Pharmaceutical organic chemistry research


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Pharmaceutical organic chemistry research

  2. 2. INTRODUCTION : Combinatorial chemistry is one of the important new methodologies developed by academics and researchers in the pharmaceutical, agrochemical, and biotechnology industries to reduce the time and costs associated with producing effective, marketable, and competitive new drugs. Simply put, scientists use combinatorial chemistry to create large populations of molecules, or libraries, that can be screened efficientlyen masse. By producing larger, more diverse compound libraries, companies increase the probability that they will find novel compounds of significant therapeutic and commercial value. The field represents a convergence of chemistry and biology, made possible by fundamental advances in miniaturization, robotics, and receptor development. And not surprisingly, it has also captured the attention of every major player in the pharmaceutical, biotechnology, and agrochemical arena. While combinatorial chemistry can be explained simply, its application can take a variety of forms, each requiring a complex interplay of classical organic synthesis techniques, rational drug design strategies, robotics, and scientific information management. This article will provide a basic overview of existing approaches to combinatorial chemistry, and will outline some of the unique information management problems that it generates.DEFINITION :Combinatorial chemistry is a technique by which large numbers of structurally distinct moleculesmay be synthesised in a time and submitted for pharmacological assay. The key ofcombinatorial chemistry is that a large range of analogues is synthesised using the samereaction conditions, the same reaction vessels. In this way, the chemist can synthesise manyhundreds or thousands of compounds in one time instead of preparing only a few by simplemethodology.In the past, chemists have traditionally made one compound at a time. For example compoundA would have been reacted with compound B to give product AB, which would have beenisolated after reaction work up and purification through crystallisation, distillation, orchromatography.In contrast to this approach, combinatorial chemistry offers the potential to make everycombination of compound A1 to An with compound B1 to Bn.The range of combinatorial techniques is highly diverse, and these products could be madeindividually in a parallel or in mixtures, using either solution or solid phase techniques.Whatever the technique used the common denominator is that productivity has been amplifiedbeyond the levels that have been routine for the last hundred years. 2
  3. 3. Application of Combinatorial Chemistry : Applications of combinatorial chemistry are very wide. For example in pharmaceutical companies for drug designs. For illustrate this, one a practical example: Transition-state analog HIV protease inhibitors. Extensive efforts toward the rational design of aspartyl protease inhibitors such as renin and HIV have led to the discovery of several transition-states analog mimics. These templates can serve as the central unit around which molecular diversity can be generated by application of appropriate chemistries. Recently, solid phase synthesis of hydroxyethylamine and 1,2-diol transition-state pharmacophore units and their utility for synthesis of HIV protease inhibitors have been reported by two different groups. The first instance, bifunctional linker are used by Wang to serve the dual purpose of protecting the hydroxyl group of these BBs and providing point for attachment on solid support. Thus, one linker possesses a vinyl ether group at one end and a free carboxylate group at the other. The vinyl ether moiety is reacted with diamino alcohol BB 1 under acid-catalysed conditions to form an acetal protecting group and the carboxylic acid group is used for ester-type linkage to the solid support. The other linker possesses a methyl ketone and carboxylic groups at the two ends, with the ketone group forming a ketal with diol 3. Resulting intermediates 2 and 4 are now well suited for a bi-directional solid phase 3
  4. 4. synthesis strategy for preparing C2 symmetric HIV protease inhibitors. The two terminal amino groups of 2 and 4 are deprotected and reacted with a variety of carboxylic acid, sulfonyl chlorides, isocyanates, and chloroformates to extend the core unit in both directions and generate a wide variety of aspartyl protease inhibitors. The authors claim that a library of 300 discrete analogs was prepared and screened against HIV protease to identify several potent inhibitors.ADVANTAGES AND DISADVANTAGES : 4
  5. 5. FUTURE ASPECTS : 5
  6. 6. REFRENCES : 1- 2- 3- 4- 5- BY SECTION(2) : 1- Jehan Essam Mahmoud (112) . 2- Aya Ahmed Saber Yossiff (86). 3- Eman Mohammed Mostafa Sherra (83). 4- Eman Ahmed Alaa Elshamy . 5- Aya Samir . 6