Lactams as prostanoid receptor ligands.: Part 4:: 2-piperidones as selective EP4 receptor agonists

被引：19

作者：

Elworthy, TR ^{[1
]}

Brill, ER ^{[1
]}

Caires, CC ^{[1
]}

Kim, W ^{[1
]}

Lach, LK ^{[1
]}

Tracy, JL ^{[1
]}

Chiou, SS ^{[1
]}

机构：

[1] Roche Palo Alto, Dept Med Chem, Palo Alto, CA 94304 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 10期

关键词：

2-piperidone; EP4; agonist; selective EP4 ligands; delta-lactams as prostanoids;

D O I：

10.1016/j.bmcl.2005.03.059

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

2-Piperidones were prepared bearing heptanoic acid or a thioether heptanoic acid at the I-position as well as appropriately substituted at the 6-position to mimic the structure of prostaglandins. The stereochemical purity at the 6-position was determined to be >= 95% ee for an advanced synthetic intermediate. The 2-piperidones were identified as potent agonists at the EP4 prostanoid receptor. They displayed a high affinity (K-i 5-130 nM) at EP4 and subtype selectivity. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：2523 / 2526

页数：4

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