(R)-5-(oxiran-2-ylmethyl)-10,11-dihydro-5H-dibenzo[b,f]azepine | 393513-30-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: (R)-5-(oxiran-2-ylmethyl)-10,11-dihydro-5H-dibenzo[b,f]azepine
• 英文别名: 11-[[(2R)-oxiran-2-yl]methyl]-5,6-dihydrobenzo[b][1]benzazepine
• CAS: 393513-30-9
• 化学式: C₁₇H₁₇NO
• 分子量: 251.328
• InChiKey: ISJPYOAVAUNLDZ-OAHLLOKOSA-N

物化性质

• 沸点：
  396.0±31.0 °C(Predicted)
• 密度：
  1.181±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  15.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-5-(oxiran-2-ylmethyl)-10,11-dihydro-5H-dibenzo[b,f]azepine 在 4-二甲氨基吡啶 、 sodium azide 、 水 、 氯化铵 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.0h， 生成 (R)-(R)-1-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-3-(4-(trifluoromethoxy)phenylsulfonamido)propan-2-yl 3,3,3-trifluoro-2-methoxy-2-phenylpropanoate
  参考文献：
  名称：

  [EN] TRICYCLIC COMPOUNDS AS ANTICANCER AGENTS
  [FR] COMPOSÉS TRICYCLIQUES EN TANT QU'AGENTS ANTICANCÉREUX

  摘要：

  公开号：

  WO2013025882A3
• 作为产物：
  描述：

  右旋环氧氯丙烷 、 亚氨基二苄 在 sodium amide 作用下， 以 甲苯 为溶剂， 反应 15.0h， 以46%的产率得到(R)-5-(oxiran-2-ylmethyl)-10,11-dihydro-5H-dibenzo[b,f]azepine
  参考文献：
  名称：

  [EN] TRICYCLIC MODULATORS OF PP2A
  [FR] MODULATEURS TRICYCLIQUES DE PP2A

  摘要：

  化学调节剂PP2A，包括三环磺胺亚胺类化合物。这些化合物对预防或治疗癌症、糖尿病、自身免疫疾病、固体器官移植排斥、移植物抗宿主病、慢性阻塞性肺疾病（COPD）、非酒精性脂肪肝病、腹主动脉瘤、慢性肝病、心力衰竭、神经退行性疾病和心肌肥大具有用处。这些化合物的化学式为（I）。

  公开号：

  WO2021170913A1

文献信息

• TRICYCLIC COMPOUNDS AS ANTICANCER AGENTS
  申请人：Ohlmeyer Michael

  公开号：US20140213578A1

  公开（公告）日：2014-07-31

  Tricyclic chemical modulators of FOXO transcription factor proteins are disclosed. The compounds are useful to treat cancer, age-onset proteotoxicity, stress-induced depression, inflammation, and acne. The compounds are of the following phenothiazine, dibenzoazepine and annulene and similar genera:

  本文披露了三环化学调节剂对FOXO转录因子蛋白的调节作用。这些化合物可用于治疗癌症、年龄相关蛋白质毒性、压力引起的抑郁症、炎症和痤疮。这些化合物属于以下苯硫噻嗪、二苯并氮杂环和环戊烯类似物系列：
• Reengineered tricyclic anti-cancer agents
  作者：David B. Kastrinsky、Jaya Sangodkar、Nilesh Zaware、Sudeh Izadmehr、Neil S. Dhawan、Goutham Narla、Michael Ohlmeyer

  DOI：10.1016/j.bmc.2015.07.007

  日期：2015.10

  The phenothiazine and dibenzazepine tricyclics are potent neurotropic drugs with a documented but underutilized anti-cancer side effect. Reengineering these agents (TFP, CPZ, CIP) by replacing the basic amine with a neutral polar functional group (e.g., RTC-1, RTC-2) abrogated their CNS effects as demonstrated by in vitro pharmacological assays and in vivo behavioral models. Further optimization generated several phenothiazines and dibenzazepines with improved anti-cancer potency, exemplified by RTC-5. This new lead demonstrated efficacy against a xenograft model of an EGFR driven cancer without the neurotropic effects exhibited by the parent molecules. Its effects were attributed to concomitant negative regulation of PI3K-AKT and RAS-ERK signaling. (C) 2015 Elsevier Ltd. All rights reserved.
• A new class of antiarrhythmic-Defibrillatory agents
  作者：Ofra Levy、Mordechai Erez、Dalia Varon、Ehud Keinan

  DOI：10.1016/s0960-894x(01)00588-1

  日期：2001.11

  Novel dibenzoazepine and 11-oxo-dibenzodiazepine derivatives area shown to be effective ventricular defibrillating drug candidates. They exhibit significant in vivo defibrillatory activity with no observed changes in ECG either before or after the VF event. These compounds also exhibit antifibrillatory activity by elevating the fibrillation threshold potential, all suggesting that such drugs could be used to treat VF either by themselves or together with electrical defibrillators. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Synthesis of 11C-labelled (R)-OHDMI and CFMME and their evaluation as candidate radioligands for imaging central norepinephrine transporters with PET
  作者：Magnus Schou、Victor W. Pike、Judit Sóvágó、Balázs Gulyás、Peter T. Gallagher、David R. Dobson、Magnus W. Walter、Helene Rudyk、Lars Farde、Christer Halldin

  DOI：10.1016/j.bmc.2006.10.065

  日期：2007.1

  (R)-1-(10,11-Dihydro-dibenzo[b,f]azepin-5-yl)-3-methylamino-propan-2-ol ((R)-OHDM1) and (S,S)-1-cyclopentyl-2-(5-fluoro-2-methoxy-phenyl)-1-morpholin-2-yl-ethanol (CFMME) were synthesized and found to be potent inhibitors of norepinephrine reuptake. Each was labelled efficiently in its methyl group with carbon-11 (t(1/2) = 20.4 min) as a prospective radioligand for imaging brain norepinephrine transporters (NET) with positron emission tomography (PET). The uptake and distribution of radioactivity in brain following intravenous injection of each radioligand into cynomolgus monkey was examined in vivo with PET. After injection of (R)-[C-11]OHDMI, the maximal whole brain uptake of radioactivity was very low (1.1% of injected dose; I.D.). For occipital cortex, thalamus, lower brainstem, mesencephalon and cerebellum, radioactivity ratios to striatum at 93 min after radioligand injection were 1.35, 1.35, 1.2, 1.2 and 1.0, respectively. After injection of [C-11]UMME, radioactivity readily entered brain (3.5% I.D.). Ratios of radioactivity to cerebellum at 93 min for thalamus, occipital cortex, region of locus coeruleus, mesencephalon and striatum were 1.35, 1.3, 1.3, 1.2 and 1.2, respectively. Radioactive metabolites in plasma were measured by radio-HPLC. (R)[C-11]OHDMI represented 75% of plasma radioactivity at 4 min after injection and 6% at 30 min. After injection of [C-11]UMME, 84% of the radioactivity in plasma represented parent at 4 min and 20% at 30 min. Since the two new hydroxylated radioligands provide only modest regional differentiation in brain uptake and form potentially troublesome lipophilic radioactive metabolites, they are concluded to be inferior to existing radioligands, such as (S,S)-[C-11]MeNER, (S,S)-[F-18]FMeNER-D-2 and (S,S)[F-18]FRB-D-4, for the study of brain NETs with PET in vivo. (c) 2006 Elsevier Ltd. All rights reserved.
• US9540358B2
  申请人：——

  公开号：US9540358B2

  公开（公告）日：2017-01-10