(R)-N-(3-(3-(4,4-difluoropiperidin-1-yl)-3-oxopropyl)-7-(3-(dimethylamino)phenoxy)-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-yl)-2-((4-(trifluoromethyl)benzyl)oxy)acetamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-N-(3-(3-(4,4-difluoropiperidin-1-yl)-3-oxopropyl)-7-(3-(dimethylamino)phenoxy)-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-yl)-2-((4-(trifluoromethyl)benzyl)oxy)acetamide
• 英文别名: (R)-N-(3-(3-(4,4-difluoropiperidin-1-yl)-3-propionyl)-7-(3-(dimethylamino)phenoxy)-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-yl)-2-((4-(trifluoromethyl)benzyl)oxy)acetamide；N-[(3R)-3-[3-(4,4-difluoropiperidin-1-yl)-3-oxopropyl]-7-[3-(dimethylamino)phenoxy]-2,5-dioxo-3,4-dihydro-1H-1,4-benzodiazepin-8-yl]-2-[[4-(trifluoromethyl)phenyl]methoxy]acetamide
• 化学式: C₃₅H₃₆F₅N₅O₆
• 分子量: 717.693
• InChiKey: RRAKXIOXRVSFLH-AREMUKBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  51
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  129
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  4-(三氟甲基)苄醇 在 N-羟基丁二酰亚胺 、 草酰氯 、 sodium hydride 、 三乙胺 、 lithium hydroxide 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 (R)-N-(3-(3-(4,4-difluoropiperidin-1-yl)-3-oxopropyl)-7-(3-(dimethylamino)phenoxy)-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-yl)-2-((4-(trifluoromethyl)benzyl)oxy)acetamide
  参考文献：
  名称：

  Discovery of 1,4-Benzodiazepine-2,5-dione (BZD) Derivatives as Dual Nucleotide Binding Oligomerization Domain Containing 1/2 (NOD1/NOD2) Antagonists Sensitizing Paclitaxel (PTX) To Suppress Lewis Lung Carcinoma (LLC) Growth in Vivo

  摘要：

  Nucleotide-binding oligomerization domain-like receptors (NLRs) are intracellular sensors of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Previously, we reported nucleotide-binding oligomerization domain-containing protein 1 (NOD1) antagonists (II, 12) and a NOD2 antagonist (9) that sensitized docetaxel (DTX) or paclitaxel (PTX) treatment for breast or lung cancer. In this article, we describe for the first time a 1,4-benzodiazepine-2,5-dione (BZD) derivative (26bh) that acts as a dual NOD1/NOD2 antagonist and inhibits both nuclear factor kappa B (NF-kappa B) and mitogen-activated protein kinase (MAPK) inflammatory signaling, thereby sensitizing PTX to suppress Lewis lung carcinoma (LLC) growth. After investigation of the compound's cytotoxicity, a systematic structure-activity relationship (SAR) was completed and revealed several key factors that were necessary to maintain antagonistic ability. This study establishes the possibility for using adjuvant treatment to combat cancer by antagonizing both NOD1 and NOD2 signaling.

  DOI：

  10.1021/acs.jmedchem.7b00608