1-(aminobutyl)-1,7-dicarba-closo-dodecaborane | 1338713-05-5

• 英文名称: 1-(aminobutyl)-1,7-dicarba-closo-dodecaborane
• 英文别名: 1-(4-aminobutyl)-1,7-dicarbadodecaborane；1-(4-aminobutyl)closo-1,7-carborane；1-(4-aminobutyl)-m-carborane
• CAS: 1338713-05-5
• 化学式: C₆H₂₁B₁₀N
• 分子量: 215.349
• InChiKey: XQIWVCLAKDCLHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  None
• 重原子数：
  None
• 可旋转键数：
  None
• 环数：
  None
• sp3杂化的碳原子比例：
  None
• 拓扑面积：
  None
• 氢给体数：
  None
• 氢受体数：
  None

反应信息

• 作为反应物：
  描述：

  1-(aminobutyl)-1,7-dicarba-closo-dodecaborane 、 3-吡啶-2-基丙-2-烯酸 在 氯化亚砜 、 N,N-二甲基甲酰胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 以69%的产率得到1-(4'-(trans-3"-(3'"pyridyl)acrylamido)butyl)-1,7-dicarba-closo-dodecaborane
  参考文献：
  名称：

  [EN] SMALL MOLECULE INHIBITORS OF NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE (NAMPT)
  [FR] INHIBITEURS À PETITE MOLÉCULE DE NICOTINAMIDE PHOSPHORIBOSYLTRANSFÉRASE (NAMPT)

  摘要：

  本发明涉及新化合物，其用作抗癌药物以及它们的合成。具体而言，这些化合物含有簇硼基团，如碳硼烷或硼氢化物，并作为酶Nampt的抑制剂。这些创新的簇硼化合物在生物抑制和抗增殖效果方面的生物学性质优于其他Nampt的小分子抑制剂。

  公开号：

  WO2013082150A1
• 作为产物：
  描述：

  1-(phthalimido-N-butyl)-1,7-dicarba-closo-dodecaborane 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以77%的产率得到1-(aminobutyl)-1,7-dicarba-closo-dodecaborane
  参考文献：
  名称：

  [EN] SMALL MOLECULE INHIBITORS OF NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE (NAMPT)
  [FR] INHIBITEURS À PETITE MOLÉCULE DE NICOTINAMIDE PHOSPHORIBOSYLTRANSFÉRASE (NAMPT)

  摘要：

  本发明涉及新化合物，其用作抗癌药物以及它们的合成。具体而言，这些化合物含有簇硼基团，如碳硼烷或硼氢化物，并作为酶Nampt的抑制剂。这些创新的簇硼化合物在生物抑制和抗增殖效果方面的生物学性质优于其他Nampt的小分子抑制剂。

  公开号：

  WO2013082150A1

文献信息

• Synthesis and evaluation of thymidine kinase 1-targeting carboranyl pyrimidine nucleoside analogs for boron neutron capture therapy of cancer
  作者：Hitesh K. Agarwal、Ahmed Khalil、Keisuke Ishita、Weilian Yang、Robin J. Nakkula、Lai-Chu Wu、Tehane Ali、Rohit Tiwari、Youngjoo Byun、Rolf F. Barth、Werner Tjarks

  DOI：10.1016/j.ejmech.2015.05.042

  日期：2015.7

  amido-substituted carboranyl pyrimidine nucleoside analogs, designed as substrates and inhibitors of thymidine kinase 1 (TK1) for potential use in boron neutron capture therapy (BNCT) of cancer, was synthesized and evaluated in enzyme kinetic-, enzyme inhibition-, metabolomic-, and biodistribution studies. One of these 2nd generation carboranyl pyrimidine nucleoside analogs (YB18A [3]), having an amino group directly

  合成了十六个第二代氨基和酰胺基取代的碳硼烷基嘧啶核苷类似物的文库，并设计为可用于癌症的硼中子捕获疗法（BNCT）的胸苷激酶1（TK1）的底物和抑制剂，并通过酶动力学进行了评估-，酶抑制-，代谢组学和生物分布研究。这些第二代碳硼烷基嘧啶核苷类似物（YB18A [ 3 ]）中的一个，氨基直接与通过乙烯间隔基束缚在胸腺嘧啶3位上的间甲碳氢化合物笼相连，具有约3-4倍的底物hTK1和抑制剂比N5 - 2OH（2-），是第一代碳硼烷基嘧啶核苷类似物。既2和3似乎是5'-单磷酸化在TK1（+）细胞RG2，无论在体外和体内。对携带脑内RG2神经胶质瘤的大鼠进行生物分布研究后，选择性摄取了3种肿瘤，瘤内浓度大约是2种的4倍。获得的结果大大提高了对TK1和碳硼烷基嘧啶核苷类似物之间结合相互作用的理解，并将深刻影响这些试剂的未来设计策略。
• Improved synthesis of MC4-PPEA and the biological evaluation of its hydroxymethyl derivative
  作者：Keivan Sadrerafi、Emilia O. Zargham、Mark W. Lee

  DOI：10.1016/j.bmcl.2015.11.068

  日期：2016.1

  our group demonstrated that carborane clusters may be used to increase the potency of small molecule inhibitors of Nampt over other, similarly sized organic moieties. Herein, we report a greatly improved, gram-scale synthesis of our most potent agent: 1-(4′-(trans-3″-(3‴-pyridyl) acrylamide)butyl)-1,7-dicarba-closo-dodecaborane (MC4-PPEA). Additionally, the carborane moiety of the molecule has been

  烟酰胺磷酸核糖基转移酶（Nampt）是许多疾病（包括癌症）的治疗靶标。先前，我们的研究小组证明，与其他类似大小的有机基团相比，碳硼烷簇可用于增强Nampt的小分子抑制剂的效力。在这里，我们报告了我们最有效的药物的极大改进的克级合成：1-（4'-（反式-3″-（3′-吡啶基）丙烯酰胺）丁基）-1,7-二氨基-叔-十二硼烷（MC4-PPEA）。另外，该分子的碳硼烷部分已被羟甲基官能团修饰，以使其共价连接至目标前药，其合成正在进行中。使用细胞活力测定，我们证明了这种新衍生物在体外对人乳腺癌细胞系表现出低至中等的纳摩尔能力。
• SMALL MOLECULE INHIBITORS OF NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE (NAMPT)
  申请人：The Curators of the University of Missouri

  公开号：US20150322093A1

  公开（公告）日：2015-11-12

  The present invention relates to novel compounds, their use as anti-cancer agents and their synthesis. In particular, the compounds contain cluster boron moieties such as carborane or a borohydride and act as inhibitors for the enzyme Nampt. The biological properties of the inventive cluster boron compounds, in terms of biological inhibition and antiproliferative effect, are greater than other small molecule inhibitors of Nampt.

  本发明涉及新型化合物，其用作抗癌剂和其合成。特别是，这些化合物包含簇硼基团，如碳硼烷或硼氢化物，并作为酶Nampt的抑制剂。创新簇硼化合物的生物学特性，在生物抑制和抗增殖效果方面，比其他Nampt小分子抑制剂更强。
• Synthesis of N3-substituted carboranyl thymidine bioconjugates and their evaluation as substrates of recombinant human thymidine kinase 1
  作者：Hitesh K. Agarwal、Craig A. McElroy、Elena Sjuvarsson、Staffan Eriksson、Michael V. Darby、Werner Tjarks

  DOI：10.1016/j.ejmech.2012.11.041

  日期：2013.2

  Four different libraries of overall twenty three N3-substituted thymidine (dThd) analogues, including eleven 3-carboranyl thymidine analogues (3CTAs), were synthesized. The latter are potential agents for Boron Neutron Capture Therapy (BNCT) of cancer. Linker between the dThd scaffold and the m-carborane cluster at the N3-position of the 3CTAs contained amidinyl-(3e and 3f), guanidyl-(7e-7g), tetrazolylmethyl-(9b1/2-9d1/2), or tetrazolyl groups (11b1/2-11d1/2) to improve human thymidine kinase 1 (hTK1) substrate characteristics and water solubilities compared with 1st generation 3CTAs, such as N5 and N5-2OH. The amidinyl- and guanidyl-type N3-substitued dThd analogues (3a-3f and 7a -7g) had hTK1 phosphorylation rates of <30% relative to that of dThd, the endogenous hTK1 substrate, whereas the tetrazolyl-type N3-substitued dThd analogues (9a, 9b1/2-9d1/2 and 11a, 11b1/2-11d1/2) had relative phosphorylation rates (rPRs) of >40%. Compounds 9a, 9b1/2-9d1/2 and 11a, 11b1/2 -11d1/2 were subjected to in-depth enzyme kinetics studies and the obtained rk(cat)/K-m (k(cat)/K-m relative to that of dThd) ranged from 2.5 to 26%. The tetrazolyl-type N3-substitued dThd analogues 9b1/2 and 11d1/2 were the best substrates of hTK1 with rPRs of 52.4% and 42.5% and rk(cat)/K-m values of 14.9% and 19.7% respectively. In comparison, the rPR and rk(cat)/K-m values of N5-2OH in this specific study were 41.5% and 10.8%, respectively. Compounds 3e and 3f were >1900 and >1500 times, respectively, better soluble in PBS (pH 7.4) than N5-2OH whereas solubilities for 9b1/2-9d1/2 and 11b1/2-11d1/2 were only 1.3-13 times better. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Carboranes Increase the Potency of Small Molecule Inhibitors of Nicotinamide Phosphoribosyltranferase
  作者：Mark W. Lee、Yulia V. Sevryugina、Aslam Khan、Shui Q. Ye

  DOI：10.1021/jm300740t

  日期：2012.8.23

  Herein we report the use of carboranes to significantly increase the potency of small molecule inhibitors of nicotinamide phosphoribosyltranferase (Nampt), an enzyme that is central to metabolism and cell survival. We compare the inclusion of carborane with other similarly sized substituents and demonstrate that, compared with their purely organic counterparts, these molecules exhibit up to 10-fold greater antiproliferative activity against cancer cells in vitro and a 100-fold increase in Nampt inhibition.