Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with aminoindane and phenylpyrrolidine P4 motifs.

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Young RJ, Adams C, Blows M, Brown D, Burns-Kurtis CL, Chan C, Chaudry L, Convery MA, Davies DE, Exall AM, Foster G, Harling JD, Hortense E, Irvine S, Irving WR, Jackson S, Kleanthous S, Pateman AJ, Patikis AN, Roethka TJ, Senger S, Stelman GJ, Toomey JR, West RI, Whittaker C, Zhou P, Watson NS

Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with aminoindane and phenylpyrrolidine P4 motifs.

Bioorg Med Chem Lett. 2011 Mar 15;21(6):1582-7. doi: 10.1016/j.bmcl.2011.01.131. Epub 2011 Feb 1.

PubMed ID

21349710 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
GW-813893	Coagulation factor X	Ki (nM)	4	N/A	N/A	Details