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However, small-molecule 3 was quite lipophilic (logD 7.4 = 5.7), resulting in high metabolic intrinsic clearance in human liver microsomes (HLM) (CL int = 130 mL/min/kg, Table S4), which would likely lead to a short pharmacokinetic half-life (t 1/2 ) and the requirement for an unacceptably high daily dose in humans