AI Article Synopsis
- The study focuses on designing and synthesizing new factor Xa inhibitors that are based on sulfonamidopyrrolidin-2-one structures with specific chemical motifs.
- The resulting compounds showed strong anticoagulant effects and favorable oral pharmacokinetics, meaning they are effective when taken by mouth.
- A concern with the aminoindane series was their significant inhibition of the P450 enzyme over time, while the phenylpyrrolidine series did not have this issue, making it more promising for once-daily dosing in humans.
Article Abstract
The rational design, syntheses and evaluation of potent sulfonamidopyrrolidin-2-one-based factor Xa inhibitors incorporating aminoindane and phenylpyrrolidine P4 motifs are described. These series delivered highly potent anticoagulant compounds with excellent oral pharmacokinetic profiles; however, significant time dependant P450 inhibition was an issue for the aminoindane series, but this was not observed with the phenylpyrrolidine motif, which produced candidate quality molecules with potential for once-daily oral dosing in humans.
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| http://dx.doi.org/10.1016/j.bmcl.2011.01.131 | DOI Listing |
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