((cyclohexyloxy)carbonyl)-1-leucine | 3309-47-5

• 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: ((cyclohexyloxy)carbonyl)-1-leucine
• 英文别名: (2S)-2-(cyclohexyloxycarbonylamino)-4-methylpentanoic acid
• CAS: 3309-47-5
• 化学式: C₁₃H₂₃NO₄
• 分子量: 257.33
• InChiKey: SRBFBUWTOMWUGE-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ((cyclohexyloxy)carbonyl)-1-leucine 在 甲醇 、 锂硼氢 、 戴斯-马丁氧化剂 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.5h， 生成 cyclohexyl ((S)-4-methyl-1-oxo-1-(((S)-1-oxo-3-((S)-2-oxopyrrolidin-3-yl)propan-2-yl)amino)pentan-2-yl)carbamate
  参考文献：
  名称：

  [EN] BROAD SPECTRUM ANTIVIRALS AGAINST CORONAVIRUS
  [FR] ANTIVIRAUX À LARGE SPECTRE CONTRE LE CORONAVIRUS

  摘要：

  显示抗病毒活性和/或针对病毒复制的抑制作用的化合物，特别是属于类似小核糖病毒超簇的病毒，包括具有以下结构的冠状病毒：（I），其中X包括一个环状基团，R2是支链或非支链烷基，环烷基，芳基，芳基烷基，烯基，炔基，氨基酸侧链，双环或三环侧链，它们的组合和取代形式，Z选自羟基烷基，醛，α-酮胺和亚硫酸盐等物种组成的群体，特别是-CH2OH，-CHO，-CH(0H)S03-Na+，以及-[0(C=0)Rw]S03-Na+。

  公开号：

  WO2021202460A1
• 作为产物：
  描述：

  (S)-(-)-2-异氰酰基-4-甲基戊酸甲酯 在 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 5.0h， 生成 ((cyclohexyloxy)carbonyl)-1-leucine
  参考文献：
  名称：

  [EN] BROAD SPECTRUM ANTIVIRALS AGAINST CORONAVIRUS
  [FR] ANTIVIRAUX À LARGE SPECTRE CONTRE LE CORONAVIRUS

  摘要：

  显示抗病毒活性和/或针对病毒复制的抑制作用的化合物，特别是属于类似小核糖病毒超簇的病毒，包括具有以下结构的冠状病毒：（I），其中X包括一个环状基团，R2是支链或非支链烷基，环烷基，芳基，芳基烷基，烯基，炔基，氨基酸侧链，双环或三环侧链，它们的组合和取代形式，Z选自羟基烷基，醛，α-酮胺和亚硫酸盐等物种组成的群体，特别是-CH2OH，-CHO，-CH(0H)S03-Na+，以及-[0(C=0)Rw]S03-Na+。

  公开号：

  WO2021202460A1

文献信息

• Cyclohexyloxycarbonyl based orthogonal solid phase peptide synthesis in Boc chemistry
  作者：Gábor Mezö、Nikolett Mihala、György Kóczán、Ferenc Hudecz

  DOI：10.1016/s0040-4020(98)00360-3

  日期：1998.6

  Application of N-cyclohexyloxycarbonyl (Choc) protection in Boc chemistry on solid phase provides a new possibility for the preparation of protected peptide fragments. A Choc/OcHex protection scheme allows also the assembly of cyclic lactam peptides linked to the resin through the C-terminus. Choc protection is stable under the 1M TMSOTf-thioanisole/TFA cleavage condition at 0 degrees C, but it is removable by anhydrous HF. We have utilized cyclohexyloxycarbonyl as an orthogonal protecting group for the synthesis of a i) bicyclic epitope peptide of glycoprotein D of HSV 1 on BHA resin and ii) fully protected hexapeptide involved in protein transport on Merrifield resin. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.
• Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 2. Peptide Structure−Activity Studies
  作者：Peter S. Dragovich、Stephen E. Webber、Robert E. Babine、Shella A. Fuhrman、Amy K. Patick、David A. Matthews、Siegfried H. Reich、Joseph T. Marakovits、Thomas J. Prins、Ru Zhou、Jayashree Tikhe、Ethel S. Littlefield、Ted M. Bleckman、Michael B. Wallace、Thomas L. Little、Clifford E. Ford、James W. Meador、Rose Ann Ferre、Edward L. Brown、Susan L. Binford、Dorothy M. DeLisle、Stephen T. Worland

  DOI：10.1021/jm9800696

  日期：1998.7.1

  The structure-based design, chemical synthesis, and biological evaluation of various peptide-derived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds are comprised of an ethyl propenoate Michael acceptor moiety and a tripeptidyl binding determinant. The systematic modification of each amino acid residue present in the binding determinant as well as the N-terminal functionality is described. Such modifications are shown to provide irreversible HRV-14 3CP inhibitors with anti-3CP activities (k(obs)/[I]) ranging from 60 to 280 000 M-1 s(-1) and antiviral EC50's which approach 0.15 mu M. An optimized inhibitor which incorporates several improvements identified by the structure-activity studies is also described. This molecule displays very rapid irreversible inhibition of HRV-14 3CP (k(obs)/[I] = 800 000 M-1 s(-1)) and potent antiviral activity against HRV-14 in cell culture (EC50 = 0.056 mu M). A 1.9 Angstrom crystal structure of an S-alkylthiocarbamate-containing inhibitor complexed with HRV-8 3CP is also detailed.
• Azole Endothelin Antagonists. 3. Using Δ log <i>P</i> as a Tool To Improve Absorption
  作者：Thomas W. von Geldern、Daniel J. Hoffman、Jeffrey A. Kester、Hugh N. Nellans、Brian D. Dayton、Samuel V. Calzadilla、Kennan C. Marsh、Lisa Hernandez、William Chiou、Douglas B. Dixon、Jinshyun R. Wu-Wong、Terry J. Opgenorth

  DOI：10.1021/jm9505932

  日期：1996.1.1

  The oral absorption profile of a family of azole-based ET(A)-selective antagonists has been improved through a rational series of structural modifications which were suggested by analysis of the physicochemical parameter Delta log P. Comparison of urea 2 with a series of well-absorbed compounds using Delta log P analysis suggested that 2 has an excess capacity for forming hydrogen bonds with solvent. A series of urea modifications were explored as a means of reducing H-bonding capacity while maintaining affinity for the ET(A)-receptor. The correlation between Delta log P values and absorption in an intraduodenal (id) bioavailability model was good; this strategy uncovered replacements for each of the urea NH groups which simultaneously improve both potency and drug absorption. A combination of these optimized modifications produces carbamate 16h, a highly-selective ET(A) antagonist with a potency/bioavailability profile consistent with an oral route of administration.