1-(3-aminopropyl)-m-carborane | 1338712-87-0

• 英文名称: 1-(3-aminopropyl)-m-carborane
• 英文别名: 1-(3-aminopropyl)closo-1,7-carborane
• CAS: 1338712-87-0
• 化学式: C₅H₁₉B₁₀N
• 分子量: 201.323
• InChiKey: ZVFNSYVYCRQJJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
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• 重原子数：
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• 可旋转键数：
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• 环数：
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• sp3杂化的碳原子比例：
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• 拓扑面积：
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• 氢给体数：
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• 氢受体数：
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反应信息

• 作为反应物：
  描述：

  3-(cyanomethyl)thymidine 、 1-(3-aminopropyl)-m-carborane 以10%的产率得到3-[2-imino-2-{3-(closo-1,7-carboranyl)propylamino}ethyl]thymidine
  参考文献：
  名称：

  Synthesis of N3-substituted carboranyl thymidine bioconjugates and their evaluation as substrates of recombinant human thymidine kinase 1

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2012.11.041

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。