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(Chemical Equation Presented) A series of N-sulfinyl dienophiles 1c-i has been screened in asymmetric hetero-Diels-Alder reactions using chiral bis(oxazoline)copper(II) and -zinc(II) triflates. The survey pointed out N-sulfine 1c (R = P(=O)(OPh)2) as the most promising N-sulfine regarding yield and stereoselectivity (up to 97% ee). The relative configurations, and in one case the absolute configuration, of the HDA adducts were established by X-ray analysis.

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(Figure Presented) The thermal rearrangements of 3-acylamino-5- methylisoxazoles 1 have been investigated under basic and neutral conditions and interpreted with the support of computational data. The density functional theory (DFT) study on the competitive routes available for the base-catalyzed thermal rearrangement of isoxazoles 1 showed that the Boulton-Katritzky (BK) rearrangement, producing the less stable 3-acetonyl-1,2,4-oxadiazoles 5, is a much more favored process than either the migration-nucleophilic attack-cyclization (MNAC) or the ring contraction-ring expansion (RCRE). In turn, an increase in reaction temperature will promote the MNAC of oxadiazoles 5, producing the more stable 2-acylaminooxazoles 8. The thermal rearrangement of 3-acylaminoisoxazoles 1 into oxazoles 8 can therefore be interpreted in terms of a cascade BK-MNAC rearrangement involving 3-acetonyl-1,2,4-oxadiazoles 5 as ancillary intermediates.

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Two catalysts containing ceria dispersed on the surface of multi-walled carbon nanotubes and activated carbon were prepared and characterized by several techniques. They were investigated as ozonation catalysts for the mineralization of the antibiotic sulfamethoxazole (SMX). Both materials enhanced the mineralization of SMX relatively to single ozonation. A strong synergetic effect between carbon materials and ceria was observed, leading to higher mineralization degrees. In the catalytic ozonation with these materials both surface and bulk reactions occur. The efficiency of catalysts was mainly affected by the amount of Ce3+ species on the surface. The presence of carbon materials containing ceria led to a faster degradation of pyruvic and maleic acids. The original sulfur of SMX was almost completely converted to sulfate and part of nitrogen was converted to NH4+ and NO3-. Microtox tests revealed that simultaneous use of ozone and the prepared catalysts originated lower acute toxicity.

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The present invention relates to compounds of general formula (I): wherein A, Y, X, n and B are as defined herein; and their use in the treatment and prevention of metabolic disorders, inflammatory conditions, allergic conditions, fever, pain including allodynia and nociception, eating disorders, cachexia, brain injuries, cancer of the genitals, sleep apnoea, cardiovascular disease, flush effect associated with nicotinic acid and related compounds or for the promotion of wound healing. Certain compounds of general formula (I) are new and the invention also relates to these compounds and to their use in medicine.

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The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof (I) wherein R1 to R4 are as defined in the claims. The invention further relates to their use as inhibitors of 17beta-HSD1 and in treatment or prevention of steroid hormone de- pendent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17beta-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the afore mentioned compounds or pharmaceutically acceptable salts thereof.

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Moderate cyclic GMP phosphodiesterase (cGMP-PDE, PDE V) inhibitor 2- phenyl-4-anilino-quinazoline (1) was identified utilizing MultiCASE assisted drug design (MCADD) technology. Modification of compound 1 was conducted at the 2-, 4-, and 6-positions of the quinazoline ring for enhancement of cGMP- PDE inhibitory activity. The 6-substituted 2-(imidazol-1-yl)-quinazolines are 1000 times more potent in in vitro PDE V enzyme assay than the well-known inhibitor zaprinast. The 6-substituted derivatives of 2-(3- pyridyl)quinazoline 84 and 2-(imidazol-1-yl)quinazoline 86 exhibited more than 1000-fold selectivity for PDE V over the other four PDE isozymes. In addition, cGMP-PDE inhibitors 64, 65, and 73 were found to have an additional property of thromboxane synthesis inhibitory activity.

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Disclosed herein are a class of compounds useful in cell culture, in particular, the in vitro culture of stem cells. The compounds have been found to promote the survival and/or maintenance of stem cells in (or during) culture and/or throughout passage.

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The ability of anthraquinone-2,6-disulfonate (AQDS) and riboflavin to enhance the sulfamethoxazole (SMX) degradation coupled with the Fe(III) reduction by Shewanella oneidensis MR-1 was investigated. The results indicated that the SMX degradation rate was 38.5% with an initial SMX concentration at 0.04 mM. For the overall performance of AQDS and riboflavin mediated SMX degradation and iron reduction, the SMX degradation rate was gradually increased with the enhancement of iron reduction. Riboflavin had a stronger enhancement on SMX degradation and iron reduction than AQDS, but the enhancement was not positively correlated with electron shuttles concentration. A quantitative characterization of the electron transfer capacity (ETC) of the electron shuttles showed that the ETC was higher for riboflavin than AQDS. The S. oneidensis MR-1 16S rRNA gene copies results indicated that electron shuttles had a positive effect on the microbial activity of S. oneidensis MR-1. The LC?MS result indicated that the products of the SMX biodegradation were 3-amino-5-methylisoxazole and 4-aminobenzenesulfonic acid, which suggested that the SMX biodegradation was caused by S?N bond cleavage. This study indicates that the biochemical mechanisms play a vital role in SMX transformation and Fe(II) generation in this system.

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Derivatives of isoxazole, isoxazolo[3,4-blpyridine, pyrazolo-[1,5- alpyrimidine and pyridin-2(1H)-one incorporating a benzothiazole-2-thio residue have been synthesised. The structures of these newly synthesised compounds are characterised by elemental analysis, IR, lH and 13C NMR, NOE and MS.

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The reaction of 2-(cyanomethyl)benzoic acid with amines RNH2 (R = Ar, Het, CH2Ar, CH2Het) leads to the formation of the corresponding 3-NHR-isoquinolin-1(2H)-ones. When R = CH2Ar and CH2Het, there is a side reaction involving hydrolysis of the hydrolytically-unstable intermediates, derivatives of 2-(2-amino-2-iminoethyl) benzoic acid, leading to 2-R-isoquinoline-1,3(2H,4H)-diones.

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