Book Overview

4.1: General Introduction Ever since, Waldman1 et.al. have carried out a quantitative analysis of physiologically active natural products and showed that ones with two or three rings were most often found in active natural products,the interest on the various facets of the chemistry and biology of small bicyclic and tricyclic (carbocyclic and heterocyclic) systems has expanded exponentially thereafter.Since then the development of small molecule libraries with potential biological activites has been a major focus of research in the area of chemical biology and medicinal chemistry.In view of this,the development of efficient methodologies to access small molecules of medicinal utility has been currently of special interest.In these efforts, particular emphasis has been placed on the preparation of compound librar- ies from the 'privileged medicinal structures2 ,or from those whose structures are akin to these. Benzodiazepine framework in general, has been recognized to belong to the family of 'privileged medicinal structures'2, by virtue of their ability to provide ligands to a number of functionally and structurally discretre biological receptors. Literature is replete with ample examples to show that the presence of an additional heterocyclic ring on to the seven memebered ring of benzodiazepines exert a profound influence on the biological activity in the resulting materials. In view of this trend,we thought that it was of interest to functionalize the benzazepin-2,5-dione system 4.057 with ketene dithioacetal function, in consideration of their amenability to the corresponding pyrazolo, isoxazolo, pyrimido, 1,5 benzodiazepino, 1,5 benzothiazepino and 1,5 benzoxazepino annulated analogues 4.059-4.068 respectively [Scheme-4.19], on the premise that their presence in tandem in the same molecular framework could inherit its positive impact on to the overall biological efficacy in the resulting materials. In this chapter,we describe the preliminary results of our endeavour, focused in this direction. 4.2: Pyrazole and Isoxazole 4.2.1: General introduction Pyrazoles exhibit a wide array of biological activities and have a variety of industrial applications3. Besides this these are also used as antioxidants4 in fuels but their major applications have been in medicinal and agricultural fields5. Isoxazoles too exhibit number of applications and have been demonstrated as versatile building blocks in organic synthesis6. The key feature of these heterocycles is that they possess the typical properties of an aromatic system but contain a weak nitrogen-oxygen bond which under certain conditions, particularly in reducing or basic conditions, is a potential site of ring cleavage. Thus, pyrazoles and isoxazoles are very useful intermediates since the ring system allows the manipulation of substituents to give functionally complex derivatives, yet it is easily cleaved when necessary6.