Two distinct classes of novel pyrazolinecarboxamides as potent cannabinoid CB1 receptor agonists

✍ Scribed by Jos H.M. Lange; Amos Attali; Martina A.W. van der Neut; Henri C. Wals; Arie Mulder; Hicham Zilaout; Ate Duursma; Hans H.M. van Aken; Bernard J. van Vliet

• Book ID: 104004662
• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 391 KB
• Volume: 20
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.07.056

✦ Synopsis

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.