N-(4-bromophenyl)-2-chlorobenzimidamide | 941867-79-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-bromophenyl)-2-chlorobenzimidamide
• 英文别名: N-(4-Bromophenyl)-2-chlorobenzenecarboximidamide；N'-(4-bromophenyl)-2-chlorobenzenecarboximidamide
• CAS: 941867-79-4
• 化学式: C₁₃H₁₀BrClN₂
• 分子量: 309.593
• InChiKey: AHHDHICLGKWLBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.4
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-(4-bromophenyl)-2-chlorobenzimidamide 在 1,2,3,4,5,6,7,8-八硫杂环辛烷 、 potassium phosphate 作用下， 以 二甲基亚砜 为溶剂， 以60.2%的产率得到N-(4-bromophenyl)benzo[d]isothiazol-3-amine
  参考文献：
  名称：

  发现一种有效的口服生物可利用的缺氧诱导因子 2α (HIF-2α) 激动剂及其与脯氨酰羟化酶抑制剂的协同治疗肾性贫血

  摘要：

  激活缺氧诱导因子 2 (HIF-2) 已成为一种有效的肾性贫血治疗策略。在这里，苯并异噻唑衍生物26被发现是一种新型 HIF-2α 激动剂，它在荧光素酶报告基因检测中首次表现出纳摩尔活性（EC 50 = 490 nM，E max = 349.2%）。分子动力学模拟表明，26可以变构增强 HIF-2 二聚化。此外，化合物26具有良好的药代动力学特征（大鼠的口服生物利用度为 41.38%）和体内安全性特征（小鼠的 LD 50大于 708 mg·kg –1）。在体内功效测定中，26和脯氨酰羟化酶抑制剂AKB-6548的组合首次被证实可协同增加小鼠血浆促红细胞生成素水平（从 260 至 2296 pg·mL –1）并缓解多柔比星诱导的斑马鱼贫血. 这些结果为 HIF-2α 激动剂和肾性贫血的治疗提供了新的见解。

  DOI：

  10.1021/acs.jmedchem.1c01479
• 作为产物：
  描述：

  邻氯苯腈 、 4-溴苯胺 在 sodium hydride 作用下， 以 二甲基亚砜 为溶剂， 生成 N-(4-bromophenyl)-2-chlorobenzimidamide
  参考文献：
  名称：

  Efficient synthesis of 1,2-benzisothiazoles from o-haloarylamidines and elemental sulfur via N–S/C–S bond formation under transition-metal-free conditions

  摘要：

  通过无过渡金属条件下从胺基甲酸盐和元素硫直接合成1,2-苯并异噻唑，形成N-S/C-S键，对各种官能团具有良好的容忍性。

  DOI：

  10.1039/c7gc03599c

文献信息

• Liver X Receptor (LXR) partial agonists: Biaryl pyrazoles and imidazoles displaying a preference for LXRβ
  作者：Ellen Kick、Richard Martin、Yinong Xie、Brenton Flatt、Edwin Schweiger、Tie-Lin Wang、Brett Busch、Michael Nyman、Xiao-Hui Gu、Grace Yan、Brandee Wagner、Max Nanao、Lam Nguyen、Thomas Stout、Artur Plonowski、Ira Schulman、Jacek Ostrowski、Todd Kirchgessner、Ruth Wexler、Raju Mohan

  DOI：10.1016/j.bmcl.2014.11.029

  日期：2015.1

  A series of biaryl pyrazole and imidazole Liver X Receptor (LXR) partial agonists has been synthesized displaying LXRβ selectivity. The LXRβ selective partial agonist 18 was identified with potent induction of ATP binding transporters ABCA1 and ABCG1 in human whole blood (EC50 = 1.2 μM, 55% efficacy). In mice 18 displayed peripheral induction of ABCA1 at 3 and 10 mpk doses with no significant elevation

  已经合成了一系列联芳基吡唑和咪唑肝X受体（LXR）部分激动剂，显示出LXRβ选择性。通过在人全血中有效诱导ATP结合转运蛋白ABCA1和ABCG1鉴定出LXRβ选择性部分激动剂18（EC 50  = 1.2μM，功效为55％）。在小鼠18中，在3和10 mpk剂量下显示出ABCA1的外周诱导，并且在这些剂量下血浆或肝甘油三酯没有明显升高，与完全泛激动剂相比，显示出改善的特性。
• Nickel‐Catalyzed Annulation of <i>o</i> ‐Haloarylamidines with Aryl Acetylenes: Synthesis of Isoquinolone and 1‐Aminoisoquinoline Derivatives
  作者：Hao Xie、Qiaoyan Xing、Zhifei Shan、Fuhong Xiao、Guo‐Jun Deng

  DOI：10.1002/adsc.201801635

  日期：2019.4.16

  An efficient method for the synthesis of substituted 1(2H)‐isoquinolone derivatives via nickel‐catalyzed annulation of substituted 2‐halobenzamidines with aryl alkynes in the presence of water is described. Benzo[4,5]imidazo[2,1‐a]isoquinolines were formed as the dominated products when dry dimethyl sulfoxide was used as the solvent. Furthermore, when benzyl substituted amidines were used as the substrates

  描述了一种在水存在下，通过镍催化的芳基炔烃与取代的2-卤代苯甲an的环合反应，合成取代的1（2 H）-异喹诺酮衍生物的有效方法。苯并[4,5]咪唑并[2,1-一个当干二甲亚砜作为溶剂]异喹啉被形成为主导的产品。此外，当使用苄基取代的idine作为底物时，发生脱苄基反应以提供各种1-氨基异喹啉产物。
• Optimization of imidazole amide derivatives as cannabinoid-1 receptor antagonists for the treatment of obesity
  作者：Roger A. Smith、Zahra Fathi、Furahi Achebe、Christiana Akuche、Su-Ellen Brown、Soongyu Choi、Jianmei Fan、Susan Jenkins、Harold C.E. Kluender、Anish Konkar、Rico Lavoie、Ronald Mays、Jennifer Natoli、Stephen J. O’Connor、Astrid A. Ortiz、Ning Su、Christy Taing、Susan Tomlinson、Theresa Tritto、Gan Wang、Stephan-Nicholas Wirtz、Wai Wong、Xiao-Fan Yang、Shihong Ying、Zhonghua Zhang

  DOI：10.1016/j.bmcl.2007.03.011

  日期：2007.5

  Several imidazole-based cyclohexyl amides were identified as potent CB-1 antagonists, but they exhibited poor oral exposure in rodents. Incorporation of a hydroxyl moiety on the cyclohexyl ring provided a dramatic improvement in oral exposure, together with a ca. 10-fold decrease in potency. Further optimization provided the imidazole 2-hydroxy-cyclohexyl amide 45, which exhibited hCB-1 K-i = 3.7 nM and caused significant appetite suppression and robust, dose-dependent reduction of body weight gain in industry-standard rat models. (c) 2007 Elsevier Ltd. All rights reserved.
• Diarylimidazolyl oxadiazole and thiadiazole derivatives as cannabinoid CB1 receptor antagonists
  作者：Jong Yup Kim、Hee Jeong Seo、Sung-Han Lee、Myung Eun Jung、Kwangwoo Ahn、Jeongmin Kim、Jinhwa Lee

  DOI：10.1016/j.bmcl.2008.10.130

  日期：2009.1

  Since the CB1 receptor antagonist SR141716 (rimonabant) was reported to modulate food intake, CB1 antagonism has been considered as a new therapeutic target in the treatment of obesity. Several series of derivatives based on diarylimidazolyl oxadiazole and thiadiazole scaffolds were synthesized and tested for CB1 receptor binding affinity. SAR studies directed toward the optimization of imidazole scaffolds resulted in the discovery of 10s which showed highest potency for CB1 receptor binding affinity (IC50 = 1.91 nM) prepared to date. (C) 2008 Elsevier Ltd. All rights reserved.
• An eco-friendly approach for the synthesis of 1,2,5-trisubstituted and 4-amino-1,2,5-tetrasubstituted imidazoles via a multi-component condensation
  作者：Hossein Mehrabi、Farzaneh Alizadeh-Bami、Azam Meydani、Soheila Besharat

  DOI：10.24820/ark.5550190.p011.442

  日期：——