Discovery of a series of 2-(1H-pyrazol-1-yl)pyridines as ALK5 inhibitors with potential utility in the prevention of dermal scarring
Discovery of a series of 2-(1H-pyrazol-1-yl)pyridines as ALK5 inhibitors with potential utility in the prevention of dermal scarring
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DOI：
10.1016/j.bmcl.2012.04.013
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发表时间：
2012-05-15
影响因子：
2.7
通讯作者：
Lala, Deepak S.
中科院分区：
文献类型：
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作者：
Boys, Mark L.;Bian, Feng;Lala, Deepak S.
一系列2-（1H-吡唑-1-基）吡啶被描述为ALK 5（TGF β受体I激酶）的抑制剂。在ALK 5激酶结构域中建模化合物能够通过吡唑核心上的取代来优化效力。其中一种化合物PF-03671148可剂量依赖性降低人成纤维细胞中TGF β诱导的纤维化基因表达。在大鼠伤口修复模型中局部应用PF-03671148时，观察到纤维化基因表达的相似降低。因此，这些化合物具有预防皮肤瘢痕形成的潜在效用。(C)2012爱思唯尔有限公司保留所有权利。
A series of 2-(1H-pyrazol-1-yl)pyridines are described as inhibitors of ALK5 (TGF beta receptor I kinase). Modeling compounds in the ALK5 kinase domain enabled some optimization of potency via substitutions on the pyrazole core. One of these compounds PF-03671148 gave a dose dependent reduction in TGF beta induced fibrotic gene expression in human fibroblasts. A similar reduction in fibrotic gene expression was observed when PF-03671148 was applied topically in a rat wound repair model. Thus these compounds have potential utility for the prevention of dermal scarring. (C) 2012 Elsevier Ltd. All rights reserved.