Identified a morpholinyl-4-piperidinylacetic acid derivative as a potent oral active VLA-4 antagonist

被引：21

作者：

Chiba, J

Machinaga, N

Takashi, T

Ejima, A

Takayama, G

Yokoyama, M

Nakayama, A

Baldwin, JJ

McDonald, E

Saionz, KW

Swanson, R

Hussain, Z

Wong, A

机构：

[1] Daiichi Pharmaceut Co Ltd, Med Chem Res Lab, Edogawa Ku, Tokyo 1348630, Japan

[2] Daiichi Pharmaceut Co Ltd, New Prod Res Labs 3, Edogawa Ku, Tokyo 1348630, Japan

[3] Pharmacopeia Drug Discovery Inc, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 01期

关键词：

VLA-4; integrin; asthma;

D O I：

10.1016/j.bmcl.2004.10.041

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

An investigation into the structure-activity relationship of a lead compound, prolyl-5-aminopentanoic acid 4, led to the identification of a novel series of 4-piperidinylacetic acid, 1-piperazinylacetic acid, and 4-aminobenzoic acid derivatives as potent VLA-4 antagonists with low nanomolar IC50 values. A representative compound morpholinyl-4-piperidinylacetic acid derivative (13d: IC50 = 4.4nM) showed efficacy in the Ascaris-antigen sensitized murine airway inflammation model by oral administration. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：41 / 45

页数：5

共 23 条

[1] CORRELATION BETWEEN ORAL-DRUG ABSORPTION IN HUMANS AND APPARENT DRUG PERMEABILITY COEFFICIENTS IN HUMAN INTESTINAL EPITHELIAL (CACO-2) CELLS [J].