Computational Medicinal Chemistry

The picture shows a ligand and its interaction with a drug target.

In computational medicinal chemistry we focus on two general research areas. One area is to develop and evaluate methods that are useful and effective for medicinal chemistry and drug discovery projects. The second area is to find promising chemical starting points for medicinal chemistry projects and aid in the development of these compounds using computer-aided drug design and multivariate analysis. The latter research area also includes theoretical investigations of reaction mechanisms in pharmaceutically relevant chemical reactions to provide a deep understanding of the reactions and to develop improved reactions protocols and reaction variants useful in the development of drugs or pharmacological probes.

Contact Christian Sköld

Contact Anders Karlén

Publications

Publications

  • Olanders, Gustav; Alogheli, Hiba; Brandt, Peter; Karlén, Anders

    Conformational Analysis of Macrocycles: Comparing General and Specialized Methods

    Part of Journal of Computer-Aided Molecular Design, p. 231-252, 2020.

    Open access
  • Theuretzbacher, Ursula; Outterson, Kevin; Engel, Aleks; Karlen, Anders

    The global preclinical antibacterial pipeline

    Part of Nature Reviews Microbiology, p. 275-285, 2020.

  • Wallinder, Charlotta; Sköld, Christian; Sundholm, Sara; Guimond, Marie-Odile et al.

    High affinity rigidified AT(2) receptor ligands with indane scaffolds

    Part of MedChemComm, p. 2146-2160, 2019.

    Open access
  • Tomberg, Anna; Muratore, Michael Eric; Johansson, Magnus Jan; Terstiege, Ina et al.

    Relative Strength of Common Directing Groups in Palladium-Catalyzed Aromatic C-H Activation

    Part of ISCIENCE, p. 373 373-+ +, 2019.

    Open access
  • Eriksson, Jonas; Roy, Tamal; Sawadjoon, Supaporn; Bachmann, Kim et al.

    Synthesis and preclinical evaluation of the CRTH2 antagonist [11C]MK-7246 as a novel PET tracer and potential surrogate marker for pancreatic beta-cell mass

    Part of Nuclear Medicine and Biology, p. 1-10, 2019.

    Open access
  • Skogh, Anna; Lesniak, Anna; Sköld, Christian; Karlgren, Maria et al.

    An imidazole based H-Phe-Phe-NH2 peptidomimetic with anti-allodynic effect in spared nerve injury mice

    Part of Bioorganic & Medicinal Chemistry Letters, p. 2446-2450, 2018.

  • Szałaj, Natalia; Lu, Lu; Benediktsdottir, Andrea; Zamaratski, Edouard et al.

    Boronic ester-linked macrocyclic lipopeptides as serine protease inhibitors targeting Escherichia coli type I signal peptidase.

    Part of European Journal of Medicinal Chemistry, p. 1346-1360, 2018.

  • De Rosa, Maria; Lu, Lu; Zamaratski, Edouard; Szałaj, Natalia et al.

    Design, synthesis and in vitro biological evaluation of oligopeptides targeting E. coli type I signal peptidase (LepB)

    Part of Bioorganic & Medicinal Chemistry, p. 897-911, 2017.

    Open access
  • Alogheli, Hiba; Olanders, Gustav; Schaal, Wesley; Brandt, Peter et al.

    Docking of Macrocycles: Comparing Rigid and Flexible Docking in Glide

    Part of Journal of Chemical Information and Modeling, p. 190-202, 2017.

  • Lindh, Martin; Karlén, Anders; Norinder, Ulf

    Predicting the Rate of Skin Penetration Using an Aggregated Conformal Prediction Framework

    Part of Molecular Pharmaceutics, p. 1571-1576, 2017.

  • Sawant, Rajiv T.; Stevens, Marc Y.; Sköld, Christian; Odell, Luke R.

    Microwave-Assisted Branching Cascades: A Route to Diverse 3,4-Dihydroquinazolinone-Embedded Polyheterocyclic Scaffolds

    Part of Organic Letters, p. 5392-5395, 2016.

  • Kostyanev, T.; Bonten, M. J. M.; O'Brien, S.; Steel, H. et al.

    The Innovative Medicines Initiative's New Drugs for Bad Bugs programme: European public-private partnerships for the development of new strategies to tackle antibiotic resistance

    Part of Journal of Antimicrobial Chemotherapy, p. 290-295, 2016.

  • Belfrage, Anna Karin; Gising, Johan; Svensson, Fredrik; Åkerblom, Eva et al.

    Efficient and Selective Palladium-Catalysed C-3 Urea Couplings to 3,5-Dichloro-2(1H)-pyrazinones

    Part of European Journal of Organic Chemistry, p. 978-986, 2015.

    Open access
  • Wallinder, Charlotta; Sköld, Christian; Botros, Milad; Guimond, Marie-Odile et al.

    Interconversion of Functional Activity by Minor Structural Alterations in Nonpeptide AT2 Receptor Ligands

    Part of ACS Medicinal Chemistry Letters, p. 178-182, 2015.

  • Russo, Francesco; Gising, Johan; Åkerbladh, Linda; Roos, Annette K. et al.

    Optimization and Evaluation of 5-Styryl-Oxathiazol-2-one Mycobacterium tuberculosis Proteasome Inhibitors as Potential Antitubercular Agents

    Part of ChemistryOpen, p. 342-362, 2015.

    Open access
  • Karlsson, Christoffer; Blom, Magnus; Johansson, Miranda; Jansson, Anna M. et al.

    Phototriggerable peptidomimetics for the inhibition of Mycobacterium turberculosis ribonucleotide reductase by targeting protein-protein binding

    Part of Organic and biomolecular chemistry, p. 2612-2621, 2015.

  • Lindh, Martin; Svensson, Fredrik; Schaal, Wesley; Zhang, Jin et al.

    Toward a Benchmarking Data Set Able to Evaluate Ligand- and Structure-based Virtual Screening Using Public HTS Data

    Part of Journal of Chemical Information and Modeling, p. 343-353, 2015.

  • Svensson, Fredrik; Engen, Karin; Lundbäck, Thomas; Larhed, Mats et al.

    Virtual Screening for Transition State Analogue Inhibitors of IRAP Based on Quantum Mechanically Derived Reaction Coordinates

    Part of Journal of Chemical Information and Modeling, p. 1984-1993, 2015.

  • Gising, Johan; Belfrage, Anna Karin; Alogheli, Hiba; Ehrenberg, Angelica et al.

    Achiral Pyrazinone-Based Inhibitors of the Hepatitis C Virus NS3 Protease and Drug-Resistant Variants with Elongated Substituents Directed Toward the S2 Pocket

    Part of Journal of Medicinal Chemistry, p. 1790-1801, 2014.

  • Hughes, Diarmaid; Karlén, Anders

    Discovery and preclinical development of new antibiotics

    Part of Upsala Journal of Medical Sciences, p. 162-169, 2014.

  • Borhade, Sanjay R; Rosenström, Ulrika; Sävmarker, Jonas; Lundbäck, Thomas et al.

    Inhibition of Insulin-Regulated Aminopeptidase (IRAP) by Arylsulfonamides

    Part of ChemistryOpen, p. 256-263, 2014.

  • Lampa, Anna; Bergman, Sara; Svahn Gustafsson, Sofia; Alogheli, Hiba et al.

    Novel Peptidomimetic Hepatitis C Virus NS3/4A Protease Inhibitors Spanning the P2–P1′ Region

    Part of ACS Medicinal Chemistry Letters, p. 249-254, 2014.

  • Skillinghaug, Bobo; Sköld, Christian; Behrends, Malte; Sävmarker, Jonas et al.

    Palladium(II) catalyzed desulfitative coupling reactions of sodium aryl sulfinates and nitriles: Scope, limitations, and mechanistic studies

    Part of Abstracts of Papers of the American Chemical Society, 2014.

  • Skillinghaug, Bobo; Sköld, Christian; Rydfjord, Jonas; Svensson, Fredrik et al.

    Palladium(II)-Catalyzed Desulfitative Synthesis of Aryl Ketones from Sodium Arylsulfinates and Nitriles: Scope, Limitations, and Mechanistic Studies

    Part of Journal of Organic Chemistry, p. 12018-12032, 2014.

  • Lampa, Anna; Alogheli, Hiba; Ehrenberg, Angelica E.; Åkerblom, Eva et al.

    Vinylated linear P2 pyrimidinyloxyphenylglycine based inhibitors of the HCV NS3/4A protease and corresponding macrocycles

    Part of Bioorganic & Medicinal Chemistry, p. 6595-6615, 2014.

  • Skogh, Anna; Fransson, Rebecca; Sköld, Christian; Larhed, Mats et al.

    Aminocarbonylation of 4-Iodo-1H-imidazoles with an Amino Acid Amide Nucleophile: Synthesis of Constrained H-Phe-Phe-NH2 Analogues

    Part of Journal of Organic Chemistry, p. 12251-12256, 2013.

  • Fransson, Rebecca; Sköld, Christian; Kratz, Jadel M; Svensson, Richard et al.

    Constrained H-Phe-Phe-NH2 Analogues With High Affinity to the Substance P 1-7 Binding Site and With Improved Metabolic Stability and Cell Permeability

    Part of Journal of Medicinal Chemistry, p. 4953-4965, 2013.

  • Rydfjord, Jonas; Svensson, Fredrik; Trejos, Alejandro; Sjöberg, Per J. R. et al.

    Decarboxylative Palladium(II)-Catalyzed Synthesis of Aryl Amidines from Aryl Carboxylic Acids: Development and Mechanistic Investigation

    Part of Chemistry - A European Journal, p. 13803-13810, 2013.

    Open access
  • Jansson, Anna; Więckowska, Anna; Björkelid, Christofer; Yahiaoui, Samir et al.

    DXR Inhibition by Potent Mono- and Disubstituted Fosmidomycin Analogues

    Part of Journal of Medicinal Chemistry, p. 6190-6199, 2013.

    Open access
  • Nurbo, Johanna; Ericsson, Daniel J.; Rosenström, Ulrika; Muthas, Daniel et al.

    Novel pseudopeptides incorporating a benzodiazepine-based turn mimetic – targeting Mycobacterium tuberculosis ribonucleotide reductase

    Part of Bioorganic & Medicinal Chemistry, p. 1992-2000, 2013.

  • Wannberg, Johan; Wallinder, Charlotta; Unlusoy, Meltem; Sköld, Christian et al.

    One-Pot, Two-Step, Microwave-Assisted Palladium-Catalyzed Conversion of Aryl Alcohols to Aryl Fluorides via Aryl Nonaflates

    Part of Journal of Organic Chemistry, p. 4184-4189, 2013.

  • Svensson, Fredrik; Mane, Rajendra S.; Sävmarker, Jonas; Larhed, Mats et al.

    Theoretical and Experimental Investigation of Palladium(II)-Catalyzed Decarboxylative Addition of Arenecarboxylic Acid to Nitrile

    Part of Organometallics, p. 490-497, 2013.

  • Andappan, Murugaiah M. S.; Wu, Xiongyu; Wallinder, Charlotta; Mahalingam, A. K. et al.

    From the First Selective Non-Peptide AT(2) Receptor Agonist to Structurally Related Antagonists

    Part of Journal of Medicinal Chemistry, p. 2265-2278, 2012.

  • Nordqvist, Anneli; Nilsson, Mikael T.; Lagerlund, Olof; Muthas, Daniel et al.

    Synthesis, biological evaluation and X-ray crystallographic studies of imidazo[1,2-a]-pyridine based Mycobacterium tuberculosis glutamine synthetase inhibitors

    Part of MedChemComm, p. 620-626, 2012.

  • Claerhout, Stijn; Sharma, Sweta; Sköld, Christian; Cavaluzzo, Claudia et al.

    Synthesis of functionalized furopyrazines as restricted dipeptidomimetics

    Part of Tetrahedron, p. 3019-3029, 2012.

  • Sköld, Christian; Kleimark, Jonatan; Trejos, Alejandro; Odell, Luke R. et al.

    Transmetallation Versus β-Hydride Elimination: The Role of 1,4 Benzoquinone in Chelation-Controlled Arylation Reactions with Arylboronic Acids

    Part of Chemistry - A European Journal, p. 4714-4722, 2012.

    Open access
  • Gising, Johan; Nilsson, Mikael T; Odell, Luke R; Yahiaoui, Samir et al.

    Trisubstituted Imidazoles as Mycobacterium tuberculosis Glutamine Synthetase Inhibitors

    Part of Journal of Medicinal Chemistry, p. 2894-2898, 2012.

    Open access
  • Svensson, Fredrik; Karlén, Anders; Sköld, Christian

    Virtual Screening Data Fusion Using Both Structure- and Ligand-Based Methods

    Part of Journal of Chemical Information and Modeling, p. 225-232, 2012.

  • Andaloussi, Mounir; Henriksson, Lena M.; Wieckowska, Anna; Lindh, Martin et al.

    Design, Synthesis, and X-ray Crystallographic Studies of alpha-Aryl Substituted Fosmidomycin Analogues as Inhibitors of Mycobacterium tuberculosis 1-Deoxy-D-xylulose 5-Phosphate Reductoisomerase

    Part of Journal of Medicinal Chemistry, p. 4964-4976, 2011.

    Open access
  • Lampa, Anna; Ehrenberg, Angelica E.; Vema, Aparna; Åkerblom, Eva et al.

    P2-P1 ' macrocyclization of P2 phenylglycine based HCV NS3 protease inhibitors using ring-closing metathesis

    Part of Bioorganic & Medicinal Chemistry, p. 4917-4927, 2011.

  • Andersson, Hanna; Demaegdt, Heidi; Johnsson, Anders; Vauquelin, Georges et al.

    Potent Macrocyclic Inhibitors of Insulin-Regulated Aminopeptidase (IRAP) by Olefin Ring-Closing Metathesis

    Part of Journal of Medicinal Chemistry, p. 3779-3792, 2011.

  • Andaloussi, Mounir; Lindh, Martin; Björkelid, Christofer; Suresh, Surisetti et al.

    Substitution of the phosphonic acid and hydroxamic acid functionalities of the DXR inhibitor FR900098: An attempt to improve the activity against Mycobacterium tuberculosis

    Part of Bioorganic & Medicinal Chemistry Letters, p. 5403-5407, 2011.

  • Nordqvist, Anneli; Björkelid, Christofer; Andaloussi, Mounir; Jansson, Anna M. et al.

    Synthesis of Functionalized Cinnamaldehyde Derivatives by an Oxidative Heck Reaction and Their Use as Starting Materials for Preparation of Mycobacterium tuberculosis 1-Deoxy-D-xylulose-5-phosphate Reductoisomerase Inhibitors

    Part of Journal of Organic Chemistry, p. 8986-8998, 2011.

    Open access
  • Örtqvist, Pernilla; Gising, Johan; Ehrenberg, Angelica; Vema, Aparna et al.

    Discovery of Achiral Inhibitors of the Hepatitis C Virus NS3 Protease based on 2(1H)-pyrazinones

    Part of Bioorganic & Medicinal Chemistry, p. 6512-6525, 2010.

  • Fransson, Rebecca; Botros, Milad; Sköld, Christian; Nyberg, Fred et al.

    Discovery of Dipeptides with High Affinity to the Specific Binding Site for Substance P1-7

    Part of Journal of Medicinal Chemistry, p. 2383-2389, 2010.

  • Andersson, Hanna; Demaegdt, Heidi; Vauquelin, Georges; Lindeberg, Gunnar et al.

    Disulfide cyclized tripeptide analogues of angiotensin IV as potent and selective inhibitors of insulin-regulated aminopeptidase (IRAP)

    Part of Journal of Medicinal Chemistry, p. 8059-8071, 2010.

  • Ax, Anna; Joshi, Advait A.; Orrling, Kristina M.; Vrang, Lotta et al.

    Synthesis of a small library of non-symmetric cyclic sulfamide HIV-1 protease inhibitors

    Part of Tetrahedron, p. 4049-4056, 2010.

  • Odell, Luke R.; Nilsson, Mikael T.; Gising, Johan; Lagerlund, Olof et al.

    Functionalized 3-amino-imidazo[1,2-a]pyridines: A novel class of drug-like Mycobacterium tuberculosis glutamine synthetase inhibitors

    Part of Bioorganic & Medicinal Chemistry Letters, p. 4790-4793, 2009.

  • Nilsson, Mikael T.; Krajewski, Wojciech W.; Srinivasa, Bachally R.; Yahiaoui, Samir et al.

    Structural basis for the inhibition of Mycobacterium tuberculosis glutamine synthetase by novel ATP-competitive inhibitors

    Part of Journal of Molecular Biology, p. 504-513, 2009.

    Open access
  • Andersson, Hanna; Demaegdt, Heidi; Vauquelin, Georges; Lindeberg, Gunnar et al.

    Ligands to the (IRAP)/AT4 receptor encompassing a 4-hydroxydiphenylmethane scaffold replacing Tyr2

    Part of Bioorganic & Medicinal Chemistry, p. 6924-6935, 2008.