{N,N'-bis(tert-butoxycarbonyl)-N''-2-azidoethyl}guanidine | 1177126-76-9

• 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,N'-bis(tert-butoxycarbonyl)-N''-2-azidoethyl}guanidine
• 英文别名: 2[2,3-bis(tert-butoxycarbonyl)guanidino]azidoethane；tert-butyl N-[N'-(2-azidoethyl)-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate
• CAS: 1177126-76-9
• 化学式: C₁₃H₂₄N₆O₄
• 分子量: 328.371
• InChiKey: CPKQLNJKNWHQBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  {N,N'-bis(tert-butoxycarbonyl)-N''-2-azidoethyl}guanidine 、 N-甲基-4-甲氧基苄胺 以 四氢呋喃 为溶剂， 反应 16.0h， 以91%的产率得到{N-(N'-p-methoxybenzyl-N'-methylcarbamoyl)-N''-(tert-butoxycarbonyl)-N'''-2-azidoethyl}guanidine
  参考文献：
  名称：

  Creation of Customized Bioactivity within a 14-Membered Macrolide Scaffold: Design, Synthesis, and Biological Evaluation Using a Family-18 Chitinase

  摘要：

  Argifin, a 17-membered pentapeptide, inhibits chitinase. As argifin has properties that render it unsuitable as a drug development candidate, we devised a mechanism to create the structural component of argifin that bestows the chitinase inhibition and introduce it into a 14-membered macrolide scaffold. Here we describe (1) the designed macrolide, which exhibits similar to 200-fold more potent chitinase inhibition than argifin, (2) the binding modes of the macrolide with Serratia marcescens chitinase B, and (3) the computed analysis explaining the reason for derivatives displaying increased inhibition compared to argifin, the macrolide aglycone displaying inhibition in a nanomolar range. This promises a class of chitinase inhibitors with novel skeletons, providing innovative insight for drug design and the use of macrolides as adaptable, flexible templates for use in drug discovery research and development.

  DOI：

  10.1021/acs.jmedchem.5b00175
• 作为产物：
  描述：

  2-叠氮基乙胺 、 N,N'-bis-Boc-S-methyl-isothiourea 在 三乙胺 、 mercury dichloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以183 mg的产率得到{N,N'-bis(tert-butoxycarbonyl)-N''-2-azidoethyl}guanidine
  参考文献：
  名称：

  开发有效和选择性的蛋白质精氨酸甲基转移酶双底物抑制剂

  摘要：

  蛋白质精氨酸甲基转移酶 (PRMT) 的原型抑制剂是通过通过可变接头将胍功能连接到细胞辅因子 ( S )-腺苷甲硫氨酸 (AdoMet)的非反应性胺类似物来构建的。对于两种这样的化合物，观察到对PRMT1 的有效抑制（IC 50为 ∼3-6 μM）以及对赖氨酸甲基转移酶 SET7 的弱抑制（在 100 μM 时的活性约为 50%）。

  DOI：

  10.1016/j.bmcl.2010.02.069

文献信息

• Synthesis and biological evaluation of a triazole-based library of pyrido[2,3-d]pyrimidines as FGFR3 tyrosine kinase inhibitors
  作者：Laurent Le Corre、Anne-Lise Girard、Johannes Aubertin、François Radvanyi、Catherine Benoist-Lasselin、Aurélie Jonquoy、Emilie Mugniery、Laurence Legeai-Mallet、Patricia Busca、Yves Le Merrer

  DOI：10.1039/b923882d

  日期：——

  A library of pyrido[2,3-d]pyrimidines was designed as inhibitors of FGFR3 tyrosine kinase allowing possible interactions with an unexploited region of the ATP binding-site. This library was built-up with an efficient step of click-chemistry giving easy access to triazole-based compounds bearing a large panel of substituents. Among the 27 analogues synthesized, more than half exhibited 55–89% inhibition of in vitro FGFR3 kinase activity at 2 μM and one (19g) was able to inhibit auto-phosphorylation of mutant FGFR3-K650M in transfected HEK cells.

  设计了一系列吡啶并[2,3-d]嘧啶类化合物作为FGFR3酪氨酸激酶的抑制剂，这些化合物可能与ATP结合位点的一个未开发区域发生相互作用。该化合物库通过高效的点击化学步骤构建，便于合成含有多种取代基的三唑类化合物。在合成的27个类似物中，超过一半的化合物在2微摩尔浓度下对体外FGFR3激酶活性表现出55-89%的抑制作用，其中一个化合物（19g）能够抑制转染HEK细胞中突变型FGFR3-K650M的自磷酸化。
• Multi-Component Sequential Synthesis of Dihydroorotic Acid-Based Amphiphilic Molecules
  作者：Alessandro Volonterio、Monica Sani、Maria Cristina Bellucci

  DOI：10.1055/a-1913-3105

  日期：2022.12

  process, which occurs in mild condition has been exploited for the synthesis of systematically modified amphiphilic molecules where the cationic head is tethered to a lipophilic tail through a dihydroorotic acid linker. The process is operatively simple, high yielding, and flexible. Such a strategy could impact combinatorial synthesis of wide libraries of amphiphilic molecules to be tested as transfection

  一种在温和条件下发生的有效的多组分顺序过程已被用于合成系统修饰的两亲分子，其中阳离子头通过二氢乳清酸接头连接到亲脂尾部。该工艺操作简单、产率高且灵活。这种策略可能会影响广泛的两亲分子文库的组合合成，以作为转染剂和/或抗菌剂进行测试。
• Toward the development of potent and selective bisubstrate inhibitors of protein arginine methyltransferases
  作者：James Dowden、Wei Hong、Richard V. Parry、Richard A. Pike、Stephen G. Ward

  DOI：10.1016/j.bmcl.2010.02.069

  日期：2010.4

  Prototype inhibitors of protein arginine methyltransferases (PRMTs) have been constructed by attaching guanidine functionality via a variable linker to non-reactive amine analogues of the cellular co-factor (S)-adenosyl methionine (AdoMet). Potent inhibition of PRMT1 (IC50 of ∼3–6 μM) combined with weak inhibition of the lysine methyltransferase SET7 (∼50% of activity at 100 μM) was observed for two

  蛋白质精氨酸甲基转移酶 (PRMT) 的原型抑制剂是通过通过可变接头将胍功能连接到细胞辅因子 ( S )-腺苷甲硫氨酸 (AdoMet)的非反应性胺类似物来构建的。对于两种这样的化合物，观察到对PRMT1 的有效抑制（IC 50为 ∼3-6 μM）以及对赖氨酸甲基转移酶 SET7 的弱抑制（在 100 μM 时的活性约为 50%）。
• Creation of Customized Bioactivity within a 14-Membered Macrolide Scaffold: Design, Synthesis, and Biological Evaluation Using a Family-18 Chitinase
  作者：Akihiro Sugawara、Nobuo Maita、Hiroaki Gouda、Tsuyoshi Yamamoto、Tomoyasu Hirose、Saori Kimura、Yoshifumi Saito、Hayato Nakano、Takako Kasai、Hirofumi Nakano、Kazuro Shiomi、Shuichi Hirono、Takeshi Watanabe、Hisaaki Taniguchi、Satoshi O̅mura、Toshiaki Sunazuka

  DOI：10.1021/acs.jmedchem.5b00175

  日期：2015.6.25

  Argifin, a 17-membered pentapeptide, inhibits chitinase. As argifin has properties that render it unsuitable as a drug development candidate, we devised a mechanism to create the structural component of argifin that bestows the chitinase inhibition and introduce it into a 14-membered macrolide scaffold. Here we describe (1) the designed macrolide, which exhibits similar to 200-fold more potent chitinase inhibition than argifin, (2) the binding modes of the macrolide with Serratia marcescens chitinase B, and (3) the computed analysis explaining the reason for derivatives displaying increased inhibition compared to argifin, the macrolide aglycone displaying inhibition in a nanomolar range. This promises a class of chitinase inhibitors with novel skeletons, providing innovative insight for drug design and the use of macrolides as adaptable, flexible templates for use in drug discovery research and development.