7-iodo-5-phenyl-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one | 60114-64-9

• 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: 7-iodo-5-phenyl-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one
• 英文别名: 7-Iodo-1,3-dihydro-5-phenyl-2h-1,4-benzodiazepin-2-one；7-iodo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one
• CAS: 60114-64-9
• 化学式: C₁₅H₁₁IN₂O
• 分子量: 362.17
• InChiKey: QZISPNVRIAMVOL-UHFFFAOYSA-N

物化性质

• 沸点：
  481.9±45.0 °C(Predicted)
• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-iodo-5-phenyl-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one 在 劳森试剂 、 hydrazine hydrate 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 3.0h， 生成 2-hydrazono-7-iodo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepine
  参考文献：
  名称：

  Dual HDAC–BRD4 inhibitors endowed with antitumor and antihyperalgesic activity

  摘要：

  组蛋白去乙酰化酶（HDAC）是调节乙酰化组蛋白浓度的酶，乙酰化组蛋白与BET（Bromodomain and Extracellular domain）蛋白的溴域（BRD）相互作用，影响转录活性。同时阻断这两个表观遗传学因子已在各种癌细胞系中显示出协同作用。本文报道了我们设计、合成和活性测试的新型双重抑制剂，通过向一些先前由我们开发的含苯二氮平核心的HDAC抑制剂添加甲基三唑基团而获得。Alphascreen FRET试验表明，这些化合物能够与BRD4-1和BRD4-2蛋白相互作用，对后者具有一定的选择性，而HDAC抑制性质则通过免疫沉淀试验测量。抗增殖活性在C26腺癌、SSMC2黑色素瘤和SHSY5Y神经母细胞瘤细胞上进行了测试。有趣的是，这两种化合物在小鼠剩余神经损伤（SNI）模型中具有抗高痛感作用。

  DOI：

  10.1007/s00044-022-02896-w
• 作为产物：
  描述：

  2-氨基二苯甲酮 在 哌啶 、 吡啶 、 N-碘代丁二酰亚胺 、 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 40.0h， 生成 7-iodo-5-phenyl-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one
  参考文献：
  名称：

  苯胺衍生的二芳基碘鎓盐的热解和放射性氟化†

  摘要：

  通过明智地利用吸电子保护基团，可以合成苯胺衍生的二芳基碘鎓盐并以良好至极好的收率进行官能化。这种简单的方法为在相对复杂的分子（如氟替莫尔）中对氨基芳烃进行放射性标记开辟了另一条途径。

  DOI：

  10.1039/c7ob00253j

文献信息

• 1-Ethanamine-triazolo-benzodiazepines as diuretics
  申请人：The Upjohn Company

  公开号：US04514407A1

  公开（公告）日：1985-04-30

  Triazolo-benzodiazepine-1-ethanamines of the formulas ##STR1## where R, R.sub.1, R.sub.2, R.sub.3, R.sub.4 and Ring A are as defined in the specification, e.g., 8-chloro-N,N-dimethyl-.beta.,6-diphenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benz odiazepine-1-ethanamine, and pharmacologically acceptable salts thereof, have been found to have substantial diuretic, natriuretic, but little, if any, kaliuretic activity, which can be used alone, or concomittently with other diuretic drugs such as furosemide or hydrochlorothiazide and/or with antihypertensive agents such as propranolo, captopril, minoxidil, prazosin, guanadrel sulfate, whose actions are supplemented by the action of a diuretic drug.

  Triazolo-苯二氮卓-1-乙胺的分子式为##STR1##其中R、R.sub.1、R.sub.2、R.sub.3、R.sub.4和环A如规范中所定义，例如8-氯-N，N-二甲基-β，6-二苯基-4H-[1,2,4]三唑并[4,3-a][1,4]苯二氮卓-1-乙胺及其药理学上可接受的盐，已被发现具有显著的利尿、排钠作用，但几乎没有钾排泄作用，可单独使用，或与其他利尿药物如呋塞米或氢氯噻嗪以及/或抗高血压药物如普萘洛尔、卡普托普利、米诺地尔、普拉唑辛、瓜那德雷酸盐同时使用，其作用被利尿药物的作用所补充。
• Stereospecific anxiolytic and anticonvulsant agents with reduced muscle-relaxant, sedative-hypnotic and ataxic effects
  申请人：Cook M. James

  公开号：US20060003995A1

  公开（公告）日：2006-01-05

  The present invention provides compositions and methods of using stereospecific benzodiazepine derivatives, their salts and prodrugs for the treatment of anxiolytic or convulsant disorders having the side effects of reduced alcohol craving in human alcoholics and a concomitant reduced sedative, hypnotic, muscle relaxant and ataxic side-effects. The invention further provides pharmaceutical compositions for treatment of anxiolytic and convulsant disorders in subjects in need thereof, comprising a compound, prodrug or a salt having a chemical structure represented by any one of Formula I-XXI and a pharmaceutically-acceptable carrier.

  本发明提供了使用立体特异性苯二氮卓类衍生物、它们的盐和前药治疗焦虑症或癫痫发作障碍的组合物和方法，该方法具有减少酒精渴望的副作用，同时减少酒精成瘾者的镇静、催眠、肌肉松弛和共济失调副作用。本发明还提供了用于治疗焦虑症和癫痫发作障碍的药物组合物，包括具有化学结构由任何一种I-XXI式表示的化合物、前药或盐，以及一种药学上可接受的载体。
• Anxiolytic agents with reduced sedative and ataxic effects
  申请人：Wisys Technology Foundation, Inc.

  公开号：EP1925614A1

  公开（公告）日：2008-05-28

  Orally active benzodiazepine derivatives and their salts are disclosed. These compounds and their salts have anxiolytic and anticonvulsant activity with reduced sedative/hypnotic/muscle relaxant/ataxic effects (formula (I)). wherein: Y and Z are taken together with the two intervening carbon atoms to form a ring selected from phenyl and thienyl, which ring is substituted at the C(7) position with at least the substituent -C≡C-R, where R is H, Si(CH3)3, t-butyl, isopropyl, methyl, or cyclopropyl; R1 is one of H, CH3, C2H4N(C2H5)2, CH2CF3, CH2CCH, cyclopropyl or methyl cyclopropyl; R2 is a substituted or unsubstituted at least partially unsaturated 5 membered or 6 membered carbocyclic ring or 5 membered or 6 membered heterocyclic ring having at least one heteroatom selected from N, O and S, wherein if substituted the substituent is at least one of F, Cl, Br, or NO2 at the 2'-position; R3 is one of H, OH, OCON(CH3)2, COOH, COOCH3, COOC2H5. Furthermore the application discloses dimeric compounds of formula (I).

  本发明公开了口服活性苯并二氮杂卓衍生物及其盐类。这些化合物及其盐类具有抗焦虑和抗惊厥活性，镇静/催眠/肌肉松弛/松弛作用减弱（式（I））。 其中 Y 和 Z 与中间的两个碳原子共同形成一个选自苯基和噻吩基的环，该环在 C(7) 位至少被取代基-C≡C-R 取代，其中 R 是 H、Si(CH3)3、叔丁基、异丙基、甲基或环丙基；R1 是 H、 、C2H4N(C2H5)2、CH2CF3、CH2CCH、环丙基或甲基环丙基中的一种；R2 是取代或未取代的至少部分不饱和的 5 位或 6 位碳环或 5 位或 6 位杂环，其中至少有一个杂原子选自 N、O 和 S，如果是取代的，则在 2'- 位上的取代基至少是 F、Cl、Br 或 NO2 中的一种；R3 是 H、OH、OCON( )2、COOH、COO 、COO 中的一种。 此外，该申请还公开了式 (I) 的二聚化合物。
• Structure–Activity Relationship Studies of Retro-1 Analogues against Shiga Toxin
  作者：Hajer Abdelkafi、Aurélien Michau、Valérie Pons、Flora Ngadjeua、Alexandra Clerget、Lilia Ait Ouarab、David-Alexandre Buisson、David Montoir、Lucie Caramelle、Daniel Gillet、Julien Barbier、Jean-Christophe Cintrat

  DOI：10.1021/acs.jmedchem.0c00298

  日期：2020.8.13

  High-throughput screening has shown that Retro-1 inhibits ricin and Shiga toxins by diminishing their intracellular trafficking via the retrograde route, from early endosomes to the Golgi apparatus. To improve the activity of Retro-1, a structure-activity relationship (SAR) study was undertaken and yielded an analogue with a roughly 70-fold better half-maximal effective concentration (EC50) against Shiga toxin cytotoxicity measured in a cell protein synthesis assay.
• 1-(2-Aminoethyl)-6-aryl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepines with diuretic and natriuretic activity
  作者：Jackson B. Hester、James H. Ludens、D. Edward Emmert、Bruce E. West

  DOI：10.1021/jm00126a003

  日期：1989.6

  A series of 1-(2-amino-1-phenylethyl)-6-phenyl-4H- [1,2,4]triazolo[4,3-a][1,4]benzodiazepines was prepared and evaluated for diuretic activity. These compounds have diuretic and natriuretic activity but no kaliuretic activity when evaluated by oral administration to the conscious rat. The structure requirements for this activity are discussed. In particular it was found that the 2-aminoethyl side chain at C-1 with hydrogen or methyl substituents on the amino group was required for diuretic activity. A substituent at C-8 was also required; soft substituents such as methylthio and iodo at this position favored activity. Compounds with both phenyl and 2-pyridyl substituents at C-6 were active; substituents on the C-6 phenyl, however, reduced or eliminated the activity. Substituents other than phenyl at the 1-position of the 2-aminoethyl side chain were detrimental to activity; phenyl substitution at this position was required for activity when the substituent at C-8 was chloro but not when it was bromo.