Synthesis and evaluation of arylalkoxy- and biarylalkoxy-phenylamide and phenylimidazoles as potent and selective sphingosine-1-phosphate receptor subtype-1 agonists

被引：10

作者：

Evindar, Ghotas ^{[1
]}

Satz, Alexander L. ^{[1
]}

Bernier, Sylvie G. ^{[2
]}

Kavarana, Malcolm J. ^{[1
]}

Doyle, Elisabeth ^{[2
]}

Lorusso, Jeanine ^{[2
]}

Taghizadeh, Nazbeh ^{[2
]}

Halley, Keith ^{[2
]}

Hutchings, Amy ^{[2
]}

Kelley, Michael S. ^{[1
]}

Wright, Albion D. ^{[2
]}

Saha, Ashis K. ^{[1
]}

Hannig, Gerhard ^{[2
]}

Morgan, Barry A. ^{[1
]}

Westlin, William F. ^{[2
]}

机构：

[1] Praecis Pharmaceut Inc, Dept Med Chem, Waltham, MA 02451 USA

[2] Praecis Pharmaceut Inc, Dept Preclin Res, Waltham, MA 02451 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 08期

关键词：

S1P; S1P1; agonist; EDG1; Lymphopenia; FTY-720; Sphingosine-1-phosphate; Arylalkoxy-phenylamide; Arylalkoxy-phenylimidazoles; Biarylalkoxy-phenylamide; Biarylalkoxyphenylimidazoles; ANALOGS;

D O I：

10.1016/j.bmcl.2009.02.073

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

In pursuit of potent and selective sphingosine-1-phosphate receptor agonists, we have utilized previously reported phenylamide and phenylimidazole scaffolds to explore extensive side-chain modi. cations to generate new molecular entities. A number of designed molecules demonstrate good selectivity and excellent in vitro and in vivo potency in both mouse and rat models. Oral administration of the lead molecule 11c (PPI-4667) demonstrated potent and dose-responsive lymphopenia. (c) 2009 Elsevier Ltd. All rights reserved.

引用

页码：2315 / 2319

页数：5

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