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

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Kleanthous S, Borthwick AD, Brown D, Burns-Kurtis CL, Campbell M, Chaudry L, Chan C, Clarte MO, Convery MA, Harling JD, Hortense E, Irving WR, Irvine S, Pateman AJ, Patikis AN, Pinto IL, Pollard DR, Roethka TJ, Senger S, Shah GP, Stelman GJ, Toomey JR, Watson NS, West RI, Whittaker C, Zhou P, Young RJ

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

Bioorg Med Chem Lett. 2010 Jan 15;20(2):618-22. doi: 10.1016/j.bmcl.2009.11.077. Epub 2009 Nov 20.

PubMed ID

20006499 [ View in PubMed

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Abstract

Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa inhibitors, incorporating neutral and basic monoaryl P4 groups, ultimately producing potent inhibitors with effective levels of anticoagulant activity and extended oral pharmacokinetic profiles. However, time dependant inhibition of Cytochrome P450 3A4 was a particular issue with this series.

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