Aprimoramento de quimioteca de substâncias bioativas candidatas a fármacos por meio do uso de estratégias de prospecção tecnológica

Abstract

A chemistry library may be defined as a collection of substances which have been bioassayed in vitro and also are arranged in a database, and organized according to various parameters, such as their specific structural or physicochemical properties. The Laboratory for Evaluation and Synthesis of Bioactive Substances - LASSBio® has a chemistry library of bioactive substances, drug candidates, public and confidential, of academic and business interest. This chemistry library was the subject of a study of this academic master's thesis that aims to improve this collection of substances, using Technological Prospecting strategies, such as the search for antecedents and data mining, aiming at confirming unmanageability, especially of stealth substances and something added value for the industrial sector and the optimization of this collection, through the chemical synthesis and pharmacological evaluation of a series of unpublished derivatives, resulting from this prospecting process. The Technological Prospecting studies of the 117 classified substances of LASSBio chemistry library were done through the use of patent bases (USPTO, ESPACENET, WIPO, INPI, SIPO, KIPO, DERWENT, among others) and chemical structures database (SCIFINDER). In addition, these substances were used in this part of the project in order to ensure the total unmanageability of the stealthy substances, through the use of the data mining strategy and to verify the profile of the inventive activity of each one. From the results of the studies of Technological Prospection a series of analogues was selected which presented a promising structural modification. The planning of the new series of compounds derived from the series LASSBio 1783 to 1790 and LASSBio 1984 to 1988 (which presented lower profiles of similarities in the studies of Technological Prospecting) was carried out using the strategies of the Chemistry of Pharmaceutical Medicine, aiming at a route of synthetic access relatively simple, few steps and also can produce the final compounds in high total yields. The synthetic route developed to obtain the analogues consisted of the synthesis of hydrazide intermediates (key intermediary) to obtain N-acylhydrazones from quinic acid, in which four new compounds were synthesized, characterized by analytical techniques ( infrared, 1H and 13C NMR, melting point) and after HPLC grade of purity certification were recorded and deposited at LASSBio chemistry library.