N,N'-bis(tert-butoxycarbonyl)-N''-(3-(hydroxymethyl)phenyl)guanidine | 203258-18-8

• 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: N,N'-bis(tert-butoxycarbonyl)-N''-(3-(hydroxymethyl)phenyl)guanidine
• 英文别名: 3-[N,N'-bis(tert-butoxycarbonyl)guanidino]benzyl alcohol；tert-butyl N-[N'-[3-(hydroxymethyl)phenyl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate
• CAS: 203258-18-8
• 化学式: C₁₈H₂₇N₃O₅
• 分子量: 365.429
• InChiKey: UZXUPQOYESPDEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N,N'-bis(tert-butoxycarbonyl)-N''-(3-(hydroxymethyl)phenyl)guanidine 在 N-溴代丁二酰亚胺(NBS) 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以72%的产率得到3-[N,N'-bis(tert-butoxycarbonyl)guanidino]benzyl bromide
  参考文献：
  名称：

  Solution phase combinatorial chemistry. Discovery of 13- and 15-membered polyazapyridinocyclophane libraries with antibacterial activity

  摘要：

  A solution phase simultaneous addition of functionalities (SPSAF) combinatorial approach was utilized to synthesize 40 polyazacyclophane libraries (total complexity of 4275). Eighteen different functionality sets, utilizing 42 functionalities, were designed to disrupt RNA-protein interactions. Guanidine functionality sets with a greater potential to form positive charges provided the most active libraries. Differences in antibacterial activity are clearly related to different ring sizes with the more rigid 13-membered scaffold affording more active libraries compared with libraries from the 15-membered scaffold. Molecular modeling established a significant difference in the shapes of 13- and 15-membered pyridinophanes. Several libraries exhibited potent antibacterial activity. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(98)00131-8
• 作为产物：
  描述：

  3-氨基苯甲醇 、 N,N'-bis-Boc-S-methyl-isothiourea 以 四氢呋喃 为溶剂， 反应 2.0h， 以82.4%的产率得到N,N'-bis(tert-butoxycarbonyl)-N''-(3-(hydroxymethyl)phenyl)guanidine
  参考文献：
  名称：

  Enhancing the Intestinal Absorption of Molecules Containing the Polar Guanidino Functionality: A Double-Targeted Prodrug Approach

  摘要：

  A prodrug strategy was applied to guanidino-containing analogues to increase oral absorption via hPEPT1 and hVACVase. L-Valine, L-isoleucine, and L-phenylalanine esters of [3-(hydroxymethyl)phenyl]guanidine (3-HPG) were synthesized and evaluated for transport and activation. In HeLa/hPEPT1 cells, Val-3-HPG and Ile-3-HPG exhibited high affinity to hPEPT1 (IC50:0.65 and 0.63 mM, respectively), and all three L-amino acid esters showed higher uptake (2.6- to 9-fold) than the parent Compound 3-HPG. Val-3-HPG and Ile-3-HPG demonstrated remarkable Caco-2 permeability enhancement, and Val-3-HPG exhibited comparable permeability to valacyclovir. In rat perfusion studies, Val-3-HPG and Ile-3-HPG permeabilities were significantly higher than 3-HPG and exceeded/matched the high-permeability standard metoprolol, respectively. All the L-amino acid 3-HPG esters were effectively activated in HeLa and Caco-2 cell homogenates and were found to be good Substrates of hVACVase (k(cat)/K-m in mM(-1).s(-1): Val-3-HPG, 3370; Ile-3-HPG, 1580; Phe-3-HPG, 1660). In conclusion, it prodrug strategy is effective at increasing the intestinal permeability of polar guanidino analogues via targeting hPEPT1 for transport and hVACVase for activation.

  DOI：

  10.1021/jm9011559

文献信息

• Glycogen synthase kinase-3 inhibitors
  申请人：Eldar-Finkelman Hagit

  公开号：US20060069066A1

  公开（公告）日：2006-03-30

  Novel compounds designed to allow interactions with binding sites of GSK-3 and hence are capable of inhibiting GSK-3 activity, via inhibition of substrate binding are disclosed. Further disclosed are pharmaceutical compositions including same and methods of using same in the treatment of GSK-3 mediated conditions.

  本发明揭示了一种新型化合物，设计用于与GSK-3的结合位点相互作用，从而能够通过抑制底物结合来抑制GSK-3活性。此外，还揭示了包括该化合物的制药组合物以及使用该组合物治疗GSK-3介导疾病的方法。
• A Convenient and Versatile Method for the Synthesis of Protected Guanidines
  作者：Zhao-Xia Guo、Andrew N. Cammidge、David C. Horwell

  DOI：10.1080/00397910008087443

  日期：2000.8

  Aromatic, aliphatic and sterically hindered amines react smoothly with commercially available N,N'-bis-BOC-S-methylisothiourea 2 in the presence of mercury chloride to give the protected guanidine in good yield. It is particularly noteworthy that 2 can also be employed in a straightforward, two-step synthesis of monoaryl internal guanidines.
• GLYCOGEN SYNTHASE KINASE-3 INHIBITORS
  申请人：Tel Aviv University Future Technology Development L.P.

  公开号：EP1824468A2

  公开（公告）日：2007-08-29
• US7378432B2
  申请人：——

  公开号：US7378432B2

  公开（公告）日：2008-05-27
• US8088941B2
  申请人：——

  公开号：US8088941B2

  公开（公告）日：2012-01-03