56049-48-0Relevant articles and documents
Discovery of N-amido-phenylsulfonamide derivatives as novel microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors
Kim, Misong,Kim, Geuntae,Kang, Minji,Ko, Dohyeong,Nam, Yunchan,Moon, Chang Sang,Kang, Heung Mo,Shin, Ji-Sun,Werz, Oliver,Lee, Kyung-Tae,Lee, Jae Yeol
, (2021)
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.
HYDRAZIDE DERIVATIVES AND THEIR SPECIFIC USE AS ANTIBACTERIAL AGENTS BY CONTROLLING ACINETOBACTER BAUMANNII BACTERIUM
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Page/Page column 49, (2020/09/08)
The present invention relates to compounds of the following general formula (I): or a pharmaceutically acceptable salt and/or solvate thereof, their use as a drug, in particular as antibacterial agent, notablyforpreventingand/or treating disorders associa
N-PHENYL-N'-PHENOXYCARBONYL-PHENYLSULFONHYDRAZIDE DERIVATIVE AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
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Paragraph 0040; 0041; 0046; 0047, (2018/02/04)
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
Synthesis, structure determination, and biological evaluation of phenylsulfonyl hydrazide derivatives as potential anti-inflammatory agents
Park, Eun Beul,Kim, Kwang Jong,Jeong, Hui Rak,Lee, Jae Kyun,Kim, Hyoung Ja,Lee, Hwi Ho,Lim, Ji Woong,Shin, Ji-Sun,Koeberle, Andreas,Werz, Oliver,Lee, Kyung-Tae,Lee, Jae Yeol
, p. 5193 - 5197 (2016/10/30)
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.
