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Hepatitis C virus is a major anti-infective research focus for many pharmaceutical companies, due to the presence of a large infected population in western society (47). HCV encoded NS3 serine protease has been under close scrutiny to develop orally bioavailable agents for many years (48-50). Due to its large and shallow binding pocket, even with the aids of X-ray crystallography and NMR studies of enzyme complex with peptide inhibitors, very few orally bioavailable small molecule inhibitors have emerged from extensive research (51,52). Recently, a macrocyclic inhibitor structurally related to 54 was reported (53,54). This highly potent NS3 inhibitors showed sub nM Ki which is more potent than the early acyclic lead 53 that has an IC50 of 15nM (55). More interestingly, a clinical trial with b.i.d. dosing at

200mg/kg for two days in 10 patients with chronic HCV infection showed at least 2 logio copies/ml reduction of HCV RNA levels with no drug related toxicity (56).

200mg/kg for two days in 10 patients with chronic HCV infection showed at least 2 logio copies/ml reduction of HCV RNA levels with no drug related toxicity (56).

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