977 resultados para foreign currency derivatives


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http://www.archive.org/details/socialprogress03dennuoft/

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http://www.archive.org/details/whyandhowofforei014010mbp

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http://www.archive.org/details/socialaspectsoff013484mbp

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http://www.archive.org/details/socialprogress02dennuoft/

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http://www.archive.org/details/firsttenannualre00amerrich

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http://www.archive.org/details/missionarysurvey13360gut

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http://www.archive.org/details/foreignmissionsa008429mbp

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http://www.archive.org/details/memorialvolumeof00andeiala

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This thesis describes work carried out on the design of new routes to a range of bisindolylmaleimide and indolo[2,3-a]carbazole analogs, and investigation of their potential as successful anti-cancer agents. Following initial investigation of classical routes to indolo[2,3-a]pyrrolo[3,4-c]carbazole aglycons, a new strategy employing base-mediated condensation of thiourea and guanidine with a bisindolyl β-ketoester intermediate afforded novel 5,6-bisindolylpyrimidin-4(3H)-ones in moderate yields. Chemical diversity within this H-bonding scaffold was then studied by substitution with a panel of biologically relevant electrophiles, and by reductive desulfurisation. Optimisation of difficult heterogeneous literature conditions for oxidative desulfurisation of thiouracils was also accomplished, enabling a mild route to a novel 5,6-bisindolyluracil pharmacophore to be developed within this work. The oxidative cyclisation of selected acyclic bisindolyl systems to form a new planar class of indolo[2,3-a]pyrimido[5,4-c]carbazoles was also investigated. Successful conditions for this transformation, as well as the limitations currently prevailing for this approach are discussed. Synthesis of 3,4-bisindolyl-5-aminopyrazole as a potential isostere of bisindolylmaleimide agents was encountered, along with a comprehensive derivatisation study, in order to probe the chemical space for potential protein backbone H-bonding interactions. Synthesis of a related 3,4-arylindolyl-5-aminopyrazole series was also undertaken, based on identification of potent kinase inhibition within a closely related heterocyclic template. Following synthesis of approximately 50 novel compounds with a diversity of H-bonding enzyme-interacting potential within these classes, biological studies confirmed that significant topo II inhibition was present for 9 lead compounds, in previously unseen pyrazolo[1,5-a]pyrimidine, indolo[2,3-c]carbazole and branched S,N-disubstituted thiouracil derivative series. NCI-60 cancer cell line growth inhibition data for 6 representative compounds also revealed interesting selectivity differences between each compound class, while a new pyrimido[5,4-c]carbazole agent strongly inhibited cancer cell division at 10 µM, with appreciable cytotoxic activity observed across several tumour types.

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This thesis describes work carried out on the synthesis of novel 5- and 11-substituted ellipticines and derivatives of the ellipticine analogues, isoellipticine and deazaellipticine, followed by investigation of their potential as anti-cancer agents. Preparation of the key 5- and 11-substituted ellipticine targets involved the development of regiospecific, sequential alkylation reactions with alkenyllithium and Grignard reagents. Investigation of these novel reactions resulted in a new route towards 5-substituted ellipticines via Grignard reaction with vinylmagnesium bromide. These novel 5-vinylellipticine derivatives were further functionalised in an ozonolysis reaction, followed by oxidation to give a range of novel 5-substituted ellipticines. Less success was encountered in the 11-substituted ellipticine series, however preparation of these derivatives using a previously published route was accomplished, and the resulting 11-formylellipticine was further derivatised to give a panel of novel 9- and 11-substituted ellipticines, incorporating amide, carboxylate, imine and amine functionality. The successful route towards 5-substituted ellipticines was applied to the preparation of a range of novel 11-substituted isoellipticines and 6-substituted deazaellipticines, the first time substantial synthesis has been undertaken with these analogues. In addition to this, the first preparation of isoellipticinium salts is described, and a panel of novel isoellipticinium, 7 formylisoellipticinium and 7-hydroxyisoellipticinium salts were synthesised in good yields. Biological evaluation of a panel of 43 novel ellipticine, isoellipticine and deazaellipticine derivatives was accomplished with a topoisomerase II decatenation assay and submission to the NCI 60-cell line screen. Four novel isoellipticine topoisomerase II inhibitors were identified from the decatenation assay, with strong activity at 10 μM. In addition to this, NCI screening identified five highly cytotoxic ellipticine and isoellipticine compounds with remarkable selectivity profiles for different cancer types. These novel lead compounds represent new templates for further research and synthesis.

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The impact of the Vietnam War conditioned the Carter administration’s response to the Nicaraguan revolution in ways that reduced US engagement with both sides of the conflict. It made the countries of Latin America counter the US approach and find their own solution to the crisis, and allowed Cuba to play a greater role in guiding the overthrow of Nicaraguan dictator Anastasio Somoza Debayle. This thesis re-evaluates Carter’s policy through the legacy of the Vietnam War, because US executive anxieties about military intervention, Congress’s increasing influence, and US public concerns about the nation’s global responsibilities, shaped the Carter approach to Nicaragua. Following a background chapter, the Carter administration’s policy towards Nicaragua is evaluated, before and after the fall of Somoza in July 1979. The extent of the Vietnam influence on US-Nicaraguan relations is developed by researching government documents on the formation of US policy, including material from the Jimmy Carter Library, the Library of Congress, the National Security Archive, the National Archives and Records Administration, and other government and media sources from the United Nations Archives, New York University, the New York Public Library, the Hoover Institution Archives, Tulane University and the Organization of American States. The thesis establishes that the Vietnam legacy played a key role in the Carter administration’s approach to Nicaragua. Before the overthrow of Somoza, the Carter administration limited their influence in Nicaragua because they felt there was no immediate threat from communism. The US feared that an active role in Nicaragua, without an established threat from Cuba or the Soviet Union, could jeopardise congressional support for other foreign policy goals deemed more important. The Carter administration, as a result, pursued a policy of non-intervention towards the Central American country. After the fall of Somoza, and the establishment of a new government with a left wing element represented by the Sandinistas, the Carter administration emphasised non-intervention in a military sense, but actively engaged with the new Nicaraguan leadership to contain the potential communist influence that could spread across Central America in the wake of the Nicaraguan revolution.