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If particles persist after 10 minutes of gentle swirling, something may be wrong with the vial

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To design 13a, 11r was modified by hiding the P3-P2 amide bond in a pyridine ring, followed by replacing hydrophobic cinnamoyl moiety with a relatively less hydrophobic Boc group to prevent cellular proteases from cleaving the amide bond and increasing solubility in plasma for a decreased plasma protein binding, respectively