7-氯-1,3-二氢-5-(4-氯苯基)-2H-1,4-苯并二氮杂-2-酮 | 5571-60-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 中文名称: 7-氯-1,3-二氢-5-(4-氯苯基)-2H-1,4-苯并二氮杂-2-酮
• 英文名称: 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one
• 英文别名: 7-chloro-1,3-dihydro-5-(4-chlorophenyl)-2H-1,4-benzodiazepin-2-one；7-chloro-5-(p-chlorophenyl)-3H-[1,4]benzodiazepin-2-one；desmethyl-4'-chlorodiazepam；chlordesmethyldiazepam；7-chloro-5-(4-chloro-phenyl)-1,3-dihydro-benzo[e][1,4]diazepin-2-one；7-Chlor-5-<4-chlor-phenyl>-2-oxo-1,2-dihydro-<1,4>benzodiazepin；7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one
• CAS: 5571-60-8
• 化学式: C₁₅H₁₀Cl₂N₂O
• 分子量: 305.163
• InChiKey: XKAHDJVCUSNHTE-UHFFFAOYSA-N

物化性质

• 熔点：
  247-248 °C
• 沸点：
  474.2±45.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)
• 溶解度：
  溶于氯仿

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 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-氯-1,3-二氢-5-(4-氯苯基)-2H-1,4-苯并二氮杂-2-酮 在 tetraphosphorus decasulfide 作用下， 以 吡啶 、 正丁醇 为溶剂， 生成
  参考文献：
  名称：

  1-(2-Aminoethyl)-6-aryl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepines with diuretic and natriuretic activity

  摘要：

  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.

  DOI：

  10.1021/jm00126a003
• 作为产物：
  描述：

  2-amino-4'-chloro-5-chlorobenzophenone 在 ammonium hydroxide 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 48.0h， 生成 7-氯-1,3-二氢-5-(4-氯苯基)-2H-1,4-苯并二氮杂-2-酮
  参考文献：
  名称：

  2-[（邻和对取代）氨基苯基] -3 H -5-[（邻和对取代）苯基] -7-氯-1,4-苯并二氮杂and的合成及光谱性质

  摘要：

  一系列12新2 - [（ø -和p -取代的）氨基苯基] -3- ħ -5 - [（ø -和p -取代的）苯基] -7-氯-1,4-苯并二氮杂类，其具有可能的药理学属性已获得。合成按照六个步骤进行。ir，1 H nmr，13 C nmr和ms证实了所有产物的结构。另外，对于化合物2-（邻氯氨基苯基）-3 H -5-（邻氟苯基）-7-氯-1,4-苯并二氮杂pine7，通过X射线衍射确认了其结构。

  DOI：

  10.1002/jhet.5570380320

文献信息

• New Insight into the Central Benzodiazepine Receptor–Ligand Interactions: Design, Synthesis, Biological Evaluation, and Molecular Modeling of 3-Substituted 6-Phenyl-4<i>H</i>-imidazo[1,5-<i>a</i>][1,4]benzodiazepines and Related Compounds
  作者：Maurizio Anzini、Salvatore Valenti、Carlo Braile、Andrea Cappelli、Salvatore Vomero、Stefano Alcaro、Francesco Ortuso、Luciana Marinelli、Vittorio Limongelli、Ettore Novellino、Laura Betti、Gino Giannaccini、Antonio Lucacchini、Simona Daniele、Claudia Martini、Carla Ghelardini、Lorenzo Di Cesare Mannelli、Gianluca Giorgi、Maria Paola Mascia、Giovanni Biggio

  DOI：10.1021/jm2001597

  日期：2011.8.25

  3-Substituted 6-phenyl-4H-imidazo[1,5-a][1,4]benzodiazepines and related compounds were synthesized as central benzodiazepine receptor (CBR) ligands. Most of the compounds showed high affinity for bovine and human CBR, their Ki values spanning from the low nanomolar to the submicromolar range. In particular, imidazoester 5f was able to promote a massive flow of 36Cl– in rat cerebrocortical synaptoneurosomes

  合成了3-取代的6-苯基-4 H-咪唑并[1,5- a ] [1,4]苯并二氮杂and和相关化合物作为中心苯并二氮杂receptor受体（CBR）配体。大多数化合物显示出对牛和人CBR的高亲和力，它们的K i值范围从低纳摩尔到亚微摩尔范围。特别是，imidazoester 5F是能够促进了大规模的流动36氯-在大鼠大脑皮层synaptoneurosomes与典型的完全激动剂的重叠其功效特征。化合物5f然后在小鼠中检查其药理作用，证明其是安全的抗焦虑药，没有经典的1,4-苯并二氮杂卓类药物的令人不悦的肌松和健忘作用。此外，一些选择的化合物的选择性已经评估了重组α 1 β 2 γ 2 L，α 2 β 1 γ 2 L，和α 5 β 2 γ 2大号人GABA甲受体。最后，将某些化合物连同Cromer GABA A同源性模型中的分子动力学模拟一起进行了分子对接计算。
• Synthesis and spectral determination of new derivatives of 1-[(<i>p</i>-substituted)phenyl]-3a-[(<i>o</i>- and<i>p</i>-substituted)phenyl]-5-chloro-9-methylthio-10,3a-dihydro-[1,2,4]-oxadiazolo[2,3-<i>b</i>][1,4]benzodiazepines
  作者：Eduardo Cortés、Erik Peréz Ramírez、Olivia García-Mellado de Cortés

  DOI：10.1002/jhet.5570440129

  日期：2007.1

  A new synthesis to obtain eight novel derivatives of 1-[(p-substituted)phenyl]-3a-[(o- and p-substituted)-phenyl]-5-chloro-9-methylthio-10,3a-dihydro-[1,2,4]-oxadiazolo[2,3-b][1,4]benzodiazepines with possible biological and pharmacological activity as anxiolytics, hypnotics, anticonvulsants in the central nervous system. The final products were obtained by condensation between 2-methylthio-5-[(o-;

  一种新的合成方法，可获得八个[1-[（对位取代的）苯基] -3a-[（o和对位取代的）-苯基] -5-氯-9-甲硫基-10,3a-二氢-[[ 1,2,4]-恶二唑并[2,3- b ] [1,4]苯并二氮杂with具有可能的生物学和药理活性，可作为中枢神经系统的抗焦虑药，催眠药和抗惊厥药。最终产物通过将2-甲硫基-5-[（o- ;对位取代）-苯基] -3 H -7-氯-[1,4]苯并二氮杂in与苯甲酰氧肟基氯在现场生成的苯甲腈缩合而获得。三乙胺。ir，1 H-nmr，13 C-nmr，具有低分辨率和高分辨率的二维实验和ms实验。
• Novel irreversible ligands specific for "peripheral" type benzodiazepine receptors: (.+-.)-, (+)- and (-)-1-(2-chlorophenyl)-N-(1-methylpropyl)-N-(2-isothiocyanatoethyl)-3-isoquinolinecarboxamide and 1-(2-isothiocyanatoethyl)-7-chloro-1,3-dihydro-5-(4-chlorophenyl)-2H-1,4-benzodiazepin-2-one
  作者：Amy Hauck Newman、Hartmut W. M. Lueddens、Phil Skolnick、Kenner C. Rice

  DOI：10.1021/jm00393a036

  日期：1987.10

  Novel ligands that bind irreversibly and selectively to "peripheral" type benzodiazepine receptors (PBR) have been prepared. These compounds inhibit radiolabeled binding to PBR in the nanomolar range. The 2-isothiocyanatoethyl analogue of Ro 5-4864 (1-methyl-7-chloro-1,3-dihydro-5-(4-chlorophenyl)-2H-1,4-benzodiazepi n-2-one) (5, AHN 086) was synthesized in three steps from desmethyl Ro 5-4864. The (+/-) (11a, AHN 070), R-(-) (11b), and S-(+) (11c) 2-isothiocyanatoethyl derivatives of PK 11195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxami de) were each prepared in three steps from PK 11209 (1-(2-chlorophenyl)-3-isoquinolinecarboxylic acid, 6). All four compounds inhibited radioligand binding to the PBR in brain and kidney. The R-(-) stereoisomer 11b was observed to be approximately 2.5-fold more potent than its enantiomer 11c; this is the first report of stereoselectivity in the isoquinoline series of ligands selective for the PBR. Furthermore, pH dependency studies showed that, at lower pH, change in the affinities for the PBR ligands is a property of the receptor, substantiating the hypothesis that a histidine moiety on the PBR is the most likely site for covalent bond formation, whereas, at higher pH, the observed changes in affinities can be attributed to properties of the compounds. All four of these novel ligands are potentially useful tools in the investigation of the PBR.
• Cortes, Eduardo Cortes; Martinez, Isidro Ebromares; Mellado, Olivia Garcia, Journal of Heterocyclic Chemistry, 2002, vol. 39, # 6, p. 1189 - 1194
  作者：Cortes, Eduardo Cortes、Martinez, Isidro Ebromares、Mellado, Olivia Garcia

  DOI：——

  日期：——
• Margonelli; Angelini; Pompili, Journal of labelled compounds and radiopharmaceuticals, 1999, vol. 42, # SUPPL. 1, p. S790-S792
  作者：Margonelli、Angelini、Pompili、Salvadori、DeLuca

  DOI：——

  日期：——