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A fancy dress accessory handbag for children was claimed by consumers to exhibit an offensive smell. Sensory characterization by an expert panel revealed, amongst others, rubber- and car tire – like notes. For elucidation of the molecular reasons of this sensory defect, the volatile fraction of the product was isolated by means of solvent extraction and high vacuum distillation. Identification of the main odorants was accomplished by means of one- and two-dimensional gas chromatography, with parallel mass spectrometric and olfactometric detection. In total more than 60 odorants were detected in the sample and more than 30 of these odour-active substances could be identified. Amongst them were a number of naphthalene derivatives as well as saturated and mono- or di-unsaturated carbonyl compounds. The naphthalene derivatives that were identified in the children’s article appeared to be mainly responsible for the characteristic off-odour. Additionally, a GC-MS-screening for polycyclic aromatic hydrocarbons (PAHs) was performed, which revealed the presence of 15 PAHs in total. However, 14 of them were of no relevance for the smell of the product.

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Reference:
Isoquinoline – Wikipedia,
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Recently we reported on overcoming the species difference of our first orally active non-peptide bradykinin (BK) B2 receptor antagonists, incorporating an 8-[[3-(N-acylglycyl-N-methylamino)-2,6-dichlorobenzyl]oxy]- 3-halo-2-methylimidazo[1,2-alpha]pyridine skeleton, leading to identification of the first Clinical candidate 4a (FR167344). With this potent new lead compound in hand, we then investigated further refinement of the basic framework by replacement of the imidazo[1,2-alpha]pyridine moiety and discovered several bioisosteric heterocycles. Extensive optimization of these new heteroaromatic derivatives revealed the detailed structure-activity relationships (SAR) around the imidazo[1,2-alpha]pyridine ring and the 2,6- dichlorobenzyl moiety, leading to the discovery of our second clinical candidate 87b (FR173657) which inhibited the specific binding of [3H]BK to recombinant human B2 receptors expressed in Chinese hamster ovary (CHO) cells and guinea pig ileum membrane preparations expressing B2 receptors with IC50’s of 1.4 and 0.46 nM, respectively. This compound also displayed excellent in vivo functional antagonistic activity against BK-induced bronchoconstriction in guinea pigs with an ED50 value of 0.075 mg/kg by oral administration. Further modifications of the terminal substituents on the pyridine moiety led to a novel pharmacophore and resulted in the identification of 99 (FR184280), whose IC50 value for human B2 receptors (0.51 nM) was comparable to that of the second-generation peptide B2 antagonist Icatibant.

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Broad spectrum cephalosporin betaine antibiotics represented by the formula STR1 wherein R’ is a heterocyclic ring, e.g. 2-aminothiazol-4-yl, 2-amino-1,3,5-thiadiazol-4-yl, or 2-aminopyridin-6-yl; R” is C1 -C4 alkyl, especially methyl, a substituted carbamoyl group, or a carboxy-substituted alkyl or cycloalkyl group; and R1 is isoquinolinium or a substituted isoquinolinium group are provided. Compounds wherein R1 is isoquinolinium are preferred especially syn-7-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-(isoquinolinium-2-ylmethyl)-3-cephem-4-carboxylate. Pharmaceutical formulations and a method for treating infectious diseases comprising the use of the antibiotics are described.

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1-Nitroisoquinolines were directly prepared from the corresponding isoquinolines with potassium nitrite and acetic anhydride in DMSO in good yields.

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The reaction of benzynes with N-heteroaromatics including quinolines, isoquinolines, and pyridines and various terminal alkynes or ketones with an a-hydrogen in the presence of KF and 18-crown-6 in THF at room temperature for 8 h gave various N-arylated 1,2-dihydroheteroaromatics in good to moderate yields. Some of these product structures are found in various naturally occurring and biologically active heterocyclic compounds. The reaction involves an unusual multiple construction of new C – C, C – N, and C – H bonds and the cleavage of a C – H bond in one pot. It is likely that the three-component coupling proceeds through the nucleophilic addition of quinoline to benzyne, which generates a zwitterionic species. The latter then attracts a proton from terminal alkyne (or ketone) to generate an N-arylated quinolinium cation and an acetylide anion. Further reaction of these two ions provides the final substituted 1,2-dihydroquinolines. In the reaction, the terminal alkyne acts first as a proton donor and then as a nucleophile. The application of a three-component coupling reaction product, 1,2-dihydro-2-pyridinyl alkyne in a stereospecific [4+2] Diels-Alder cycloaddition reaction with N-phenyl maleimide to give an isoquinuclidine derivative, an important core present in various natural products, is demonstrated.

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Palladium-catalyzed site selective arylation reactions of both sp2 and benzylic sp3 sites on azine and diazine N-oxide substrates are described that occur in good to excellent yield and with complete selectivity for reaction at the desired position. These studies have uncovered the need to properly control the metal to ligand ratio in sp2 arylation and necessitated a complete reinvestigation of all reaction parameters for sp3 arylation. From these studies, the choice of base emerged as a pivotal component for site selectivity, pointing to its intimate involvement in the mechanism of direct arylation. These site selective reactions have been validated in both divergent and sequential derivatizations of heterocyclic compounds represent an attractive alternative to other routes to this class of molecule. Copyright

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Group III alkyl complexes supported by a ferrocene diamide ligand (1,1?-fc(NSitBuMe2)2) have been found to be reactive toward aromatic N-heterocycles such as 1-methylimidazole and pyridines. These reactions were investigated experimentally and computationally. An initial C-H activation event is followed by a coupling reaction to form biheterocyclic complexes, in which one of the rings is dearomatized. In the case of 1-methylimidazole, the biheterocyclic compound could not be isolated and further led to an imidazole ring-opened product; in the case of pyridines, it transformed into an isomer with extended conjugation of double bonds. Mechanisms for both reactions are proposed on the basis of experimental and computational results. DFT calculations were also used to show that an energetically accessible pathway for the ring-opening of pyridines exists.

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Polymerization initiators are produced by contacting elemental calcium metal with pyridine-type compounds.

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Potassium tert-butoxide-promoted acceptorless dehydrogenation of N-heterocycles was efficiently realized for the generation of N-heteroarenes and hydrogen gas under transition-metal-free conditions. In the presence of KOtBu base, a variety of six- and five-membered N-heterocyclic compounds efficiently underwent acceptorless dehydrogenation to afford the corresponding N-heteroarenes and H2 gas in o-xylene at 140 C. The present protocol provides a convenient route to aromatic nitrogen-containing compounds and H2 gas. (Figure presented.).

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Anodic axidation of primary N-tosylamines in methanol containing halide ion gave alpha-(N-tosylamino) aldehyde dimethyl acetals, synthetically useful intermediates equivalent to alpha-amino aldehydes.

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