N-[[1-[[hydroxy[2-phenyl-1(R)-[[(phenylmethoxy)carbonyl]amino]ethyl]phosphinyl]methyl]cyclopentyl]carbonyl]-L-tyrosine

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-[[1-[[hydroxy[2-phenyl-1(R)-[[(phenylmethoxy)carbonyl]amino]ethyl]phosphinyl]methyl]cyclopentyl]carbonyl]-L-tyrosine
• 英文别名: (S)-2-({1-[((R)-1-Benzyloxycarbonylamino-2-phenyl-ethyl)-hydroxy-phosphinoylmethyl]-cyclopentanecarbonyl}-amino)-3-(4-hydroxy-phenyl)-propionic acid；(2S)-3-(4-hydroxyphenyl)-2-[[1-[[hydroxy-[(1R)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]methyl]cyclopentanecarbonyl]amino]propanoic acid
• 化学式: C₃₂H₃₇N₂O₈P
• 分子量: 608.628
• InChiKey: BCKVBGRPLOTFSR-WUFINQPMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  43
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  162
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  t-Butyl 1-(Hydroxymethyl)cyclopentanecarboxylate 在 N-甲基吗啉 、 盐酸 、 lithium hydroxide 、 N,N'-羰基二咪唑 、 三氟乙酸 、 lithium diisopropyl amide 作用下， 以 1,4-二氧六环 、 吡啶 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-[[1-[[hydroxy[2-phenyl-1(R)-[[(phenylmethoxy)carbonyl]amino]ethyl]phosphinyl]methyl]cyclopentyl]carbonyl]-L-tyrosine
  参考文献：
  名称：

  Design and synthesis of phosphinic acids that triply inhibit endothelin converting enzyme, angiotensin converting enzyme and neutral endopeptidase 24.11

  摘要：

  We have synthesized a series of phosphinic acids as inhibitors of a metalloprotease endothelin converting enzyme (ECE). Potent ECE inhibitors 4g and 4o were identified. These compounds are members of a novel class of ECE inhibitors that are also potent inhibitors of angiotensin converting enzyme and neutral endopeptidase. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00297-1

文献信息

• PHOSPHINIC ACID DERIVATIVES
  申请人：SCHERING CORPORATION

  公开号：EP0767794A1

  公开（公告）日：1997-04-16
• [EN] PHOSPHINIC ACID DERIVATIVES<br/>[FR] DERIVES D'ACIDE PHOSPHINIQUE
  申请人：——

  公开号：WO1996000732A1

  公开（公告）日：1996-01-11

  [EN] Phosphinic acid derivatives of structural formula (I) or a pharmaceutically acceptable salt thereof, wherein R is H, alkyl or alkanoyloxymethylene; R1, R2, R3 and R4 are H, alkyl, alkenyl, alkenylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxyalkyl, carboxyalkyl, thioalkyl, alkoxythioalkyl, aminoalkyl, alkylaminoalkyl, cycloalkyl-substituted alkyl or heterocycloalkyl; or R1 and R2 form a cycloalkyl ring of 3-8 members and R3 and R4 are as defined; or R3 and R4 form a cycloalkyl ring of 3-7 members and R1 and R2 are as defined; or R1 and R2 together, and R3 and R4 together, each form a cycloalkyl ring; R5 is -OR9 or -NHR9, wherein R9 is hydrogen or alkyl; n is 0 or 1; A1 is p-aminobenzoyl or p-aminobenzenesulfonyl, or A1 and R5 together form a radical of an alpha -aminoacyl derivative; and R6 is phenylmethoxycarbonyl, arylcarbonyl, heteroarylcarbonyl or -A2-R7, wherein A2 is a divalent alpha -iminoacyl radical, and R7 is a substituent on the alpha -imino atom selected from H, R8OCO-, R8SO2- and R8NHCO-, wherein R8 is aryl, arylmethyl or (C1-C8)alkyl; are disclosed for use as endothelin converting enzyme inhibitors; also disclosed are a genus of novel compounds wherein R<3> and R<4> form a cycloalkyl ring, and pharmaceutical compositions comprising said novel compounds.
  [FR] Cette invention concerne des dérivés d'acide phosphinique de formule (I) ou un sel pharmaceutiqement acceptable de ces derniers. Dans la formule R représente H, alkyle ou alcanoyloxyméthylène; R1, R2, R3 et R4 représentent H, alkyle, alcényle, alcénylalkyle, aryle, arylalkyle, hétéroaryle, hétéroarylalkyle, hydroxyalkyle, carboxyalkyle, thioalkyle, alcoxythioalkyle, aminoalkyle, alkylaminoalkyle, alkyle ou hétérocycloalkyle à substitution cycloalkyle; ou R1 et R2 forment un cycle cycloalkyle composé de 3 à 8 éléments et R3 et R4 sont tels que définis ci-avant; ou R3 et R4 forment un cycle cycloalkyle composé de 3 à 7 éléments et R1 et R2 sont tels que définis ci-avant; ou bien encore R1 et R2 ensemble, et R3 et R4 ensemble, forment chacun un cycle cycloalkyle; R5 représente -OR9 ou -NHR9, R9 représentant hydrogène ou alkyle; n représente 0 ou 1; A1 représente p-aminobenzoyle ou p-aminobenzènesulfonyle, ou A1 et R5 forment ensemble un radical ou un dérivé alpha -aminoacyle; et R6 représente phénylméthoxycarbonyle, arylcarbonyle, hétéroarylcarbonyle ou -A2-R7, A2 représentant un radical alpha -iminoacyle bivalent, et R7 représentant un substituant situé sur l'atome alpha -imino sélectioné parmi H, R8OCO-, R8SO2- et R8NHCO-, R8 représentant aryle, arylméthyle ou alkyle (C1-C8). Ces dérivés d'acide phosphinique ou leurs sels pharmaceutiquement acceptables sont utilisés comme inhibiteurs de l'enzyme de conversion de l'endothéline. Cette invention concerne également un genre de nouveaux composés dans lesquels R<3> et R<4> forment un cycle cycloalkyle; ainsi que des compositions pharmaceutiques contenant lesdits nouveaux composés.
• Design and synthesis of phosphinic acids that triply inhibit endothelin converting enzyme, angiotensin converting enzyme and neutral endopeptidase 24.11
  作者：Brian A. McKittrick、Andrew W. Stamford、Xiaoyu Weng、Ke Ma、Samuel Chackalamannil、Michael Czarniecki、ReneéM. Cleven、Ahmad B. Fawzi

  DOI：10.1016/0960-894x(96)00297-1

  日期：1996.7

  We have synthesized a series of phosphinic acids as inhibitors of a metalloprotease endothelin converting enzyme (ECE). Potent ECE inhibitors 4g and 4o were identified. These compounds are members of a novel class of ECE inhibitors that are also potent inhibitors of angiotensin converting enzyme and neutral endopeptidase. Copyright (C) 1996 Elsevier Science Ltd