tetraethyl [(4-biphenylamino)methyl]-1,1-bisphosphonate | 1021698-64-5

• 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: tetraethyl [(4-biphenylamino)methyl]-1,1-bisphosphonate
• CAS: 1021698-64-5
• 化学式: C₂₁H₃₁NO₆P₂
• 分子量: 455.428
• InChiKey: AODOGOAQUWCYOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.58
• 重原子数：
  30.0
• 可旋转键数：
  13.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  83.09
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tetraethyl [(4-biphenylamino)methyl]-1,1-bisphosphonate 在 盐酸 作用下， 反应 6.0h， 以966 mg的产率得到(biphenyl-4-yl)-aminomethylene-1,1-bisphosphonate
  参考文献：
  名称：

  Effects of Bisphosphonates on the Growth of Entamoeba histolytica and Plasmodium Species in Vitro and in Vivo

  摘要：

  The effects of a series of 102 bisphosphonates on the inhibition of growth of Entamoeba histolytica and Plasmodium falciparum in vitro have been determined, and selected compounds were further investigated for their in vivo activity. Forty-seven compounds tested were active (IC50 < 200 muM) versus E. histolytica growth in vitro. The most active compounds (IC50 similar to 4-9 muM) were nitrogen-containing bisphosphonates with relatively large aromatic side chains. Simple n-alkyl-1-hydroxy-1,1-bisphosphonates, known inhibitors of the enzyme farnesylpyrophosphate (FPP) synthase, were also active, with optimal activity being found with C9-C10 side chains. However, numerous other nitrogen-containing bisphosphonates known to be potent FPP synthase inhibitors, such as risedronate or pamidronate, had little or no activity. Several pyridine-derived bisphosphonates were quite active (IC50 similar to 10-20 muM), and this activity was shown to correlate with the basicity of the aromatic group, with activity decreasing with increasing pK(a) values. The activities of all compounds were tested versus a human nasopharyngeal carcinoma (KB) cell line to enable an estimate of the therapeutic index (TI). Five bisphosphonates were selected and then screened for their ability to delay the development of amebic liver abscess formation in an E. histolytica infected hamster model. Two compounds were found to decrease liver abscess formation at 10 mg/kg ip with little or no effect on normal liver mass. With P. falciparum, 35 compounds had IC50 values <200 muM in an in vitro assay. The most active compounds were also simple n-alkyl-1-hydroxy-1,1-bisphosphonates, having IC50 values around 1 muM. Five compounds were again selected for in vivo investigation in a Plasmodium berghei ANKA BALB/c mouse suppressive test. The most active compound, a C9 n-alkyl side chain containing bisphosphonate, caused an 80% reduction in parasitemia with no overt toxicity. Taken together, these results show that bisphosphonates appear to be useful lead compounds for the development of novel antiamebic and antimalarial drugs.

  DOI：

  10.1021/jm030084x
• 作为产物：
  描述：

  tetraethyl diphosphonodiazomethane 、 4-氨基联苯 在 Rh₂(CF₃CONH)₄ 作用下， 以 甲苯 为溶剂， 反应 12.0h， 以78%的产率得到tetraethyl [(4-biphenylamino)methyl]-1,1-bisphosphonate
  参考文献：
  名称：

  通过铑类胡萝卜素介导的NH插入反应，可轻松合成氨基亚甲基双膦酸酯。在制备强大的铀酰配体中的应用

  摘要：

  描述了确保双膦酸酯部分锚定在芳族胺上的直接方法。该方法产生已知显示多种生物活性的氨基芳基1，1-双膦酸酯。所描述的方法也已被用于合成其铀酰结合性质已被研究的配体。

  DOI：

  10.1016/j.tetlet.2008.01.127

文献信息

• Sulfonic acid functionalized hyper-cross-linked polymer: An efficient heterogeneous acid catalyst for the synthesis of N-containing bisphosphonates
  作者：Sirigireddy Sudharsan Reddy、Reddi Mohan Naidu Kalla、Anuraj Varyambath、Il Kim

  DOI：10.1016/j.catcom.2019.04.009

  日期：2019.6

  then functionalized by chlorosulfonic acid to obtain sulfonated HCBP (HCBP-SO3H) having surface area of 452 m2/g. The synthesized HCBP and HCBP-SO3H were characterized systematically by spectroscopic techniques. Further, the catalytic potential was evaluated towards the one-pot synthesis of N-containing bisphosphonates (N-BPs). To the delight, catalyst showed excellent activity in the synthesis of various

  一种新的微多孔超交联2,2'-联苯酚聚合物（氯代联苯）与770微米的良好的比表面积2 / g的合成，然后通过氯磺酸官能化以获得磺化氯代联苯（氯代联苯-SO 3 1H）具有表面积为452m 2 / g。用光谱技术对合成的HCBP和HCBP-SO 3 H进行了系统表征。此外，催化电位朝向一锅合成的评价Ñ含双膦酸盐（Ñ -bps）。令人高兴的是，催化剂在合成各种具有生物活性的芳族和杂芳族N时表现出出色的活性。-血压。值得注意的是，它可以循环使用七个周期，而其酸官能度没有任何重大损失。
• Arylamino methylene bisphosphonate derivatives as bone seeking matrix metalloproteinase inhibitors
  作者：Marilena Tauro、Antonio Laghezza、Fulvio Loiodice、Mariangela Agamennone、Cristina Campestre、Paolo Tortorella

  DOI：10.1016/j.bmc.2013.08.054

  日期：2013.11

  The complexity of matrix metalloproteinase inhibitors (MMPIs) design derives from the difficulty in carefully addressing their inhibitory activity towards the MMP isoforms involved in many pathological conditions. In particular, specific metalloproteinases, such as MMP-2 and MMP-9, are key regulators of the 'vicious cycle' occurring between tumor metastases growth and bone remodeling. In an attempt to devise new approaches to selective inhibitor derivatives, we describe novel bisphosphonate bone seeking MMP inhibitors (BP-MMPIs), capable to be selectively targeted and to overcome undesired side effects of broad spectrum MMPIs.In vitro activity (IC50 values) for each inhibitor was determined against MMP-2, -8, -9 and -14, because of their relevant role in skeletal development and renewal. The results show that BP-MMPIs reached IC50 values of enzymatic inhibition in the low micromolar range. Computational studies, used to rationalize some trends in the observed inhibitory profiles, suggest a possible differential binding mode in MMP-2 that explains the selective inhibition of this isoform.In addition, survival assay was conducted on J774 cell line, a well known model system used to evaluate the structure-activity relationship of BPs for inhibiting bone resorption. The resulting data, confirming the specific activity of BP-MMPIs, and their additional proved propensity to bind hydroxyapatite powder in vitro, suggest a potential use of BP-MMPIs in skeletal malignancies. (C) 2013 Elsevier Ltd. All rights reserved.