3-aminopiperidine-2,6-dione hydrobromide | 90802-45-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-aminopiperidine-2,6-dione hydrobromide
• 英文别名: DL-3-amino-2,6-piperidinone hydrobromide；2,6-dioxo-3-piperidinylammonium bromide；3-aminopiperidine-2,6-dione;hydrobromide
• CAS: 90802-45-2
• 化学式: BrH*C₅H₈N₂O₂
• 分子量: 209.043
• InChiKey: PWGRLXLAQOHQKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.67
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  72.2
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  3-aminopiperidine-2,6-dione hydrobromide 在 四乙基氟化铵水合物 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 150.0h， 生成 tert-butyl (2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)ethyl)carbamate
  参考文献：
  名称：

  Modified DNA Aptamer That Binds the (R)-Isomer of a Thalidomide Derivative with High Enantioselectivity

  摘要：

  A thalidomide-binding aptamer was produced by systematic evolution of ligands by exponential enrichment from a library of non-natural DNA in which thymidine had been replaced with a modified deoxyuridine bearing a cationic functional group via a hydrophobic methylene linker at the C5 position. The additional functional group in the modified DNA aptamer could improve stability against nucleases and increase the binding affinity to thalidomide. The selected aptamer could recognize thalidomide enantioselectively, although a racemic thalidomide-attached gel was used for the selection. Surface plasmon resonance and fluorescence titration studies revealed that the selected modified DNA aptamer and a truncated version bound with an (R)-thalidomide derivative with high enantioselectivity, but not with the (S)-form. The modified group in the DNA aptamer is indispensable for the interaction with thalidomide, as the corresponding natural type DNA bearing the same base sequence showed no binding affinity with (R)- nor (S)-thalidomide. Computational sequence analysis suggested that the selected apatamer (108mer) could fold into a three-way junction structure; however, truncation of this aptamer (31mer) revealed that the thalidomide-binding site is a hairpin-bulge region that is a component of one of the arms of the three-way junction structure. The K-d value of the truncated 31mer aptamer for binding with the (R)-thalidomide derivative was 1.0 mu M estimated from fluorescence titration study. The aptamer that can recognize a single enantiomer of thalidomide will be useful as a biochemical tool for the analysis and study of the biological action of thalidomide enantiomers.

  DOI：

  10.1021/ja067098n
• 作为产物：
  描述：

  3-N-叔丁氧羰基氨基-2,6-二氧代哌啶 在 氢溴酸 、 溶剂黄146 作用下， 反应 0.5h， 以98%的产率得到3-aminopiperidine-2,6-dione hydrobromide
  参考文献：
  名称：

  Mono- and Dihydroxylated Metabolites of Thalidomide: Synthesis and TNF-.ALPHA. Production-Inhibitory Activity

  摘要：

  少量和双羟基化的沙利度胺代谢物被高效制备和表征，并评估了它们对人单核细胞白血病细胞系 THP-1 中肿瘤坏死因子 (TNF)-α 生产的抑制活性。5,N-二羟基沙利度胺是一种比沙利度胺更强效的 TNF-α 生产抑制剂。

  DOI：

  10.1248/cpb.54.1709

文献信息

• Mono- and Dihydroxylated Metabolites of Thalidomide: Synthesis and TNF-.ALPHA. Production-Inhibitory Activity
  作者：Takanori Nakamura、Tomomi Noguchi、Hisayoshi Kobayashi、Hiroyuki Miyachi、Yuichi Hashimoto

  DOI：10.1248/cpb.54.1709

  日期：——

  Mono- and dihydroxylated metabolites of thalidomide were efficiently prepared and characterized, and their inhibitory activity on tumor necrosis factor (TNF)-α production in the human monocytic leukemia cell line THP-1 was evaluated. 5,N-Dihydroxythalidomide was a much more potent TNF-α production inhibitor than thalidomide.

  少量和双羟基化的沙利度胺代谢物被高效制备和表征，并评估了它们对人单核细胞白血病细胞系 THP-1 中肿瘤坏死因子 (TNF)-α 生产的抑制活性。5,N-二羟基沙利度胺是一种比沙利度胺更强效的 TNF-α 生产抑制剂。
• Studies on synthesis and anticancer activity of selected N-(2-fluoroethyl)-N-nitrosoureas
  作者：Thomas P. Johnston、Conrad L. Kussner、Ronald L. Carter、Jerry L. Frye、Nancita R. Lomax、Jacqueline Plowman、V. L. Narayanan

  DOI：10.1021/jm00377a008

  日期：1984.11

  prepare the urea from which the essentially water-insoluble N-(2,6-dioxo-3-piperidinyl)-N-(2-fluoroethyl)-N-nitrosourea (6e) was derived. The anticancer activity of these nitrosoureas was determined against the murine tumors B16 melanoma and Lewis lung carcinoma and found to be significant and comparable to their chloroethyl counterparts. On the basis of results from both systems, the dihydroxycyclohexyl

  活化的氨基甲酸酯2-硝基苯基（2-氟乙基）亚硝基氨基甲酸酯（3）用于从2-氨基乙醇合成水溶性（2-氟乙基）亚硝基脲6a-d（1α，2β ，3α）-2-氨基-1，3-环己二醇，顺-2-羟基环己醇和2-氨基-2-脱氧-D-葡萄糖。在该方法的变型中，使用2,4,5-三氯苯基（2-氟乙基）氨基甲酸酯（4）制备尿素，基本上不溶于水的N-（2,6-二氧代-3-哌啶基）-衍生出N-（2-氟乙基）-N-亚硝基脲（6e）。确定了这些亚硝基脲对鼠类肿瘤B16黑色素瘤和Lewis肺癌的抗癌活性，发现它们具有显着的可比性，与它们的氯乙基同类物相当。基于两个系统的结果，二羟基环己基衍生物6b可能是最有效的。
• 一种来那度胺的制备方法
  申请人：石家庄度恩医药科技有限公司

  公开号：CN109776493A

  公开（公告）日：2019-05-21

  本发明公开了一种来那度胺的制备方法，属于有机合成领域。通过以2‑甲基‑3‑硝基苯甲酸甲酯和3‑N‑苄氧基羰基‑L‑谷氨酰胺为起始原料，2‑甲基‑3‑硝基苯甲酸甲酯经溴代反应，得到重要中间体2‑溴甲基‑3‑硝基苯甲酸甲酯。3‑N‑苄氧基羰基‑L‑谷氨酰胺在催化作用下进行环合反应，生成3‑N‑苄氧羰基氨基‑2,6‑二氧代哌啶，氨基脱保护生成3‑氨基‑2,6‑哌啶二酮氢卤酸盐，然后与2‑溴甲基‑3‑硝基苯甲酸甲酯经胺解反应得到3‑(4‑硝基‑1‑氧代‑1,3‑二氢异吲哚‑2‑基)哌啶‑2,6‑二酮，经还原反应制得来那度胺。该路线具有原料成本低、后处理简便，收率高等优点，使来那度胺原料药的生产成本大幅降低。本发明是一种便利、高效的适合于工业生产的来那度胺合成方法。
• Studies towards the synthesis of the benzodiazepine alkaloid auranthine
  作者：Anette Witt、Annika Gustavsson、Jan Bergan

  DOI：10.1002/jhet.5570400103

  日期：2003.1

  approaches towards the synthesis of auranthine have been investigated. A completed synthesis of 3-[2-(4-oxo-3,4-dihydro-quinazolin-2-yl)-3,4-dihydro-1H-benzo[e][1,4]-diazepine-2,5-dione, an auranthine precursor, which after dehydration with 50% propylphophonic acid anhydride solution in ethl acetate and DMA gave a C-acetyl derivative of aurnathine. Additionally studies towards the synthesis of fused

  已经研究了合成金嘌呤的不同方法。3- [2-（4-oxo-3,4-dihydro-quinazolin-2-yl）-3,4-dihydro-1H-benzo [e] [1,4] -diazepine-2,5的完整合成-二酮，一种鸟嘌呤的前体，用乙酸乙酯中的50％丙基膦酸酸酐溶液和DMA脱水后，得到一种鸟嘌呤的C-乙酰基衍生物。另外，关于合成稠合喹唑啉酮的研究产生了C-乙酰化的吡啶并[2,1-b]喹唑啉酮或丁酸衍生物。
• Selective Wee1 degradation by PROTAC degraders recruiting VHL and CRBN E3 ubiquitin ligases
  作者：Marine C. Aublette、Tom A. Harrison、Elizabeth J. Thorpe、Morgan S. Gadd

  DOI：10.1016/j.bmcl.2022.128636

  日期：2022.5

  have off target effects towards other protein kinases with similar potency. Here we describe the synthesis and assessment of a series of Wee1-degrading PROTACs using AZD1775 linked to either the VHL ligand VH032 or to the CRBN ligand pomalidomide using different types and lengths of linkers. The conversion of AZD1775 into a PROTAC induces selective Wee1 degradation for compounds of both series depending

  当 DNA 受损时，Ser/Thr 蛋白激酶 Wee1 通过磷酸化 CDK1 来在 G 2 /M 检查点发挥调节作用，从而为 DNA 留出时间进行修复，破坏修复是使癌细胞对 DNA 损伤疗法敏感的关键方法。然而，在临床试验中正在开发的 Wee1 的主要选择性抑制剂 AZD1775 已被证明对其他具有相似效力的蛋白激酶具有脱靶效应。在这里，我们描述了一系列 Wee1 降解 PROTAC 的合成和评估，使用 AZD1775 使用不同类型和长度的接头连接到 VHL 配体 VH032 或 CRBN 配体泊马度胺。根据接头的性质，将 AZD1775 转化为 PROTAC 会诱导两个系列化合物的选择性 Wee1 降解。