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Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Keynote review: Medicinal chemistry strategies to CB1 cannabinoid receptor antagonists
1Solvay Pharmaceuticals, Research Laboratories, C. J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands. jos.lange@solvay.com
Abstract:
The proven clinical efficacy of the CB(1) cannabinoid receptor antagonist rimonabant in both obesity and smoking cessation and its therapeutic potential in other disorders has given a tremendous impetus to the discovery of novel CB(1) antagonists. The number of disclosed patents wherein novel chemical entities having CB(1) antagonistic or inverse agonistic properties have been claimed has exploded. Besides novel compound classes that were identified in screening, rational medicinal chemistry approaches such as conformational constraint and scaffold hopping have been successfully applied. CB(1) receptor modelling has provided insight into crucial receptor-ligand interaction points thereby leading to a general CB(1) inverse agonist pharmacophore model.
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