DESIGN, SYNTHESIS AND STUDY OF NEW DRUGS

Author: BONACHE DE MARCOS M. ANGELES.
Year: 2004.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: INSTITUTO DE QUÍMICA MÉDICA (CSIC).QUÍMICA ORGÁNICA "MANUEL LORA TAMAYO".

Summary: In recent years there has been a resurgence of interest in the development of synthesis methods stereo and enantioselectivos of 2-azetidinonas highly funcionalizadas because, on one hand, are synthetic precursors to generate molecular diversity and on the other hand, are proving to be very useful medical chemistry for their many biological applications, it is therefore of great interest to deepen the synthesis and study of new beta-lactamas enantioméricamente pure. Chapter 2 of the thesis is devoted to explore the potential applicability of the phenomenon of memory quiralidad for the asymmetric synthesis of beta-lactamas from aminoácidos.Para ellose has studied the influence of different factors such as the conditions of reaction, the amino acid structure of partiday the presence of additives. To further the use of these beta-lactmas as versatile intermediates for the generation of molecular diversity, in the third chapter investigates the transformation of these 2-azetidinonas other heterocyclic systems for interés.En particular, we study the reduction quimioselectiva to for azetidinas, synthesized espiro beta-lactamas and controlled opening of 1-acil-beta-lactamas (monocíclicas and espiránica) to drive new alpha and beta amino acids, bearers of different systems heterocícliclos. In the fourth chapter of the thesis deals with the implementation of these systems novel heterocyclic compounds in the search for assets in SNC.Dado that the current interest group focuses mainly on finding new neuroprotective agents, in the first place have been prepared and studied different similar conformacionalmente restricted acid glutámco as liandos potential recipients glutamato.Por Furthermore, based on the knowledge that the dipéptidos Arg-Trp (PSN) and Trp (PSN) -Arg originating in the group, are capable of in a dual block NMDA receptors and vainilloide (TRPV1), have prepared a series of similar conformacionalmente restricted, in order to try to obtain compounds targeted by one or other receptor.En particular, the restriction conformacional has been incorporated into the basic residue replacing the natural amino acid by their equivalent non proteinogénico with a ring azetidina.

Author: JIMÉNEZ ARENAS VÍCTOR.
Year: 2005.
University: VALENCIA [www.uv.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: HOSPITAL UNIVERSITARIO DR. PESET (VALENCIA).

Summary: Breast cancer is the highest incidence of malignancy in the female population. It is estimated that die each year 500,000 women around the world. Incidence rates vary from low-incidence areas such as Asia or Africa with 10 new cases per 100,000 inhabitants per year, a high-incidence areas such as the United States and Europe with between 80 and 100 new cases per 100,000 inhabitants per year. In the year 2005, in the region of Valencia were recorded 738 new cases of this disease. The natural evolution of the disease crosses 4 stages: from the stage I, where the tumor less than 2 cm, is confined to the breast and no lymph node involvement, to the stadium IV, which appear metastases in organs such as distance may be the liver or bones. Breast cancer will jeopardize the survival of patients according Stadium at diagnosis, so that a patient diagnosed at stage I have a chance of being alive 5-year close to 100%, while a late diagnosis, disease stage IV, the same chance to cut only 15% survival at 5 years. Moreover, the situation in which it is the disease at the time of diagnosis will be conditional intent with the design treatment for the patient. If the diagnosis is prior to the occurrence of metastasis, the primary goal of treatment is to cure the patient, whereas if diagnosed in stage IV, the intention is palliative, with the possibility of increasing survival, but not its cure. In the decision process associated with the therapeutic treatment of cancer, there inevitably benefits, as measured ideally overall survival, and costs, referring to both the economic cost and the effect on the quality of life of patients undergoing treatment. This memory doctoral thesis has been done with a population of 387 women diagnosed with breast cancer and treated at the University Hospital Dr. Peset Valencia, from January 1, 1999 until December 31, 2004. The approach of the major goals and secondary tries to approach the quality of care, through the evaluation of the treatments that patients using clinical and economic performance extracted care practice. The criteria used for selection of the patient population, have enabled the processing of data in terms of direct costs (associated with antineoplastic treatment and support), disease-free survival (PFS) and overall survival (GS); also as results surrogates or substitutes have been established values of dose intensity and compliance relating to the components already used in schemes antineoplastic patients, to be considered clinical risk factors. The limited information in the literature on the cost comparison between treatment schemes in breast cancer, enhances the value of the results of cost to be used as comparators or standard reference for further studies of this nature. The average cost of treatment antineoplastic more factors stimulating blood cells, differentiated patient is 920 â ¬ (only antineoplastic) and 1,336 â ¬ (antineoplastic + factors), and 3,306 â ¬ (only antineoplastic) and 4,485 â ¬ ( antineoplastic + factors), indications of adjuvant and no adjuvant, respectively. The study of survival has focused on a subpopulation of 204 patients, indicating adjuvant and schemes farmacoterapéuticos AC and FEC600. The percentage of breast cancer patients free of relapse at 6 years stands at 89.5% and the percentage of patients who live to 6 years stands at 8 with 89.9 56b%, regardless of the scheme Pharmaco received. One way of dealing with the influence of the variables analyzed the results of survival in question, is posing a regression model of risk ratios according to the stratification of the patient population according to submit lymph emotions and affections, and had not been treated with AC and CHF. It appealed to the Cox regression to see the association of variables dose intensity, compliance and age, and the likelihood of relapse and éxitus. The values obtained Hazard Ratio and 95% CI show that there is no association between these variables and the likelihood of relapse and éxitus.