Stereoselective synthesis of biologically active novel heterocycles in drug discovery

Many of the drugs in human medicine are chiral because they bind to enzymes and receptors to elicit biological activity. Both enzymes and receptors are chiral and therefore in a chiral drug molecule one of the enantiomer is more active than the other. Most of the drugs are also heterocyclic in nature. The objective of this thesis is to conceive ideas of what heterocycles might show activity against a particular disease based on their bindings at enzyme or receptor level and to investigate the role of chirality in these molecules. We have developed novel synthetic methodologies for enantioselective synthesis of these heterocycles possessing chiral centers and we believe these synthetic methodologies will be useful for the synthesis of other drugs.;Using the above general concepts we have synthesized enantiomerically pure chiral heterocycles such as 5-aryl oxindoles, which have shown potent activity as progesterone receptor antagonists, spiro-pyrrolidine-oxindoles, for possible use as cancer therapeutics, ortho-ortho disubstituted bipheyl lactams, for possible implications in CNS and cancer therapy and conformationally restricted sulfonamides, which have shown potent HIV protease inhibitory activity for the treatment of AIDS.