1-benzoyl-1,4-diazepine | 59939-75-2

• 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: 1-benzoyl-1,4-diazepine
• 英文别名: (1,4-diazepan-1-yl)(phenyl)methanone；1-Benzoyl-hexahydro-1,4-diazepin；1-Benzoyl-1,4-diazepane；1,4-diazepan-1-yl(phenyl)methanone
• CAS: 59939-75-2
• 化学式: C₁₂H₁₆N₂O
• mdl: MFCD05879210
• 分子量: 204.272
• InChiKey: OXDBLZCQNCJHHX-UHFFFAOYSA-N

物化性质

• 沸点：
  166-171 °C(Press: 0.1 Torr)
• 密度：
  1.084±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.416
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-benzoyl-1,4-diazepine 在 氢溴酸 、 碳酸氢钠 、 三乙胺 、 lithium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 27.67h， 生成 3,3'-(2-methyl-5-nitropyrimidine-4,6-diyl)bis-3,13-diaza-7,10-diazoniadispiro[6.2.6.2]octadecane tetrabromide
  参考文献：
  名称：

  [EN] PYRIMIDYL-DI(DIAZASPIRO-ALKANES) WITH ANTIVIRAL ACTIVITY
  [FR] PYRIMIDYL-DI(DIAZASPIRO-ALCANES) PRÉSENTANT UNE ACTIVITÉ ANTIVIRALE

  摘要：

  该发明涉及公式（I）的新型嘧啶基二（二氮杂螺环烷基）衍生物或其药用可接受的酸添加盐。这些化合物对疱疹病毒、人类免疫缺陷病毒、乳头状瘤病毒和肝炎病毒表现出广谱抗病毒活性。该发明还涉及使用公式（I）的化合物，以及制备这些化合物的方法和利用所述化合物进行治疗的方法。一般公式如下：（I）A代表嘧啶-4,6-二基或嘧啶-2,4-15-二基，可以包括H、NO2、CHO、OH、OAlk、卤素、NH（Alk）或N（Alk）2作为取代基；Hal代表氯或溴；Alk是具有1至4个碳原子的线性或支链取代基。

  公开号：

  WO2017069661A1
• 作为产物：
  描述：

  1,4-二氮杂环庚烷-1-甲酸叔丁酯 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 1-benzoyl-1,4-diazepine
  参考文献：
  名称：

  Synthesis, Cytotoxicity Evaluation, and Computational Insights of Novel 1,4-Diazepane-Based Sigma Ligands

  摘要：

  Among several potential applications, sigma receptor ligands can be used as antipsychotics, antiamnesics, and against other neurodegenerative disorders as well as neuroprotective agents. We present herein a new series of diazepane-containing derivatives as sigma R ligands obtained by a conformational expansion approach of our previously synthesized piperidine-based compounds. The best results were reached by benzofurane 2c, 3c and quinoline 2d, 3d-substituted diazepane derivatives, which showed the highest sigma R affinity. The cytotoxic activities of synthesized compounds were evaluated against two cancer cell lines, and the results indicated that none of the compounds induced significant toxicity in these cells. We also evaluated the antioxidant activity by radical scavenging capacity of our best compounds on ABTS and H2O2. The results obtained reveal that our new derivatives possess an excellent antioxidant profile and could be protective for the cells. Overall, the benzofurane derivative 2c due to its strong interaction with the active site of the receptor, as confirmed by molecular dynamic simulations, emerged as the optimum compound with high sigma 1R affinity, low cytotoxicity, and a potent antioxidant activity.

  DOI：

  10.1021/acsmedchemlett.9b00524

文献信息

• Secondary Amides of (<i>R</i>)-3,3,3-Trifluoro-2-hydroxy-2-methylpropionic Acid as Inhibitors of Pyruvate Dehydrogenase Kinase
  作者：Thomas D. Aicher、Robert C. Anderson、Jiaping Gao、Suraj S. Shetty、Gary M. Coppola、James L. Stanton、Douglas C. Knorr、Donald M. Sperbeck、Leonard J. Brand、Christine C. Vinluan、Emma L. Kaplan、Carol J. Dragland、Hollis C. Tomaselli、Amin Islam、Robert J. Lozito、Xilin Liu、Wieslawa M. Maniara、William S. Fillers、Dominick DelGrande、R. Eric Walter、William R. Mann

  DOI：10.1021/jm990358+

  日期：2000.1.1

  6-tetrahydropyridine)thiourea, SDZ048-619 (1), is a modest inhibitor (IC(50) = 180 microM) of pyruvate dehydrogenase kinase (PDHK). In an optimization of the N-methylcarbothioamide moiety of 1, it was discovered that amides with a small acyl group, in particular appropriately substituted amides of (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid, are inhibitors of PDHK. Utilizing this acyl moiety, herein is

  N'-甲基-N-（4-叔丁基-1,2,5,6-四氢吡啶）硫脲SDZ048-619（1）是丙酮酸脱氢酶激酶的适度抑制剂（IC（50）= 180 microM） （PDHK）。在最优化1的N-甲基碳硫酰胺部分时，发现具有小的酰基的酰胺，特别是（R）-3,3,3-三氟-2-羟基-2-甲基-2-丙酸的适当取代的酰胺，是PDHK的抑制剂。本文报道了利用该酰基部分的原理，其导致一系列酰化哌嗪衍生物的优化。哌嗪在2和5位上的甲基取代（具有S和R绝对立体化学）显着提高了前导化合物的效价（> 1,000倍）。当哌嗪的4位被电子贫乏的苯甲酰基部分取代时，该系列化合物的口服生物利用度良好且最佳（通过AUC测定）。（+）-1-N- [2,5-（S，R）-二甲基-4-N-（4-氰基苯甲酰基）哌嗪]-（R）-3,3，3-三氟-2-羟基-2 -甲基丙酰胺（14e）抑制PDHK在主要酶促测定中的IC（50）为16 +/-
• Selective Monoacylation of Symmetrical Diamines via Prior Complexation with Boron
  作者：Zhongxing Zhang、Zhiwei Yin、Nicholas A. Meanwell、John F. Kadow、Tao Wang

  DOI：10.1021/ol0300773

  日期：2003.9.1

  [reaction: see text] Pretreatment of a symmetrical primary or secondary diamine with 9-BBN prior to the addition of an acyl chloride significantly suppressed undesired diacylation, and the product of monoacylation predominated. The reactive preference is interpreted as the result of a selective deactivation of one nitrogen atom of the diamine by 9-BBN.

  [反应：见正文]在添加酰氯之前，用9-BBN预处理对称的伯或仲二胺会显着抑制不希望的二酰化作用，并且单酰化产物占主导地位。反应性偏爱被解释为二胺的一个氮原子被9-BBN选择性失活的结果。
• [EN] PYRIMIDYL-DI(DIAZASPIRO-ALKANES) WITH ANTIVIRAL ACTIVITY<br/>[FR] PYRIMIDYL-DI(DIAZASPIRO-ALCANES) PRÉSENTANT UNE ACTIVITÉ ANTIVIRALE
  申请人：LTD LIABILITY COMPANY “NEARMEDIC PLUS”

  公开号：WO2017069661A1

  公开（公告）日：2017-04-27

  The invention relates to novel pyrimidyl-di(diazaspiro-alkane) derivatives of formula (I) or a pharmaceutically acceptable acid additive salt thereof. The compounds exhibit a wide spectrum of antiviral activity against herpes virus, human immunodeficiency virus, papillomavirus, and hepatitis virus. The invention also relates to use of the compounds of formula (I), a method for preparing thereof, and a method for treating by using the claimed compounds. The general formula is: (I) A represents pyrimidine-4,6-diyl or pyrimidine-2,4-15 diyl that can comprise H, NO2, CHO, OH, OAlk, halogen, NH(Alk), or N(Alk)2 as a substituent; Hal represents chlorine or bromine; Alk is a linear or branched substituent having 1 to 4 carbon atoms.

  该发明涉及公式（I）的新型嘧啶基二（二氮杂螺环烷基）衍生物或其药用可接受的酸添加盐。这些化合物对疱疹病毒、人类免疫缺陷病毒、乳头状瘤病毒和肝炎病毒表现出广谱抗病毒活性。该发明还涉及使用公式（I）的化合物，以及制备这些化合物的方法和利用所述化合物进行治疗的方法。一般公式如下：（I）A代表嘧啶-4,6-二基或嘧啶-2,4-15-二基，可以包括H、NO2、CHO、OH、OAlk、卤素、NH（Alk）或N（Alk）2作为取代基；Hal代表氯或溴；Alk是具有1至4个碳原子的线性或支链取代基。
• Imidazole-Catalyzed Monoacylation of Symmetrical Diamines
  作者：Sanjeev K. Verma、B. N. Acharya、M. P. Kaushik

  DOI：10.1021/ol101604q

  日期：2010.10.1

  An imidazole-catalyzed protocol for monoacylation of symmetrical diamines has been developed. The protocol gave selective monoacylation of aliphatic (cyclic and acyclic) primary and secondary diamines. In the reaction, imidazole acts as both catalyst and a leaving group. Different monoacylated piperazines and other diamines were synthesized at room temperature in an ethanol/water solvent system.

  已经开发了咪唑催化的对称二胺单酰基化方案。该方案给出了脂族（环状和无环）伯和仲二胺的选择性单酰化作用。在反应中，咪唑既充当催化剂又充当离去基团。在乙醇/水溶剂体系中，在室温下合成了不同的单酰化哌嗪和其他二胺。
• Efficient and continuous monoacylation with superior selectivity of symmetrical diamines in microreactors
  作者：Ram Awatar Maurya、Phan Huy Hoang、Dong-Pyo Kim

  DOI：10.1039/c1lc20765b

  日期：——

  Efficient and continuous monoacylation of symmetrical diamines performed in microreactors yielded superior selectivity to that predicted by statistical considerations. It is highly valuable that the kinetically controlled product in high yields was achieved without any special catalyst at ambient temperature.

  在微型反应器中对对称二胺进行高效连续的单酰化反应，其选择性优于统计考虑的预测值。在环境温度下无需任何特殊催化剂即可获得高收率的动力学控制产品，这一点非常有价值。