We take a creative approach and combine state-of-the-art computational techniques to design new valuable tool compounds for in vitro and in vivo studies in the CNS. We work closely with pharmacologists at the department and around the world to achieve these goals! Our work span several targets:

• Ionotropic glutamate receptors (iGluRs)
  • First GluK5-selective ligand: submitted for publication 2024
  • First GluK3-selective antagonist: ACS Chem Neurosci 2022
  • Proline analogs: ACS ChemNeurosci 2020 - and references therein
    
    
• Metabotropic glutamate receptors (mGluRs)
  • Picomolar and selective mGlu2 agonist LBG30300: J Med Chem 2024
    
    
  • Introducing a "MAGIC" methyl group, LBG30120: Eur J Med Chem 2024
    
    
• Excitatory amino acid transporters (EAATs)
  • Selective EAAT1 NAM, UCPH-101: J Med Chem 2010
  • Selective EAAT1 NAM, UCPH-102: ChemMedChem 2016
  • Selective EAAT1 NAM, UCPH-41003: J Med Chem 2016
  • Selective EAAT3 NAM, UCPH-42000: ACS Chem Neurosci 2019 

• GABAA receptors
  • Methaqualone analogs: ACS Chem Neurosci 2020
    
    
• Mixed targets
  • Putative 5HT2a-mGlu2 receptor complex: J Med Chem 2020

We are committed to discover new synthetic methodology relevant for medicinal chemistry. This be efficient synthesis of chemically complex fragments, new planar heterocycles, new/improved protecting group chemistry and more! Recent and ongoing work is:

Expedite Synthesis of Polysubstituted meta-Halophenols (Chem Eur J 2021)

Phenols are frequent motifs in pharmaceutical agents as well as in agrochemicals. Thus, their halo-functionalized analogues are highly valuable building blocks in the synthesis thereof. We have demonstrated the expedite synthesis of polysubstituted meta-halo phenols by the first-time reported anion-accelerated 2-pi-electrocyclic ring-opening reaction:

Transition Metal-free Synthesis of Poly-substituted Anilins (Chem Eur J 2022)

The anion-accelerated 2-pi-electrocyclic ring-opening reaction methodology was expanded to the synthesis of anilins - another important motif in medicinal chemistry:

We continue to explore the scope and limitations of this new and exciting methodology!

Novel Planar Heterocycles

Chemical space is enormous! It is estimated to comprise some 10(200) distinct drug-like molecules which every single one displays a unique biological activity profile. We are interested in the development of new methodology for the synthesis of new planar heterocycles as such can be incorporated in novel drug-candidates to induce target selectivity, increase potency and/or fine-tune the bioavailability profile.

We have disclosed the first synthesis of oxazolo[4,5-b]pyrazines by a new palladium-catalyzed domino reaction with an intramolecular ring closure of an N-(2-chloro-3-heteroaryl)arylamide:

Published in: Adv Synth & Cat 2014
Highlighted in: Synfacts 2014

Methodology for its functionalization was investigated in collaboration with Prof. Florence Mongin, France and published in Eur J Org Chem

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TBAF Cleaves Boroxazolidones to Corresponding Free Amino Acids

Protection of α-amino acids with 9-borabicyclo[3.3.1]nonane (9-BBN) to give their corresponding boroxazolidones is highly attractive as it concurrently masks both the amino and the carboxylic acid functionalities. However, the required harsh methods for their deprotection have limited its use. In this work we report that tetrabutylammonium fluoride (TBAF) is a mild and versatile reagent for cleaving boroxazolidones to their corresponding free α-amino acids, in high yields.

Published in: Eur J Org Chem 2017