144-83-2Relevant academic research and scientific papers
Enzyme-responsive controlled release of covalently bound prodrug from functional mesoporous silica nanospheres
Popat, Amirali,Ross, Benjamin P.,Liu, Jian,Jambhrunkar, Siddharth,Kleitz, Freddy,Qiao, Shi Zhang
, (2012)
I want to break free: Mesoporous silica nanoparticles are functionalized with sulfasalazine (SZ; see scheme), a prodrug of 5-aminosalicylic acid (5-ASA) and sulfapyridine, to generate enzyme-responsive nanocarriers. In the presence of the colon-specific e
Design, synthesis and biological evaluation of novel naphthoquinone-4-aminobenzensulfonamide/carboxamide derivatives as proteasome inhibitors
Uysal, Sirin,Soyer, Zeynep,Saylam, Merve,Tarikogullari, Ayse H.,Yilmaz, Sinem,Kirmizibayrak, Petek Ballar
, (2020/10/12)
A series of novel 4-aminobenzensulfonamide/carboxamide derivatives bearing naphthoquinone pharmacophore were designed, sythesized and evaluated for their proteasome inhibitory and antiproliferative activities against human breast cancer cell line (MCF-7). The structures of the synthesized compounds were confirmed by spectral and elemental analyses. The proteasome inhibitory activity studies were carried out using cell-based assay. The antiproteasomal activity results revealed that most of the compounds exhibited inhibitory activity with different percentages against the caspase-like (C-L, β1 subunit), trypsin-like (T-L, β2 subunit) and chymotrypsin-like (ChT-L, β5 subunit) activities of proteasome. Among the tested compounds, compound 14 bearing 5-chloro-2-pyridyl ring on the nitrogen atom of sulfonamide group is the most active compound in the series and displayed higher inhibition with IC50 values of 9.90 ± 0.61, 44.83 ± 4.23 and 22.27 ± 0.15 μM against ChT-L, C-L and T-L activities of proteasome compared to the lead compound PI-083 (IC50 = 12.47 ± 0.21, 53.12 ± 2.56 and 26.37 ± 0.5 μM), respectively. The antiproliferative activity was also determined by MTT (3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay in vitro. According to the antiproliferative activity results, all of the compounds exhibited cell growth inhibitory activity in a range of IC50 = 1.72 ± 0.14–20.8 ± 0.5 μM and compounds 13 and 28 were found to be the most active compounds with IC50 values of 1.79 ± 0.21 and 1.72 ± 0.14 μM, respectively. Furthermore, molecular modeling studies were carried out for the compounds 13, 14 and 28 to investigate the ligand-enzyme binding interactions.
Structure-activity relationships of agonists for the orphan G protein-coupled receptor GPR27
Blavier, Jeremy,Charles, Ma?lle,Hanson, Julien,Kronenberger, Thales,Laschet, Céline,Müller, Christa E.,Pillaiyar, Thanigaimalai,Rosato, Francesca,Wozniak, Monika
, (2021/08/27)
GPR27 belongs, with GPR85 and GPR173, to a small subfamily of three receptors called “Super-Conserved Receptors Expressed in the Brain” (SREB). It has been postulated to participate in key physiological processes such as neuronal plasticity, energy metabolism, and pancreatic β-cell insulin secretion and regulation. Recently, we reported the first selective GPR27 agonist, 2,4-dichloro-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (I, pEC50 6.34, Emax 100%). Here, we describe the synthesis and structure-activity relationships of a series of new derivatives and analogs of I. All products were evaluated for their ability to activate GPR27 in an arrestin recruitment assay. As a result, agonists were identified with a broad range of efficacies including partial and full agonists, showing higher efficacies than the lead compound I. The most potent agonist was 4-chloro-2,5-difluoro-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (7y, pEC50 6.85, Emax 37%), and the agonists with higher efficacies were 4-chloro-2-methyl-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (7p, pEC50 6.04, Emax 123%), and 2-bromo-4-chloro-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (7r, pEC50 5.99, Emax 123%). Docking studies predicted the putative binding site and interactions of agonist 7p with GPR27. Selected potent agonists were found to be soluble and devoid of cellular toxicity within the range of their pharmacological activity. Therefore, they represent important new tools to further characterize the (patho)physiological roles of GPR27.
Preparing method of sulfanilamide compound
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Paragraph 0038; 0039; 0040; 0041; 0042, (2017/06/02)
The invention belongs to the technical field of organic synthesis and the field of sulfonamides, and in particular discloses a preparing method of a sulfanilamide compound. The preparing method particularly comprises the steps of reacting bis (2-nitrophenyl) disulfide and miscellaneous aromatic amine compound under conditions of reducing agent, oxidant and solvent to obtain the sulfanilamide compound. According to the preparing method of a sulfanilamide compound, cheap zirconium salt and copper salt are adopted as catalyst, stable and low toxic disulfide is directly used as sulfonylation reagent, sulfonylation for amine is conducted directly, finishing at usual atmospheric pressure avoids the step of preparing sulfonyl chloride, therefore avoiding using strong corrosive substances as shlorine, thionyl chloride and the like. And the method is more simple and environment-friendly, conforming to the demand of developing green chemical industry in the current world.
Structure-based virtual screening and optimization of modulators targeting Hsp90-Cdc37 interaction
Wang, Lei,Li, Li,Zhou, Zi-Han,Jiang, Zheng-Yu,You, Qi-Dong,Xu, Xiao-Li
, p. 63 - 73 (2017/05/10)
Identification of novel Hsp90 inhibitors to disrupt Hsp90-Cdc37 protein-protein interaction (PPI) could be an alternative strategy to achieve Hsp90 inhibition. In this paper, a series of small molecules targeting Hsp90-Cdc37 complex are addressed and characterized. The molecules' key characters are determined by utilizing a structure-based virtual screening workflow, derivatives synthesis, and biological evaluation. Structural optimization and structure–activity relationship (SAR) analysis were then carried out on the virtual hit of VS-8 with potent activity, which resulted in the discovery of compound 10 as a more potent regulator of Hsp90-Cdc37 interaction with a promising inhibitory effect (IC50?=?27?μM), a moderate binding capacity (KD?=?40?μM) and a preferable antiproliferative activity against several cancer lines including MCF-7, SKBR3 and A549?cell lines (IC50?=?26?μM, 15?μM and 38?μM respectively). All the data suggest that compound 10 exhibits moderate inhibitory effect on Hsp90-Cdc37 and could be regard as a first evidence of a non-natural compound targeting Hsp90-Cdc37 PPI.
Method for synthesizing salazosulfapyridine by utilizing 2-aminopyridine as raw material
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Paragraph 0044, (2016/10/10)
The invention discloses a method for synthesizing salazosulfapyridine by utilizing 2-aminopyridine as a raw material. The method comprises the steps: step 1, performing a sulfamation reaction on 2-aminopyridine and para-acetylaminobenzene sulfonyl chloride in an aqueous solution of potassium carbonate; step 2, firstly performing hydrolyzation in DMSO-water mixed solution of sodium hydroxide, and then performing hydrochloric acid acidification; step 3, performing a diazo-reaction in an aqueous solution dissolving hydrochloric acid and sodium nitrite; step 4, performing a coupling reaction on diazonium salt and salicylic acid in an aqueous solution of sodium hydroxide. According to the method for synthesizing salazosulfapyridine by utilizing the 2-aminopyridine as the raw material, the 2-aminopyridine is taken as a starting raw material, and then is sequentially subjected to the sulfamation reaction, the hydrolyzation, the acidification, the diazo-reaction and the coupling reaction to obtain the salazosulfapyridine. The diazo-reaction and the coupling reaction have high conversation rate and a few side reaction so as to improve the purity of products and ensure the efficiency; furthermore, the source of the 2-aminopyridine is easy, the production cost is reduced, and the industrial production cost is large.
Structure-guided design of potent diazobenzene inhibitors for the BET bromodomains
Zhang, Guangtao,Plotnikov, Alexander N.,Rusinova, Elena,Shen, Tong,Morohashi, Keita,Joshua, Jennifer,Zeng, Lei,Mujtaba, Shiraz,Ohlmeyer, Michael,Zhou, Ming-Ming
, p. 9251 - 9264 (2014/01/06)
BRD4, characterized by two acetyl-lysine binding bromodomains and an extra-terminal (ET) domain, is a key chromatin organizer that directs gene activation in chromatin through transcription factor recruitment, enhancer assembly, and pause release of the RNA polymerase II complex for transcription elongation. BRD4 has been recently validated as a new epigenetic drug target for cancer and inflammation. Our current knowledge of the functional differences of the two bromodomains of BRD4, however, is limited and is hindered by the lack of selective inhibitors. Here, we report our structure-guided development of diazobenzene-based small-molecule inhibitors for the BRD4 bromodomains that have over 90% sequence identity at the acetyl-lysine binding site. Our lead compound, MS436, through a set of water-mediated interactions, exhibits low nanomolar affinity (estimated Ki of 30-50 nM), with preference for the first bromodomain over the second. We demonstrated that MS436 effectively inhibits BRD4 activity in NF-κB-directed production of nitric oxide and proinflammatory cytokine interleukin-6 in murine macrophages. MS436 represents a new class of bromodomain inhibitors and will facilitate further investigation of the biological functions of the two bromodomains of BRD4 in gene expression.
Process for formulating a synthetic drug for use in animal feed, and resulting formulation
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, (2008/06/13)
A method of formulating a synthetic drug for use in animal feed, for the purpose of reducing carry-over of the synthetic drug to subsequent lots of animal feed in the feed mill.
