diethyl N-[(S)-1-cyclohexylethyl]carbamoylphosphonate

• 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: diethyl N-[(S)-1-cyclohexylethyl]carbamoylphosphonate
• 英文别名: diethyl N-[(S)-(+)-1-cyclohexylethyl]carbamoylphosphonate；N-[(1S)-1-cyclohexylethyl]-1-diethoxyphosphorylformamide
• 化学式: C₁₃H₂₆NO₄P
• 分子量: 291.327
• InChiKey: AZTKETOWYFBHJZ-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  diethyl N-[(S)-1-cyclohexylethyl]carbamoylphosphonate 在 三甲基溴硅烷 作用下， 以 乙腈 为溶剂， 反应 2.5h， 以99%的产率得到N-(S)-(-)-(1-cyclohexylethyl)carbamoylphosphonic acid
  参考文献：
  名称：

  [EN] NEW CARBAMOYL-AND THIOCARBAMOYL-PHOSPHONATES AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM
  [FR] NOUVEAUX PHOSPHONATES DE CARBAMOYLE ET DE THIOCARBAMOYLE ET COMPOSITIONS PHARMACEUTIQUES LES COMPRENANT

  摘要：

  公开号：

  WO2004089962A3
• 作为产物：
  描述：

  [(1S)-1-cyclohexylethyl]amine 、 triethyl phosphonothiolformate 以 乙腈 为溶剂， 以76%的产率得到diethyl N-[(S)-1-cyclohexylethyl]carbamoylphosphonate
  参考文献：
  名称：

  Carbamoylphosphonate MMP inhibitors. Part 4: The influence of chirality and geometrical isomerism on the potency and selectivity of inhibition

  摘要：

  Matrix metalloproteinases (MMPs) are a family of over twenty zinc-dependent enzymes that hydrolyze connective tissue and are involved in a variety of diseases, which are associated with undesired tissue breakdown. Previously we described the synthesis of a series of achiral alkyl and cycloalkylcarbamoylphosphonic acids and their biological evaluation. Herein we report the effect of chirality and geometrical isomerism on the potency and selectivity of inhibition. The inhibitory potencies of pairs of enantiomeric and stereoisomeric alkyl and cycloalkylcarbamoylphosphonic acids were evaluated on recombinant MMP-1, MMP-2, MMP-3. MMP-8, and MMP-9 enzymes. The results show that the enantiomers and stereoisomers studied differ considerably in their inhibitory potencies and selectivities on the enzyme subtypes studied. Such a result is consistent with the assumption that the carbamoylphosphonates interact with a chiral environment such as an enzyme. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2004.07.002

文献信息

• Novel substituted imides
  申请人：Muller W. George

  公开号：US20050090516A1

  公开（公告）日：2005-04-28

  Novel imides are inhibitors of tumor necrosis factor alpha and can be used to combat cachexia, endotoxic shock, and retrovirus replication. A typical embodiment is (R)-2-Phthalimido-3-(3′,4′-dimethoxyphenyl)propane.

  新型咪唑衍生物是肿瘤坏死因子α的抑制剂，可用于对抗消瘦症、内毒素休克和逆转录病毒复制。典型的实施例是（R）-2-邻苯二甲酰亚胺基-3-（3′，4′-二甲氧基苯基）丙烷。
• Carbamoyl-and thiocarbamoyl-phosphonates and pharmaceutical compositions comprising them
  申请人：Breuer Eli

  公开号：US20060111328A1

  公开（公告）日：2006-05-25

  The present invention provides a compound of the following formula I: R 3 —NH—C(═X)—P(═O)OR 1 OR 2 including pharmaceutically acceptable salts, solvates, hydrates and polymorphs of the compounds of formula I, as well as geometrical isomers and optically active forms of the compounds of formula I and pharmaceutically acceptable salts, solvates, hydrates and polymorphs of said isomers and forms, wherein R 1 and R 2 may be the same or different and are each selected from hydrogen, acyloxyalkyl and aryl or R 1 and R 2 may form together with the oxygen and phosphorus atoms a dioxaphosphacycloalkane ring; X is O or S; and R 3 is selected, when X is O, from bicycloalkyl, cycloalkylalkyl and substituted cycloalkyl by at least one of alkyl, amino, amidino and guanidino; and R 3 is selected, when X is S, from bicycloalkyl, cycloalkylalkyl and cycloalkyl optionally substituted by at least one of alkyl, amino, amidino and guanidino; with the proviso that: when X is O, R 3 is not cyclohexylmethyl, and when X is S, R 3 is not cyclohexyl. The invention further provides pharmaceutical compositions comprising the above compounds and their use in medicine.

  本发明提供了下式 I 的化合物： R 3 -NH-C(═X)-P(═O)或 1 或 2 包括式 I 化合物的药学上可接受的盐、溶液、水合物和多晶型，以及式 I 化合物的几何异构体和光学活性形式，以及上述异构体和形式的药学上可接受的盐、溶液、水合物和多晶型，其中 R 1 和 R 2 可以相同或不同，且各自选自氢、酰氧基烷基和芳基或 R 1 和 R 2 可与氧原子和磷原子一起形成二氧磷环；X 是 O 或 S；以及 R 3 当 X 为 O 时，选自双环烷基、环烷基烷基和被烷基、氨基、脒基和胍基中至少一种取代的环烷基；和 R 3 当 X 为 S 时，选自双环烷基、环烷基烷基和被烷基、氨基、脒基和胍基中至少一种任选取代的环烷基；但有以下条件 当 X 为 O 时，R 3 不是环己基甲基，以及 当 X 为 S 时，R 3 不是环己基。本发明进一步提供了包含上述化合物的药物组合物及其在医学中的应用。
• [EN] NEW CARBAMOYL-AND THIOCARBAMOYL-PHOSPHONATES AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM<br/>[FR] NOUVEAUX PHOSPHONATES DE CARBAMOYLE ET DE THIOCARBAMOYLE ET COMPOSITIONS PHARMACEUTIQUES LES COMPRENANT
  申请人：YISSUM RES DEV CO

  公开号：WO2004089962A3

  公开（公告）日：2005-07-21
• EP1611143A2
  申请人：——

  公开号：EP1611143A2

  公开（公告）日：2006-01-04
• US6844359B2
  申请人：——

  公开号：US6844359B2

  公开（公告）日：2005-01-18