N-(biphenyl-3-yl)-2-bromoacetamide | 918408-68-1

• 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-(biphenyl-3-yl)-2-bromoacetamide
• 英文别名: N-([1,1'-Biphenyl]-3-yl)-2-bromoacetamide；2-bromo-N-(3-phenylphenyl)acetamide
• CAS: 918408-68-1
• 化学式: C₁₄H₁₂BrNO
• 分子量: 290.159
• InChiKey: YYOHYDSPCPGYAO-UHFFFAOYSA-N

物化性质

• 沸点：
  467.9±38.0 °C(Predicted)
• 密度：
  1.443±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1',2',3',4',5',6'-hexahydro-2'H-[2,4'-bipyridine] N-oxide 、 N-(biphenyl-3-yl)-2-bromoacetamide 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 以26%的产率得到2-{1-[2-(1,1'-biphenyl-3-ylamino)-2-oxoethyl]piperidin-4-yl}pyridinium N-oxide
  参考文献：
  名称：

  Discovery of 3-Methyl-N-(1-oxy-3‘,4‘,5‘,6‘-tetrahydro-2‘H-[2,4‘-bipyridine]-1‘-ylmethyl)benzamide (ABT-670), an Orally Bioavailable Dopamine D₄ Agonist for the Treatment of Erectile Dysfunction

  摘要：

  The goal of this study was to identify a structurally distinct D-4-selective agonist with superior oral bioavailability to our first-generation clinical candidate 1a (ABT-724) for the potential treatment of erectile dysfunction. Arylpiperazines such as (heteroarylmethyl) piperazine 1a, benzamide 2, and acetamides such as 3a,b exhibit poor oral bioavailability. Structure-activity relationship (SAR) studies with the arylpiperidine template provided potent partial agonists such as 4d and 5k that demonstrated no improvement in oral bioavailability. Further optimization with the (N-oxy-2-pyridinyl) piperidine template led to the discovery of compound 6b (ABT-670), which exhibited excellent oral bioavailability in rat, dog, and monkey (68%, 85%, and 91%, respectively) with comparable efficacy, safety, and tolerability to 1a. The N-oxy-2-pyridinyl moiety not only provided the structural motif required for agonist function but also reduced metabolism rates. The SAR study leading to the discovery of 6b is described herein.

  DOI：

  10.1021/jm060662k
• 作为产物：
  描述：

  溴乙酰氯 、 3-氨基联苯 在 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 生成 N-(biphenyl-3-yl)-2-bromoacetamide
  参考文献：
  名称：

  Discovery of 3-Methyl-N-(1-oxy-3‘,4‘,5‘,6‘-tetrahydro-2‘H-[2,4‘-bipyridine]-1‘-ylmethyl)benzamide (ABT-670), an Orally Bioavailable Dopamine D₄ Agonist for the Treatment of Erectile Dysfunction

  摘要：

  The goal of this study was to identify a structurally distinct D-4-selective agonist with superior oral bioavailability to our first-generation clinical candidate 1a (ABT-724) for the potential treatment of erectile dysfunction. Arylpiperazines such as (heteroarylmethyl) piperazine 1a, benzamide 2, and acetamides such as 3a,b exhibit poor oral bioavailability. Structure-activity relationship (SAR) studies with the arylpiperidine template provided potent partial agonists such as 4d and 5k that demonstrated no improvement in oral bioavailability. Further optimization with the (N-oxy-2-pyridinyl) piperidine template led to the discovery of compound 6b (ABT-670), which exhibited excellent oral bioavailability in rat, dog, and monkey (68%, 85%, and 91%, respectively) with comparable efficacy, safety, and tolerability to 1a. The N-oxy-2-pyridinyl moiety not only provided the structural motif required for agonist function but also reduced metabolism rates. The SAR study leading to the discovery of 6b is described herein.

  DOI：

  10.1021/jm060662k

文献信息

• Evolution and Discovery of Matrine Derivatives as a New Class of Anti-Hepatic Fibrosis Agents Targeting Ewing Sarcoma Breakpoint Region 1 (EWSR1)
  作者：Yunyang Bao、Tianyu Niu、Jingyang Zhu、Yuheng Mei、Yulong Shi、Runze Meng、Qionglu Duan、Na Zhang、Tianyun Fan、Yanxiang Wang、Yudong Pang、Yinghong Li、Hongwei He、Danqing Song

  DOI：10.1021/acs.jmedchem.3c00286

  日期：2023.6.22

  to Ewing sarcoma breakpoint region 1 (EWSR1) to inhibit its function and affect the expression of downstream liver fibrosis-related genes and thus regulate liver fibrosis. These results provided a potential novel target for the treatment of liver fibrosis and powerful information for the development of tricyclic matrinanes into promising anti-hepatic fibrosis agents.

  不断合成了一系列新型三环苦参烷衍生物，并在细胞水平评估了其对肝纤维化相关基因和蛋白的抑制作用，包括I型胶原α1链（COL1A1）、α平滑肌肌动蛋白（α-SMA）、结缔组织组织生长因子 (CTGF) 和基质金属蛋白 2 (MMP-2)。其中，化合物6k发挥了诱人的功效，显着减轻了胆管结扎 (BDL) 大鼠和 Mdr2 敲除小鼠的肝损伤和纤维化。基于活性的蛋白质分析 (ABPP) 测定表明6k可能直接与尤文肉瘤断点区1（EWSR1）结合，抑制其功能，影响下游肝纤维化相关基因的表达，从而调节肝纤维化。这些结果为治疗肝纤维化提供了潜在的新靶点，并为将三环苦参烷开发成有前景的抗肝纤维化药物提供了有力的信息。