N-[3-[[2-(4-氨基呋咱-3-基)-1-乙基-1H-咪唑并[4,5-C]吡啶-6-基]氧]苯基]-4-[[2-(4-吗啉基)乙基]氧]苯甲酰胺 | 850664-21-0

• 物质功能分类: 医药中间体 - 杂环化合物 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-[3-[[2-(4-氨基呋咱-3-基)-1-乙基-1H-咪唑并[4,5-C]吡啶-6-基]氧]苯基]-4-[[2-(4-吗啉基)乙基]氧]苯甲酰胺
• 中文别名: N-(3-{[2-(4-氨基-1,2,5-恶二唑-3-基)-1-乙基-1H-咪唑并[4,5-c]吡啶-6-基]氧基}苯基)-4-[2-(4-吗啉基)乙氧基]苯甲酰胺
• 英文名称: N-[3-([2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-1H-imidazo(4,5-c)pyridin-6-yl]oxy)phenyl]-4-[2-(4-morpholinyl)ethoxy]benzamide
• 英文别名: GSK 269962；GSK269962A；N-[3-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethylimidazo[4,5-c]pyridin-6-yl]oxyphenyl]-4-(2-morpholin-4-ylethoxy)benzamide
• CAS: 850664-21-0；925213-63-4
• 化学式: C₂₉H₃₀N₈O₅
• 分子量: 570.608
• InChiKey: YOVNFNXUCOWYSG-UHFFFAOYSA-N

物化性质

• 熔点：
  125 - 127°C
• 密度：
  1.45
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  156
• 氢给体数：
  2
• 氢受体数：
  11

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为产物：
  描述：

  4-羟基-3-硝基吡啶 在 palladium on activated charcoal 吡啶 、 盐酸 、 叔丁基过氧化氢 、 硫酸 、 potassium tert-butylate 、 氢气 、 羟胺 、 potassium carbonate 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium nitrite 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 癸烷 、 二氯甲烷 、 氨 、 水 、 重水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， -35.0~110.0 ℃ 、500.0 kPa 条件下， 反应 109.0h， 生成 N-[3-[[2-(4-氨基呋咱-3-基)-1-乙基-1H-咪唑并[4,5-C]吡啶-6-基]氧]苯基]-4-[[2-(4-吗啉基)乙基]氧]苯甲酰胺
  参考文献：
  名称：

  Discovery of Aminofurazan-azabenzimidazoles as Inhibitors of Rho-Kinase with High Kinase Selectivity and Antihypertensive Activity

  摘要：

  The discovery, proposed binding mode, and optimization of a novel class of Rho-kinase inhibitors are presented. Appropriate substitution on the 6-position of the azabenzimidazole core provided subnanomolar enzyme potency in vitro while dramatically improving selectivity over a panel of other kinases. Pharmacokinetic data was obtained for the most potent and selective examples and one (6n) has been shown to lower blood pressure in a rat model of hypertension.

  DOI：

  10.1021/jm060873p

文献信息

• Preparation of 1,6-Disubstituted Azabenzimidazoles as Kinase Inhibitors
  申请人：Lee Dennis

  公开号：US20080234261A1

  公开（公告）日：2008-09-25

  Novel inhibitors of Rho-kinases are disclosed.

  本发明揭示了Rho激酶的新型抑制剂。
• Preparation of 1,6-disubstituted azabenzimidazoles as kinase inhibitors
  申请人：Glaxo Group Limited

  公开号：US07547779B2

  公开（公告）日：2009-06-16

  Novel inhibitors of Rho-kinases are disclosed.

  本发明公开了Rho激酶的新型抑制剂。
• MODIFIED BIO-RELATED SUBSTANCE, PROCESS FOR PRODUCING THE SAME, AND INTERMEDIATE
  申请人：NAKAMOTO Ken-ichiro

  公开号：US20090192320A1

  公开（公告）日：2009-07-30

  A modified bio-related substance, wherein at least one poly(alkylene glycol)oxy group represented by the following formula (1) is combined in a molecule: wherein R is a hydrocarbon group having 1 to 24 carbon atoms, OA 1 and OA 2 are each an oxyalkylene group having 2 to 4 carbon atoms, the groups represented by R are the same or different from each other in one molecule, and the groups represented by OA 2 are the same or different from each other in one molecule, n and m are each average number of moles of the oxyalkylene group added, n represents 0 to 1000, and m represents 10 to 1000.

  一种改性的生物相关物质，其中至少有一个由以下公式（1）表示的聚（烷基氧基乙二醇）氧基团结合在分子中：其中R是具有1至24个碳原子的碳氢基团，OA1和OA2分别是具有2至4个碳原子的氧烷基团，由R表示的基团在一个分子中相同或不同，由OA2表示的基团在一个分子中相同或不同，n和m分别是添加的氧烷基团的平均摩尔数，n表示0至1000，m表示10至1000。
• METHOD FOR PROLIFERATION OF PANCREATIC PROGENITOR CELLS
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP3178924A1

  公开（公告）日：2017-06-14

  The present invention relates to a method for preparing highly pure pancreatic progenitor cells by using pluripotent stem cells such as ES cells or iPS cells as a source, inducing their differentiation into pancreatic progenitor cells, and culturing and proliferating the pancreatic progenitor cells. Specifically, the present invention relates to a method for proliferation of pancreatic progenitor cells, comprising the step of culturing the pancreatic progenitor cells in a medium containing (i) an EGF signal transduction activator and/or an FGF signal transduction activator and (ii) a ROCK inhibitor.

  本发明涉及一种制备高纯度胰腺祖细胞的方法，该方法以ES细胞或iPS细胞等多能干细胞为来源，诱导其分化为胰腺祖细胞，并培养和增殖胰腺祖细胞。具体而言，本发明涉及一种增殖胰腺祖细胞的方法，包括在含有(i)EGF信号转导激活剂和/或FGF信号转导激活剂和(ii)ROCK抑制剂的培养基中培养胰腺祖细胞的步骤。
• METHOD FOR INDUCING DIFFERENTIATION OF CORNEAL EPITHELIAL CELLS FROM PLURIPOTENT STEM CELLS
  申请人：Osaka University

  公开号：EP3246394A1

  公开（公告）日：2017-11-22

  The present invention relates to a method for inducing the differentiation of corneal epithelial cells from pluripotent stem cells. More specifically, the present invention relates to a method for autonomously differentiating pluripotent stem cells, such as human iPS cells, into ectodermal cell lineage in a serum-free medium without using feeder cells and inducing the differentiation of the resultant ocular surface ectodermal lineage cells into corneal epithelial cells.

  本发明涉及一种诱导多能干细胞分化角膜上皮细胞的方法。更具体地说，本发明涉及一种在无血清培养基中不使用饲养细胞而将多能干细胞（如人类 iPS 细胞）自主分化为外胚层细胞系，并将分化出的眼表外胚层细胞系细胞诱导分化为角膜上皮细胞的方法。