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Synthetic cannabinoids in drug discovery. Design, synthesis and evaluation of modified coumarins as CB receptor ligands

Beiträge zur organischen Synthese, Bd. 88

Florian Mohr

ISBN 978-3-8325-5103-2
354 pages, year of publication: 2020
price: 52.50 €
The endocannabinoid system represents a highly complex lipid-based (neuro-) transmitter system and can be found in nearly all animals. Since the discovery of the two main cannabinoid receptors CB1 and CB2 in the early '90, intensive research reviled a substantial influence of this system on many physiological and pathophysiological processes. Direct and selective targeting of the system bears a huge potential for the development of novel therapeutic approaches, especially for the treatment of chronical pain, inflammation or other neurological disorders. Therefore, the endocannabinoid system is a promising target in drug development.

In the presented thesis, the design, syntheses and pharmacologic evaluation of substituted coumarins as potential new drug candidates as selective synthetic cannabinoids were investigated. In a combinatorial synthetic approach, several new libraries of new ligands were synthesised and subsequently pharmacological tested.

Additionally, in a second project, novel reversible monoacylglycerol lipase (MAGL) inhibitors have been synthesized and pharmacologically evaluated. Thereby, several important structure-activity relationships for high potency or selectivity were found. Nearly all potencies of the developed inhibitors were determined in the nanomolar regions.

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Table of contents (PDF)

Keywords:

  • Synthetic cannabinoids
  • GPCR
  • cannabinoid receptor
  • drug discovery
  • MAGL

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