710299-13-1Relevant academic research and scientific papers
Synthesis and structure-activity relationships (SARs) of 1,5-diarylpyrazole cannabinoid type-1 (CB1) receptor ligands for potential use in molecular imaging
Donohue, Sean R.,Halldin, Christer,Pike, Victor W.
, p. 3712 - 3720 (2007/10/03)
Cannabinoid type-1 (CB1) receptor ligands, derived from the 1,5-diarylpyrazole core template of rimonabant (Acomplia), have been the focus of several studies aimed at examining structure-activity relationships (SARs). The purpose of this study was to design and synthesize a set of compounds based on the 1,5-diarylpyrazole template while focusing on the potential for discovery of CB1 receptor radioligands that might be used as probes with in vivo molecular imaging. Each synthesized ligand was evaluated for potency as an antagonist at CB1 and cannabinoid type-2 (CB2) receptors in vitro using a GTPγ35S-binding assay. c log P values were calculated with Pallas 3.0. The antagonist binding affinities (KB) at CB1 receptors ranged from 11 to >16,000 nM, CB1 versus CB2 selectivities from 0.6 to 773, and c log Ps from 3.61 to 6.25. An interesting new ligand, namely N-(piperidin-1-yl)-1-(2-bromophenyl)-5-(4-methoxyphenyl)-4-methyl-1H-pyrazole-3-carboxamide (9j), emerged from the synthesized set with appealing properties (KB = 11 nM; CB1 selectivity > 773; c log P = 5.85), for labeling with carbon-11 and development as a radioligand for imaging brain CB1 receptors in vivo with positron emission tomography (PET).
Synthesis of [O-methyl-11C]1-(2-chlorophenyl)-5-(4- methoxyphenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide: A potential PET ligand for CB1 receptors
Kumar, J.S. Dileep,Prabhakaran, Jaya,Arango, Victoria,Parsey, Ramin V.,Underwood, Mark D.,Simpson, Norman R.,Kassir, Suham A.,Majo, Vattoly J.,Van Heertum, Ronald L.,Mann, J. John
, p. 2393 - 2396 (2007/10/03)
Synthesis and in vitro evaluation of [O-methyl-11C]1-(2- chlorophenyl)-5-(4-methoxyphenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide ([11C]-1), a potential imaging agent for CB 1 receptors using PET is described. 1-(2-Chlorophenyl)-5-(4- hydroxyphenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide (5), the precursor for radiolabeling, was synthesized from 4-OTBDPS-propiophenone (2) in five steps with 30% overall yield. The reaction of alcohol 5 with [ 11C]MeOTf at 60°C afforded [11C]-1 with an average radiochemical yield of 14.5% (EOS) and >2000Ci/mmol specific activity. The radiotracer was found to selectively label CB1 receptors in slide-mounted sections of postmortem human brain containing prefrontal cortex as demonstrated by in vitro autoradiography using phosphor imaging.
