P,P'-[2-(1H-benzimidazol-1-yl)-ethylidene]bisphosphonic acid | 847738-31-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: P,P'-[2-(1H-benzimidazol-1-yl)-ethylidene]bisphosphonic acid
• 英文别名: [2-(benzoimidazol-1-yl)ethylidene]bisphosphonic acid；[2-(benzimidazol-1-yl)-1-phosphonoethyl]phosphonic acid
• CAS: 847738-31-2
• 化学式: C₉H₁₂N₂O₆P₂
• 分子量: 306.152
• InChiKey: ISSICOMKRRPVPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  133
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  tetraethyl 2-(1H-benzimidazol-1-yl)ethylidenediphosphonate 在 盐酸 作用下， 以 水 为溶剂， 生成 P,P'-[2-(1H-benzimidazol-1-yl)-ethylidene]bisphosphonic acid
  参考文献：
  名称：

  新型苯并咪唑膦酸酯类可能作为蛋白质异戊二烯化的抑制剂。

  摘要：

  已经制备了苯并咪唑羧基膦酸酯和双膦酸酯，并评估了它们作为蛋白质异戊二烯化或类异戊二烯生物合成抑制剂的活性。发现膦酸酯头基的性质决定了酶的特异性。羧基膦酸铅抑制了香叶基香叶基转移酶II，而其相应的双膦酸酯类似物则有效地抑制了法呢基二磷酸合酶。活性最高的抑制剂可有效破坏人类多发性骨髓瘤细胞中的蛋白质异戊二烯化。

  DOI：

  10.1016/j.bmcl.2019.126757

文献信息

• MEVALONATE PATHWAY INHIBITOR AS HIGHLY-EFFECTIVE VACCINE ADJUVANT
  申请人：Tsinghua University

  公开号：EP3348269A1

  公开（公告）日：2018-07-18

  Disclosed are inhibitors of mevalonate pathway as an efficient vaccine adjuvant and use thereof. In particular, the inhibitor is an acetoacetyl-CoA transferase inhibitor, a HMG-CoA synthase inhibitor, a HMG-CoA reductase inhibitor, a mevalonate kinase inhibitor, a phosphomevalonate kinase inhibitor, a mevalonate-5-pyrophosphate decarboxylase inhibitor, an isopentenyl pyrophosphate isomerase inhibitor, a farnesyl pyrophosphate synthase inhibitor, a geranylgeranyl pyrophosphate synthase inhibitor or a geranylgeranyl transferase (I, II) inhibitor. Also disclosed is an immunogenic composition comprising inhibitors of mevalonate pathway as an adjuvant.

  所公开的是作为高效疫苗佐剂的甲羟戊酸途径抑制剂及其用途。特别是，抑制剂是乙酰乙酰-CoA 转移酶抑制剂、HMG-CoA 合成酶抑制剂、HMG-CoA 还原酶抑制剂、甲羟戊酸激酶抑制剂、磷酸甲羟戊酸激酶抑制剂、甲羟戊酸-5-焦磷酸脱羧酶抑制剂、焦磷酸异戊烯酯异构酶抑制剂、焦磷酸法呢酯合成酶抑制剂、焦磷酸香叶酯合成酶抑制剂或香叶基香叶基转移酶 (I, II) 抑制剂。还公开了一种免疫原组合物，该组合物包含作为佐剂的甲羟戊酸途径抑制剂。
• Mevalonate pathway inhibitor as highly-efficient vaccine adjuvant
  申请人：Tsinghua University

  公开号：US11382971B2

  公开（公告）日：2022-07-12

  Disclosed are inhibitors of mevalonate pathway as an efficient vaccine adjuvant and use thereof. In particular, the inhibitor is an acetoacetyl-CoA transferase inhibitor, a HMG-CoA synthase inhibitor, a HMG-CoA reductase inhibitor, a mevalonate kinase inhibitor, a phosphomevalonate kinase inhibitor, a mevalonate-5-pyrophosphate decarboxylase inhibitor, an isopentenyl pyrophosphate isomerase inhibitor, a farnesyl pyrophosphate synthase inhibitor, a geranylgeranyl pyrophosphate synthase inhibitor or a geranylgeranyl transferase (I, II) inhibitor. Also disclosed is an immunogenic composition comprising inhibitors of mevalonate pathway as an adjuvant.

  所公开的是作为高效疫苗佐剂的甲羟戊酸途径抑制剂及其用途。特别是，抑制剂是乙酰乙酰-CoA 转移酶抑制剂、HMG-CoA 合成酶抑制剂、HMG-CoA 还原酶抑制剂、甲羟戊酸激酶抑制剂、磷酸甲羟戊酸激酶抑制剂、甲羟戊酸-5-焦磷酸脱羧酶抑制剂、焦磷酸异戊烯酯异构酶抑制剂、焦磷酸法呢酯合成酶抑制剂、焦磷酸香叶酯合成酶抑制剂或香叶基香叶基转移酶 (I, II) 抑制剂。还公开了一种免疫原组合物，该组合物包含作为佐剂的甲羟戊酸途径抑制剂。
• Design, Synthesis, and Biological Evaluation of Novel Aminobisphosphonates Possessing an in Vivo Antitumor Activity Through a γδ-T Lymphocytes-Mediated Activation Mechanism
  作者：Daniele Simoni、Nicola Gebbia、Francesco Paolo Invidiata、Marco Eleopra、Paolo Marchetti、Riccardo Rondanin、Riccardo Baruchello、Stefano Provera、Carla Marchioro、Manlio Tolomeo、Luciana Marinelli、Vittorio Limongelli、Ettore Novellino、Aaron Kwaasi、James Dunford、Simona Buccheri、Nadia Caccamo、Francesco Dieli

  DOI：10.1021/jm801003y

  日期：2008.11.13

  A small series of aminobisphosphonates (N-BPs) structurally related to zoledronic acid was synthesized with the aim of improving activity toward activation of human gamma delta T cells and in turn their in vivo antitumor activity. The absence of the 1-OH moiety, together with the position and the different basicity of the nitrogen, appears crucial for antitumor activity. In comparison to zoledronic acid, compound 6a shows a greater ability to activate gamma delta T cells expression (100 times more) and a proapoptotic effect that is better than zoledronic acid. The potent activation of gamma delta T cells, in addition to evidence of the in vivo antitumor activity of 6a, suggests it may be a new potential drug candidate for cancer treatment.
• MEVALONATE PATHWAY INHIBITOR AS HIGHLY-EFFICIENT VACCINE ADJUVANT
  申请人：Tsinghua University

  公开号：US20190321465A1

  公开（公告）日：2019-10-24

  Disclosed are inhibitors of mevalonate pathway as an efficient vaccine adjuvant and use thereof. In particular, the inhibitor is an acetoacetyl-CoA transferase inhibitor, a HMG-CoA synthase inhibitor, a HMG-CoA reductase inhibitor, a mevalonate kinase inhibitor, a phosphomevalonate kinase inhibitor, a mevalonate-5-pyrophosphate decarboxylase inhibitor, an isopentenyl pyrophosphate isomerase inhibitor, a farnesyl pyrophosphate synthase inhibitor, a geranylgeranyl pyrophosphate synthase inhibitor or a geranylgeranyl transferase (I, II) inhibitor. Also disclosed is an immunogenic composition comprising inhibitors of mevalonate to pathway as an adjuvant.