N-(3-phenylpropionyl)-L-phenylalanine methyl ester | 21888-31-3

• 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: N-(3-phenylpropionyl)-L-phenylalanine methyl ester
• 英文别名: 3-phenyl-2-(3-phenylpropionylamino)propionic acid methyl ester；(S)-3-Phenyl-2-(3-phenyl-propionylamino)-propionic acid methyl ester；methyl (2S)-3-phenyl-2-(3-phenylpropanoylamino)propanoate
• CAS: 21888-31-3
• 化学式: C₁₉H₂₁NO₃
• 分子量: 311.381
• InChiKey: ITMGOEJLSLAEDI-KRWDZBQOSA-N

物化性质

• 熔点：
  70-71.5 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  507.0±45.0 °C(Predicted)
• 密度：
  1.131±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-phenylpropionyl)-L-phenylalanine methyl ester 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 0.33h， 生成 beta-苯基丙酰-L-苯丙氨酸
  参考文献：
  名称：

  α-Ketoamides as Broad-Spectrum Inhibitors of Coronavirus and Enterovirus Replication: Structure-Based Design, Synthesis, and Activity Assessment

  摘要：

  The main protease of coronaviruses and the 3C protease of enteroviruses share a similar active-site architecture and a unique requirement for glutamine in the P1 position of the substrate. Because of their unique specificity and essential role in viral polyprotein processing, these proteases are suitable targets for the development of antiviral drugs. In order to obtain near-equipotent, broad-spectrum antivirals against alphacoronaviruses, betacoronaviruses, and enteroviruses, we pursued a structure-based design of peptidomimetic alpha-ketoamides as inhibitors of main and 3C proteases. Six crystal structures of protease-inhibitor complexes were determined as part of this study. Compounds synthesized were tested against the recombinant proteases as well as in viral replicons and virus-infected cell cultures; most of them were not cell-toxic. Optimization of the P2 substituent of the alpha-ketoamides proved crucial for achieving near-equipotency against the three virus genera. The best near-equipotent inhibitors, 11u (P2 = cyclopentylmethyl) and 11r (P2 = cyclo-hexylmethyl), display low-micromolar EC50 values against enteroviruses, alphacoronaviruses, and betacoronaviruses in cell cultures. In Huh7 cells, 11r exhibits three-digit picomolar activity against the Middle East Respiratory Syndrome coronavirus.

  DOI：

  10.1021/acs.jmedchem.9b01828
• 作为产物：
  描述：

  L-苯丙氨酸甲酯盐酸盐 、 3-苯基丙酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以81%的产率得到N-(3-phenylpropionyl)-L-phenylalanine methyl ester
  参考文献：
  名称：

  Inhibition of Peptidylglycine .alpha.-Amidating Monooxygenase by N-Substituted Homocysteine Analogs

  摘要：

  C-terminal amidation is a posttranslational modification found in many neuropeptides. Peptidylglycine cl-amidating monooxygenase (PAM) catalyzes the synthesis of the biologically essential C-terminal amide from a glycine-extended precursor peptide. Reported herein are the first potent inhibitors of PAM. Dipeptides containing a C-terminal homocysteine and an N-acylated hydrophobic amino acid were found to inhibit PAM with IC(50)s in the low nanomolar range. Inhibition potency was dependent on both the carboxylate and the thiolate functionalities of the homocysteine and on the hydrophobic groups of the second amino acid. The thiolate was postulated to produce high binding affinities through coordination with the active-site copper. The compound series also exhibited potent inhibition of PAM in rat dorsal root ganglion cells as demonstrated by a dose-dependent increase in the substance P-Gly/substance P ratio. These results indicate that the compounds have sufficient potency and intracellular bioavailability to aid future studies focused on neuropeptide function and the contributions of neuropeptides to various disease processes.

  DOI：

  10.1021/jm00052a002

文献信息

• Mechanistic studies of DCC/HOBt-mediated reaction of 3-phenylpropionic acid with benzyl alcohol and studies on the reactivities of ‘active ester’ and the related derivatives with nucleophiles
  作者：Md. Chanmiya Sheikh、Shunsuke Takagi、Toshiaki Yoshimura、Hiroyuki Morita

  DOI：10.1016/j.tet.2010.07.011

  日期：2010.9

  extensive study for peptide synthesis, DCC-mediated esterification is left still unclear. Therefore, DCC- and DCC/HOBt-mediated reactions of 3-phenylpropionic acid (1) with benzyl alcohol were carried out under several mechanistic considerations. Further, in order to determine the reactivities of the so-called ‘active esters’ compounds changing the substituents bearing carbonyl and related derivatives group

  尽管对肽合成进行了广泛的研究，但DCC介导的酯化反应仍不清楚。因此，在多种机理上考虑了进行3-苯基丙酸（1）与苯甲醇的DCC和DCC / HOBt介导的反应。此外，为了确定新的“非对称交联剂”的开发目的，为了确定改变带有羰基和相关衍生物基团的取代基的所谓“活性酯”化合物的反应性，我们研究了模型化合物，N-（3-苯基丙酰氧基）苯并三唑（6），N-（3-苯基丙酰氧基）苯邻二甲酰亚胺（7），3-苯基丙酰氧基苯并噻唑（8）和进行N-（3-苯基丙酰基）苯并三唑（9）与各种亲核试剂在相似条件下的比较。它显示出具有6 >> 8 > 9 > 7的顺序。
• PHENYL-CONTAINING N-ACYL AMINE AND AMINOACID DERIVATIVES, METHODS FOR THE PRODUCTION THEREOF, A PHARMACEUTICAL COMPOSITION AND THE USE THEREOF
  申请人：Obschestvo S Ogranichennoi Otvetstennostiyu "Pharmenterprises"

  公开号：EP1876169A1

  公开（公告）日：2008-01-09

  The present invention relates to novel phenyl-N-acyl derivatives of biogenic amines and amino acids of general formula (I) as cyclooxynease inhibitors, possessing analgetic and anti-inflammatory properties and devoid of side effects in particular ulcerogeneity and pro-spasmodic actions, as well as capability to potentiate effect of other analgetics, and possessing in addition antihypoxic, antidepressant and anti-Parkinsonistic action; as well as to the processes for the preparation novel and known phenyl-N-acyl derivatives of biogenic amines, to a pharmaceutical composition and to an agent comprising compounds of general formula (I) as well as to use thereof and a method of treating.

  本发明涉及作为环氧化酶抑制剂的通式（I）生物胺和氨基酸的新型苯基-N-酰基衍生物，该衍生物具有镇痛和抗炎特性，无副作用，特别是无溃疡性和促痉挛作用，并能增强其他镇痛药的效果，此外还具有抗缺氧、抗抑郁和抗帕金森病作用；以及生物胺的新型和已知苯基-N-酰基衍生物的制备工艺、药物组合物和包含通式（I）化合物的制剂及其用途和治疗方法。
• Design, synthesis and SAR studies of tripeptide analogs with the scaffold 3-phenylpropane-1,2-diamine as aminopeptidase N/CD13 inhibitors
  作者：Luqing Shang、Hao Fang、Huawei Zhu、Xuejian Wang、Qiang Wang、Jiajia Mu、Binghe Wang、Shiroh Kishioka、Wenfang Xu

  DOI：10.1016/j.bmc.2009.02.034

  日期：2009.4

  Aminopeptidase N (APN), belonged to metalloproteinase, is an essential peptidase involved in the process of tumor invasion and metastasis. A series of tripeptide analogs with the scaffold 3-phenylpropane-1,2-diamine were designed, synthesized and evaluated for their ability to inhibit APN. Preliminary activity evaluation showed that most of target compounds possessed potent inhibitory activities against APN. With in this series, compound A6 and B6 exhibited good potency with the IC50 values of 8.8 +/- 1.3 mu M and 8.6 +/- 1.1 mu M, respectively. (c) 2009 Elsevier Ltd. All rights reserved.
• Davies, John S.; Merritt, Raymond K.; Treadgold, Richard C., Journal of the Chemical Society. Perkin transactions I, 1982, # 12, p. 2939 - 2948
  作者：Davies, John S.、Merritt, Raymond K.、Treadgold, Richard C.、Morley, John S.

  DOI：——

  日期：——
• Phenyl-containing n-acyl amine and aminoacid derivatives, methods for the production thereof, a pharmaceutical composition and the use thereof
  申请人：Nebolsin Vladimir Evgenievich

  公开号：US20090111874A1

  公开（公告）日：2009-04-30

  The present invention relates to novel phenyl-N-acyl derivatives of biogenic amines and amino acids of general formula (I) as cyclooxynease inhibitors, possessing analgetic and anti-inflammatory properties and devoid of side effects in particular ulcerogeneity and pro-spasmodic actions, as well as capability to potentiate effect of other analgetics, and possessing in addition antihypoxic, antidepressant and anti-Parkinsonistic action; as well as to the processes for the preparation novel and known phenyl-N-acyl derivatives of biogenic amines, to a pharmaceutical composition and to an agent comprising compounds of general formula (I) as well as to use thereof and a method of treating.