3-amino-3-(4-methylphenyl)propionic acid methyl ester | 198959-38-5

• 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: 3-amino-3-(4-methylphenyl)propionic acid methyl ester
• 英文别名: methyl 3-amino-3-(4-tolyl)propionate；Methyl 3-amino-3-(4-methylphenyl)propanoate
• CAS: 198959-38-5
• 化学式: C₁₁H₁₅NO₂
• mdl: MFCD06200592
• 分子量: 193.246
• InChiKey: PNLNOOURNGVKGL-UHFFFAOYSA-N

物化性质

• 沸点：
  302.7±30.0 °C(Predicted)
• 密度：
  1.076±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-amino-3-(4-methylphenyl)propionic acid methyl ester 在 盐酸 、 异丁基硼酸 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 、 sodium hydroxide 作用下， 以 甲醇 、 四氯化碳 、 正己烷 、 二氯甲烷 、 水 、 丙酮 为溶剂， 生成 (R)-1-[3-benzamido-3-(4-methylphenyl)propanamido]-3-methylbutyl boronic acid
  参考文献：
  名称：

  Synthesis, in Vitro and in Vivo Biological Evaluation, and Comprehensive Understanding of Structure−Activity Relationships of Dipeptidyl Boronic Acid Proteasome Inhibitors Constructed from β-Amino Acids

  摘要：

  An extensive structure-activity relationship (SAR) study of 72 dipeptidyl boronic acid proteasome inhibitors constructed from beta-amino acids is reported. SAR analysis revealed that bicyclic groups at the RI position, 3-F substituents at the R-2 position, and bulky aliphatic groups at the R-3 position were favorable to the activities. Enzymatic screening results showed that compound 78, comprising all of these features, was the most active inhibitor against the 20S human proteasome at less than a 2 nM level, as active as the marketed drug bortezomib. Cellular assays confirmed that compound 78 was the most potent against two hematologic and some solid tumor cells with IC50 values less than 1 mu M. Pharmacokinetic profiles suggested that 78 showed higher plasma exposure and a longer half-life than bortezomib.

  DOI：

  10.1021/jm1009742
• 作为产物：
  描述：

  对甲基苯甲醛 在 氯化亚砜 、 ammonium acetate 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 3-amino-3-(4-methylphenyl)propionic acid methyl ester
  参考文献：
  名称：

  Synthesis and biological evaluation of 3-phenyl-3-aryl carboxamido propanoic acid derivatives as small molecule inhibitors of retinoic acid 4-hydroxylase (CYP26A1)

  摘要：

  All-trans-retinoic acid (ATRA), the biologically active metabolite of vitamin A, is used medicinally for the treatment of hyperproliferative diseases and cancers. However, it is easily metabolized. In this study, the leading compound S8 was found based on virtual screening. To improve the activity of the leading compound S8, a series of novel S8 derivatives were designed, synthesized and evaluated for their in vitro biological activities.All of the prepared compounds showed that substituting the 5-chloro-3-methyl-1-phenyl-1H-pyrazole group for the 2-tertbutyl-5-methylfuran scaffold led to a clear increase in the biological activity. The most promising compound 32, with a CYP26A1 IC50 value of 1.36 mu M (compared to liarozole (IC50 = 2.45 mu M) and S8 (IC50 = 3.21 mu M)) displayed strong inhibitory and differentiation activity against HL60 cells. In addition, the study focused on the effect of beta-phenylalanine, which forms the coordination bond with the heme of CYP26A1. These studies suggest that the compound 32 can be used as an appropriate candidate for future development. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.11.036

文献信息

• Stereoselective Chemoenzymatic Preparation of β-Amino Esters: Molecular Modelling Considerations in Lipase-Mediated Processes and Application to the Synthesis of (<i>S</i>)-Dapoxetine
  作者：María Rodríguez-Mata、Eduardo García-Urdiales、Vicente Gotor-Fernández、Vicente Gotor

  DOI：10.1002/adsc.200900676

  日期：2010.2.15

  the kinetic resolution of the corresponding β-amino esters. Although the enzymatic acylations of the amino group with ethyl methoxyacetate showed synthetically useful enantioselectivities, the hydrolyses of the ester group catalyzed by lipase from Pseudomonas cepacia have been identified as the optimal processes concerning both activity and enantioselectivity. The enantiopreference of this lipase in these

  已经通过立体选择性化学酶法制备了多种旋光的3-氨基-3-芳基丙酸衍生物。关键步骤是相应的β-氨基酯的动力学拆分。尽管氨基用甲氧基乙酸乙酯的酶促酰化显示了合成上有用的对映选择性，但是已经鉴定出由洋葱假单胞菌的脂肪酶催化的酯基的水解是关于活性和对映选择性的最佳方法。在分子水平上，已通过使用基于片段的方法解释了这些脂​​肪酶在这些反应中的对映体优先性，其中最有利的苯环结合位点和最稳定的3-氨基丙酸酯核心构象与（小号）-主要产品的配置。为了理解苯环中存在的不同取代模式的影响，已经比较了酶促反应的转化率和对映选择性值。该化学酶途径已成功地用于制备（S）-达泊西汀合成中的有价值的中间体，该中间体已经以优异的光学纯度化学合成。
• Carboxylic Acid O–H Insertion Reaction of β-Ester Diazos Enabling Synthesis of β-Acyloxy Esters
  作者：Ziyi Li、Xinyu Yao、Xin Zhang、Haibo Mei、Jianlin Han

  DOI：10.1021/acs.joc.2c02023

  日期：2022.11.18

  β-ester diazos and their applications in carboxylic acid O–H insertion reactions have been reported, which afford β-acyloxy esters in excellent yield. Varieties of aryl- and alkyl-substituted diazos are well tolerated in this insertion reaction under mild and convenient conditions. Moreover, structural modification of the natural product and molecular drug can also be achieved in this reaction. This

  已经报道了非稳定化 β-酯重氮化合物的生成及其在羧酸 O-H 插入反应中的应用，从而以优异的收率提供 β-酰氧基酯。在温和方便的条件下，在此插入反应中可以很好地耐受各种芳基和烷基取代的重氮化合物。此外，该反应还可以实现天然产物和分子药物的结构修饰。该方案不仅实现了涉及不稳定β-酯重氮的反应，而且为合成β-酰氧基酯提供了一种有效的策略。
• <i>N</i>-Arylation of Amino Acid Esters via an I₂-Mediated Metal-Free Multicomponent Benzannulation Strategy
  作者：Wenbo Huang、Xiaofeng Rao、Liqiao Shi、Bing Yang、Buxiao Kuang、Hongqu Wu、Shaoyong Ke、Changhui Liu

  DOI：10.1021/acs.joc.3c01907

  日期：2023.12.1

  Herein, we present a novel method for the N-arylation of amino acid esters using α-bromoacetaldehyde acetal and acetoacetate via an I2-mediated metal-free benzannulation strategy, which disclosed the first synthetic application of N-arylation of amino acids using nonaromatic building blocks. The synthesized N-arylated amino acid derivatives were found to possess promising selective inhibition against human

  在此，我们提出了一种使用α-溴乙醛缩醛和乙酰乙酸酯通过I 2介导的无金属苯并环化策略对氨基酸酯进行N-芳基化的新方法，该方法首次公开了使用非芳香族化合物对氨基酸进行N-芳基化的合成应用。建筑模块。合成的N-芳基化氨基酸衍生物对人肝癌细胞、人黑色素瘤细胞和人正常肝细胞具有良好的选择性抑制作用，IC 50值低至16.79 μg·mL –1 。
• Carboxamide derivatives of pyrrolidine, piperidine and hexahydroazepine for the treatment of thrombosis disorders
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1184374B1

  公开（公告）日：2009-01-28
• Derivatives of tetrahydroisoquinoline: Synthesis and initial evaluation of novel non-peptide antagonists of the αIIbβ3-integrin
  作者：Andrei A. Krysko、Olga L. Krysko、Tatyana A. Kabanova、Sergei A. Andronati、Vladimir M. Kabanov

  DOI：10.1016/j.bmcl.2010.06.051

  日期：2010.8

  The novel RGDF mimetics were synthesized with the use of 4-(1,2,3,4-tetrahydroisoquinoline-7-yl)amino- 4-oxobutyric or 5-(1,2,3,4-tetrahydroisoquinoline-7-yl)amino-5-oxopentanoic acids as a surrogate of Arg-Gly motif. The synthesized compounds have demonstrated a high potency to inhibit platelet aggregation in vitro and to block FITC-Fg binding to alpha(IIb)beta(3) on washed human platelets. (C) 2010 Elsevier Ltd. All rights reserved.