Identification and structure-activity relationships of ortho-biphenyl carboxamides as potent Smoothened antagonists inhibiting the Hedgehog signaling pathway

被引：32

作者：

Peukert, Stefan ^{[1
]}

Jain, Rishi K. ^{[1
]}

Geisser, Adrian ^{[1
]}

Sun, Yingchuan ^{[1
]}

Zhang, Rui ^{[1
]}

Bourret, Aaron ^{[1
]}

Carlson, Adam ^{[1
]}

DaSilva, Jennifer ^{[1
]}

Ramamurthy, Arun ^{[1
]}

Kelleher, Joseph F. ^{[1
]}

机构：

[1] Novartis Inst BioMed Res Inc, Cambridge, MA 02139 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 02期

关键词：

Hedgehog inhibitor; Smoothened antagonist; Antiproliferative agent; SAR; CANCER; MEDULLOBLASTOMA; MICE;

D O I：

10.1016/j.bmcl.2008.11.096

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Ortho-biphenyl carboxamides, originally prepared as inhibitors of microsomal triglyceride transfer protein (MTP) have been identified as novel inhibitors of the Hedgehog signaling pathway. Structure-activity relationship studies for this class of compounds reduced MTP inhibitory activity and led to low nanomolar Hedgehog inhibitors. Binding assays revealed that the compounds act as antagonists of Smoothened and show cross-reactivity for both the human and mouse receptor. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：328 / 331

页数：4

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