4-(2-acetyl-5-ethyl-7,7,10,10-tetramethyl-7,8-9,10-tetrahydro-5H-5,13-diazabenzo[4,5]cyclohepta[1,2-b]naphthalene-12-yl)-3-fluorobenzoic acid | 777074-39-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 4-(2-acetyl-5-ethyl-7,7,10,10-tetramethyl-7,8-9,10-tetrahydro-5H-5,13-diazabenzo[4,5]cyclohepta[1,2-b]naphthalene-12-yl)-3-fluorobenzoic acid
• 英文别名: 4-(2-acetyl-5-ethyl-7,7,10,10-pentamethyl-7,8,9,10-tetrahydro-5H-5,13-diazabenzo[4,5]cyclohepta[1,2-b]naphthalen-12-yl)-3-fluorobenzoic acid；4-(2-Acetyl-5-ethyl-7,7,10,10-tetramethyl-8,9-dihydronaphtho[2,3-b][1,5]benzodiazepin-12-yl)-3-fluorobenzoic acid
• CAS: 777074-39-2
• 化学式: C₃₂H₃₃FN₂O₃
• 分子量: 512.624
• InChiKey: DRLADIVXUVDIQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  38
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  70
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 甲醇 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以89 %的产率得到4-(2-acetyl-5-ethyl-7,7,10,10-tetramethyl-7,8-9,10-tetrahydro-5H-5,13-diazabenzo[4,5]cyclohepta[1,2-b]naphthalene-12-yl)-3-fluorobenzoic acid
  参考文献：
  名称：

  铜催化硝基烷烃与（杂）芳基溴化物/碘化物的 α-芳基化

  摘要：

  这里描述了硝基烷烃与（杂）芳基/烯基卤化物（Br，I）的第一个铜催化偶联反应。该方法依赖于使用一些新开发的草酰胺配体，并产生多种多样的偶联产物。由于偶联产物可以方便地转化为相应的α-（杂）芳基胺、酮、羧酸和醛，因此我们的方法为从容易获得的（杂）芳基卤化物制备这些化合物提供了一种极具竞争力的方法。

  DOI：

  10.1002/anie.202315994

文献信息

• [EN] 11-PHENYL-DIBENZODIAZEPINE DERIVATIVES AS RXR-ANTAGONISTS<br/>[FR] DERIVES DE 11-PHENYL-DIBENZODIAZEPINE EN TANT QU'ANTAGONISTES DU RXR
  申请人：NOVARTIS AG

  公开号：WO2004089916A1

  公开（公告）日：2004-10-21

  The present invention relates to novel benzodiazepine compounds exhibiting RXR-antagonist efficacy, for delaying progression of, preventing or treating a condition or disease being associated with RXR-antagonism, in particular selected from diabetes, complication of diabetes such as retinopathy, nephropathy, neuropathy, and hyperlipidemia, obesity, dyslipidemia, and osteoporosis.

  本发明涉及一种新型苯二氮卓类化合物，具有RXR拮抗剂功效，用于延缓、预防或治疗与RXR拮抗作用相关的疾病或病症，特别是包括糖尿病、糖尿病并发症如视网膜病变、肾病、神经病变和高脂血症、肥胖、血脂异常和骨质疏松症。
• A Practical Synthesis of a Diazepinylbenzoic Acid, a Retinoid X Receptor Antagonist
  作者：Xinglong Jiang、George T. Lee、Kapa Prasad、Oljan Repič

  DOI：10.1021/op800142b

  日期：2008.11.21

  An optimized convergent synthetic route for the preparation of retinoid X receptor (RXR) antagonist (1) in an overall yield of 35% is described. The formation of the benzodiazepine was achieved in 85% yield using POCl3 in toluene. The drug substance 14 was obtained by treatment of aryl bromide with vinyl butyl ether in the presence of palladium acetate, DPPP, and cesium carbonate This one-pot operation

  描述了用于制备类视黄醇X受体（RXR）拮抗剂（1）的优化的收敛性合成途径，其总产率为35％。在甲苯中使用POCl 3可以85％的收率形成苯并二氮杂pine 。通过在乙酸钯，DPPP和碳酸铯的存在下用乙烯基丁基醚处理芳基溴化物来获得药物14。该一锅操作包括三个化学转化（即，Heck反应，乙烯基醚的水解和三氯甲烷的水解）。酯）的产率为85％。
• 11-Phenyl-dibenzodiazepine derivatives as rxr-antagonists
  申请人：Sakaki Junichi

  公开号：US20070043029A1

  公开（公告）日：2007-02-22

  The present invention relates to novel benzodiazepine compounds exhibiting RXR-antagonist efficacy, for delaying progression of, preventing or treating a condition or disease being associated with RXR-antagonism, in particular selected from diabetes, complication of diabetes such as retinopathy, nephropathy, neuropathy, and hyperlipidemia, obesity, dyslipidemia, and osteoporosis.

  本发明涉及新型苯二氮平类化合物，展现出RXR拮抗剂功效，用于延缓、预防或治疗与RXR拮抗有关的疾病或症状，特别是糖尿病、糖尿病并发症如视网膜病变、肾病、神经病变和高脂血症、肥胖症、血脂异常和骨质疏松症。
• Organic Compounds
  申请人：SAKAKI JUNICHI

  公开号：US20100173896A1

  公开（公告）日：2010-07-08

  The present invention relates to novel benzodiazepine compounds exhibiting RXR-antagonist efficacy, to the manufacture and to the use thereof.

  本发明涉及新型苯二氮平化合物，具有RXR拮抗剂功效，以及其制造和使用。
• Synthesis and structure–activity relationship of novel RXR antagonists: Orally active anti-diabetic and anti-obesity agents
  作者：Junichi Sakaki、Masashi Kishida、Kazuhide Konishi、Hiroki Gunji、Atsushi Toyao、Yuki Matsumoto、Takanori Kanazawa、Hidefumi Uchiyama、Hiroaki Fukaya、Hironobu Mitani、Yoshie Arai、Masaaki Kimura

  DOI：10.1016/j.bmcl.2007.06.080

  日期：2007.9

  A series of diazepinylbenzoic acid derivatives were synthesized and tested in the inhibition assay of the transactivation of RXR. Oral treatment of cyano derivatives (16f) was found to show anti-diabetic and anti-obesity effects in KK-A(y) mice. (c) 2007 Elsevier Ltd. All rights reserved.