(4-(ethylamino)-3-nitrophenyl)methanol

• 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: (4-(ethylamino)-3-nitrophenyl)methanol
• 英文别名: 3-nitro-4-ethylaminobenzyl alcohol；[4-(Ethylamino)-3-nitrophenyl]methanol
• 化学式: C₉H₁₂N₂O₃
• 分子量: 196.206
• InChiKey: GIXMZKYXLBWIIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-(ethylamino)-3-nitrophenyl)methanol 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 、 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 65.0 ℃ 、101.33 kPa 条件下， 反应 6.0h， 生成 (R)-4-chloro-N-(1-(1-ethyl-5-(hydroxymethyl)-1H-benzo[d]imidazol-2-yl)ethyl)benzenesulfonamide
  参考文献：
  名称：

  Identification and Optimization of Benzimidazole Sulfonamides as Orally Bioavailable Sphingosine 1-Phosphate Receptor 1 Antagonists with in Vivo Activity

  摘要：

  We report here a novel series of benzimidazole sulfonamides that act as antagonists of the S1P(1) receptor, identified by exploiting an understanding of the pharmacophore of a high throughput screening (HTS)-derived series of compounds described previously. Lead compound 2 potently inhibits SIP-induced receptor internalization in a cell-based assay (EC50 = 0.05 mu M), but has poor physical properties and metabolic stability. Evolution of this compound through structure-activity relationship development and property optimization led to in vivo probes such as 4. However, this compound was unexpectedly found to be a potent CYP3A inducer in human hepatocytes, and thus further chemistry efforts were directed at addressing this liability. By employing a pregnane X receptor (PXR) reporter gene assay to prioritize compounds for further testing in human hepatocytes, we identified lipophilicity as a key molecular property influencing the likelihood of P450 induction. Ultimately, we have identified compounds such as 46 and 47, which demonstrate the desired S1P(1) antagonist activity while having greatly reduced risk of CYP3A induction in humans. These compounds have excellent oral bioavailability in preclinical species and exhibit pharmacodynamic effects of S1P(1) antagonism in several in vivo models following oral dosing. Relatively modest antitumor activity was observed in multiple xenograft models, however, suggesting that selective S1P(1) antagonists would have limited utility as anticancer therapeutics as single agents.

  DOI：

  10.1021/acs.jmedchem.5b01078
• 作为产物：
  描述：

  4-乙酰胺基-3-硝基苯甲酸 在 硼烷四氢呋喃络合物 、 甲醇 作用下， 以 四氢呋喃 为溶剂， 以95 %的产率得到(4-(ethylamino)-3-nitrophenyl)methanol
  参考文献：
  名称：

  CN116217416

  摘要：

  公开号：

文献信息

• [EN] BENZIMIDAZOLE DERIVATIVES AS BROMODOMAIN INHIBITORS<br/>[FR] DÉRIVÉS DE BENZIMIDAZOLE COMME INHIBITEURS DES BROMODOMAINES
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2016146738A1

  公开（公告）日：2016-09-22

  Compounds of formula (I) and salts thereof: wherein R1, R2, R3, R4 are defined herein. Compounds of formula (I) and salts thereof have been found to inhibit the binding of the BET family of bromodomain proteins to, for example, acetylated lysine residues and thus may have use in therapy, for example in the treatment of autoimmune and inflammatory diseases, such as rheumatoid arthritis; and cancers.

  式（I）的化合物及其盐：其中R1、R2、R3、R4在此处定义。已发现式（I）的化合物及其盐能够抑制BET家族的溴结构域蛋白与例如乙酰化赖氨酸残基的结合，因此可能在治疗中发挥作用，例如在治疗自身免疫和炎症性疾病（如类风湿性关节炎）和癌症方面。
• Benzimidazole derivatives as bromodomain inhibitors
  申请人：GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED

  公开号：US10442786B2

  公开（公告）日：2019-10-15

  Compounds of formula (I) and salts thereof: wherein R1, R2, R3, R4 are defined herein. Compounds of formula (I) and salts thereof have been found to inhibit the binding of the BET family of bromodomain proteins to, for example, acetylated lysine residues and thus may have use in therapy, for example in the treatment of autoimmune and inflammatory diseases, such as rheumatoid arthritis; and cancers.

  式 (I) 化合物及其盐类： 其中 R1、R2、R3、R4 在本文中定义。已发现式（I）化合物及其盐类可抑制 BET 家族溴域蛋白与乙酰化赖氨酸残基等的结合，因此可用于治疗，例如治疗自身免疫性和炎症性疾病，如类风湿性关节炎；以及癌症。
• Substituted acid derivatives useful as antidiabetic and antiobesity agents and method
  申请人：——

  公开号：US20030130306A1

  公开（公告）日：2003-07-10

  Compounds are provided which have the structure 1 wherein Q is C or N, X 1 is CH or N and, A, E, M, G, X 2 , X 3 , X 4 , R 1 , R 2 , R 2a , R 2b , R 2c , R 3 , Y, x, m, and n are as defined herein, which compounds are useful as antidiabetic, hypolipidemic, and antiobesity agents.

  提供的化合物具有如下结构 1 其中 Q 是 C 或 N，X 1 是 CH 或 N，以及 A、E、M、G、X 2 , X 3 , X 4 , R 1 , R 2 , R 2a , R 2b , R 2c , R 3 Y、x、m 和 n 如本文所定义，这些化合物可用作抗糖尿病、降血脂和抗肥胖药物。
• SUBSTITUTED ACID DERIVATIVES USEFUL AS ANTIDIABETIC AND ANTIOBESITY AGENTS AND METHOD
  申请人：Bristol-Myers Squibb Company

  公开号：EP1442028A1

  公开（公告）日：2004-08-04
• BENZIMIDAZOLE DERIVATIVES AS BROMODOMAIN INHIBITORS
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：EP3271349B1

  公开（公告）日：2019-05-15