3-<amino>-1-bromopropane | 171858-38-1

• 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: 3-<amino>-1-bromopropane
• 英文别名: 3-[N-t-Butoxycarbonyl-(S)-isoleucinyl]amino-1-bromopropane；tert-butyl N-[(2S,3S)-1-(3-bromopropylamino)-3-methyl-1-oxopentan-2-yl]carbamate
• CAS: 171858-38-1
• 化学式: C₁₄H₂₇BrN₂O₃
• 分子量: 351.284
• InChiKey: VGOAACQCCDBLJY-QWRGUYRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-<amino>-1-bromopropane 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 生成 11-amino-7,10-dioxo-8-(1-methylpropyl)-2-oxa-6,9-diazabicyclo<11.2.2>heptadeca-13,15,16-triene
  参考文献：
  名称：

  使用新型酶结合模式抑制 HIV-1 蛋白酶的 Phe-Ile-Val 的基于底物的环状肽模拟物

  摘要：

  HIV-1 蛋白酶抑制剂的结果展示了开发肽模拟物的新策略，包括用构象受限的水解稳定大环结构模拟物替换肽底物的柔性片段。设计了一个模仿三肽 Phe-IIe-Val 的 15 元大环并将其整合到 Ac-Leu-Val-Phe-CHOHCH2-{Phe-Ile-Val}-NH2 的 C 端，一种 HIV-I 蛋白酶抑制剂源自底物序列。大环相对于无环肽的优点包括将其组分限制在其生物活性构象中并保护酰胺键免于酶促降解，该循环对酸、胃蛋白酶和血浆稳定。分子建模和 X 射线结构研究表明，环状抑制剂具有独特的酶结合模式，空间上不受限制的羟乙胺等排体通过其羟基和质子化氮与阴离子 Asp25 催化残基结合。新的大环化合物很好地叠加在线性肽抑制剂上，它被设计为结构模拟物。结构模拟导致功能模拟，如环状和非环状分子对蛋白酶的可比抑制所示。对无环 N 末端 (Leu-Val-Phe) 的进一步修饰产生了稳定的、水溶性的、有效的

  DOI：

  10.1021/ja953790z
• 作为产物：
  描述：

  BOC-L-异亮氨酸 、 3-溴丙胺氢溴酸盐 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 生成 3-<amino>-1-bromopropane
  参考文献：
  名称：

  Regioselective structural and functional mimicry of peptides. Design of hydrolytically-stable cyclic peptidomimetic inhibitors of HIV-1 protease.

  摘要：

  Hydrolytically-stable cyclic mimetics of the tripeptides Leu-Asn-Phe and Phe-Ile-Val were designed and incorporated into peptidic inhibitors, Ac-{Leu-Asn-Phe}-CHOHCH2-Pro-Ile-Val-NH2 and Ac-Leu-Val-Phe-CHOHCH2-{Phe-Ile-Val}-NH2, of HIV-1 protease. Structural mimicry has been established through molecular modeling and X-ray crystallographic studies of inhibitors bound to HIV-1 protease. Cyclic and acyclic inhibitors had similar conformations that were superimposable and formed similar interactions with the enzyme. Functional mimicry was demonstrated by comparable inhibition of the protease by acyclic and cyclic molecules. Further substitution of the residual acyclic Pro-Ile-Val or Leu-Val-Phe inhibitor components, with Pip-NHtBu or Boc-Phe, respectively, gave hydrolytically stable, water-soluble, lipophilic inhibitors of similar potency. The use of cycles to fix the conformations of amino acid sequences in peptides allows regioselective structural mimicry leading to functional mimicry and also permits localized structure-activity optimization in inhibitors of HIV-1 protease. This approach might be usefully applied to inhibitors of other proteins.

  DOI：

  10.1021/ja00146a007

文献信息

• HIV protease inhibitors
  申请人：The University of Queensland

  公开号：US06043357A1

  公开（公告）日：2000-03-28

  A HIV-1 protease inhibitor which includes a n-terminal cycle (A) or a C-terminal cycle (B) or both cycles (A) and (B) wherein Y is selected from side chains of Asn or Ilc or Val or Glu and alkyl of 1-6 carbon atoms inclusive of linear branched chains as well as cycloalkyl; and X is selected from (CH2)n where n=3-6, --CH(OH)--CH(OH)--CH2; CH(CO2H)--CH2--CH2; CH2CONHCHR where R=D or L amino acids and alkyl of 1-6 carbon atoms inclusive of linear or branched chains.

  一种HIV-1蛋白酶抑制剂，其中包括一个N-末端环（A）或一个C-末端环（B）或两个环（A）和（B），其中Y选自Asn或Ilc或Val或Glu的侧链和1-6个碳原子的直链或支链的烷基以及环烷基; X选自（CH2）n，其中n = 3-6，-CH（OH）-CH（OH）-CH2; CH（CO2H）-CH2-CH2; CH2CONHCHR，其中R = D或L氨基酸和1-6个碳原子的直链或支链的烷基。
• [EN] HIV PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE LA PROTEASE DU VIH
  申请人：THE UNIVERSITY OF QUEENSLAND

  公开号：WO1996016950A1

  公开（公告）日：1996-06-06

  (EN) A HIV-1 protease inhibitor which includes an N-terminal cycle (A) or a C-terminal cycle (B) or both cycles (A) and (B) wherein Y is selected from side chains of Asn or Ile or Val or Glu and alkyl of 1-6 carbon atoms inclusive of linear or branched chains as well as cycloalkyl; and X is selected from (CH2)n where n = 3-6, -CH(OH)-CH(OH)-CH2-, CH(CO2H)-CH2-CH2, CH2CONHCHR where R = D or L amino acids and alkyl of 1-6 carbon atoms inclusive of linear or branched chains.(FR) L'invention concerne un inhibiteur de la protéase du VIH-1 comprenant un cycle N-terminal ayant la formule (A) ou un cycle C-terminal ayant la formule (B), ou encore les deux. Dans ces formules, Y est choisi parmi des chaînes latérales d'Asn, d'Ile, de Val ou de Glu et alkyle à 1-6 atomes de carbone linéaire, ramifié ou cyclique, X est choisi parmi (CH2)n, où n = 3-6, -CH(OH)-CH(OH)-CH2-, CH(CO2H)-CH2-CH2, CH2CONHCHR où R est un acide aminé D ou L ou un alkyle à 1-6 atomes de carbone linéaire ou ramifié.

  一种 HIV-1 蛋白酶抑制剂，包含 N端循环（A）或 C端循环（B）或两者，其中 Y 是丝氨酸、色氨酸、丙氨酸或谷氨酸的侧链，选自 1-6 个碳原子的烷基（包括直链、分支链或环烷基）；X 是选自（CH2)n（此处，n = 3-6），-CH(OH)-CH(OH)-CH2-，CH(CO2H)-CH2-CH2，CH2CONHCHR，其中 R 是 L 或 D 赝氨酸以及 1-6 个碳原子的烷基（直链或分支链）。
• US6043357A
  申请人：——

  公开号：US6043357A

  公开（公告）日：2000-03-28
• Regioselective structural and functional mimicry of peptides. Design of hydrolytically-stable cyclic peptidomimetic inhibitors of HIV-1 protease.
  作者：G. Abbenante、D. R. March、D. A. Bergman、P. A. Hunt、B. Garnham、R. J. Dancer、J. L. Martin、D. P. Fairlie

  DOI：10.1021/ja00146a007

  日期：1995.10

  Hydrolytically-stable cyclic mimetics of the tripeptides Leu-Asn-Phe and Phe-Ile-Val were designed and incorporated into peptidic inhibitors, Ac-Leu-Asn-Phe}-CHOHCH2-Pro-Ile-Val-NH2 and Ac-Leu-Val-Phe-CHOHCH2-Phe-Ile-Val}-NH2, of HIV-1 protease. Structural mimicry has been established through molecular modeling and X-ray crystallographic studies of inhibitors bound to HIV-1 protease. Cyclic and acyclic inhibitors had similar conformations that were superimposable and formed similar interactions with the enzyme. Functional mimicry was demonstrated by comparable inhibition of the protease by acyclic and cyclic molecules. Further substitution of the residual acyclic Pro-Ile-Val or Leu-Val-Phe inhibitor components, with Pip-NHtBu or Boc-Phe, respectively, gave hydrolytically stable, water-soluble, lipophilic inhibitors of similar potency. The use of cycles to fix the conformations of amino acid sequences in peptides allows regioselective structural mimicry leading to functional mimicry and also permits localized structure-activity optimization in inhibitors of HIV-1 protease. This approach might be usefully applied to inhibitors of other proteins.
• Substrate-Based Cyclic Peptidomimetics of Phe-Ile-Val That Inhibit HIV-1 Protease Using a Novel Enzyme-Binding Mode
  作者：Darren R. March、Giovanni Abbenante、Douglas A. Bergman、Ross I. Brinkworth、Wasantha Wickramasinghe、Jake Begun、Jennifer L. Martin、David P. Fairlie

  DOI：10.1021/ja953790z

  日期：1996.1.1

  catalytic residues. The novel macrocycle superimposes well on the linear peptidic inhibitor for which it was designed as a structural mimic. Structural mimicry led to functional mimicry as shown by comparable inhibition of the protease by cyclic and acyclic molecules. Further modification of the acyclic N-terminus (Leu-Val-Phe) gave stable, water-soluble, potent inhibitors of HIV-1 protease. This approach

  HIV-1 蛋白酶抑制剂的结果展示了开发肽模拟物的新策略，包括用构象受限的水解稳定大环结构模拟物替换肽底物的柔性片段。设计了一个模仿三肽 Phe-IIe-Val 的 15 元大环并将其整合到 Ac-Leu-Val-Phe-CHOHCH2-Phe-Ile-Val}-NH2 的 C 端，一种 HIV-I 蛋白酶抑制剂源自底物序列。大环相对于无环肽的优点包括将其组分限制在其生物活性构象中并保护酰胺键免于酶促降解，该循环对酸、胃蛋白酶和血浆稳定。分子建模和 X 射线结构研究表明，环状抑制剂具有独特的酶结合模式，空间上不受限制的羟乙胺等排体通过其羟基和质子化氮与阴离子 Asp25 催化残基结合。新的大环化合物很好地叠加在线性肽抑制剂上，它被设计为结构模拟物。结构模拟导致功能模拟，如环状和非环状分子对蛋白酶的可比抑制所示。对无环 N 末端 (Leu-Val-Phe) 的进一步修饰产生了稳定的、水溶性的、有效的