52177-75-0

Upstream product

• 75-44-5 phosgene 
• 103-16-2 4-Benzyloxyphenol 
• 32315-10-9 bis(trichloromethyl) carbonate 

Downstream Products

• 1002101-08-7 C₂₄H₂₂N₂O₄ 

Relevant academic research and scientific papers

Discovery of N-amido-phenylsulfonamide derivatives as novel microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors

Our previous research showed that N-carboxy-phenylsulfonyl hydrazide (scaffold A) could reduce LPS-stimulated PGE2 levels in RAW 264.7 macrophage cells by an inhibition of mPGES-1 enzyme. However, a number of scaffold A derivatives showed the drawbacks such as the formation of regioisomers and poor liver metabolic stability. In order to overcome these synthetic and metabolic problems, therefore, we decided to replace N-carboxy-phenylsulfonyl hydrazide (scaffold A) with N-carboxy-phenylsulfonamide (scaffold B) or N-amido-phenylsulfonamide frameworks (scaffold C) as a bioisosteric replacement. Among them, MPO-0186 (scaffold C) inhibited the production of PGE2 (IC50: 0.24 μM) in A549 cells via inhibition of mPGES-1 (IC50: 0.49 μM in a cell-free assay) and was found to be approximately 9- and 8-fold more potent than MK-886 as a reference inhibitor, respectively. A molecular docking study theoretically suggests that MPO-0186 could inhibit PGE2 production by blocking the PGH2 binding site of mPGES-1 enzyme. Furthermore, MPO-0186 demonstrated good liver metabolic stability and no significant inhibition observed in clinically relevant CYP isoforms except CYP2C19. This result provides a potential starting point for the development of selective and potent mPGES-1 inhibitor with a novel scaffold.

N-PHENYL-N'-PHENOXYCARBONYL-PHENYLSULFONHYDRAZIDE DERIVATIVE AND PHARMACEUTICAL COMPOSITION COMPRISING SAME

The present invention relates to a N-phenyl-N'-phenoxycarbonyl-phenylsulfonhydrazide derivative with excellent inhibitory activity on PGE2 production, a method for preparing the same and a pharmaceutical composition comprising the same as an ac

Hit-to-lead optimization of phenylsulfonyl hydrazides for a potent suppressor of PGE2 production: Synthesis, biological activity, and molecular docking study

Preliminary hit-to-lead optimization of a novel series of phenylsulfonyl hydrazide derivatives, which were derived from the high throughput screening hit compound 1 (IC50 = 5700 nM against PGE2 production), for a potent suppressor of

Synthesis, structure determination, and biological evaluation of phenylsulfonyl hydrazide derivatives as potential anti-inflammatory agents

In our previous research, a novel series of phenylsulfonyl hydrazide derivatives were found to reduce LPS-induced PGE2levels in RAW 264.7 macrophage cells via an inhibition of mPGES-1 enzyme. Recently, it was found that a regioisomeric mixture of phenylsulfonyl hydrazide was formed depending on the reaction conditions, which favor either of two regioisomers. One regioisomer corresponds to a kinetic product (7a–7c) and the other regioisomer corresponds to a thermodynamic product (8a–8c). Among them, the structure of kinetic product 7b was confirmed by measuring single X-ray crystallography. In vitro PGE2assay studies showed that the kinetic product (7a and 7b; IC50= 0.69 and 0.55 μM against PGE2) is generally more potent than the thermodynamic product (8a and 8b; IC50= >10 and 0.79 μM against PGE2). A molecular docking study also exhibited that the kinetic product (7a) has a higher MolDock Score (?147.4) than that of 8a (?142.4), which is consistent with the PGE2assay results. A new potent phenylsulfonyl hydrazide (7d; IC50= 0.06 μM against PGE2) without affecting COX-1 and COX-2 enzyme activities was identified based on these overall results.

New N-arachidonoylserotonin analogues with potential "dual" mechanism of action against pain

N-Arachidonoylserotonin (AA-5-HT, 1a) is an inhibitor of fatty acid amide hydrolase (FAAH) that acts also as an antagonist of transient receptor potential vanilloid-type 1 (TRPV1) channels and is analgesic in rodents. We modified the chemical structure of 1a with the aim of developing "hybrid" FAAH/TRPV1 blockers more potent than the parent compound or obtaining analogues with single activity at either of the two targets to study the mechanism of the analgesic action of 1a. Thirty-eight AA-5-HT analogues, containing a serotonin "head" bound to a variety of lipophilic moieties via amide, urea, or carbamate functionalities, were synthesized. Unlike 1a, most of the new compounds possessed activity at only one of the two considered targets. The amides 1b and 1c of α- and γ-linolenic acid, however, showed "hybrid" activity similar to 1a. The carbamate 3f (OMDM106), although unable to antagonize TRPV1 receptors, was the most potent FAAH inhibitor in this study (IC50 = 0.5 μM). Compounds 3f and 1m (OMDM129), which exhibited activity at only FAAH or TRPV1, respectively, were 10-fold less potent than 1a at preventing formalin-induced hyperalgesia in mice.