5-(4-(piperazin-1-yl)phenyl)-3-(3,4,5-trimethoxyphenyl)pyridin-2-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5-(4-(piperazin-1-yl)phenyl)-3-(3,4,5-trimethoxyphenyl)pyridin-2-amine
• 英文别名: 5-(4-Piperazin-1-ylphenyl)-3-(3,4,5-trimethoxyphenyl)pyridin-2-amine；5-(4-piperazin-1-ylphenyl)-3-(3,4,5-trimethoxyphenyl)pyridin-2-amine
• 化学式: C₂₄H₂₈N₄O₃
• 分子量: 420.511
• InChiKey: SJOCBUINMBQCTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  81.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氨基-5-溴-3-碘吡啶 在 四(三苯基膦)钯 、 sodium carbonate 、 三氟乙酸 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 16.0h， 生成 5-(4-(piperazin-1-yl)phenyl)-3-(3,4,5-trimethoxyphenyl)pyridin-2-amine
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS FOR INHIBITING BMP
  [FR] COMPOSITIONS ET PROCÉDÉS D'INHIBITION DE LA BMP

  摘要：

  本发明提供了BMP信号通路的小分子抑制剂，以及用于抑制BMP信号通路的组成物和方法。这些化合物和组成物可用于调节细胞生长、分化、增殖和凋亡，因此可用于治疗与BMP信号通路相关的疾病或病况，包括炎症、心血管疾病、血液疾病、癌症和骨骼疾病，以及用于调节细胞分化和/或增殖。这些化合物和组成物也可用于减少ApoB-100或LDL的循环水平，治疗或预防获得性或先天性高胆固醇血症或高脂蛋白血症；与脂质吸收或代谢缺陷相关的疾病、疾病或综合症；或由高脂血症引起的疾病、疾病或综合症。

  公开号：

  WO2015148654A1

文献信息

• Structure–Activity Relationship of 3,5-Diaryl-2-aminopyridine ALK2 Inhibitors Reveals Unaltered Binding Affinity for Fibrodysplasia Ossificans Progressiva Causing Mutants
  作者：Agustin H. Mohedas、You Wang、Caroline E. Sanvitale、Peter Canning、Sungwoon Choi、Xuechao Xing、Alex N. Bullock、Gregory D. Cuny、Paul B. Yu

  DOI：10.1021/jm501177w

  日期：2014.10.9

  There are currently no effective therapies for fibrodysplasia ossificans progressiva (FOP), a debilitating and progressive heterotopic ossification disease caused by activating mutations of ACVR1 encoding the BMP type I receptor kinase ALK2. Recently, a subset of these same mutations of ACVR1 have been identified in-diffuse intrinsic pontine ghoma (DIPG) tumors. Here we describe the structure-activity relationship for a series of novel ALK2 inhibitors based on the 2-aminopyridine compound K02288. Several modifications increased potency in kinase, thermal shift, or cell-based assays of BMP signaling and transcription, as well as selectivity for ALK2 versus closely related BMP AND TGF-beta type I receptor kinases. Compounds in this series exhibited a wide range of in vitro cytotoxicity that was not correlated with potency or selectivity, suggesting mechanisms independent of BMP or TGF-beta inhibiton. This study also highlights a potent 2-methylpyridine derivative 10 (LDN 214117) with a high degree of selectivity for ALK2 and low cytotoxicity that could provide a template for preclinical development. contrary to the notion that activating mutations of ALK2 might alter inhibitor efficacy due to potential conformational changes in the ATP-binding site, the compounds demonstrated consistent binding to a panel of mutant and wild-type ALK2 proteins. Thus, BMP inhibitors identified via activity against wild-type ALK2 signaling are likely to be of clinical relevance for the diverse ALK2 mutant proteins associated with FOP and DIPG.
• Compositions and Methods for Inhibiting BMP
  申请人：THE BRIGHAM AND WOMAN'S HOSPITAL, INC.

  公开号：US20170190705A1

  公开（公告）日：2017-07-06

  The present invention provides small molecules inhibitors of BMP signaling and compositions and methods for inhibiting BMP signaling. These compounds and compositions may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds and compositions may also be used to reduce circulating levels of ApoB-100 or LDL and treat or prevent acquired or congenital hypercholesterolemia or hyperlipoproteinemia; diseases, disorders, or syndromes associated with defects in lipid absorption or metabolism; or diseases, disorders, or syndromes caused by hyperlipidemia.