ethyl (R)-4-((tert-butoxycarbonyl)amino)-5-phenylpentanoate | 368870-66-0

• 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: ethyl (R)-4-((tert-butoxycarbonyl)amino)-5-phenylpentanoate
• 英文别名: ethyl (4R)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-phenylpentanoate
• CAS: 368870-66-0
• 化学式: C₁₈H₂₇NO₄
• 分子量: 321.417
• InChiKey: VTNMBJFMLIWRJC-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (R)-4-((tert-butoxycarbonyl)amino)-5-phenylpentanoate 在 palladium dihydroxide 4-二甲氨基吡啶 、 sodium hydroxide 、 2,4,6-三氯苯甲酰氯 、 氢气 、 sodium hydride 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 2.0h， 生成 (2S,5R,10R,11S)-5-Benzyl-10-heptyl-2-isopropyl-4,11-dimethyl-1,9-dioxa-4-aza-cyclododecane-3,8,12-trione
  参考文献：
  名称：

  碱性磷酸酶和类似物作为MDR逆转剂的合成和评估。

  摘要：

  制备了掺入系统取代基缺失或变异的海洋天然产物哈帕洛辛和22种类似物。在基于细胞的分析中评估了这些化合物的MDR逆转活性和一般的细胞毒性。一些取代基修饰导致较低的细胞毒性，但大多数结构变化对MDR逆转活性有害或没有严重改变。

  DOI：

  10.1016/s0960-894x(99)00243-7
• 作为产物：
  描述：

  N-叔丁氧羰基-L-苯丙氨酸甲酯 在 palladium 10% on activated carbon 、 氢气 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 环己烷 为溶剂， -80.0~20.0 ℃ 、206.85 kPa 条件下， 反应 5.75h， 生成 ethyl (R)-4-((tert-butoxycarbonyl)amino)-5-phenylpentanoate
  参考文献：
  名称：

  Antiplasmodial activity of new 4-aminoquinoline derivatives against chloroquine resistant strain

  摘要：

  Emergence and spread of multidrug resistant strains of Plasmodium falciparum has severely limited the antimalarial chemotherapeutic options. In order to overcome the obstacle, a set of new side-chain modified 4-aminoquinolines were synthesized and screened against chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of P. falciparum. The key feature of the designed molecules is the use of methylpiperazine linked α, β(3)- and γ-amino acids to generate novel side chain modified 4-aminoquinoline analogues. Among the evaluated compounds, 20c and 30 were found more potent than CQ against K1 and displayed a four-fold and a three-fold higher activity respectively, with a good selectivity index (SI=5846 and 11,350). All synthesized compounds had resistance index between 1.06 and >14.13 as against 47.2 for chloroquine. Biophysical studies suggested that this series of compounds act on heme polymerization target.

  DOI：

  10.1016/j.bmc.2014.05.024

文献信息

• Structure‐Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2
  作者：Anders Højgaard Hansen、Henriette B. Christensen、Sunil K. Pandey、Eugenia Sergeev、Alice Valentini、Julia Dunlop、Domonkos Dedeo、Simone Fratta、Brian D. Hudson、Graeme Milligan、Trond Ulven、Elisabeth Rexen Ulven

  DOI：10.1002/cmdc.202100356

  日期：2021.11.5

  Antagonist as the hero: The short-chain fatty acid receptor FFA2 is a promising drug target for metabolic and inflammatory diseases. Herein we present the SAR exploration of an antagonist series, leading to the discovery of a more potent antagonist with favorable solubility and pharmacokinetic properties.

  拮抗剂为英雄：短链脂肪酸受体 FFA2 是一种很有前途的代谢和炎症疾病的药物靶点。在这里，我们介绍了拮抗剂系列的 SAR 探索，从而发现了一种更有效的拮抗剂，具有良好的溶解度和药代动力学特性。
• Structure−Activity Relationships of 6-Methyl-benzo[<i>b</i>]thiophene-2-carboxylic Acid (1-{(<i>S</i>)-1-Benzyl-4-[4-(tetrahydropyran-4-ylmethyl)piperazin-1-yl]butylcarbamoyl}cyclopentyl)amide, Potent Antagonist of the Neurokinin-2 Receptor
  作者：Daniela Fattori、Marina Porcelloni、Piero D’Andrea、Rose-Marie Catalioto、Alessandro Ettorre、Sandro Giuliani、Elena Marastoni、Sandro Mauro、Stefania Meini、Cristina Rossi、Maria Altamura、Carlo A. Maggi

  DOI：10.1021/jm100176s

  日期：2010.5.27

  As part of a project aimed at the identification of a series of small, orally available antagonists for the hNK(2) receptor, starting from one of our capped dipeptide libraries, we succeeded in the chemical optimization of the first identified leads, finally producing a class of molecules with significant activity in our animal model after iv administration. We herein report the results of further chemical modifications made to reduce the overall peptide character of this series and the consequent improvement of their in vivo antagonist activity. The present work identified 6-methylbenzo[b]thiophene-2-carboxylic acid (1-(S)-1-benzyl-4-[4-(tetrahydropyran-4-ylmethyl)piperazin-1-yl]butylcarbamoyl}cyclopentyl)amide (10i), endowed with subnanomolar potency in all the in vitro tests and being highly potent and of long duration upon in vivo testing after both iv and id dosing.
• Consequence of Hapten Stereochemistry: An Efficacious Methamphetamine Vaccine
  作者：Margaret E. Olson、Takashi Sugane、Bin Zhou、Kim D. Janda

  DOI：10.1021/jacs.9b07294

  日期：2019.9.11

  Recent trends in methamphetamine (METH) misuse and overdose suggest society is inadvertently overlooking a brewing METH crisis. In the past decade, psychostimulant-related lethal overdoses and hospitalizations have skyrocketed 127 and 245%, respectively. Unlike the opioid crisis, no pharmaceutical interventions are available for treating METH use disorder or reversing overdose. Herein, we report the first active vaccine that offers protection from lethal (+)-METH challenge in male Swiss Webster mice. This vaccine formulation of (S)MLMH-TT adjuvanted with CpG ODN 1826 + alum successfully raised anti-METH antibodies in high titers, reduced (+)-METH distribution to the brain, and lowered (+)-METH-associated stereotypies in a hyperlocomotion assay. A comparison of enantiomeric haptens and the racemate elucidated the importance of employing (S)-stereochemistry in METH hapten design for optimal protection.