2.7. Pharmacokinetic in vitro studies. Metabolic stability is the basic prerequisite for the start of further in vivo studies. Initially, we investigated the metabolic stability of compound 11b in mouse liver microsomes (MLMs) and human liver microsomes (HLMs) in vitro (Figure ). It was observed that 11b was metabolized to an extent of only 23% by HLMs after 120 min (Table ). Although 11b underwent substantially higher metabolization in MLMs, nearly 50% of the compound was still retained. We next assessed the metabolic stability of a compound from our study that is distinguished by its antiviral activity, i.e., 11e. In contrast to 11b, compound 11e was entirely stable in MLMs and HLMs, with half-lives (t1/2) of more than 60 min each. In addition, the intrinsic clearance of 11e was determined in the mouse model and, gratifyingly, was below 23 µL/min/mg, indicating that the compound is stable. Encouraged by these results, we assessed plasma stability as well as plasma protein binding (PPB) in the next step. Again, 11e was very stable in mouse and human plasma, as no degradation was observed up to 240 min. With respect to PPB, 11e exhibited a high protein binding in mouse and human of about 99%. In summary, 11e showed favorable pharmacokinetic properties for further preclinical development.