4-(dibenzylphosphonyl)butanoic acid | 212780-49-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: 4-(dibenzylphosphonyl)butanoic acid
• 英文别名: 4-(Bis-benzyloxy-phosphoryl)-butyric acid；4-bis(phenylmethoxy)phosphorylbutanoic acid
• CAS: 212780-49-9
• 化学式: C₁₈H₂₁O₅P
• 分子量: 348.336
• InChiKey: XTNVRMHSBABEPB-UHFFFAOYSA-N

物化性质

• 沸点：
  544.7±50.0 °C(Predicted)
• 密度：
  1.241±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(dibenzylphosphonyl)butanoic acid 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 14.0h， 生成 5-(4-dibenzylphosphonobutyryl)amino-6-D-ribitylaminouracil
  参考文献：
  名称：

  Incorporation of an Amide into 5-Phosphonoalkyl-6-d-ribitylaminopyrimidinedione Lumazine Synthase Inhibitors Results in an Unexpected Reversal of Selectivity for Riboflavin Synthase vs Lumazine Synthase

  摘要：

  Several analogues of a hypothetical intermediate in the reaction catalyzed by lumazine synthase were synthesized and tested as inhibitors of both Bacillus subtilis lumazine synthase and Escherichia coli riboflavin synthase. The new compounds were designed by replacement of a two-carbon fragment of several 5-phosphonoalkyl-6-D-ribitylaminopyrimidinedione lumazine synthase inhibitors with an amide linkage that was envisioned as an analogue of a Schiff base moiety of a hypothetical intermediate in the enzyme-catalyzed reaction. The incorporation of the amide group led to an unexpected reversal in selectivity for inhibition of lumazine synthase vs riboflavin synthase. Whereas the parent 5-phosphonoalkyl-6-D-ribitylaminopyrimidinediones were lumazine synthase inhibitors and did not inhibit riboflavin synthase, the amide-containing derivatives inhibited riboflavin synthase and were only very weak or inactive as lumazine synthase inhibitors. Molecular modeling of inhibitor-lumazine synthase complexes did not reveal a structural basis for these unexpected findings. However, molecular modeling of one of the inhibitors with E. coli riboflavin synthase demonstrated that the active site of the enzyme could readily accommodate two ligand molecules.

  DOI：

  10.1021/jo020144r
• 作为产物：
  描述：

  亚磷酸二苄酯 在 lithium hydroxide 、 sodium hydride 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.5h， 生成 4-(dibenzylphosphonyl)butanoic acid
  参考文献：
  名称：

  Incorporation of an Amide into 5-Phosphonoalkyl-6-d-ribitylaminopyrimidinedione Lumazine Synthase Inhibitors Results in an Unexpected Reversal of Selectivity for Riboflavin Synthase vs Lumazine Synthase

  摘要：

  Several analogues of a hypothetical intermediate in the reaction catalyzed by lumazine synthase were synthesized and tested as inhibitors of both Bacillus subtilis lumazine synthase and Escherichia coli riboflavin synthase. The new compounds were designed by replacement of a two-carbon fragment of several 5-phosphonoalkyl-6-D-ribitylaminopyrimidinedione lumazine synthase inhibitors with an amide linkage that was envisioned as an analogue of a Schiff base moiety of a hypothetical intermediate in the enzyme-catalyzed reaction. The incorporation of the amide group led to an unexpected reversal in selectivity for inhibition of lumazine synthase vs riboflavin synthase. Whereas the parent 5-phosphonoalkyl-6-D-ribitylaminopyrimidinediones were lumazine synthase inhibitors and did not inhibit riboflavin synthase, the amide-containing derivatives inhibited riboflavin synthase and were only very weak or inactive as lumazine synthase inhibitors. Molecular modeling of inhibitor-lumazine synthase complexes did not reveal a structural basis for these unexpected findings. However, molecular modeling of one of the inhibitors with E. coli riboflavin synthase demonstrated that the active site of the enzyme could readily accommodate two ligand molecules.

  DOI：

  10.1021/jo020144r

文献信息

• Synthetic Fosmidomycin Analogues with Altered Chelating Moieties Do Not Inhibit 1-Deoxy-D-xylulose 5-phosphate Reductoisomerase or Plasmodium falciparum Growth In Vitro
  作者：René Chofor、Martijn Risseeuw、Jenny Pouyez、Chinchu Johny、Johan Wouters、Cynthia Dowd、Robin Couch、Serge Van Calenbergh

  DOI：10.3390/molecules19022571

  日期：——

  Fourteen new fosmidomycin analogues with altered metal chelating groups were prepared and evaluated for inhibition of E. coli Dxr, M. tuberculosis Dxr and the growth of P. falciparum K1 in human erythrocytes. None of the synthesized compounds showed activity against either enzyme or the Plasmodia. This study further underlines the importance of the hydroxamate functionality and illustrates that identifying effective alternative bidentate ligands for this target enzyme is challenging.

  制备了14种改变了金属配位基团的磷霉素类似物，并评估了它们对大肠杆菌Dxr、结核分枝杆菌Dxr的抑制作用以及在人类红细胞中对恶性疟原虫K1生长的抑制作用。合成的化合物均未显示对任一酶或疟原虫的活性。这项研究进一步强调了羟肟酸基团的重要性，并表明确定该靶酶的有效替代双齿配体具有挑战性。
• Parallel Synthesis of Sialyl Lewis X Mimetics on a Solid Phase: Access to a Library of Fucopeptides
  作者：Thomas F. J. Lampe、Gabriele Weitz-Schmidt、Chi-Huey Wong

  DOI：10.1002/(sici)1521-3773(19980703)37:12<1707::aid-anie1707>3.0.co;2-v

  日期：1998.7.3

  bidirectional functionalization of glycosylated amino acid derivatives and thus the rapid parallel synthesis of fucopeptides as sialyl Lewis X mimetics on a solid phase [Eq. (a), PEG-PS=poly(ethylene glycol) graft copolymer]. This led to the discovery of new mimetics against P-selectin with IC50 values in the low μM range.

  新的锚定基团对-（酰氧基甲基）亚苄基乙缩醛（p-AMBA）使糖基化的氨基酸衍生物能够双向功能化，因此可以在固相上快速并行合成烟酰胺肽作为唾液酸化的路易斯X模拟物。（a），PEG-PS ＝聚（乙二醇）接枝共聚物]。这导致发现了针对P-选择素的新模拟物，其IC 50值在低μM范围内。
• Derivatives of succinic and glutaric acids and analogs thereof useful as inhibitors of phex
  申请人：Gravel Denis

  公开号：US20060135480A1

  公开（公告）日：2006-06-22

  The present invention relates to derivatives of succinic and glutaric acids and analogues thereof, having the following general formula (I), useful as inhibitors of PHEX. These derivatives are useful for promoting generation of bone mass and treating or preventing diseases or conditions associated with a phosphate metabolism defect. Methods for preparation and intermediates are also disclosed.

  本发明涉及琥珀酸和戊二酸的衍生物及其类似物，具有以下一般式（I），可用作PHEX的抑制剂。这些衍生物有助于促进骨量的生成，并治疗或预防与磷酸盐代谢缺陷相关的疾病或病症。本发明还公开了制备方法和中间体。
• Derivatives of succinic and glutaric acids and analogs thereof useful as inhibitors of PHEX
  申请人：Gravel Denis

  公开号：US20060287280A1

  公开（公告）日：2006-12-21

  The present invention relates to derivatives of succinic and glutaric acids and analogues thereof, having the following general formula: useful as inhibitors of PHEX. These derivatives are useful for promoting generation of bone mass and treating or preventing diseases or conditions associated with a phosphate metabolism defect. Methods for preparation and intermediates are also disclosed.

  本发明涉及琥珀酸和戊二酸及其类似物的衍生物，其具有以下一般式：用作PHEX的抑制剂。这些衍生物有助于促进骨量的生成，并用于治疗或预防与磷酸盐代谢缺陷有关的疾病或病况。本发明还公开了制备方法和中间体。
• [EN] DERIVATIVES OF SUCCINIC AND GLUTARIC ACIDS AND ANALOGS THEREOF USEFUL AS INHIBITORS OF PHEX<br/>[FR] DERIVES D'ACIDES SUCCINIQUE ET GLUTARIQUE ET LEURS ANALOGUES UTILISES COMME INHIBITEURS DE PHEX
  申请人：BIOMEP INC

  公开号：WO2004050620A3

  公开（公告）日：2004-08-19