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This paper presents an evaluation of UV/PAA process for degradation of four pharmaceuticals venlafaxine (VEN), sulfamethoxazole (SFX), fluoxetine (FLU) and carbamazepine (CBZ) with comparison to UV/H2O2 process. The effectiveness of combining PAA and H2O2 at various proportions while irradiating with UVC were also evaluated. UVC/PAA (lambda = 254 nm) was effective in degrading all four pharmaceuticals and followed pseudo first-order kinetics. Increasing PAA dosage or UVC intensity resulted in a linear increase in pseudo-first order rate coefficient. Both PAA in dark conditions and UVA/PAA (lambda = 360 nm) were marginally effective to degrade SFX and ineffective to degrade VEN, CBZ and FLU; indicating the need for UVC irradiation for activation of PAA. For similar oxidant dosages of 50 mg/L UVC/H2O2 was found to be faster than UV/PAA for VEN, CBZ and FLU by 55%, 75% and 33%, respectively. Under similar conditions, SFX was degraded 24% faster by UV/PAA. Increase in the proportion of H2O2 to PAA in UVC/PAA/H2O2 improved kinetics of degradation compared to PAA alone. Tests on TOC were conducted to determine the amount of acetic acid that is released to water when treatment by UVC/PAA is conducted. Results demonstrated that 70% of PAA by mass was ultimately converted to acetic acid and remained in the treated solutions. Hydroxyl radical attack is hypothesized to be the main mechanism of degradation by UV/PAA as degradation intermediates identified for all the target pharmaceuticals coincided with by-products identified during UV/H2O2 process.

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The key intermediate 3-amino-5-methylisoxazole (1) was allowed to react with phthalic anhydride and/or maleic anhydride under different conditions to produce different isoxazole products. Schiff bases 9a-c obtained via the reaction of 1 with different aldehydes were condensed with thioglycolic acid to afford the corresponding thiazolidin-4-one derivatives 10a, b. Furthermore, condensation of the Schiff bases 9a, c with various secondary amines produced the corresponding 5-substituted pyrazole derivatives 11a-d, respectively. The anticancer activity of some of the newly synthesized compounds was evaluated against Panc-1 and Caco-2 cell lines using doxorubicin as a standard drug. Most of the tested derivatives exhibited high cytotoxic potency against Panc-1 carcinoma cell lines, but moderate to weak activity was obtained against Caco-2 cell lines.

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Microbacterium sp. strain BR1 is among the first bacterial isolates which were proven to degrade sulfonamide antibiotics. The degradation is initiated by an ipso-substitution, initiating the decay of the molecule into sulfur dioxide, the substrate specific heterocyclic moiety as a stable metabolite and benzoquinone imine. The latter appears to be instantaneously reduced to p-aminophenol, as that in turn was detected as the first stable intermediate. This study investigated the downstream pathway of sulfonamide antibiotics by testing the strain’s ability to degrade suspected intermediates of this pathway. While p-aminophenol was degraded, degradation products could not be identified. Benzoquinone was shown to be degraded to hydroquinone and hydroquinone in turn was shown to be degraded to 1,2,4-trihydroxybenzene. The latter is assumed to be the potential substrate for aromatic ring cleavage. However, no products from the degradation of 1,2,4-trihydroxybenzene could be identified. There are no signs of accumulation of intermediates causing oxidative stress, which makes Microbacterium sp. strain BR1 an interesting candidate for industrial waste water treatment.

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The known azaiminium intermediate, 1-chloro-1,3-bis(dimethylamino)-3-phenyl-2-azaprop-2-en-1-ylium perchlorate 1, reacts with 2-aminothiazole to yield the fully conjugated condensed 1,3,5-triazinium salt 7.Various suitably substituted heterocyclic compounds react similarly to afford the corresponding condensed 1,3,5-triazinium salts.The diazaiminium intermediates 2-5 obtained from several secondary amides give identical products when treated with the same starting compounds.The procedure appears to be of wide application.

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Compounds of Formula (I), including pharmaceutically acceptable salts of the compounds, are CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis. In the compounds of Formula (I), A1 and A2 are each an aromatic ring, a 5-6-membered heterocyclic ring, an aromatic ring fused to a heterocyclic ring, a phenyl ring fused to a heterocyclic ring, or a cycloalkyl ring, and Z is an aromatic or heterocyclic ring.

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Background: Bromodomain-containing protein 4 (BRD4) inhibitors synthesized with trimethoxy-ring refer to a new series of small molecular inhibitors. Currently, BRD4 offers the potential for research as a cancer therapeutic target. Based on previous studies, 17 trimethoxy-ring derivatives were designed as novel BRD4 inhibitors. Methods: All these new compounds were synthesized via the amide reaction. Their structures were identified by 1H NRM,13C NRM spectra and HRMS. In vitro antitumor activities of the new compounds were evaluated by MTT. Molecular docking studies were conducted to explain the binding interactions of these compounds with BRD4 protein. Results: A series of novel trimethoxy-ring derivatives were synthesized as BRD4 inhibitors and screened by testing their inhibition against HCT116, MCF-7, K562 and KMS-1 cell lines. Most of the newly synthesized compounds exhibited moderate-to-good inhibitory activity against HCT116, MCF-7, and K562 cell lines, whereas some showed inhibitory activity against the KMS-1 cell line. Conclusion: Compound 3g demonstrated the most potent anti-tumor activity against breast (MCF-7), leukemia (K562), multiple myeloma (KMS-1), and colon cancer (HCT116) cell lines.

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A series of quinoline derivatives were designed and synthesized as tyrosine kinase inhibitors. Exploration of the structure-activity relationships resulted in compounds that are potent in vitro. In addition, compound 10f was found to be a potent and selective Raf kinase inhibitor. The Royal Society of Chemistry.

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Accidental events concerning process industries can affect not only the staff working in, but also the environment and people living next to the factory. For this reason a regulation is imposed by the European Community to prevent accidents that could represent a risk for the population and the environment. In particular, Directive 96/82/CE, the so-called ‘Seveso II directive’, requests a risk analysis involving also the hazardous materials generated in accidental events. Therefore, it is necessary to develop simple and economic procedure to foresee the hazardous materials that can be produced in the case of major accidents, among which the accidental heating of a chemical due to a fire or a runaway reaction is one of the most frequent. The procedure proposed in this work is based on evolved gas analysis methodology that consists in coupling two instruments: a thermogravimetric analyzer or a flash pyrolyzer, that are employed to simulate accident conditions, and a FTIR spectrometer that can be used to detect the evolved gas composition. More than 40 materials have been examined in various accident scenarios and the obtained data have been statistically analyzed in order to identify meaningful correlations between the presence of a chemical group in the molecule of a chemical and the presence of a given hazardous species in the fume produced.

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The interaction of 4-cinnamylideneamino-3-methyl-5-styrylisoxazoles (1) with dimethyl acetylenedicarboxylate has given an isoxazolyldihydropyridine (2) as major and an isoxazolylaminofumarate (3) as minor products respectively. 3-Cinnamylideneamino-5-methylisoxazoles (4) behave similarly.Isoxazolylaminofumarates (3 and 6) have been identified by unambiguous synthesis.

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This Letter describes a chemical lead optimization campaign directed at VU0108370, a weak M1 PAM hit with a novel chemical scaffold from a functional HTS screen within the MLPCN. An iterative parallel synthesis approach rapidly established SAR for this series and afforded VU0405652 (ML169), a potent, selective and brain penetrant M1 PAM with an in vitro profile comparable to the prototypical M1 PAM, BQCA, but with an improved brain to plasma ratio.

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