92367-07-2Relevant academic research and scientific papers
Salicylanilides Reduce SARS-CoV-2 Replication and Suppress Induction of Inflammatory Cytokines in a Rodent Model
Beutler, Nathan,Blake, Steven,Eubanks, Lisa M.,Janda, Kim D.,Ji, Henry,Manning, John T.,Maruyama, Junki,Paessler, Slobodan,Shaabani, Namir,Teijaro, John R.
, p. 2229 - 2237 (2021/08/24)
SARS-CoV-2 virus has recently given rise to the current COVID-19 pandemic where infected individuals can range from being asymptomatic, yet highly contagious, to dying from acute respiratory distress syndrome. Although the world has mobilized to create antiviral vaccines and therapeutics to combat the scourge, their long-term efficacy remains in question especially with the emergence of new variants. In this work, we exploit a class of compounds that has previously shown success against various viruses. A salicylanilide library was first screened in a SARS-CoV-2 activity assay in Vero cells. The most efficacious derivative was further evaluated in a prophylactic mouse model of SARS-CoV-2 infection unveiling a salicylanilide that can reduce viral loads, modulate key cytokines, and mitigate severe weight loss involved in COVID-19 infections. The combination of anti-SARS-CoV-2 activity, cytokine inhibitory activity, and a previously established favorable pharmacokinetic profile for the lead salicylanilide renders salicylanilides in general as promising therapeutics for COVID-19.
Salicylanilide Analog Minimizes Relapse of Clostridioides difficile Infection in Mice
Blake, Steven,Thanissery, Rajani,Rivera, Alissa J.,Hixon, Mark S.,Lin, Mingliang,Theriot, Casey M.,Janda, Kim D.
, p. 6898 - 6908 (2020/07/28)
Clostridioides difficile infection (CDI) causes serious and sometimes fatal symptoms like diarrhea and pseudomembranous colitis. Although antibiotics for CDI exist, they are either expensive or cause recurrence of the infection due to their altering the colonic microbiota, which is necessary to suppress the infection. Here, we leverage a class of known membrane-targeting compounds that we previously showed to have broad inhibitory activity across multiple Clostridioides difficile strains while preserving the microbiome to develop an efficacious agent. A new series of salicylanilides was synthesized, and the most potent analog was selected through an in vitro inhibitory assay to evaluate its pharmacokinetic parameters and potency in a CDI mouse model. The results revealed reduced recurrence of CDI and diminished disturbance of the microbiota in mice compared to standard-of-care vancomycin, thus paving the way for novel therapy that can potentially target the cell membrane of C. difficile to minimize relapse in the recovering patient.
Synthesis and Energetic Properties of 4-Diazo-2,6-dinitrophenol and 6-Diazo-3-hydroxy-2,4-dinitrophenol
Klap?tke, Thomas M.,Preimesser, Andreas,Stierstorfer, J?rg
, p. 4311 - 4315 (2015/07/27)
4-Amino-3,5-dinitroaniline (3) was synthesized by fluorine/amine exchange of 4-fluoro-3,5-dinitroaniline in ethanol. 4-Diazo-2,6-dinitrophenol (Iso-DDNP, 4) was obtained after nitration in HNO3 (100%) and acetic anhydrid. 4-Amino-2,3,5-trinitrophenol (7) was obtained by nitration of N-(4-acetoxyphenyl)acetamide and deprotection of the amine. Further nitration resulted in 6-diazo-3-hydroxy-2,4-dinitrophenol (8). The thermal stability and sensitivity of 4 and 8 toward impact and friction was compared to commercially used DDNP (2-diazo-4,6-dinitrophenol). All target compounds were characterized by single-crystal X-ray diffraction, NMR and elemental analysis and DSC. The sensitivities were determined by BAM methods (drophammer and friction tester). The heats of formation were calculated by using CBS-4M electronic enthalpies and the atomization method. Various detonation parameters such as detonation velocity and pressure were computed by using the EXPLO5 computer code V6.01. The very sensitive diazophenol derivatives diazo-2,6-dinitrophenol and 6-diazo-3-hydroxy-2,4-dinitrophenol could be synthesized by nitration reactions. They are promising alternatives to the commercially used sensitizer DDNP (2-diazo-4,6-dinitrophenol).
Design, synthesis, and biological evaluation of (E)-N-Aryl-2- arylethenesulfonamide analogues as potent and orally bioavailable microtubule-targeted anticancer agents
Reddy, M. V. Ramana,Mallireddigari, Muralidhar R.,Pallela, Venkat R.,Cosenza, Stephen C.,Billa, Vinay K.,Akula, Balaiah,Subbaiah, D. R. C. Venkata,Bharathi, E. Vijaya,Padgaonkar, Amol,Lv, Hua,Gallo, James M.,Reddy, E. Premkumar
, p. 5562 - 5586 (2013/07/26)
A series of novel (E)-N-aryl-2-arylethenesulfonamides (6) were synthesized and evaluated for their anticancer activity. Some of the compounds in this series showed potent cytotoxicity against a wide spectrum of cancer cell-lines (IC50 values ranging from 5 to 10 nM) including all drug resistant cell-lines. Nude mice xenograft assays with compound (E)-N-(3-amino-4- methoxyphenyl)-2-(2′,4′,6′-trimethoxyphenyl)ethenesulfonamide (6t) showed dramatic reduction in tumor size, indicating their in vivo potential as anticancer agents. A preliminary drug development study with compound 6t is predicted to have increased blood-brain barrier permeability relative to many clinically used antimitotic agents. Mechanistic studies indicate that 6t and some other analogues disrupted microtubule formation, formation of mitotic spindles, and arrest of cells in mitotic phase. Compound 6t inhibited purified tubulin polymerization in vitro and in vivo and circumvented drug resistance mediated by P-glycoprotein. Compound 6t specifically competed with colchicine binding to tubulin and with similar avidity as podophylltoxin, indicating its binding site on tubulin.
Nitrocarbons. 4. Reaction of Polynitrobenzenes with Hydrogen Halides. Formation of Polynitrohalobenzenes
Nielsen, Arnold T.,Chafin, Andrew P.,Christian, Stephen L.
, p. 4575 - 4580 (2007/10/02)
Hexanitrobenzene and pentanitrobenzene in benzene solution react with hydrogen halides (HCl, HBr, HI, but not HF) at 25 deg C to produce high yields of pentanitrohalobenzenes and 2,3,4,6-tetranitrohalobenzenes, respectively.Pentanitrofluorobenzene also reacts readily with HCl to yield 3-chloro-2,4,5,6-tetranitrofluorobenzene, but the other pentanitrohalobenzenes are much less reactive. 1,2,3,5- and 1,2,4,5-tetranitrobenzenes react rapidly with concentrated hydrochloric or hydrobromic acids at reflux to form picryl halides and 1-halo-2,4,5-trinitrobenzenes, respectively; pentanitrotoluene reacts very slowly under these conditions to form 3-halo-2,4,5,6-tetranitrotoluenes in lower yields.The scope and limitations of this regioselective reaction are defined, and comparison is made to related reactions.A mechanism is presented and discussed.
