(2S)-2-Boc-amino-1-(2-aminoimidazo[1,2-a]pyridin-3-yl)propan-1-one | 1369586-10-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: (2S)-2-Boc-amino-1-(2-aminoimidazo[1,2-a]pyridin-3-yl)propan-1-one
• 英文别名: tert-butyl N-[(2S)-1-(2-aminoimidazo[1,2-a]pyridin-3-yl)-1-oxopropan-2-yl]carbamate
• CAS: 1369586-10-6
• 化学式: C₁₅H₂₀N₄O₃
• 分子量: 304.349
• InChiKey: BJBYYHBQQFXOOB-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  98.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S)-2-Boc-amino-1-(2-aminoimidazo[1,2-a]pyridin-3-yl)propan-1-one 在 盐酸 、 ammonium hydroxide 作用下， 以 水 为溶剂， 反应 1.0h， 以92%的产率得到(2S)-2-amino-1-(2-aminoimidazo[1,2-a]pyridin-3-yl)-propan-1-one
  参考文献：
  名称：

  2-氨基咪唑并[1,2- a ]吡啶的选择性C-酰化反应：在咪唑并吡啶[1,3]二氮杂吡啶酮类化合物的合成中的应用

  摘要：

  一系列20个光学纯的3,4-二氢-5 H-吡啶并[1'，2'：1,2]咪唑并[4,5- d ] [1,3]二氮杂-5-酮形成一个新家族分四步合成了氮杂杂环融合的[1,3]二氮杂ze，总产率为17-66％。关键步骤包括在C-3处容易获得的2-氨基咪唑并[1,2- a ]吡啶的选择性C-酰化反应。

  DOI：

  10.1021/jo300364d
• 作为产物：
  描述：

  N-(2-pyridyl)-p-toluenesulfonamide 在 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 (2S)-2-Boc-amino-1-(2-aminoimidazo[1,2-a]pyridin-3-yl)propan-1-one
  参考文献：
  名称：

  2-氨基咪唑并[1,2- a ]吡啶的选择性C-酰化反应：在咪唑并吡啶[1,3]二氮杂吡啶酮类化合物的合成中的应用

  摘要：

  一系列20个光学纯的3,4-二氢-5 H-吡啶并[1'，2'：1,2]咪唑并[4,5- d ] [1,3]二氮杂-5-酮形成一个新家族分四步合成了氮杂杂环融合的[1,3]二氮杂ze，总产率为17-66％。关键步骤包括在C-3处容易获得的2-氨基咪唑并[1,2- a ]吡啶的选择性C-酰化反应。

  DOI：

  10.1021/jo300364d

文献信息

• Imidazopyridine-fused [1,3]diazepinones: modulations of positions 2 to 4 and their impacts on the anti-melanoma activity
  作者：Paul Le Baccon-Sollier、Yohan Malki、Morgane Maye、Lamiaa M. A. Ali、Laure Lichon、Pierre Cuq、Laure-Anaïs Vincent、Nicolas Masurier

  DOI：10.1080/14756366.2020.1748024

  日期：2020.1.1

  A series of 19 novel pyrido-imidazodiazepinones, with modulations of positions 2, 3 and 4 of the diazepine ring were synthesised and screened for their in vitro cytotoxic activities against two melanoma cell lines (A375 and MDA-MB-435) and for their potential toxicity against NIH-3T3 non-cancerous cells. Selected compounds were also evaluated on the NCI-60 cell line panel. The SAR study revealed that the molecular volume and the cLogP of compounds modified at position 2 were significantly correlated with the activity of these compounds on melanoma cell lines. Moreover, introduction of a heterocyclic group at position 2 or an azido-alkyl chain at position 4 led to compounds displaying a significantly different activity profile on the NCI-60 cell line panel, compared to phenyl-substituted compounds at position 2 of the diazepinone. This study provides us crucial information for the development of new derivatives active against melanoma.
• Pyrido-imidazodiazepinones as a new class of reversible inhibitors of human kallikrein 7
  作者：Dominique P. Arama、Feryel Soualmia、Vincent Lisowski、Jean-François Longevial、Elodie Bosc、Ludovic T. Maillard、Jean Martinez、Nicolas Masurier、Chahrazade El Amri

  DOI：10.1016/j.ejmech.2015.02.008

  日期：2015.3

  The human tissue kallikrein-7 (KLK7) is a chymotryptic serine protease member of tissue kallikrein family. KLK7 is involved in skin homeostasis and inflammation. Excess of KLK7 activity is also associated with tumor metastasis processes, especially in ovarian carcinomas, prostatic and pancreatic cancers. Development of Kallikrein 7 inhibitors is thus of great interest in oncology but also for treating skin diseases. Most of the developed synthetic inhibitors present several drawbacks such as poor selectivity and unsuitable physico-chemical properties for in vivo use. Recently, we described a practical sequence for the synthesis of imidazopyridine-fused [1,3]-diazepines. Here, we report the identification of pyrido-imidazodiazepinone core as a new potential scaffold to develop selective and competitive inhibitors of kallikrein-related peptidase 7. Structure-activity relationships (SAR), inhibition mechanisms and selectivity as well as cytotoxicity against selected cancer cell lines were investigated. (C) 2015 Elsevier Masson SAS. All rights reserved.
• An efficient synthesis of pyrido-imidazodiazepinediones
  作者：Dominique P. Arama、Vincent Lisowski、Eliana Scarlata、Pierre Fulcrand、Ludovic T. Maillard、Jean Martinez、Nicolas Masurier

  DOI：10.1016/j.tetlet.2012.12.087

  日期：2013.3

  We herein report the synthesis of a series of 12 optically pure 3,4-dihydro-1H-pyrido-[1',2':1,21-imidazo[4,5-d][1,31diazepine-2,5-diones, which form a new family of azaheterocycle-fused [1,3]diazepines. The key step of the synthesis consists in a selective C-acylation of 2-amino-imidazo[1,2-a]pyridine by various natural amino-acids, followed by an intracarbonylation reaction. (C) 2012 Elsevier Ltd. All rights reserved.
• Imidazopyridine-fused [1,3]-diazepinones: Synthesis and antiproliferative activity
  作者：Audrey Gallud、Ophélie Vaillant、Ludovic T. Maillard、Dominique P. Arama、Joëlle Dubois、Marie Maynadier、Vincent Lisowski、Marcel Garcia、Jean Martinez、Nicolas Masurier

  DOI：10.1016/j.ejmech.2014.01.044

  日期：2014.3

  A series of 15 pyrido-imidazo-1,3-diazepin-5-ones and pyrido-1,3-diazepine-2,5-diones were synthesized and their anticancer activities were evaluated. Among tested compounds on a cell lines panel, compound 6a presents the best growth inhibition activity on 21 cell lines with a cytotoxic effect on MDA-MB-435 melanoma cells. This compound led to deep cell morphological changes and revealed to be an inhibitor of the Hepatocyte progenitor kinase-like kinase (HGK), which is known to be implicated in the migration, adhesion and invasion of various tumor cells. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Imidazopyridine-fused [1,3]-diazepinones part 2: Structure-activity relationships and antiproliferative activity against melanoma cells
  作者：Virginie Bellet、Laure Lichon、Dominique P. Arama、Audrey Gallud、Vincent Lisowski、Ludovic T. Maillard、Marcel Garcia、Jean Martinez、Nicolas Masurier

  DOI：10.1016/j.ejmech.2016.11.023

  日期：2017.1

  We recently described a pyrido-imidazodiazepinone derivative which could be a promising hit compound for the development of new drugs acting against melanoma cells. In this study, a series of 28 novel pyrido-imidazodiazepinones were synthesized and screened for their in vitro cytotoxic activities against the melanoma MDA-MB-435 cell line. Among the derivatives, seven of them showed 50% growth inhibitory activity at 1 mu M concentration, and high selectivity against the melanoma cell line MDA-MB-435. (C) 2016 Elsevier Masson SAS. All rights reserved.