I) Catalyzed [3 + 2] Asymmetric Cycloaddition Process for the Manufacture of Idasanutlin.
               Org. Process Res. Dev. 2016, 20(12), 2057-2066.





Fluorescently labeled antibiotics for investigating phenotypic properties of mutant bacteria

In a collaborative project with Prof. Tom Coenye, a large collections of evolved mutants with reduced susceptibility will be generated applying an experimental evolution approach. Our group will synthesize fluorescently labelled antibiotics to compare the mutants’ antibiotic uptake and efflux with that of WT strains.

The synthesis of fluorescently-labelled antibiotics has been reported in literature, but such molecules are not commercially available and often suffer from the drawback that they lose (part) of their antimicrobial activity. To obtain labelled antibiotics, we will prepare azide-modified analogues of various classes of antimicrobials commencing from the parent agent or a commercially available precursor thereof. The azide moiety will allow conjugation by means of CuAAC methodology to BODIPY-fluorophores that are equipped with a terminal alkyne.
















General overview of the labelling reaction (‘click chemistry’) (upper panel) and examples of labeled antibiotics that will be synthesized (lower panels).

The azide-modified antibiotics are designed to allow introduction of the fluorophore as the final synthetic step under mild conditions, whilst paying close attention to the known structure-activity relationship (SAR) of the compound as not to compromise the antibacterial activity.

For the majority of the classes of antibiotics from our panel, the commercially available agents do not allow direct azide introduction without compromising the SAR, although some can be functionalized in an indirect fashion. Hence, most derivatives have to be prepared from their synthetic precursors (simple or advanced) or can only be accessed through extensive protective group manipulations.

Purine nucleoside library

The nucleoside scaffold has traditionally been considered a privileged scaffold for the discovery of antiviral and antitumor agents. This has resulted in the FDA-approval or clinical use of 43 nucleoside analogues. Therefore, it can be stated that the evaluation of nucleoside libraries remains a potential source to identify interesting starting points for further development in these indications. Particularly, the evaluation of new or underexplored modifications to the nucleoside scaffold is of interest.

Extensive literature evaluation (published journal articles and patent literature) uncovered significant ‘gaps’ in prepared nucleoside analogues (e.g. several sugar-ring modifications have only been explored with a pyrimidine nucleobase; the sugar ring of some purine nucleoside analogues was never thoroughly investigated). Additionally, the evaluation of libraries containing purine C-nucleosides, analogues that feature a carbon atom as the connecting element to the sugar, as opposed to the canonical nitrogen, has been seldom performed. Thus, in the LMC we have taken a ligand-based approach to construct a purine nucleoside library, based on the primary structure of the nucleoside (‘sugar ring’ and ‘nucleobase’) as the design principle.

In this regard, several sugar ring and heterocycle scaffolds were separately selected, then recombined and the corresponding nucleoside synthesized to create library members. The inclusion of scaffolds was inspired by their presence in the structure of FDA-approved nucleoside drugs, advanced clinical candidates or from other known bioactive scaffolds. This latter group was mainly inspired by so-called nucleoside antibiotics such as tubercidin (7-deazaadenosine) and cordycepin (3’-deoxyadenosine). An overview of the current nucleoside library is depicted in Figure 1.


Figure 1: Overview of nucleoside modifications present in the LMC purine library.

Currently, our library consists of over 600 novel and structurally diverse purine nucleoside analogues. Additionally, the LMC has access to significant amounts of advanced intermediates for the swift generation of follow-up analogues to enable hit expansion/lead optimization efforts.

As a proof-of-principle for the potential usefulness of this purine nucleoside library, these analogues have been extensively profiled for activity against pathogenic protozoa, such as the kinetoplastid parasites Trypanosoma brucei spp., Trypanosoma cruzi and Leishmania spp. This screening has resulted in a significant hit rate of ~5-8% confirmed hits, of which several series were subsequently optimized to yield lead analogues showing promising activity in relevant animal models after oral dosing.1-4



  1. Hulpia, F.;  Van Hecke, K.;  Franca da Silva, C.;  da Gama Jaen Batista, D.;  Maes, L.;  Caljon, G.;  de Nazare, C. S. M.; Van Calenbergh, S., Discovery of novel 7-aryl 7-deazapurine 3'-deoxy-ribofuranosyl nucleosides with potent activity against Trypanosoma cruzi. J. Med. Chem. 2018, 61 (20), 9287-9300.
  2. Hulpia, F.;  Campagnaro, G. D.;  Scortichini, M.;  Van Hecke, K.;  Maes, L.;  de Koning, H. P.;  Caljon, G.; Van Calenbergh, S., Revisiting tubercidin against kinetoplastid parasites: aromatic substitutions at position 7 improve activity and reduce toxicity. Eur. J. Med. Chem. 2019, 164, 689-705.
  3. Hulpia, F.;  Mabille, D.;  Campagnaro, G. D.;  Schumann, G.;  Maes, L.;  Roditi, I.;  Hofer, A.;  de Koning, H. P.;  Caljon, G.; Van Calenbergh, S., Combining tubercidin and cordycepin scaffolds results in highly active candidates to treat late-stage sleeping sickness. Nat. Commun. 2019, 10 (1), 5564.
  4. Lin, C.;  Hulpia, F.;  da Silva, C. F.;  Batista, D.;  Van Hecke, K.;  Maes, L.;  Caljon, G.;  Soeiro, M. N. C.; Van Calenbergh, S., Discovery of pyrrolo[2,3-b]pyridine (1,7-dideazapurine) nucleoside analogues as anti-Trypanosoma cruzi agents. J. Med. Chem. 2019, 62 (19), 8847-8865.

New leads for infectious protozoan diseases


Infectious tropical diseases (ITDs) that disproportionally affect the world’s poorest people have traditionally been neglected from research efforts toward the discovery and development of new and effective therapies. Currently available therapies for many ITDs are unsatisfactory due to their low efficacy, the rise of drug resistance, side-effects leading to treatment discontinuation, non-oral administration route, etc. In this project we therefore aim at identifying new hits for the treatment of ITDs with high unmet medical needs, caused by parasitic protozoa (human African trypanosomiasis, Chagas disease, leishmaniasis, cryptosporidiosis, malaria, …).

Virtually all parasitic protozoa are purine auxotroph, meaning that they rely exclusively on the acquisition and processing of pre-formed purines from their host(s). These organisms have acquired high-affinity uptake systems coupled to an enzymatic machinery that allows them to salvage and interconvert nucleosides and nucleotides to sustain DNA and RNA synthesis. Synthetic purine nucleoside analogues have shown to be competent substrates of transporter-mediated uptake,[1] as well as modulators of one/several purine salvage pathway enzyme(s).[2] Thus, purine nucleoside analogues represent a ‘privileged’ compound class to uncover bioactive antiprotozoal compounds.

Therefore, a few years ago we started with the synthesis of a focused purine nucleoside library (still expanding) to discover new antiprotozoal agents. This proved to be a viable strategy to discover new antiprotozoal analogues.[3],[4],[5],[6],[7]

Collaboration with University of Antwerp (Prof. Guy Caljon & Prof. Louis Maes), University of Glasgow (Prof. Harry P. de Koning) and University of Pennsylvania (Prof. Boris Striepen).

[1] de Koning, H. P.;  et al. FEMS Microbiol. Rev. 2005, 29 (5), 987-1020.

[2] Berg, M.;  et al. Curr. Med. Chem. 2010, 17 (23), 2456-2481.

[3] Hulpia, F.;  et al. J. Med. Chem. 2018, 61 (20), 9287-9300.

[4] Hulpia, F.;  et al. Eur. J. Med. Chem. 2019, 164, 689-705.

[5] Hulpia, F.;  et al. Nat. Commun. 2019, 10 (1), 5564.

[6] Lin, C.;  et al. J. Med. Chem. 2019, 62 (19), 8847-8865.

[7] Hulpia, F.;  et al. Eur. J. Med. Chem. 2020, 188, 112018.