Synthesis and SAR of pyridazinone-substituted phenylalanine amide α4 integrin antagonists

被引：16

作者：

Gong, Yong ^{[1
]}

Barbay, J. Kent ^{[1
]}

Kimball, Edward S. ^{[1
]}

Santulli, Rosemary J. ^{[1
]}

Fisher, M. Carolyn ^{[1
]}

Dyatkin, Alexey B. ^{[1
]}

Miskowski, Tamara A. ^{[1
]}

Hornby, Pamela J. ^{[1
]}

He, Wei ^{[1
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev LLC, Spring House, PA 19477 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 04期

关键词：

pyridazinone; phenylalanine; alpha(4) integrin antagonist;

D O I：

10.1016/j.bmcl.2008.01.022

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Structural modi. cation and cellular adhesion inhibition activities of pyridazinone-substituted phenylalanine amide alpha(4) integrin antagonists are described. Functionality requirements for the arylamide moiety and the carboxylic acid group were demonstrated. The study also revealed novel structure - activity relationships (SAR) for arylated pyridazinones. A correlation between bioavailability and permeability was also explored. A selected compound showed effectiveness in a mouse leukocytosis study. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：1331 / 1335

页数：5

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