Synthesis and characterization of some active pharmaceutical Indole derivatives and their analogs

Abstract

Thesis entitled ?SYNTHESIS AND CHARACTERIZATION OF SOME ACTIVE PHARMACEUTICAL INDOLE DERIVATIVES AND THEIR ANALOGS? has been presented as five chapters.Chapter-1 deals with the general introduction and biological importance of indole derivatives and fused indole derivatives. Also presents, a brief introduction to process development, importance of impurity profile (Related substances) and polymorphic studies in the process development. Chapter-2 comprises process development of zafirlukast, an anti-asthma drug, preparation of stable amorphous and new acetonitrile solvate polymorph. Chapter-3 deals with a complete impurity profile of zafirlukast including identification, synthesis, characterization and root cause of their formation. Chapter-4 explains the synthesis and characterization of new zafirlukast related analogs. Chapter-5 presents an alternative synthesis of tadalafil from D-tryptophan and sarcosine ethyl ester. Described the impurity profile of two commercial viable schemes with the identification, synthesis, characterization and root cause of their formation.Chapter-1: Introduction to process development of APIs and a brief review on indole and fused indole derivatives In this chapter introduction and biological importance of indole derivatives and fused indole derivatives were described. Also, a brief introduction to the process development, importance of impurity profile and polymorphic studies in the process development was presented.Chapter-2: An improved process for the preparation of Zafirlukast-an anti asthma drug Zafirlukast (1) is a selective and competitive oral leukotriene receptor antagonist (LTRA) marketed under the brand name accolate.Figure 1: Zafirlukast 1 Explains the improved synthesis for zafirlukast from 3-methoxy-4-methyl benzoicacid 2 (scheme 1). Esterification of acid 2 in the presence of thionyl chloride in methanol produced ester 3, which was subjected to benzylic bromination under DBDMH and AIBN in cyclohexane to provide bromo derivative.