dibenzyl 4-phenylbutylphosphonate | 115947-38-1

• 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: dibenzyl 4-phenylbutylphosphonate
• 英文别名: (4-Phenylbutyl)phosphonic acid, dibenzyl ester；4-bis(phenylmethoxy)phosphorylbutylbenzene
• CAS: 115947-38-1
• 化学式: C₂₄H₂₇O₃P
• 分子量: 394.45
• InChiKey: FJSNJVGAJRWOBT-UHFFFAOYSA-N

物化性质

• 沸点：
  547.0±49.0 °C(Predicted)
• 密度：
  1.138±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  dibenzyl 4-phenylbutylphosphonate 在 草酰氯 、 N,N-二甲基甲酰胺 、 sodium iodide 作用下， 以 二氯甲烷 、 丁酮 为溶剂， 反应 2.5h， 生成 N-[benzyloxy(4-phenylbutyl)phosphinyl]-L-glutamic acid dibenzyl ester
  参考文献：
  名称：

  Probing for a hydrophobic a binding register in prostate-specific membrane antigen with phenylalkylphosphonamidates

  摘要：

  To explore for the existence of an auxiliary hydrophobic binding register remote from the active site of PSMA a series of phenylalkylphosphonamidate derivatives of glutamic acid were synthesized and evaluated for their inhibitory potencies against PSMA. Both the phenyl- and benzylphosphonamidates (1a and 1b) exhibited only modest inhibitory potency against. The phenethyl analog 1c was intermediate in inhibitory potency while inhibitors possessing a longer alkyl tether from the phenyl ring, resulted in markedly improved K-i values. The greatest inhibitory potency was obtained for the inhibitors in which the phenyl ring was extended furthest from the central phosphorus (if, n = 5 and I g, n = 6). The slightly serrated pattern that emerged as the alkyl tether increased from three to six methylene units suggests that inhibitory potency is not simply correlated to increased hydrophobicity imparted by the phenylalkyl chain, but rather that one or more hydrophobic binding registers may exist remote from the substrate recognition architecture in the active site of PSMA. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.031
• 作为产物：
  描述：

  4-苯基-1-丁基溴 、 膦酸,甲基-,二(苯基甲基)酯 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 以42.9%的产率得到dibenzyl 4-phenylbutylphosphonate
  参考文献：
  名称：

  Probing for a hydrophobic a binding register in prostate-specific membrane antigen with phenylalkylphosphonamidates

  摘要：

  To explore for the existence of an auxiliary hydrophobic binding register remote from the active site of PSMA a series of phenylalkylphosphonamidate derivatives of glutamic acid were synthesized and evaluated for their inhibitory potencies against PSMA. Both the phenyl- and benzylphosphonamidates (1a and 1b) exhibited only modest inhibitory potency against. The phenethyl analog 1c was intermediate in inhibitory potency while inhibitors possessing a longer alkyl tether from the phenyl ring, resulted in markedly improved K-i values. The greatest inhibitory potency was obtained for the inhibitors in which the phenyl ring was extended furthest from the central phosphorus (if, n = 5 and I g, n = 6). The slightly serrated pattern that emerged as the alkyl tether increased from three to six methylene units suggests that inhibitory potency is not simply correlated to increased hydrophobicity imparted by the phenylalkyl chain, but rather that one or more hydrophobic binding registers may exist remote from the substrate recognition architecture in the active site of PSMA. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.031

文献信息

• (Phosphinyloxy)acyl amino acid inhibitors of angiotensin converting enzyme (ACE). 1. Discovery of (S)-1-[6-amino-2-[[hydroxy(4-phenylbutyl)phosphinyl]oxy]-1-oxohexyl]-L-proline, a novel orally active inhibitor of ACE
  作者：Donald S. Karanewsky、Michael C. Badia、David W. Cushman、Jack M. DeForrest、Tamara Dejneka、Melanie J. Loots、Maria G. Perri、Edward W. Petrillo、James R. Powell

  DOI：10.1021/jm00396a033

  日期：1988.1

  active, phosphinyloxyacyl proline inhibitors of angiotensin converting enzyme (ACE) is described. The in vitro and in vivo ACE inhibitory activities are reported for each compound. The structure-activity relationship for this series of compounds in relation to the carboxyalkyl dipeptide ACE inhibitors as well as other types of hydroxyphosphinyl-containing ACE inhibitors (e.g., the corresponding nitrogen

  描述了一系列血管紧张素转化酶（ACE）的口服活性，次膦酰氧基酰基脯氨酸抑制剂的合成。报告了每种化合物的体外和体内ACE抑制活性。讨论了该系列化合物与羧烷基二肽ACE抑制剂以及其他类型的含羟基亚膦酰基的ACE抑制剂（例如，相应的氮和碳等排烃）的结构活性关系。在基于赖氨酰脯氨酸末端二肽序列的一系列等排的含磷抑制剂中，只有膦酸酯（氧等排体）显示出高水平的口服活性。膦酸酯系列中的最佳效力和口服活性与（苯基丁基）-和正己基膦酸酯侧链一起发生。P1'中的氨基丁基侧链 残留物是完整表达口腔活性的绝对要求。这些化合物中最有效的化合物8b（SQ 29,852）的静脉和口服活性在血压正常的大鼠中均优于卡托普利。
• Orally active phosphonyl hydroxyacyl prolines
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04745196A1

  公开（公告）日：1988-05-17

  This invention is directed to orally active antihypertensive agents of the formula ##STR1## wherein R.sub.1 is certain alkyl or aralkyl groups.

  本发明涉及公式##STR1##中R.sub.1为特定的烷基或芳基烷基的口服降压剂。
• KARANEWSKY, DONALD S.;BADIA, MICHAEL C.;CUSHMAN, DAVID W.;DEFORREST, JACK+, J. MED. CHEM., 31,(1988) N 1, 204-212
  作者：KARANEWSKY, DONALD S.、BADIA, MICHAEL C.、CUSHMAN, DAVID W.、DEFORREST, JACK+

  DOI：——

  日期：——
• Probing for a hydrophobic a binding register in prostate-specific membrane antigen with phenylalkylphosphonamidates
  作者：Jack Maung、Jeremy P. Mallari、Teri A. Girtsman、Lisa Y. Wu、Jennifer A. Rowley、Nicholas M. Santiago、Alan N. Brunelle、Clifford E. Berkman

  DOI：10.1016/j.bmc.2004.06.031

  日期：2004.9

  To explore for the existence of an auxiliary hydrophobic binding register remote from the active site of PSMA a series of phenylalkylphosphonamidate derivatives of glutamic acid were synthesized and evaluated for their inhibitory potencies against PSMA. Both the phenyl- and benzylphosphonamidates (1a and 1b) exhibited only modest inhibitory potency against. The phenethyl analog 1c was intermediate in inhibitory potency while inhibitors possessing a longer alkyl tether from the phenyl ring, resulted in markedly improved K-i values. The greatest inhibitory potency was obtained for the inhibitors in which the phenyl ring was extended furthest from the central phosphorus (if, n = 5 and I g, n = 6). The slightly serrated pattern that emerged as the alkyl tether increased from three to six methylene units suggests that inhibitory potency is not simply correlated to increased hydrophobicity imparted by the phenylalkyl chain, but rather that one or more hydrophobic binding registers may exist remote from the substrate recognition architecture in the active site of PSMA. (C) 2004 Elsevier Ltd. All rights reserved.