Hydroalkylation of Vinylarenes by Transition‐Metal‐Free In Situ Generation of Benzylic Nucleophiles Using Tetramethyldisiloxane and Potassium tert‐Butoxide

Article

Author: Nugraha, Hana ; Newman, Stephen G. ; Onge, Piers St.

AbstractHydrosilanes and Lewis bases are known to promote various reductive defunctionalizations, rearrangements, and silylation reactions, facilitated by enigmatic silicon/Lewis base‐derived reactive intermediates. Despite the wide variety of transformations enabled by this reagent combination, no examples of intermolecular C(sp3)−C(sp3) forming reactions have been reported. In this work, we've identified 1,1,3,3‐tetramethyldisiloxane (TMDSO) and KOtBu as a unique reagent combination capable of generating benzylic nucleophiles in situ from styrene derivatives, which can subsequently react with alkyl halides to give a new C(sp3)−C(sp3) linkage via formal hydroalkylation. Mechanistic experiments suggest that the reaction proceeds through a key hydrogen atom transfer (HAT) step from a hydrosilane reducing agent to styrene, affording a benzylic radical that undergoes reductive radical polar crossover (RRPC) and subsequent SN2 alkylation.

13 Dec 2024·ACS Pharmacology & Translational Science

Repurposing Drugs and Synergistic Combinations as Potential Therapies for Inhibiting SARS-CoV-2 and Coronavirus Replication

Article

Author: Anton, Anaïs ; Farahani, Majid D. ; Ayotte, Yann ; Boulon, Richard ; Chatel-Chaix, Laurent ; LaPlante, Steven R. ; Lamarre, Alain ; Iddir, Mustapha ; Charpentier, Tania ; Broquière, Mathilde ; Woo, Simon ; Mazeaud, Clément

Drug repurposing can serve an important role in rapidly discovering medicament options for emerging microbial pandemics. In this study, a pragmatic approach is demonstrated for screening and testing drug combinations as potential broad-spectrum therapies against SARS-CoV-2 and other betacoronaviruses. Rapid cell-based phenotypic small molecule screens were executed using related common-cold-causing HCoV-OC43 betacoronavirus to identify replication inhibitors from a library of drugs approved by regulatory agencies for other indications. Given the best inhibitors, an expedient checkerboard strategy then served to identify synergistic drug combinations. These combinations were then validated using more challenging assays involving SARS-CoV-2 and variants. Promising drug combinations against multiple viral variants were discovered and involved Tilorone with Nelfinavir or Molnupiravir.

01 Dec 2024·Science of The Total Environment

Temporal trends and sources of organic micropollutants in wastewater

Article

Author: Christensen, Jan H ; Mortensen, Peter ; Jørgensen, Mathias B ; Tisler, Selina ; Kilpinen, Kristoffer

Effluent wastewater from conventional wastewater treatment plants (WWTPs) is a source of environmental micropollutants. This study investigated temporal trends of organic micropollutants in effluent wastewater, aiming to identify underlying drivers and their implications for treatment efficiency. From September to December 2022, we collected 168 effluent and 10 influent samples. These samples were concentrated using a three-layer solid-phase extraction method and analyzed by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Both targeted and suspect screening approaches were employed, allowing for the full quantification of 64 micropollutants and the identification of 90 additional compounds through suspect screening. Correlations revealed distinct groups of micropollutants with similar temporal trends, indicating common sources or behaviors during treatment. Notably, caffeine and paracetamol showed strong correlations with influent flow rates, indicating their removal efficiency is significantly influenced by hydraulic conditions. PFAS compounds, tire-wear chemicals, and biocides correlated with rain events. Micropollutants were categorized into nine groups based on their temporal trends, linking them to sources and persistence in the WWTP. Industrial discharges significantly contributed to spikes in pharmaceuticals like amitriptyline and citalopram. Metabolite analysis effectively distinguishing between sources of consumption and industrial discharge. These findings underscore the need for regulatory frameworks addressing a broader range of micropollutants. Key events such as rain and industrial discharges impact micropollutant composition and concentrations in effluent wastewater. Our study provides insights into their dynamics within WWTPs, informing improved treatment strategies.

100 Deals associated with Chlorprothixene hydrochloride

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KEGG	Wiki	ATC	Drug Bank
D02162	Chlorprothixene hydrochloride	N05AF03	-

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Indication	Country/Location	Organization	Date
Behavioural disorders	China	Heilongjiang Ruige Pharmaceutical Co., Ltd.	-

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