86790-39-8

Upstream product

• 17639-93-9 2-chloro-propionic acid methyl ester 
• 1493-27-2 ortho-nitrofluorobenzene 
• 67-56-1 methanol 

Downstream Products

• 90500-55-3 (±)-methyl 2-(4-amino-3-fluorophenyl)propanoate 
• 1402585-79-8 (±)-methyl 2-(3-fluoro-4-iodophenyl)propanoate 
• 5104-49-4 (S)-(+)-flurbiprofen 
• 5104-49-4 (R)-flurbiprofen 
• 749917-25-7 2-(3-fluoro-4-iodophenyl)propionic acid 
• 1428765-65-4 tert-butyl N-(2-fluoro-4-(1-oxo-1-((2-m-tolyl-6-(trifluoromethyl)pyridin-3-yl)methylamino)propan-2-yl)benzyl)sulfamoylcarbamate 
• 1428765-64-3 2-(4-(aminomethyl)-3-fluorophenyl)-N-((2-m-tolyl-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide 
• 1428765-63-2 2-(4-cyano-3-fluorophenyl)-N-((2-m-tolyl-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide 
• 1402585-20-9 2-(4-cyano-3-fluorophenyl)propanoic acid 
• 1428765-01-8 2-(3-fluoro-4-((sulfamoylamino)methyl)phenyl)-N-((2-m-tolyl-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide 
• 403-21-4 3-fluoro-4-nitrobenzoic acid 

Relevant academic research and scientific papers

Potent multitarget FAAH-COX inhibitors: Design and structure-activity relationship studies

Non-steroidal anti-inflammatory drugs (NSAIDs) exert their pharmacological effects by inhibiting cyclooxygenase (COX)-1 and COX-2. Though widely prescribed for pain and inflammation, these agents have limited utility in chronic diseases due to serious mechanism-based adverse events such as gastrointestinal damage. Concomitant blockade of fatty acid amide hydrolase (FAAH) enhances the therapeutic effects of the NSAIDs while attenuating their propensity to cause gastrointestinal injury. This favorable interaction is attributed to the accumulation of protective FAAH substrates, such as the endocannabinoid anandamide, and suggests that agents simultaneously targeting COX and FAAH might provide an innovative strategy to combat pain and inflammation with reduced side effects. Here, we describe the rational design and structure-active relationship (SAR) properties of the first class of potent multitarget FAAH-COX inhibitors. A focused SAR exploration around the prototype 10r (ARN2508) led to the identification of achiral (18b) as well as racemic (29a-c and 29e) analogs. Absolute configurational assignment and pharmacological evaluation of single enantiomers of 10r are also presented. (S)-(+)-10r is the first highly potent and selective chiral inhibitor of FAAH-COX with marked in vivo activity, and represents a promising lead to discover novel analgesics and anti-inflammatory drugs.

MULTITARGET FAAH AND COX INHIBITORS AND THERAPEUTICAL USES THEREOF

Multitarget inhibitors of the enzymes Fatty Acid Amide Hydrolase (FAAH), Cyclooxygenase-1 (COX-1) and/or Cyclooxygenase-2 (COX-2) having a specific carbamate moiety on the meta or ortho position of the A ring of a substituted biphenyl core and having an h

MULTITARGET FAAH AND COX INHIBITORS AND THERAPEUTICAL USES THEREOF

The invention provides novel multitarget inhibitors of the enzymes Fatty Acid Amide Hydrolase (FAAH), Cyclooxygenase-1 (COX-1) and/or Cyclooxygenase-2 (COX-2) having a specific carbamate moiety on the meta or ortho position of the A ring of a substituted

MULTITARGET FAAH AND COX INHIBITORS AND THERAPEUTICAL USES THEREOF

The invention provides novel multitarget inhibitors of the enzymes Fatty Acid Amide Hydrolase (FAAH), Cyclooxygenase-1 (COX-1) and/or Cyclooxygenase-2 (COX-2) having a specific carbamate moiety on the meta or ortho position of the A ring of a substituted

Aryl or N-heteroaryl Substituted Methanesulfonamide Derivatives as Vanilloid Receptor Ligands

The invention relates to aryl or N-heteroaryl substituted methanesulfonamide derivatives as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.

ARYL OR N-HETEROARYL SUBSTITUTED METHANESULFONAMIDE DERIVATIVES AS VANILLOID RECEPTOR LIGANDS

The invention relates to aryl or N-heteroaryl substituted methanesulfonamide derivatives of Formula (I) as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.

Elucidation of the vicarious nucleophilic substitution of hydrogen mechanism via studies of competition between substitution of hydrogen, deuterium, and fluorine

Relations of rates of the vicarious nucleophilic substitution of hydrogen (VNS) and SNAr substitution of fluorine in 2-fluoronitrobenzenes with chloroalkyl aryl sulfone carbanions were determined from competitive experiments carried out at various concentrations of base. The observed dependence of the VNS/SNAr rate ratio on the base concentration confirmed the two-step mechanism of the VNS, which consists of reversible formation of σH adducts of the α-chlorocarbanion to nitroarene, followed by base-induced β-elimination of HCl. It was also evidenced that both of these processes can be the rate-limiting steps: the β-elimination at low base concentration and the nucleophilic addition at high base concentration. Consistent with that conclusion is the finding that the kinetic isotope effect in the VNS reaction decreases from 4.2 (a value typical of a primary KIE) to 0.8 (a value typical of a secondary KIE) with increasing base concentration. Also reported is our discovery that the SNAr substitution of the 2-fluoronitrobenzenes studied in this work was subject to base catalysis under some of the experimental conditions employed in our competitive experiments.

Synthesis of selectively deuterated nitrobenzene derivatives

Selectively ortho-deuterated nitroarenes of high isotopic purity are prepared via acid catalysed H→D exchange in para-substituted anilines followed by oxidation of the amino groups.

Synthesis of 2-(4-Nitroaryl)propionate Esters

Alkyl 2-chloropropionates react with nitroaromatic compounds on treatment with base to give alkyl 2-(4-nitroaryl)propionates in good yield.