1140917-50-5

Upstream product

• 207981-46-2 2-fluoro-5-(trifluoromethyl)benzoyl chloride 
• 1141016-83-2 (R)-3-(tert-butyl)-1-((tetrahydrofuran-2-yl)methyl)-1H-pyrazol-5-amine 
• 1140917-39-0 (R)-3-tert-butyl-1-((tetrahydrofuran-2-yl)methyl)-1H-pyrazol-5-amine 
• 1140917-98-1 (R)-3-tert-butyl-1-((tetrahydrofuran-2-yl)methyl)-1H-pyrazol-5-amine hydrochloride 
• 59997-51-2 trimethylacetylacetonitrile 
• 115029-23-7 2-fluoro-5-(trifluoromethyl)benzoic acid 
• 3282-30-2 pivaloyl chloride 

Downstream Products

• 1217406-00-2 methyl 3-[2-[({(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}amino)carbonyl]-4-(trifluoromethyl)phenoxy]-2,2-dimethylpropanoate 
• 1140917-51-6 N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-fluoro-5-(trifluoromethyl)benzamide 

Relevant academic research and scientific papers

The discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine cannabinoid type 2 receptor agonist

The development of selective CB2 receptor agonists is a promising therapeutic approach for the treatment of inflammatory diseases, without CB1 receptor mediated psychoactive side effects. Preliminary structure-activity relationship studies on pyrazoylidene benzamide agonists revealed the -ylidene benzamide moiety was crucial for functional activity at the CB2 receptor. A small library of compounds with varying linkage moieties between the pyrazole and substituted phenyl group has culminated in the discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine agonist 19 (CB2R EC50 = 19 nM, CB1R EC50 > 10 μM). Docking studies have revealed key structural features of the linkage group that are important for potent functional activity.

Synthesis and evaluation of various heteroaromatic benzamides as analogues of –ylidene-benzamide cannabinoid type 2 receptor agonists

The CB2 receptor is an attractive target for the treatment of a wide range of diseases and pathological conditions. Compounds that selectively activate the CB2 receptor are desirable as this avoids CB1-mediated psychoactive effects. Heteroarylidene-benzamides have demonstrated efficacy as selective CB2 receptor agonists. We aimed to expand the structure-activity relationship studies of this series of compounds by investigating the heteroaromatic core via the synthesis and in vitro evaluation of a small library of various heteroaromatic benzamide analogues. As heteroaromatic amides are privileged scaffolds in drug design, methods to synthesise them are of interest. Concise and reliable synthetic strategies were developed to access these novel analogues. The –ylidene-benzamide moiety is shown to be essential for CB activity as all amide derivatives exhibit no functional activity at either CB2 or CB1 receptors.

COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS

Disclosed herein are compounds of formula (I) wherein Ring A and R1 are as defined in the specification. Pharmaceutical compositions comprising such compounds, and methods for treating conditions and disorders using such compounds and pharmaceutical compositions are also disclosed.

NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS

Disclosed herein are cannabinoid receptor ligands of formula (I) wherein A1, A5, Rx, X4, and z are as defined in the specification. Compositions comprising such compounds, and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS

Disclosed herein are cannabinoid receptor ligands of formula (I) wherein Y, X1, X2, X3, R1, and R2 are as defined in the specification. Compositions comprising such compounds, and methods for treating conditions and disorders using such compounds and compositions are also disclosed.