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

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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

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,

doi

10.1016/j.bmcl.2011.01.131

subject

Has Abstract

pub_date

2011-03-15 00:00:00

pages

1582-7

issue

6

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)00165-X

journal_volume

21

pub_type

杂志文章

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