Synthesis of substituted 3-anilino-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepine-2-ones and their evaluation as cholecystokinin-ligands

3-Amino-1,4-benzodiazepines as well as chemically related diverse amines were prepared from oxazepam and subsequently screened on the cholecystokinin receptor in a radiolabel binding assay. Oxazepam 2 was activated via its 3-chloro-1,4-benzodiazepine intermediate 3 and was reacted with a large series of aliphatic and aromatic amines. The substituted 3-anilino-1,4-benzodiazepine structure was identified as lead structure in a diverse series of 3-amino-1,4-benzodiazepines 4-38 and the full SAR (structure-activity relationship) optimisation provided 3-anilinobenzodiazepines 16-38 with CCK 1 receptor selectivity to CCK 2. The compounds 18, 24, 28 and 33 have shown affinities at the CCK 1 receptor of 11, 10, 11 and 9 nM, respectively. These equipotent CCK 1 ligands were fully evaluated in behaviour pharmacological essays. An antidepressant effect was identified in the tail suspension- and the Porsolt swimming-test. The ED 50 values for 24 and 28 were determined in these assays as 0.46 and 0.49 mg/kg. The mixed antagonist 37 showed in addition to the antidepressant effects anxiolytic properties. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.

On some Optimal (n,t,1,2) and (n,t,1,3) Super Imposed Codes

Partially supported by the Technical University of Gabrovo under Grant C-801/2008

Marl Prairie/Slough Gradients; Patterns and Trends in Shark Slough and Adjacent Marl Prairies (CERP monitoring activity 3.1.3.5), First Annual Report (2005)

The work on CERP monitoring item 3.1.3.5 (Marl prairie/slough gradients) is being conducted by Florida International University (Dr Michael Ross, Project Leader), with Everglades National Park (Dr. Craig Smith) providing administrative support and technical consultation. As of January 2006 the funds transferred by ACOE to ENP, and subsequently to FIU, have been entirely expended or encumbered in salaries or wages. The project work for 2005 started rather late in the fiscal year, but ultimately accomplished the Year 1 goals of securing a permit to conduct the research in Everglades National Park, finalizing a detailed scope of work, and sampling marsh sites which are most easily accessed during the wet season. 46 plots were sampled in detail, and a preliminary vegetation classification distinguished three groups among these sites (Sawgrass marsh, sawgrass and other, and slough) which may be arranged roughly along a hydrologic gradient from least to most persistently inundated . We also made coarser observations of vegetation type at 5-m intervals along 2 transects totaling ~ 5 km. When these data were compared with similar observations made in 1998-99, it appeared that vegetation in the western portion of Northeast Shark Slough (immediately east of the L-67 extension) had shifted toward a more hydric type during the last 6 years, while vegetation further east was unchanged in this respect. Because this classification and trend analysis is based on a small fraction of the data set that will be available after the first cycle of sampling (3 years from now), the results should not be interpreted too expansively. However, they do demonstrate the potential for gaining a more comprehensive view of marsh vegetation structure and dynamics in the Everglades, and will provide a sound basis for adaptive management.

Fragm. lat. V 97 - Summa casuum (Zu den Dekretalen Gregors IX.: 2.27 - 28; 3.1 - 3, 8, 10)

Trägerband: Inc. qu. 960; Vorbesitzer: Zacharias Konrad von Uffenbach

(Tables 1-3) Water chemistry of cloud forest streams at baseflow conditions, Rio San Francisco, Ecuador

We investigated controls on the water chemistry of a South Ecuadorian cloud forest catchment which is partly pristine, and partly converted to extensive pasture. From April 2007 to May 2008 water samples were taken weekly to biweekly at nine different subcatchments, and were screened for differences in electric conductivity, pH, anion, as well as element composition. A principal component analysis was conducted to reduce dimensionality of the data set and define major factors explaining variation in the data. Three main factors were isolated by a subset of 10 elements (Ca2+, Ce, Gd, K+, Mg2+, Na+, Nd, Rb, Sr, Y), explaining around 90% of the data variation. Land-use was the major factor controlling and changing water chemistry of the subcatchments. A second factor was associated with the concentration of rare earth elements in water, presumably highlighting other anthropogenic influences such as gravel excavation or road construction. Around 12% of the variation was explained by the third component, which was defined by the occurrence of Rb and K and represents the influence of vegetation dynamics on element accumulation and wash-out. Comparison of base- and fast flow concentrations led to the assumption that a significant portion of soil water from around 30 cm depth contributes to storm flow, as revealed by increased rare earth element concentrations in fast flow samples. Our findings demonstrate the utility of multi-tracer principal component analysis to study tropical headwater streams, and emphasize the need for effective land management in cloud forest catchments.

(Tables 1, 3) Details of Agassiz trawl stations and numbers of specimens per macro- and megazoobenthic taxon collected during POLARSTERN cruise ANT-XXII/3 (ANDEEP III)

The assemblages inhabiting the continental shelf around Antarctica are known to be very patchy, in large part due to deep iceberg impacts. The present study shows that richness and abundance of much deeper benthos, at slope and abyssal depths, also vary greatly in the Southern and South Atlantic oceans. On the ANDEEP III expedition, we deployed 16 Agassiz trawls to sample the zoobenthos at depths from 1055 to 4930 m across the northern Weddell Sea and two South Atlantic basins. A total of 5933 specimens, belonging to 44 higher taxonomic groups, were collected. Overall the most frequent taxa were Ophiuroidea, Bivalvia, Polychaeta and Asteroidea, and the most abundant taxa were Malacostraca, Polychaeta and Bivalvia. Species richness per station varied from 6 to 148. The taxonomic composition of assemblages, based on relative taxon richness, varied considerably between sites but showed no relation to depth. The former three most abundant taxa accounted for 10-30% each of all taxa present. Standardised abundances based on trawl catches varied between 1 and 252 individuals per 1000 m2. Abundance significantly decreased with increasing depth, and assemblages showed high patchiness in their distribution. Cluster analysis based on relative abundance showed changes of community structure that were not linked to depth, area, sediment grain size or temperature. Generally abundances of zoobenthos in the abyssal Weddell Sea are lower than shelf abundances by several orders of magnitude.

Coordination networks of Cu2+ ions with 1,3-bis[2-(4-pyridyl)ethyl]benzene : strong structure-directing role of the counter ion (nitrate, acetate and sulphate), leading to clusters, sheets and chains

Date of Acceptance: 16/10/2015

Coordination networks of Cu2+ ions with 1,3-bis[2-(4-pyridyl)ethyl]benzene : strong structure-directing role of the counter ion (nitrate, acetate and sulphate), leading to clusters, sheets and chains

Date of Acceptance: 16/10/2015

Rôle du facteur de croissance transforming growth factor beta-1 (TGF[beta]1) dans la synthèse d'oestradiol par les follicules ovariens bovins

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Prophecy as a narrative world : a study of the world-constructing conventions and narrative techniques in Hosea 1-3

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Aplicação informática para verificação de perfis enformados a frio segundo a EN1993-1-3

Os perfis enformados a frio estão em crescente uso na indústria da construção, utilizados como estruturas secundárias e primárias, por apresentar resistência em relação ao baixo peso, facilidade de utilização em obra e sustentabilidade. A norma europeia EN1993-1-3, também adotada em Portugal, que apresenta as especificações normativas sobre o uso estrutural de perfis enformados a frio é de difícil aplicação para os projetistas devido à quantidade e complexidade de cálculos para que sejam efetuadas as verificações de segurança necessárias, pelas limitações dos programas informáticos e complexidade de compreensão dos fenómenos da instabilidade local e distorcional que condicionam o comportamento deste tipo de secções, classificadas como de classe 4. O presente trabalho procura explicar os procedimentos do eurocódigo e os seus aspetos mais controversos, como, por exemplo, o processo de cálculo da distribuição de tensões numa secção arbitrária constituída por segmentos retos, o cálculo de larguras efetivas e espessuras reduzidas e as verificações de segurança em termos de resistência e estabilidade global requeridos pela norma. O principal objetivo deste trabalho é o desenvolvimento um programa de cálculo para verificar barras com secções de classe 4 que tenha a abrangência das especificações do Eurocódigo (EC3-1-3), que possa auxiliar engenheiros no processo de projeto, dimensionamento e verificação regulamentar de estruturas metálicas que utilizem este tipo de secções. Para isso foi criada uma aplicação informática, em ambiente Windows®, que está ligada ao programa Autodesk® Robot Structural Analisys® para obtenção de dados de cálculo e executar os cálculos de secções efetivas e verificações de segurança de acordo com a norma europeia. São apresentados diagramas de blocos com a sequência do procedimento de cálculo das várias fases de cálculo de secções efetivas e de verificação de barras, com vista a mostrar a lógica de funcionamento interno da aplicação criada no âmbito deste trabalho. Por fim desenvolve-se um manual de utilização da aplicação e um exemplo comparativo, de cálculo das propriedades efetivas de uma secção, entre os resultados do programa e documentos de referência com cálculos manuais

Gas/particle partitioning of carbonyls in the photooxidation of isoprene and 1,3,5-trimethylbenzene

A new denuder-filter sampling technique has been used to investigate the gas/particle partitioning behaviour of the carbonyl products from the photooxidation of isoprene and 1,3,5-trimethylbenzene. A series of experiments was performed in two atmospheric simulation chambers at atmospheric pressure and ambient temperature in the presence of NOx and at a relative humidity of approximately 50%. The denuder and filter were both coated with the derivatizing agent O-(2,3,4,5,6-pentafluorobenzyl)-hydroxylamine (PFBHA) to enable the efficient collection of gas- and particle-phase carbonyls respectively. The tubes and filters were extracted and carbonyls identified as their oxime derivatives by GC-MS. The carbonyl products identified in the experiments accounted for around 5% and 10% of the mass of secondary organic aerosol formed from the photooxidation of isoprene and 1,3,5-trimethylbenzene respectively. Experimental gas/particle partitioning coefficients were determined for a wide range of carbonyl products formed from the photooxidation of isoprene and 1,3,5-trimethylbenzene and compared with the theoretical values based on standard absorptive partitioning theory. Photooxidation products with a single carbonyl moiety were not observed in the particle phase, but dicarbonyls, and in particular, glyoxal and methylglyoxal, exhibited gas/particle partitioning coefficients several orders of magnitude higher than expected theoretically. These findings support the importance of heterogeneous and particle-phase chemical reactions for SOA formation and growth during the atmospheric degradation of anthropogenic and biogenic hydrocarbons.

New methods for the asymmetric synthesis of α-alkylated ketones and 1,3-amino alcohols

A large number of optically active drugs and natural products contain α-functionalised ketones or simple derivatives thereof. Furthermore, chiral α-alkylated ketones are useful synthons and have found widespread use in total synthesis. The asymmetric alkylation of ketones represents one of the most powerful and longstanding procedures in organic chemistry. Surprisingly, however, only one effective methodology is available, and this involves the use of chiral auxiliaries. This is discussed in Chapter 1, which also provides a background of other key topics discussed throughout the thesis. Expanding on the existing methodology of chiral auxiliaries, Chapter 2 details the synthesis of a novel chiral auxiliary containing a pyrrolidine ring and its use in the asymmetric preparation of α-alkylated ketones with good enantioselectivity. The synthesis of racemic α-alkylated ketones as reference standards for GC chromatography is also reported in this chapter. Chapter 3 details a new approach to chiral α-alkylated ketones using an intermolecular chirality transfer methodology. This approach employs the use of simple non-chiral dimethylhydrazones and their asymmetric alkylation using the chiral diamine ligands, (+)- and (-)-sparteine. The methodology described represents the first example of an asymmetric alkylation of non-chiral azaenolates. Enantiomeric ratios up to 83 : 17 are observed. Chapter 4 introduces the first aldol-Tishchenko reaction of an imine derivative for the preparation of 1,3-aminoalcohol precursors. 1,3-Aminoalcohols can be synthesised via indirect routes involving various permutations of stepwise construction with asymmetric induction. Our approach offers an alternative highly diastereomeric route to the synthesis of this important moiety utilising N-tert-butanesulfinyl imines in an aldol-Tishchenko-type reaction. Chapter 5 details the experimental procedures for all of the above work. Chapter 6 discusses the results of a separate research project undertaken during this PhD. 2-alkyl-quinolin-4-ones and their N-substituted derivatives have several important biological functions such as the role of Pseudomonas quinolone signal (PQS) in quorum sensing. Herein, we report the synthesis of its biological precursor, 2-heptyl-4-hydroxy-quinoline (HHQ) and possible isosteres of PQS; the C-3 Cl, Br and I analogues. N-Methylation of the iodide was also feasible and the usefulness of this compound showcased in Pd-catalysed cross-coupling reactions, thus allowing access to a diverse set of biologically important molecules.