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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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Godlewska, Klaudia ; Białk-Bielińska, Anna ; Rostkowski, Pawel ; Paszkiewicz, Monika ;
Abstract: Tire wear particles are generated during driving a vehicle as a result of friction between tires and road surfaces and are released into environment. Knowledge of their environmental occurrence and fate is still limited. In this study, we investigated the presence of 16 tire wear contaminants (TWCs) and their transformation products in the surface waters, tap water and soils in Poland.The developed extraction methods were used with recoveries in the range of 71–100% (except for 2-methylthio-benzothiazole - 51%) for water samples and in the range of 62–97% for soil samples. Ten TWCs were detected in soil samples, with the highest concentration of benzothiazole (BTH)(387 ng/g). Meanwhile, all analytes were detected in water samples, also with the highest concentration of BTH (326 ng/L). N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-Q), 1,3-diphenylguanidine (DPG) and BTH were detected in all examined surface waters. P-phenylenediamine-quinones(PPD-Qs)were detected in higher concentrations (1.85–297 ng/l) compared to the parent compounds (0.50–58 ng/l) in surface waters. Conversely, for soil samples, PPDs (0.170–116 ng/g) were more prevalent than PPD-Qs (0.167–4.71 ng/g). 6PPD-Q showed high ecological risks at all surface water sites. This is the first report on the TWCs levels in the environment in Poland.
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Keywords: Tire wear contaminants ; Transformation products ; 6PPD-Q ; Environmental analysis ; Environmental risk assessment
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Ru(ii)–arene azole complexes as anti-amyloid-β agents
Ryan M. Hacker ; Daniela M. Grimard ; Katie A. Morgan ; Eaman Saleh ; Morgan M. Wrublik ; Cade J. Meiss , et al.
Abstract: With the recent clinical success of anti-amyloid-β (Aβ) monoclonal antibodies, there is a renewed interest in agents which target the Aβ peptide of Alzheimer's disease (AD). Metal complexes are particularly well-suited for this development, given their structural versatility and ability to form stabile interactions with soluble Aβ. In this report, a small series of ruthenium–arene complexes were evaluated for their respective ability to modulate both the aggregation and cytotoxicity of Aβ. First, the stability of the complexes was evaluated in a variety of aqueous media where the complexes demonstrated exceptional stability. Next, the ability to coordinate and modulate the Aβ peptide was evaluated using several spectroscopic methods, including thioflavin T (ThT) fluorescence, dynamic light scattering (DLS), and transmission electron microscopy (TEM). Overall, the complex RuBO consistently gave the greatest inhibitory action towards Aβ aggregation, which correlated with its ability to coordinate to Aβ in solution. Furthermore, RuBO also had the lowest affinity for serum albumin, which is a key consideration for a neurotherapeutic, as this protein does not cross the blood brain barrier. Lastly, RuBO also displayed promising neuroprotective properties, as it had the greatest inhibition of Aβ-inducted cytotoxicity.
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Novel amides of mycophenolic acid and some heterocyclic derivatives as immunosuppressive agents
Walczak, Juliusz Maksymilian ; Iwaszkiewicz-Grzes, Dorota ; Ziomkowska, Michalina ; Sliwka-Kaszynska, Magdalena ; Dasko, Mateusz ; Trzonkowski, Piotr , et al.
Abstract: The group of 18 new amide derivatives of mycophenolic acid (MPA) and selected heterocyclic amines was synthesised as potential immunosuppressive agents functioning as inosine-5′-monophosphate dehydrogenase (IMPDH) uncompetitive inhibitors. The synthesis of 14 of them employed uronium-type activating system (TBTU/HOBt/DIPEA) while 4 of them concerned phosphonic acid anhydride method (T3P/Py) facilitating amides to be obtained in moderate to excellent yields without the need of phenolic group protection. Most of optimised protocols did not require complicated reaction work-ups, including chromatographic, solvent-consuming methods. The biological activity assay was performed on the T-Jurkat cell line and peripheral mononuclear blood cells (PBMCs) which are both dedicated for antiproliferative activity determination. Each of designed derivatives was characterised by reduced cytotoxicity and benzoxazole analogue (A2) revealed the most promising activity. Subsequently, an observed structure-activity relationship was discussed.
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Keywords: Mycophenolic acid ; amide derivatives ; heterocycles ; benzoxazole ; IMPDH inhibition
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Purchased from AmBeed: 934-32-7 ; 1477-42-5 ; 5464-79-9 ; 5464-79-9 ; 136-95-8 ; 95-24-9 ; 533-30-2 ; 1123-93-9 ; 6285-57-0 ; 15864-32-1 ; 29927-08-0 ; 348-40-3 ; 58-63-9 ; 4570-41-6 ; 75985-45-4 ; 24280-93-1 ; 2536-91-6 ; 19952-47-7 ; 1747-60-0 ; 777-12-8 ; 63837-12-7 ; 58-63-9
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CAS No. : | 136-95-8 |
Formula : | C7H6N2S |
M.W : | 150.20 |
SMILES Code : | NC1=NC2=CC=CC=C2S1 |
MDL No. : | MFCD00005785 |
InChI Key : | UHGULLIUJBCTEF-UHFFFAOYSA-N |
Pubchem ID : | 8706 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H319 |
Precautionary Statements: | P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: we started with the4-methyl-1-piperazine carbonyl chloride (Scheme 1). By reactionof this compound with the corresponding amine in dry pyridineas solvent, at room temperature, the urea derivative crystallizedas hydrochloride. The hydrochloride was dissolved in water, basifiedwith aqueous Na2CO3 (10%) and extracted with CH2Cl2. The organiclayer was dried over Na2SO4 and the solvent was removed toafford a residue, which was purified by chromatography column toobtain the corresponding ureas 1-5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | In toluene; at 100℃; for 0.166667h;Microwave irradiation; Sealed tube; | General procedure: General Procedure (GP): In a MW sealed-tube equipped with a magnetic stirring bar, to a 0.5 M solution of aldehyde (1.0 equiv.) in anhydrous toluene [0.5 M], amine (1.0 equiv.) and isocyanide (1.0 equiv.) were added sequentially and the reaction mixture was MW-heated (100 oC,150 W) for 10 minutes. Then, the solvent was removed until dryness and the crude was immediately purified by silica-gel column chromatography using a mixture of hexanes with ethyl acetate (7/3; v/v) to afford the corresponding products 1a-w. |