Discovery of potent and orally bioavailable N,N′-diarylurea antagonists for the CXCR2 chemokine receptor

被引：36

作者：

Jin, Q ^{[1
]}

Nie, H ^{[1
]}

McCleland, BW ^{[1
]}

Widdowson, KL ^{[1
]}

Palovich, MR ^{[1
]}

Elliott, JD ^{[1
]}

Goodman, RM ^{[1
]}

Burman, M ^{[1
]}

Sarau, HM ^{[1
]}

Ward, KW ^{[1
]}

Nord, M ^{[1
]}

Orr, BM ^{[1
]}

Gorycki, PD ^{[1
]}

Busch-Petersen, J ^{[1
]}

机构：

[1] GlaxoSmithKline, King Of Prussia, PA 19406 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 17期

关键词：

CXCR2; IL-8; diarylureas;

D O I：

10.1016/j.bmcl.2004.06.097

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 3-substituted N,N'-diarylureas was prepared and the structure-activity relationship relative to CXCR2 receptor affinity as well as their pharmacokinetic properties were examined. In vitro microsomal metabolism studies indicated that the lower clearance rates of the 3-sulfonamido-substituted compounds were most likely due to the suppression of glucuronidation. (C) 2004 Elsevier Ltd. All rights reserved.

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页码：4375 / 4378

页数：4

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