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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
Two distinct classes of novel pyrazolinecarboxamides as potent cannabinoid CB1 receptor agonists
Jos H M Lange1, Amos Attali, Martina A W van der Neut
1Abbott Healthcare Products BV, Chemical Design & Synthesis Unit, Weesp, The Netherlands. jos.lange@abbott.com
Abstract:
The synthesis and SAR of 3-alkyl-4-aryl-4,5-dihydropyrazole-1-carboxamides 1-23 and 1-alkyl-5-aryl-4,5-dihydropyrazole-3-carboxamides 24-27 as two novel cannabinoid CB(1) receptor agonist classes were described. The target compounds elicited high affinities to the CB(1) as well as the CB(2) receptor and were found to act as CB(1) receptor agonists. The key compound 19 elicited potent CB(1) agonistic and CB(2) inverse agonistic properties in vitro and showed in vivo activity in a rodent model for multiple sclerosis after oral administration.
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