913624-95-0Relevant academic research and scientific papers
N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazole-3-carboxamide (SR141716A) interaction with LYS 3.28(192) is crucial for its inverse agonism at the cannabinoid CB1 receptor
Hurst, Dow P.,Lynch, Diane L.,Barnett-Norris, Judy,Hyatt, Stephen M.,Seltzman, Herbert H.,Zhong, Miao,Song, Zhao-Hui,Nie, Jingjiang,Lewis, Deborah,Reggio, Patricia H.
, p. 1274 - 1287 (2002)
In superior cervical ganglion neurons, N-(piperidiny-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazole-3-carboxamide (SR141716A) competitively antagonizes the Ca2+ current effect of the cannabinoid (CB) agonist (R)-(+)-[2,3-
2-(5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-N-(2-hydroxyethyl)-2-oxoacetamide (CDMPO) has anti-inflammatory properties in microglial cells and prevents neuronal and behavioral deficits in MPTP mouse model of Parkinson's disease
Cho, Duk-Yeon,Choi, Dong-Kug,Kim, Byungwook,Ko, Hyun Myung,Park, Ju-Young,Yoon, Sung-Hwa
, (2020)
Parkinson's disease (PD) is characterized by the selective loss of nigrostriatal dopamine neurons associated with microglial activation. Inhibition of the inflammatory response elicited by activated microglia could be an effective strategy to alleviate the progression of PD. Here, we synthesized 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-N-(2-hydroxyethyl)-2-oxoacetamide (CDMPO) and studied its protective anti-inflammatory mechanisms following lipopolysaccharide (LPS)-induced neuroinflammation in vitro and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in vivo. CDMPO and its parent compound, rimonabant, significantly attenuated nitric oxide (NO) production in LPS-stimulated primary microglia and BV2 cells. Furthermore, CDMPO significantly inhibited the release of proinflammatory cytokines and prostaglandin E2 (PGE2) by activated BV2 cells, also suppressed expression of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Mechanistically, CDMPO attenuated LPS-induced activation of nuclear factor-kappa B (NF-κB), inhibitor of kappa B alpha (IκBα), and p38 phosphorylation in BV2 cells. MPTP intoxication of mice results in glial activation, tyrosine hydroxylase (TH) depletion, and significant behavioral deficits. Prophylactic treatment with CDMPO decreased proinflammatory molecules via NF-κB and p38 mitogen-activated protein kinase signaling, resulting in protection of dopaminergic neurons and improved behavioral impairments. These results suggest that CDMPO is a promising neuroprotective agent for the prevention and treatment of microglia-mediated neuroinflammatory conditions and may be useful for behavioral improvement in PD phenotype.
Design, synthesis and biological evaluation of CB1 cannabinoid receptor ligands derived from the 1,5-diarylpyrazole scaffold
Tu, Guogang,Xiong, Fang,Huang, Huiming,Kuang, Binhai,Li, Shaohua
, p. 222 - 230 (2011/11/06)
The CB1 receptor belongs to the G-protein-coupled receptor superfamily. CB1 antagonism has been considered as a new therapeutic target for the treatment of obesity. In this study, we report the synthesis and in vitro binding affinity assay of some 1,5-dia
Biarylpyrazole inverse agonists at the cannabinoid CB1 receptor: Importance of the C-3 carboxamide oxygen/lysine3.28(192) interaction
Hurst, Dow,Umejiego, Uju,Lynch, Diane,Seltzman, Herbert,Hyatt, Steven,Roche, Michael,McAllister, Sean,Fleischer, Daniel,Kapur, Ankur,Abood, Mary,Shi, Shanping,Jones, Jannie,Lewis, Deborah,Reggio, Patricia
, p. 5969 - 5987 (2007/10/03)
The biarylpyrazole, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1#-pyrazole-3-carboxamide (SR141716; 1) has been shown to act as an inverse agonist/antagonist at the cannabinoid CB1 receptor. Our previous mutant cycle study sugg
