Medicinal Chemistry – Lead IdentificationNational facility
The Medicinal Chemistry - Lead Identification facility will take on, explore, and optimize molecules in drug discovery projects. Synthetic and computational chemistry will be at the core of the so-called Design-Make-Test-Analyze cycle that characterizes a small molecule drug discovery program. The mission is to deliver small drug-like molecules with potency, selectivity, physicochemical and ADMET properties of sufficient quality to allow proof-of-concept animal studies. We work in close collaboration with our colleges in the hit-to lead facility https://www.scilifelab.se/facilities/hit2lead/.
- Organic synthesis of bioactive compounds (small molecules and peptides).
- Medicinal chemistry expertize.
- Iterative design, synthesis and analysis of assay data to improve compound properties.
- Compound characterization, structure determination and purity analysis.
- Quantitative structure based activity relationships.
- Scale-up synthesis of bioactive compounds.
- Selection and purchase of commercial compounds.
- Synthesis of reference compounds.
- Competitive Intelligence
- In collaboration with Medicinal chemistry Hit2Lead
- Computer-based drug design
- Analytical UHPLC-MS.
- Automated flash chromatography systems.
- GCMS instruments.
- Hardware and software for Computer-Aided Drug Design.
- Microwave batch reactors.
- Microwave continuous flow reactors.
- NMR spectrometers.
- Peptide synthesizer.
- Preparative HPLC instruments.
R. Isaksson, I. Kumpiņa, J. Sävmarker, M. Larhed, J. Wannberg*: Rapid and straightforward transesterification of sulfonyl carbamates. Tetrahedron Lett 57 (2016) 1476-1478. .DOI 10.1016/j.tetlet.2016.02.071
I. Kumpiņa, R. Isaksson, J. Sävmarker, J. Wannberg, M. Larhed*: Microwave Promoted Transcarbamylation Reaction of Sulfonylcarbamates under Continuous-Flow Conditions. Org. Process Res. Dev.20 (2016) 440-445.DOI 10.1021/acs.oprd.5b00323
P. Wakchaure, U. Bremberg, J. Wannberg, M. Larhed*: Synthesis of enantiopure angiotensin II type 2 receptor [AT2R] antagonist EMA401. Tetrahedron 71 (2015), 6881-6887. DOI: 10.1016/j.tet.2015.07.08
A. Jansson, A. Więckowska, C. Björkelid, S. Yahiaoui, S. Sooriyaarachchi, M. Lindh, T. Bergfors, S. Dharavath, M. Desroses, S. Suresh, M. Andaloussi, R. Nikhil, S. Sreevalli, B. Srinivasa, M. Larhed, T. A. Jones, A. Karlén*, S. L. Mowbray*: DXR inhibition by potent mono- and disubstituted fosmidomycin analogues. J. Med. Chem. 56 (2013), 6190-6199. DOI: 10.1021/jm4006498
J. Gising, M. T. Nilsson, L. Odell, S. Yahiaoui, M. Lindh, H. Iyer, B. R. Srinivasa, M. Larhed, S. L. Mowbray, A. Karlén*: Tri-Substituted Imidazoles as Mycobacterium tuberculosis Glutamine-Synthetase Inhibitors. J. Med. Chem. 55 (2012). 2894−2898. DOI: 10.1021/jm201212h