diisopropyl 4-nitrophenoxycarbonylphosphonoformate | 83877-27-4

• 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: diisopropyl 4-nitrophenoxycarbonylphosphonoformate
• 英文别名: diisopropyl 4-nitrophenoxycarbonylphosphonate；Phosphinecarboxylic acid, bis(1-methylethoxy)-, 4-nitrophenyl ester, oxide；(4-nitrophenyl) di(propan-2-yloxy)phosphorylformate
• CAS: 83877-27-4
• 化学式: C₁₃H₁₈NO₇P
• 分子量: 331.262
• InChiKey: DQACQTNYLKASSY-UHFFFAOYSA-N

物化性质

• 沸点：
  410.6±47.0 °C(Predicted)
• 密度：
  1.278±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diisopropyl 4-nitrophenoxycarbonylphosphonoformate 在 三苯基膦 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 23.58h， 生成 diisopropyl (S)-2-benzyloxycarbonylamino-3-(4-phenoxybenzenesulfonamido)propylcarbamoylphosphonate
  参考文献：
  名称：

  对映体氨基烷基氨基甲酰基膦酸酯的合成及其作为双作用抗癌 MMP 和碳酸酐酶抑制剂的评价

  摘要：

  氨基甲酰膦酸盐 (CPO) 最近被鉴定为癌症和促进转移的细胞外酶、碳酸酐酶 (CA) IX 和 XII 以及基质金属蛋白酶 2 (MMP-2) 的细胞外活性抑制剂。本文介绍了立体选择性合成和对一对对映体氨基烷基氨基甲酰基膦酸酯的生物学特性的评估，它们是使用官能团转化从 l-丝氨酸对映选择性合成的。对映体产物的结构已通过 X 射线晶体学确定。化合物的对映体纯度已通过手性位移试剂 NMR 实验和圆二色性得到证实。合成的 CPO 的体外评估表明它们对 CAIX 和 CAXII 具有微摩尔 IC50 抑制作用。两种对映异构体以及外消旋或光学非活性异构体与先前报道的 CPO 的 CA 抑制值没有任何显着差异。另一方面，MMPs 抑制活性较弱；只有 MMP-2 显示出显着的 IC50 值。

  DOI：

  10.1002/hc.21256
• 作为产物：
  描述：

  三异丙基亚磷酸酯 、 对硝基苯基氯甲酸酯 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 diisopropyl 4-nitrophenoxycarbonylphosphonoformate
  参考文献：
  名称：

  氨基甲酰基膦酸酯第7部分。使用4-硝基苯氧基羰基膦酸酯二酯合成受阻氨基甲酰基膦酸酯的有效方法

  摘要：

  可以通过4-硝基苯氧基羰基膦酸酯二酯以高收率和温和的条件将抗其他试剂的受阻伯胺转化为氨基甲酰基膦酸酯。

  DOI：

  10.1016/j.tetlet.2008.03.036

文献信息

• [EN] CARJBAMOYLPHOSPHONATES AS INHIBITORS AND USES THEREOF<br/>[FR] CARBAMOYLPHOSPHONATES EN TANT QU'INHIBITEURS ET LEURS UTILISATIONS
  申请人：YISSUM RES DEV CO

  公开号：WO2010089752A1

  公开（公告）日：2010-08-12

  The present invention relates to novel metalloproteinase inhibitors having an aryloxybenzenesulfonamide moiety and a carbamoylphosphonic acid moiety, to pharmaceutical compositions comprising them, and to their uses in the prevention and/or treatment of disease or disorder associated with MMP.

  本发明涉及具有芳氧基苯磺酰胺基团和氨基甲酰磷酸基团的新型金属蛋白酶抑制剂，以及包含它们的药物组合物，以及它们在预防和/或治疗与MMP相关的疾病或紊乱中的用途。
• CARBAMOYLPHOSPHONATES AS INHIBITORS AND USES THEREOF
  申请人：Breuer Eli

  公开号：US20120035140A1

  公开（公告）日：2012-02-09

  The present invention relates to novel metalloproteinase inhibitors having an aryloxybenzenesulfonamide moiety and a carbamoylphosphonic acid moiety, to pharmaceutical compositions comprising them, and to their uses in the prevention and/or treatment of disease or disorder associated with MMP.

  本发明涉及具有芳氧基苯磺酰胺基团和氨基甲酰磷酸基团的新型金属蛋白酶抑制剂，涉及包含它们的制药组合物，以及它们在预防和/或治疗与MMP相关的疾病或疾病中的应用。
• Carbamoylphosphonates as inhibitors and uses thereof
  申请人：Breuer Eli

  公开号：US08993544B2

  公开（公告）日：2015-03-31

  The present invention relates to novel metalloproteinase inhibitors having an aryloxybenzenesulfonamide moiety and a carbamoylphosphonic acid moiety, to pharmaceutical compositions comprising them, and to their uses in the prevention and/or treatment of disease or disorder associated with MMP.

  本发明涉及具有芳氧基苯磺酰胺基团和氨基甲酸磷酸酯基团的新型金属蛋白酶抑制剂，以及包含它们的制药组合物，以及它们在预防和/或治疗与MMP相关的疾病或障碍中的用途。
• Synthesis of esters of phosphonoformic acid and their antiherpes activity
  作者：Jan O. Noren、Erik Helgstrand、Nils G. Johansson、Alfons Misiorny、Goeran Stening

  DOI：10.1021/jm00356a028

  日期：1983.2

  Aliphatic and aromatic mono-, di-, and triesters of phosphonoformic acid (foscarnet) were synthesized. The triesters were prepared by the Michaelis-Arbuzov reaction and were hydrolyzed to di- and monoesters. The compounds were tested for antiviral activity on isolated herpes simplex virus type 1 (HSV-1) DNA polymerase, in a HSV-1 plaque reduction assay, and on a cutaneous HSV-1 infection in guinea pigs. None of the esters inhibited the activity of isolated HSV-1 polymerases. Monoesters with a free carboxylic group and diesters with an aromatic carboxylic ester function were active against the cutaneous herpes infection. Mono- and diesters with an aromatic phosphonic ester group also showed activity in the plaque-reduction assay. However, mono- and diesters with an aromatic phosphonic ester group also showed activity in the plaque-reduction assay. However, mono- and diesters with aliphatic carboxylic ester groups were inactive in all test systems. The results show that all three acidic groups of phosphonoformic acid must be free in order to get antiviral activity at the enzyme level. However, certain esters of this acid may be biotransformed to the acid itself to give antiherpes activity.
• Carbamoylphosphonates Control Tumor Cell Proliferation and Dissemination by Simultaneously Inhibiting Carbonic Anhydrase IX and Matrix Metalloproteinase-2. Toward Nontoxic Chemotherapy Targeting Tumor Microenvironment
  作者：Reuven Reich、Amnon Hoffman、Ainelly Veerendhar、Alfonso Maresca、Alessio Innocenti、Claudiu T. Supuran、Eli Breuer

  DOI：10.1021/jm300981b

  日期：2012.9.13

  Carbamoylphosphonates (CPOs) have been identified as inhibitors of matrix metalloproteinases (MMPs) and as orally active, bioavailable, and safe antimetastatic agents. In this article, we focus on the direct antitumor activity of the CPOs. We discovered that CPOs also inhibit carbonic anhydrases (CAs), especially the IX and XII isoforms identified as cancer promoting factors. Thus, CPOs can be regarded as novel nontoxic drug candidates for tumor microenvironment targeted chemotherapy acting by two synergistic mechanisms, namely, inhibiting CAs and MMPs simultaneously. We have also demonstrated that the ionized CPO acid is unable to cross the cell membrane and thus limited to interact with the extracellular domains of isozymes CAIX and CAXII. Finally, applying CPOs against cancer cells in hypoxic conditions resulted in the dose dependent release of lactate dehydrogenase, confirming the direct interaction of the CPOs with the cancer related isozymes CAIX and XII and thereby promoting cellular damage.