N-Acetyl-N'-<(tert-butyloxy)carbonyl>hexane-1,6-diamine | 145118-23-6

• 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: N-Acetyl-N'-<(tert-butyloxy)carbonyl>hexane-1,6-diamine
• 英文别名: N-acetyl-N'-(tert-butoxycarbonyl)hexane-1,6-diamine；tert-butyl N-(6-acetamidohexyl)carbamate
• CAS: 145118-23-6
• 化学式: C₁₃H₂₆N₂O₃
• 分子量: 258.361
• InChiKey: CIIFXEUWIQDABW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-Acetyl-N'-<(tert-butyloxy)carbonyl>hexane-1,6-diamine 在 potassium carbonate 、 三氯乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Lead optimization of HMBA to develop potent HEXIM1 inducers

  摘要：

  The potency of a series of Hexamethylene bis-acetamide (HMBA) derivatives inducing Hexamethylene bis-acetamide inducible protein 1 (HEXIM1) was determined in LNCaP prostate cancer cells. Several compounds with unsymmetrical structures showed significantly improved activity. Distinct from HMBA, these analogs have increased hydrophobicity and can improve the short half-life of HMBA, which is one of the factors that have limited the application of HMBA in clinics. The unsymmetrical scaffolds of the new analogs provide the basis for further lead optimization of the compounds using combinatorial chemistry strategy. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2014.01.025
• 作为产物：
  描述：

  N-Boc-1,6-己二胺 在 三乙胺 、 N,N-二异丙基乙胺 、 锌 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 N-Acetyl-N'-<(tert-butyloxy)carbonyl>hexane-1,6-diamine
  参考文献：
  名称：

  Selective Conversion ofN-Trichloroethoxycarbonyl (Troc) GroupsintoN-Acetyl Groups in thePresence ofN-tert-Butoxycarbonyl(Boc) Protecting Groups

  摘要：

  用锌在乙酸酐中对 N-三氯乙氧羰基（Troc）进行脱保护反应，也会裂解 N-叔丁氧羰基（Boc），从而释放出氨基，氨基会立即被 N-乙酰化。在有三乙胺存在的情况下进行该反应时，只有 Troc 基团会被选择性地裂解，这一点已在多个实例中得到证实。

  DOI：

  10.1055/s-2003-39405

文献信息

• Synthetic Analogues of Naturally Occurring Spider Toxins
  作者：Lajos Kovács、Manfred Hesse

  DOI：10.1002/hlca.19920750617

  日期：1992.10.2

  Naturally occurring spider toxins are potent inhibitors of glutamate receptors of the central nervous system and have the general structure (hetero)arylacylaminoacyl(I)polyamineaminoacyl(II) (the arrow indicates the direction of an amide linkage). In the present paper, the synthesis of the ten spider-toxin analogues 13, 18, 21, 28, 35, 37, 39, 41, 45, and 53 are reported (Schemes 1–12). These compounds

  天然产生的蜘蛛毒素是中枢神经系统谷氨酸受体的有效抑制剂，并具有一般结构（杂）芳基氨基酰胺基（Ⅰ）多胺氨基酰基（Ⅱ）（箭头表示酰胺键的方向）。在本文件中，十蜘蛛毒素的合成类似物13，18，21，28，35，37，39，41，45，和53被报告（方案1-12）。这些化合物的亚基不同，在某些情况下，这些部分的顺序也不同。
• [EN] COMPOSITIONS AND METHODS FOR MODULATING HEXIM1 EXPRESSION<br/>[FR] COMPOSITIONS ET PROCÉDÉS DE MODULATION DE L'EXPRESSION D'HEXIM1
  申请人：UNIV CASE WESTERN RESERVE

  公开号：WO2015116968A1

  公开（公告）日：2015-08-06

  The potency of a series of Hexamethylene bis-acetamide (HMBA) derivatives of formula I, that induce Hexamethylene bis-acetamide inducible protein 1 (HEXIM1 ) was determined in cancer cells. The method of inducing HEXIM1 expression and cell differentiation in cancer and HIV cells are disclosed. Optimization of HMBA analogs that are symmetrical and unsymmetrical are also discussed.

  一系列诱导己六亚甲基双乙酰胺（HMBA）衍生物（化学式I）的效力，能够诱导己六亚甲基双乙酰胺诱导蛋白1（HEXIM1）在癌细胞中的表达已经确定。揭示了在癌细胞和HIV细胞中诱导HEXIM1表达和细胞分化的方法。还讨论了对称和非对称的HMBA类似物的优化。
• Compositions and methods for modulating HEXM1 expression
  申请人：CASE WESTERN RESERVE UNIVERSITY

  公开号：US10959966B2

  公开（公告）日：2021-03-30

  The potency of a series of Hexamethylene bis-acetamide (HMBA) derivatives of formula I, that induce Hexamethylene bis-acetamide inducible protein 1 (HEXIM1) was determined in cancer cells. The method of inducing HEXIM1 expression and cell differentiation in cancer and HIV cells are disclosed. Optimization of HMBA analogs that are symmetrical and unsymmetrical are also discussed.

  测定了一系列式 I 的六亚甲基双乙酰胺（HMBA）衍生物在癌细胞中诱导六亚甲基双乙酰胺诱导蛋白 1（HEXIM1）的效力。公开了在癌细胞和 HIV 细胞中诱导 HEXIM1 表达和细胞分化的方法。还讨论了对称和不对称 HMBA 类似物的优化问题。
• Synthesis of Imides,N-Acyl Vinylogous Carbamates and Ureas, and Nitriles by Oxidation of Amides and Amines with Dess-Martin Periodinane
  作者：K. C. Nicolaou、Casey J. N. Mathison

  DOI：10.1002/anie.200501853

  日期：2005.9.19
• The structure-activity profile of mercaptobenzamides’ anti-HIV activity suggests that thermodynamics of metabolism is more important than binding affinity to the target
  作者：Herman Nikolayevskiy、Marco Robello、Michael T. Scerba、Evan H. Pasternak、Mrinmoy Saha、Tracy L. Hartman、Caitlin A. Buchholz、Robert W. Buckheit、Stewart R. Durell、Daniel H. Appella

  DOI：10.1016/j.ejmech.2019.06.020

  日期：2019.9

  Mercaptobenzamide thioesters and thioethers are chemically simple HIV-1 maturation inhibitors with a unique mechanism of action, low toxicity, and a high barrier to viral resistance. A structure-activity relationship (SAR) profile based on 39 mercaptobenzamide prodrug analogs exposed divergent activity/toxicity roles for the internal and terminal amides. To probe the relationship between antiviral activity and toxicity, we generated an improved computational model for the binding of mercaptobenzamide thioesters (SAMTs) to the HIV-1 NCp7 C-terminal zinc finger, revealing the presence of a second low-energy binding orientation, hitherto undisclosed. Finally, using NMR-derived thiol -thioester exchange equilibrium constants, we propose that thermodynamics plays a role in determining the antiviral activity observed in the SAR profile. (C) 2019 Published by Elsevier Masson SAS.