Two distinct classes of novel pyrazolinecarboxamides as potent cannabinoid CB1 receptor agonists.
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.
Lange
Jos H M
JH
Abbott Healthcare Products BV, Chemical Design & Synthesis Unit, Weesp, The Netherlands. jos.lange@abbott.com
Attali
Amos
A
van der Neut
Martina A W
MA
Wals
Henri C
HC
Mulder
Arie
A
Zilaout
Hicham
H
Duursma
Ate
A
van Aken
Hans H M
HH
van Vliet
Bernard J
BJ
D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*
D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1