[1-(1-carbamoyl-2-phenylethylcarbamoyl)-2-methylbutyl]carbamic acid tert-butyl ester | 120636-88-6

• 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: [1-(1-carbamoyl-2-phenylethylcarbamoyl)-2-methylbutyl]carbamic acid tert-butyl ester
• 英文别名: Boc-Ile-Phe-NH2；tert-butyl N-[(2S,3S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamate
• CAS: 120636-88-6
• 化学式: C₂₀H₃₁N₃O₄
• 分子量: 377.484
• InChiKey: CJJOLVPFUXNOHV-BPUTZDHNSA-N

物化性质

• 沸点：
  615.6±55.0 °C(Predicted)
• 密度：
  1.108±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [1-(1-carbamoyl-2-phenylethylcarbamoyl)-2-methylbutyl]carbamic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (2S)-2-[[(2S)-2-[[16-[[(2S,3S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-16-oxohexadecanoyl]amino]-3-methylbutanoyl]amino]-3-phenylpropanoic acid
  参考文献：
  名称：

  低分子量HIV-1蛋白酶二聚抑制剂的开发。

  摘要：

  HIV蛋白酶在病毒复制中的作用使其成为重要的抑制靶标。我们研究的重点是针对HIV-1蛋白酶的二聚界面，因为二聚体的破坏会抑制酶的活性。最初的策略始于源自HIV蛋白酶界面的交联肽。在本文中，我们描述了基于HIV-1蛋白酶二聚化抑制作用的最小药效基团的试剂集中库的设计。

  DOI：

  10.1021/jm049581j
• 作为产物：
  描述：

  BOC-L-异亮氨酸 、 L-苯丙氨酰胺盐酸盐 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.17h， 以80%的产率得到[1-(1-carbamoyl-2-phenylethylcarbamoyl)-2-methylbutyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  Sidechain-linked inhibitors of HIV-1 protease dimerization

  摘要：

  There is a great need for alternative modes of inhibition for the design of anti-HIV therapies, due to the increased resistance of HIV to currently approved drugs. A novel strategy for generating potent dimerization inhibitors of HIV-1 protease is described based on sidechain-linked interfacial peptides. In a number of cases the activity of these agents against HIV-1 protease was found to be among the most potent reported, with inhibitory constants in the low nM range. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.02.060

文献信息

• Peptide Inhibitors of Aspartic Proteinases with Hydroxyethylene Isostere Replacement of Peptide Bond. II. Preparation of Pseudotetrapeptides Derived from Diastereoisomeric 5-Amino-2-benzyl-4-hydroxy-6-phenylhexanoic Acids
  作者：Jaroslav Litera、Jan Weber、Ivana Křížová、Iva Pichová、Jan Konvalinka、Martin Fusek、Milan Souček

  DOI：10.1135/cccc19980541

  日期：——

  Twelve pseudotetrapeptides, Boc-NHCH(CH₂Ph)CH(OH)CH₂CH(CH₂Ph) CO-Xaa-Phe-NH₂ 9-11, were prepared by [(benzotriazol-1-yl)oxy]tris(dimethylamino)phosphonium hexafluorophosphate-mediated couplings of diastereoisomeric O-silylated (2R or 2S,4R or 4S,5S)-2-benzyl-5-(tert-butoxycarbonyl)amino-4-hydroxy-6-phenylhexanoic acids 1 with dipeptides H-Xaa-Phe-NH₂ (Xaa = Gln, Glu(OBzl) or Ile) 3-5, followed by O-deprotection. Pseudotetrapeptides 9-11 were tested for inhibition of aspartic proteinases secreted by Candida albicans and C. tropicalis. The level of inhibition of both yeast proteinases was very low, contrasting with the nanomolar IC₅₀ values obtained for inhibition of HIV-1 proteinase.

  十二种伪四肽Boc-NHCH(CH2Ph)CH(OH)CH2CH(CH2Ph)CO-Xaa-Phe-NH2（9-11）通过[(苯并三唑-1-基氧基)三(二甲基氨基)磷酸六氟磷酸盐]介导的偶联反应制备，反应物为对映异构的O-硅烷基化(2R或2S,4R或4S,5S)-2-苄基-5-(tert-丁氧羰基)氨基-4-羟基-6-苯基己酸1与二肽H-Xaa-Phe-NH2（Xaa = 谷氨酰谷氨酸、谷氨酸(OBzl)或异亮氨酸）（3-5），然后进行O-去保护。伪四肽9-11被用于抑制由白念珠菌和热带白念珠菌分泌的天冬氨酸蛋白酶。两种酵母蛋白酶的抑制水平非常低，与抑制HIV-1蛋白酶所获得的纳摩尔IC50值形成对比。
• Renin inhibitors. Synthesis of transition-state analog inhibitors containing phosphorus acid derivatives at the scissile bond
  作者：Mark C. Allen、Walter Fuhrer、Brian Tuck、Roy Wade、Jeanette M. Wood

  DOI：10.1021/jm00127a041

  日期：1989.7

  The synthesis of five amino phosphorus derivatives, 1a-e, is described. The derivatives were incorporated into a series (18) of analogues of the 5-14 portion of angiotensinogen, in most cases at the scissile Leu-Val bond. The resultant compounds were tested in vitro for their ability to inhibit human plasma renin. Replacement of the scissile bond with the phosphinic analogue of Leu10-Val11 (1b) gave the most potent inhibitors, having IC50 = 7.5 x 10(-8) M for H-Pro-His-Pro-Phe-His-(1b)-Ile-His-Lys-OH and IC50 = 1.0 x 10(-7) M for Z-Arg-Arg-Pro-Phe-His-(1b)-Ile-His-NH2. The shorter phosphonic acid sequence Z-Pro-Phe-His-(1d) retained biological activity with an IC50 = 6.4 x 10(-6) M.
• Pseudodipeptide Inhibitors of Protein Farnesyltransferase
  作者：S. Jane deSolms、Albert A. Deana、Elizabeth A. Giuliani、Samuel L. Graham、Nancy E. Kohl、Scott D. Mosser、Allen I. Oliff、David L. Pompliano、Elaine Rands

  DOI：10.1021/jm00020a010

  日期：1995.9

  A series of pseudodipeptide amides are described that inhibit Ras protein farnesyltransferase (PFTase). These inhibitors are truncated versions of the C-terminal tetrapeptide (CAAX motif) of Ras that serves as the signal sequence for PFTase-catalyzed protein farnesylation. In contrast to CAAX peptidomimetics previously reported, these inhibitors do not have a C-terminal carboxyl moiety, yet they inhibit farnesylation in vitro at <100 nM. Despite the absence of the X residue in the CAAX motif, which normally directs prenylation specificity, these pseudodipeptides are greater than 100-fold selective for PFTase over type 1 protein geranylgeranyltransferase.
• Development of Low Molecular Weight HIV-1 Protease Dimerization Inhibitors
  作者：You Seok Hwang、Jean Chmielewski

  DOI：10.1021/jm049581j

  日期：2005.3.1

  The role of HIV protease in viral replication has made it a significant target for inhibition. The focus of our studies is to target the dimerization interface of HIV-1 protease because disruption of the dimer will inhibit enzymatic activity. The initial strategy began with cross-linked peptides derived from the interface of HIV protease. Herein we describe the design of a focused library of agents

  HIV蛋白酶在病毒复制中的作用使其成为重要的抑制靶标。我们研究的重点是针对HIV-1蛋白酶的二聚界面，因为二聚体的破坏会抑制酶的活性。最初的策略始于源自HIV蛋白酶界面的交联肽。在本文中，我们描述了基于HIV-1蛋白酶二聚化抑制作用的最小药效基团的试剂集中库的设计。
• Sidechain-linked inhibitors of HIV-1 protease dimerization
  作者：Michael J. Bowman、Jean Chmielewski

  DOI：10.1016/j.bmc.2008.02.060

  日期：2009.2

  There is a great need for alternative modes of inhibition for the design of anti-HIV therapies, due to the increased resistance of HIV to currently approved drugs. A novel strategy for generating potent dimerization inhibitors of HIV-1 protease is described based on sidechain-linked interfacial peptides. In a number of cases the activity of these agents against HIV-1 protease was found to be among the most potent reported, with inhibitory constants in the low nM range. (C) 2008 Elsevier Ltd. All rights reserved.