Applied Organic Chemistry is a research group in the Department of Chemistry and Biomedical Science at NTNU. We use synthetic organic chemistry as the primary tool to address challenges at the intersection of medicine and biology — designing, building, and testing new molecules with pharmaceutical relevance.

Our core focus is medicinal chemistry: the rational design and synthesis of heterocyclic small molecules as inhibitors of disease-relevant enzymes. Over the past two decades we have built a sustained programme around kinase inhibitors for cancer treatment, targeting EGFR and, more recently, CSF1R — a kinase implicated in inflammation and osteoclast-driven bone disease. Alongside this, we develop antibacterial compounds targeting novel bacterial targets such as the DNA β-clamp, addressing the urgent challenge of antibiotic resistance.

Underpinning all our medicinal chemistry work is a strong foundation in synthetic organic chemistry and asymmetric synthesis — enabling efficient access to enantiopure drug candidates and building blocks. We also have a long-standing interest in fluorine chemistry — incorporating fluorine atoms into biologically active molecules to modulate potency, metabolic stability, and pharmacokinetics.

The group is led by Professor Bård Helge Hoff and Professor Eirik Sundby. Together they have co-authored over 50 peer-reviewed papers and represent one of Norway's most active academic medicinal chemistry programmes.

• Erasmus Students: Contact to NTNU should be done via official channels

Kinase Inhibitors

Protein kinases are central regulators of cell proliferation, survival, and differentiation, and their dysregulation drives many cancers and other diseases. We design and synthesise small-molecule inhibitors targeting two main kinases:

CSF1R (Colony Stimulating Factor 1 Receptor)

CSF1R controls macrophage differentiation and is a key driver of tumour-associated inflammation and osteoclast-mediated bone destruction. Since 2022 we have built a dedicated programme targeting CSF1R, in close collaboration with the Lead Discovery Center (Dortmund, Germany). Our work has produced highly selective inhibitors targeting the autoinhibited form of the kinase (published in Journal of Medicinal Chemistry, 2023) and the first 18F-radiolabelled pyrrolopyrimidine ligand for CSF1R PET imaging (2025). We work in collaboration with cancer biology groups and clinical medicine at NTNU and have a long-standing partnership with the Pridans Lab (University of Edinburgh), whose expertise in microglial biology and CSF1R mouse models has been central to validating our compounds in neuroinflammation contexts..

EGFR (Epidermal Growth Factor Receptor)

Overactivation of EGFR drives lung cancer, colon cancer, and others. Starting from the erlotinib scaffold, we have carried out extensive structure-activity relationship (SAR) studies across pyrrolopyrimidine, thienopyrimidine, and furopyrimidine scaffolds, producing inhibitors with sub-nanomolar potency, improved metabolic stability, and favourable ADME profiles. Our 2014 paper identifying a highly active thienopyrimidine EGFR inhibitor has been cited over 66 times.

2. Antibacterial Compounds — Targeting the DNA β-Clamp

With antibiotic resistance declared a global health emergency, we are developing a new class of antibacterial compounds targeting the bacterial DNA β-clamp. a replication processivity factor with no equivalent in human cells. Halogenated pyrrolopyrimidines synthesised in our laboratory show low MIC values against Staphylococcus aureus, including resistant strains, and exhibit strong synergistic effects when combined with the antimicrobial peptide BTP-001. We use a combined synthetic and proteomic/metabolomic approach (in collaboration with the Otterlei and Bruheim labs) to understand the molecular basis for these effects.

3. Asymmetric Synthesis and Biocatalysis

Chirality is critical in drug development — enantiomers of the same compound can have entirely different biological profiles. We develop efficient routes to enantiomerically pure building blocks and drug candidates, primarily using asymmetric transfer hydrogenation with ruthenium-arene-diamine catalysts, including mechanistic studies on the origins of enantioselection. Our synthetic work has been demonstrated in total syntheses of (+)-goniothalamin, duloxetine, fluoxetine, and lubeluzole.

4. Fluorine Chemistry in Drug Discovery

Fluorine substituents are present in approximately 20% of all approved pharmaceuticals, yet their incorporation requires specialised chemistry. We have developed methodology for:

    Microwave-assisted electrophilic α-fluorination of aryl ketones using Selectfluor™

    Synthesis of chiral α-fluoroalkylamines and α-fluoroalkanols via asymmetric reduction and lipase resolution

    Incorporation of fluorinated groups into kinase inhibitor scaffolds to modulate potency and metabolic stability

    2H, 13C- and 18F-labelled compounds for LC-MS/MS quantification and PET imaging

Group Leaders

Bård Helge Hoff — Professor

Email: bard.h.hoff@ntnu.no

Bård has led the Applied Organic Chemistry group since 2000. He holds a PhD from NTNU and has published over 96 peer-reviewed papers across medicinal chemistry, biocatalysis, heterocyclic synthesis, and fluorine chemistry (h-index 26, >1660 citations). He is the group's principal investigator for kinase inhibitor and heterocyclic chemistry programmes, and holds extensive expertise in synthetic methodology, reaction design, and pharmaceutical chemistry. He is also group leader for the Organic Chemistry section at IKB.

Eirik Sundby — Professor

Email: eirik.sundby@ntnu.no

Eirik joined IKB from the Department of Materials Science and Engineering (IMA), where he held a full professorship. He has published 64 peer-reviewed papers (h-index 17, >820 citations), in medicinal chemistry, asymmetric synthesis, fluorine chemistry, and kinase inhibitor programmes targeting EGFR and CSF1R. Computational approaches, including molecular modelling, docking, and in silico screening, are integrated throughout his research and have been central to compound design and SAR rationalisation. He has been a close collaborator of Prof. Hoff for over 25 years, with more than 50 jointly authored publications. Eirik also has a strong interest in chemistry education and AI-assisted methods in organic chemistry research.

April 2026 — Prof. Sundby joins the Applied Organic Chemistry group at IKB, strengthening the medicinal chemistry team.

2025 — Five new papers published, including two on CSF1R inhibitors (Molecules, Pharmaceuticals), the first 18F-radiolabelled CSF1R PET imaging ligand (J. Labelled Compd. Radiopharm.), a glioblastoma RNaseH2 study (Scientific Reports), and a fluorinated β-clamp probe paper (Bioorg. Med. Chem.).

2024 — Six new papers published, including two X-ray crystallographic structure studies of guanidine scaffolds.

2023 — Landmark CSF1R paper published in Journal of Medicinal Chemistry: highly selective pyrrolo[2,3-d]pyrimidine inhibitors targeting the autoinhibited form of CSF1R. Antibacterial combination study (JK-274 + BTP-001) published in Frontiers in Microbiology.

2018 — Prof. Hoff published a comprehensive review on acetonitrile as a building block and reactant in organic synthesis (Synthesis, 32 citations).

108 peer-reviewed publications  •  1995–2025  •  Combined: Hoff & Sundby

2025

Cherukupalli S.; Eickhoff J.; Degenhart C.; Habenberger P.; Unger A.; Hoff B.H.; Sundby E. "Evaluating Triazole-Substituted Pyrrolopyrimidines as CSF1R Inhibitors." Molecules, 30(12), 2641. https://doi.org/10.3390/molecules30122641

Cherukupalli S.; Degenhart C.; Habenberger P.; Unger A.; Eickhoff J.; Hoff B.H.; Sundby E. "Design and Synthesis of Pyridine-Based Pyrrolo[2,3-d]pyrimidine Analogs as CSF1R Inhibitors: Molecular Hybridization and Scaffold Hopping Approach." Pharmaceuticals, 18(6), 814. https://doi.org/10.3390/ph18060814

Kissova M. et al.; Hoff B.H.; Sundby E. et al. "RNaseH2 inhibition potentiates temozolomide response in patient derived glioblastoma cells." Scientific Reports, 15(1), 41486. https://doi.org/10.1038/s41598-025-25298-5

Olsen C.E.; Simonsen S.; Merugu S.R.; Eigner V.; Aachmann F.L.; Kragelund B.B.; Sundby E.; Hoff B.H. "Synthesis and evaluation of fluorinated tetrahydrocarbazoles as probes in NMR based binding assay of the E. coli beta sliding clamp." Bioorganic and Medicinal Chemistry, 122, 118139. https://doi.org/10.1016/j.bmc.2025.118139

Cherukupalli S.; Karlsen M.; Hoff B.; Sundby E. "Design and Synthesis of a 18F-Radiolabeled Pyrrolo[2,3-d]pyrimidine Ligand as a CSF1R Receptor PET Imaging Agent." J. Labelled Compd. Radiopharm., 68(1-2), e4131. https://doi.org/10.1002/jlcr.4131

2024

Elumalai V.; Vaclav E.; Visnes T.; Sundby E.; Hoff B.H. "Improved Synthetic Methodology, Substrate Scope and X-ray Crystal Structure for N,N'-disubstituted Guanidines." ChemistrySelect, 9(2), e202304381. https://doi.org/10.1002/slct.202304381

Ostby L.; Sundby E.; Jakobsen A.N. "Authentic Hands-On Learning Approaches for Bulky Student Cohorts in General Chemistry Laboratory Using Case and Peer Assessment." Journal of Chemical Education, 101(11), 4614-4623. https://doi.org/10.1021/acs.jchemed.4c00815

Elumalai V.; Eigner V.; Janjua N.A.; Astrand P.-O.; Visnes T.; Sundby E.; Hoff B.H. "X-ray Structure of Eleven New N,N'-Substituted Guanidines: Effect of Substituents on Tautomer Structure in the Solid State." Crystals, 14(10), 884. https://doi.org/10.3390/cryst14100884

Bjornstad F.; Havik S.; Aarhus T.I.; Mahdi I.; Unger A.; Habenberger P.; Degenhart C.; Eickhoff J.; Klebl B.M.; Sundby E.; Hoff B.H. "Pyrrolopyrimidine based CSF1R inhibitors: Attempted departure from Flatland." European Journal of Medicinal Chemistry, 265, 116053. https://doi.org/10.1016/j.ejmech.2023.116053

Merugu S.R.; Selmer-Olsen S.; Kaada C.J.; Sundby E.; Hoff B.H. "Synthetic Routes to 2-aryl-1H-pyrrolo[2,3-b]pyridin-4-amines: Cross-Coupling and Challenges in SEM-Deprotection." Molecules, 29(19), 4743. https://doi.org/10.3390/molecules29194743

Yasuda S.; Svergja H.; Olsen C.E.; Hoff B.H. "Promotion of Water as Solvent in Amination of 4-Chloropyrrolopyrimidines and Related Heterocycles under Acidic Conditions." ACS Omega, 9(12), 14142-14152. https://doi.org/10.1021/acsomega.3c09673

2023

Singleton A.H.; Bergum O.E.T.; Sogaard C.K.; Rost L.M.; Olsen C.E.; Blindheim F.H.; Raeder S.B.; Bjornstad F.A.; Sundby E.; Hoff B.H.; Bruheim P.; Otterlei M. "Activation of multiple stress responses in Staphylococcus aureus substantially lowers the minimal inhibitory concentration when combining two novel antibiotic drug candidates." Frontiers in Microbiology, 14, 1260120. https://doi.org/10.3389/fmicb.2023.1260120

Aarhus T.I.; Teksum V.; Unger A.; Habenberger P.; Wolf A.; Eickhoff J.; Klebl B.; Wolowczyk C.; Bjorkoy G.; Sundby E.; Hoff B.H. "Negishi Cross-Coupling in the Preparation of Benzyl Substituted Pyrrolo[2,3-d]pyrimidine Based CSF1R Inhibitors." European Journal of Organic Chemistry, 26(12), e202300052. https://doi.org/10.1002/ejoc.202300052

Bjornstad F.; Sundby E.; Hoff B.H. "Directed Lithiation of Protected 4-Chloropyrrolopyrimidine: Addition to Aldehydes and Ketones Aided by Bis(2-dimethylaminoethyl)ether." Molecules, 28(3), 932. https://doi.org/10.3390/molecules28030932

Aarhus T.I.; Bjornstad F.; Wolowczyk C.; Larsen K.U.; Rognstad L.; Leithaug T.; Unger A.; Habenberger P.; Wolf A.; Bjorkoy G.; Pridans C.; Eickhoff J.; Klebl B.; Hoff B.H.; Sundby E. "Synthesis and Development of Highly Selective Pyrrolo[2,3-d]pyrimidine CSF1R Inhibitors Targeting the Autoinhibited Form." Journal of Medicinal Chemistry, 66(10), 6959-6980. https://doi.org/10.1021/acs.jmedchem.3c00428

Aarhus T.I.; Eickhoff J.; Klebl B.; Unger A.; Boros J.; Choidas A.; Zischinsky M.-L.; Wolowczyk C.; Bjorkoy G.; Sundby E.; Hoff B.H. "A highly selective purine-based inhibitor of CSF1R potently inhibits osteoclast differentiation." European Journal of Medicinal Chemistry, 255, 115344. https://doi.org/10.1016/j.ejmech.2023.115344

Stromsodd E.A.; Buene A.F.; Almenningen D.M.; Gautun O.R.; Hoff B.H. "Strategies for successful Suzuki-Miyaura cross-couplings with thienylboronic acids." Dyes and Pigments, 209, 110899. https://doi.org/10.1016/j.dyepig.2022.110899

2022

Olsen C.E.; Blindheim F.H.; Sogaard C.K.; Rost L.M.; Singleton A.H.; Bergum O.E.T.; Bruheim P.; Otterlei M.; Sundby E.; Hoff B.H. "Halogenated Pyrrolopyrimidines with Low MIC on Staphylococcus aureus and Synergistic Effects with an Antimicrobial Peptide." Antibiotics, 11(8), 984. https://doi.org/10.3390/antibiotics11080984

Almenningen D.M.; Haga B.S.; Hansen H.E.; Buene A.F.; Hoff B.H.; Gautun O.R. "Adamantyl Side Chains as Anti-Aggregating Moieties in Dyes for Dye-Sensitized Solar Cells." Chemistry - A European Journal, 28(51), e202201726. https://doi.org/10.1002/chem.202201726

Gederaas O.A.; Sorensen A.S.; Lindgren M.; Melo T.B.; Altin D.; Flatby E.M.; Hogset A.; Hoff B.H. "Synthesis and in vitro evaluation of a novel thienopyrimidine with phototoxicity towards rat glioma F98 cells." Journal of Photochemistry and Photobiology, 10, 100114. https://doi.org/10.1016/j.jpap.2022.100114

Almenningen D.M.; Hansen H.E.; Buene A.F.; Hoff B.H.; Gautun O.R. "Effect of seven different terthiophene pi-spacers on dye performance in dye-sensitized solar cells." Dyes and Pigments, 207, 110700. https://doi.org/10.1016/j.dyepig.2022.110700

Almenningen D.M.; Engh V.M.; Stromsodd E.A.; Hansen H.E.; Buene A.F.; Hoff B.H.; Gautun O.R. "Synthetic Efforts to Investigate the Effect of Planarizing the Triarylamine Geometry in Dyes for Dye-Sensitized Solar Cells." ACS Omega, 7(25), 22046-22057. https://doi.org/10.1021/acsomega.2c03163

2021

Blindheim F.H.; Olsen C.E.; Krogh Sogaard C.; Otterlei M.; Sundby E.; Hoff B.H. "Synthetic Strategies towards Imidazopyridinones and 7-Azaoxindoles and their Evaluation as Antibacterial Agents." European Journal of Organic Chemistry, 2021(18), 2701-2712. https://doi.org/10.1002/ejoc.202100172

Blindheim F.H.; Malme A.T.; Dalhus B.; Sundby E.; Hoff B.H. "Synthesis and Evaluation of Fused Pyrimidines as E. coli Thymidylate Monophosphate Kinase Inhibitors." ChemistrySelect, 6(45), 12852-12857. https://doi.org/10.1002/slct.202103796

El-Behairy M.F.; Hassan R.M.; Sundby E. "Enantioselective chromatographic separation and lipase catalyzed asymmetric resolution of biologically important chiral amines." Separations, 8(10), 165. https://doi.org/10.3390/separations8100165

Almenningen D.M.; Hansen H.E.; Vold M.F.; Buene A.F.; Venkatraman V.; Sunde S.; Hoff B.H.; Gautun O.R. "Effect of thiophene-based pi-spacers on N-arylphenothiazine dyes for dye-sensitized solar cells." Dyes and Pigments, 185, 108951. https://doi.org/10.1016/j.dyepig.2020.108951

Luo S.; Hoff B.H.; Maier S.A.; de Mello J.C. "Scalable Fabrication of Metallic Nanogaps at the Sub-10 nm Level." Advanced Science, 8(24), 2102756. https://doi.org/10.1002/advs.202102756

Luo S.; Mancini A.; Berte R.; Hoff B.H.; Maier S.A.; de Mello J.C. "Massively Parallel Arrays of Size-Controlled Metallic Nanogaps with Gap-Widths Down to the Sub-3-nm Level." Advanced Materials, 33(20), 2100491. https://doi.org/10.1002/adma.202100491

Master's Students

We regularly supervise master's thesis projects in medicinal chemistry and synthetic organic chemistry. Projects typically involve multi-step synthesis, characterisation, and biological evaluation. Contact Prof. Hoff or Prof. Sundby with a CV and brief motivation letter.

PhD Candidates

No PhD positions are available at the moment. Future PhD positions will be announced via Jobbnorge (www.jobbnorge.no) when funded positions are available. Unsolicited applications from highly motivated candidates with independent funding (e.g. NFR, Marie Skłodowska-Curie, Erasmus Mundus) are also welcome.

Postdoctoral Researchers

We are open to hosting postdoctoral researchers with their own funding. Relevant funding schemes include:

Marie Skłodowska-Curie Postdoctoral Fellowships — https://marie-sklodowska-curie-actions.ec.europa.eu/

Research Council of Norway (NFR) Mobility Grants — https://www.forskningsradet.no/en/

Fulbright Norway — https://www.fulbright.no/

Exchange Students

We host exchange students through Erasmus+ and bilateral university agreements. Minimum stay: 3 months.

Contact: bard.h.hoff@ntnu.no  |  eirik.sundby@ntnu.no

Post.Docs

S. Cherukupalli

S.R. Merugu

V. Elumala

PhD

C.E. Olsen

F. Bjornstad

F.H. Blindheim

 T.I. Aarhus

S. Bugge

S.J. Kaspersen

J. Han

T.H. Krane Thvedt

A.M. Esmurziev

E. Fuglseth

Master students

A.F. Buene

L. Rognstad,

T. Leithaug

A.C. Reiersolmoen

N. Uggerud

S.M. Lystve

Others

S. Yasuda