Design and Synthesis of Novel Oxygen Heterocycles as Versatile Biodynamic Agents

Abstract

Coumarins are an important class of oxygen heterocycles which have attracted researchers in recent years because of their diverse pharmacological properties. Coumarins have important effects in plant biochemistry and physiology, acting as antioxidants, enzyme inhibitors and precursors of toxic substances. These scaffolds have long been recognized to possess anti-coagulant, antioxidant, anticancer, antiinflammatory, lipid lowering, hepatoprotective, antithrombotic, antiviral activities. Therefore we designed, synthesized and evaluated this class of compounds for various biological activities. The thesis entitled “Design and Synthesis of Novel Oxygen Heterocycles as Versatile Biodynamic Agents” describes our synthetic efforts towards the development of novel and potential pharmaceutical agents. The thesis has been organized under five main chapters as summarized below: The chapter 1 presents available literature comprising important information about diverse coumarin based scaffolds including drugs, natural products and synthetic polycycles associated with biological activities has been reviewed. The chapter 2.1 describes coumarin-dihydropyridine hybrids: Synthesis, in vitro and in vivo evaluation as anti-osteoporotic agents. Chapter 2.2 describes coumarin-based fibrates as potential hypolipidemic and anti-adipogenic agents. The chapter 3.1 describes discovery and synthesis of novel substituted benzocoumarins as orally active lipid modulating agents. Chapter 3.2 deals with synthesis and anti-inflammatory activity of novel biscoumarin-chalcone hybrids. The chapter 4.1 comprises a simple and efficient access to new functionalized 4- phenacylideneflavenes. The chapter 4.2 describes a novel route to synthesis of flavones from salicylaldehyde and acetophenone derivatives. During our course of studies we also observed some miscellaneous results which are described in chapter 5. The chapter 5.1 describes indole-based fibrates as potential hypolipidemic and anti-obesity agents. The chapter 5.2 deals with anti-plasmodial activity of novel keto-enamine chalcone-chloroquine based hybrid pharmacophores