benzyl 1-(1-methoxy-2-oxo-5-phenylpentan-3-ylamino)-4-methyl-1-oxopentan-2-ylcarbamate

• 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: benzyl 1-(1-methoxy-2-oxo-5-phenylpentan-3-ylamino)-4-methyl-1-oxopentan-2-ylcarbamate
• 英文别名: [(S)-1-((S)-3-Methoxy-2-oxo-1-phenethyl-propylcarbamoyl)-3-methyl-butyl]-carbamic acid benzyl ester；benzyl N-[(2S)-1-[[(3S)-1-methoxy-2-oxo-5-phenylpentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate
• 化学式: C₂₆H₃₄N₂O₅
• 分子量: 454.566
• InChiKey: LFBQUZAMAXVHFV-GOTSBHOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  33
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  adamantan-2-one O-methyloxime 、 benzyl 1-(1-methoxy-2-oxo-5-phenylpentan-3-ylamino)-4-methyl-1-oxopentan-2-ylcarbamate 在 臭氧 作用下， 以 二氯甲烷 、 正戊烷 为溶剂， 以32%的产率得到benzyl N-[(2S)-1-[[(1S)-1-[3-(methoxymethyl)spiro[1,2,4-trioxolane-5,2'-adamantane]-3-yl]-3-phenylpropyl]amino]-4-methyl-1-oxopentan-2-yl]carbamate
  参考文献：
  名称：

  Endoperoxide Carbonyl Falcipain 2/3 Inhibitor Hybrids: Toward Combination Chemotherapy of Malaria through a Single Chemical Entity

  摘要：

  We extend our approach of combination chemotherapy through a single prodrug entity (O'Neill et al. Angew. Chem., Int. Ed. 2004, 43, 4193) by using a 1,2,4-trioxolane as a protease inhibitor carbonyl-masking group. These molecules are designed to target the malaria parasite through two independent mechanisms of action: iron(II) decomposition releases the carbonyl protease inhibitor and potentially eytotoxic C-radical species in tandem. Using a proposed target "heme", we also demonstrate heme alkylation/carbonyl inhibitor release and quantitatively measure endoperoxide turnover in parasitized red blood cells.

  DOI：

  10.1021/jm1009567
• 作为产物：
  描述：

  2-(2-{[(benzyloxy)carbonyl]amino}-4-methylpentanoylamino)-4-phenylbutanoic acid methyl ester 在 4-二甲氨基吡啶 、 水 、 1-羟基苯并三唑 、 magnesium 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 mercury dichloride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 0.75h， 生成 benzyl 1-(1-methoxy-2-oxo-5-phenylpentan-3-ylamino)-4-methyl-1-oxopentan-2-ylcarbamate
  参考文献：
  名称：

  Endoperoxide Carbonyl Falcipain 2/3 Inhibitor Hybrids: Toward Combination Chemotherapy of Malaria through a Single Chemical Entity

  摘要：

  We extend our approach of combination chemotherapy through a single prodrug entity (O'Neill et al. Angew. Chem., Int. Ed. 2004, 43, 4193) by using a 1,2,4-trioxolane as a protease inhibitor carbonyl-masking group. These molecules are designed to target the malaria parasite through two independent mechanisms of action: iron(II) decomposition releases the carbonyl protease inhibitor and potentially eytotoxic C-radical species in tandem. Using a proposed target "heme", we also demonstrate heme alkylation/carbonyl inhibitor release and quantitatively measure endoperoxide turnover in parasitized red blood cells.

  DOI：

  10.1021/jm1009567

文献信息

• Novel route to the synthesis of peptides containing 2-amino-1′-hydroxymethyl ketones and their application as cathepsin K inhibitors
  作者：Rohan V Mendonca、Shankar Venkatraman、James T Palmer

  DOI：10.1016/s0960-894x(02)00611-x

  日期：2002.10

  Cathepsin K is highly expressed in human osteoclasts, and is implicated in bone resorption. This makes it an attractive target for the treatment of osteoporosis. Peptides containing 2-amino-1'-hydroxymethyl ketones and 2-amino-1'-alkoxymethyl ketones were discovered as potent inhibitors of cathepsin K. A novel synthetic route was devised to facilitate rapid elucidation of the SAR of these inhibitors. The synthesis and SAR of hydroxymethyl ketones are presented. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Endoluminal medical device for local delivery of cathepsin inhibitors, method of making and treating
  申请人：Biggs P. David

  公开号：US20070293937A1

  公开（公告）日：2007-12-20

  An endoluminal medical device comprises a drug release system that releases a cathepsin inhibitor at a predetermined location within a lumen of a patient. The endoluminal devices and methods of treatment of disease can treat illnesses such as aneurysms and aortic dissections.
• US6506733B1
  申请人：——

  公开号：US6506733B1

  公开（公告）日：2003-01-14
• Endoperoxide Carbonyl Falcipain 2/3 Inhibitor Hybrids: Toward Combination Chemotherapy of Malaria through a Single Chemical Entity
  作者：Peter Gibbons、Edite Verissimo、Nuna C. Araujo、Victoria Barton、Gemma L. Nixon、Richard K. Amewu、James Chadwick、Paul A. Stocks、Giancarlo A. Biagini、Abhishek Srivastava、Philip J. Rosenthal、Jiri Gut、Rita C. Guedes、Rui Moreira、Raman Sharma、Neil Berry、M. Lurdes S. Cristiano、Alison E. Shone、Stephen A. Ward、Paul M. O’Neill

  DOI：10.1021/jm1009567

  日期：2010.11.25

  We extend our approach of combination chemotherapy through a single prodrug entity (O'Neill et al. Angew. Chem., Int. Ed. 2004, 43, 4193) by using a 1,2,4-trioxolane as a protease inhibitor carbonyl-masking group. These molecules are designed to target the malaria parasite through two independent mechanisms of action: iron(II) decomposition releases the carbonyl protease inhibitor and potentially eytotoxic C-radical species in tandem. Using a proposed target "heme", we also demonstrate heme alkylation/carbonyl inhibitor release and quantitatively measure endoperoxide turnover in parasitized red blood cells.