CCR5,the chemokine co-receptor for HIV-1,has become a very popular target for blocking the entry of this deadly virus into cells.Several small molecule inhibitors of the CCR5 co-receptor,which belongs to the super family of G-proteincoupled receptors (GPCRs),have been reported.In this presentation,the discovery of Vicriviroc (Sch 417690),a CCR5 antagonist built on a piperazino-piperidine core,would be described from a Lead to the Clinic perspective.Defining minimum structural requirements for CCR5 affinity and including the requirement for functional activity helped transform our initial hits to leads.Designing in structural features to enhance receptor Selectivity and pharmacokinetics helped transform the leads to drug-like molecules.Stringent criteria for broad spectrum potency and pharmacological safety led to the choice of a preclinical drug candidate.The development of efficient enantio-anddiastereoselective synthetic routes to these compounds was also essential for rapid SAR development and drug safety evaluation.The presentation would showcase chemistry as the central science that interacts with Biology and Pharmacokinetics to create novel drug entities for serving clinical needs.