3-氨基-3-(4-叔丁基苯基)丙酸 | 282524-82-7

• 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
• 中文名称: 3-氨基-3-(4-叔丁基苯基)丙酸
• 英文名称: (RS)-3-amino-3-(4-tert-butylphenyl)propionic acid
• 英文别名: 3-amino-3-(4-(tert-butyl)phenyl)propanoic acid；3-amino-3-(4-tert-butylphenyl)propionic acid；3-amino-4,4-dimethyl-pentanoic acid；3-Azaniumyl-3-(4-tert-butylphenyl)propanoate
• CAS: 282524-82-7
• 化学式: C₁₃H₁₉NO₂
• mdl: MFCD02153019
• 分子量: 221.299
• InChiKey: QVTSIUCKEVJNGO-UHFFFAOYSA-N

物化性质

• 熔点：
  240-242°C
• 沸点：
  352.2±30.0 °C(Predicted)
• 密度：
  1.082±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.461
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2922499990

反应信息

• 作为反应物：
  描述：

  3-氨基-3-(4-叔丁基苯基)丙酸 在 氯化亚砜 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 3-[(5-tert-butyl-2-methyl-1-propyl-1H-pyrrole-3-carbonyl)amino]-3-(4-tert-butylphenyl)propionic acid
  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
• 作为产物：
  描述：

  DL-4-叔丁基苯丙氨酸 在 phenylalanine aminomutase 作用下， 反应 2.0h， 生成 3-氨基-3-(4-叔丁基苯基)丙酸
  参考文献：
  名称：

  β-Styryl- and β-Aryl-β-alanine Products of Phenylalanine Aminomutase Catalysis

  摘要：

  The substrate specificity of a Taxus-derived phenylalanine aminomutase (PAM) was investigated, and the enzyme was found to catalyze the conversion of variously substituted vinyl- and aryl-S-alpha-alanines to corresponding beta-amino acids. This study shows the broad substrate specificity of PAM and thus demonstrates a potential, practical biosynthetic route toward unnatural beta-amino acid subunits of Taxol analogues and beta-peptides.

  DOI：

  10.1021/ja071328w

文献信息

• Design, synthesis and structure-activity relationship of a focused library of β-phenylalanine derivatives as novel eEF2K inhibitors with apoptosis-inducing mechanisms in breast cancer
  作者：Yongzhi Guo、Yuqian Zhao、Guan Wang、Yi Chen、Yingnan Jiang、Liang Ouyang、Bo Liu

  DOI：10.1016/j.ejmech.2017.11.065

  日期：2018.1

  many types of cancer; therefore, eEF2K would be regarded as a promising therapeutic target. In this study, we discovered a β-phenylalanine scaffold by virtual high-throughput screening, as well as designed and synthesized 46 derivatives with assessment of inhibition activity against eEF2K and cytotoxicity. After several rounds of kinase and anti-proliferative activity screening, we discovered an eEF2K

  真核延伸因子2激酶（eEF2K）是一种Ca2 + /钙调蛋白依赖性蛋白激酶，属于非典型Ser / Thr蛋白激酶的小家族。最近有报道称eEF2K在许多类型的癌症中被高度激活或过表达。因此，eEF2K被认为是有希望的治疗靶标。在这项研究中，我们通过虚拟高通量筛选发现了β-苯丙氨酸支架，并设计和合成了46种衍生物，评估了其对eEF2K的抑制活性和细胞毒性。经过几轮激酶和抗增殖活性筛选后，我们发现了具有最佳eEF2K酶促活性（IC50为5.5μM）和抗增殖活性（MDA-MB-231细胞，IC50为12.6μM，MDA）的eEF2K抑制剂（21l） -MB-436细胞，IC50为19.8μM。而且，我们发现21l可以通过MDA-MB-231和MDA-MB-436细胞的凋亡途径诱导细胞死亡。随后，我们评估了其在体内的抗肿瘤活性和诱导细胞凋亡的机制。这些结果表明21l通过在乳腺癌的异种移植小鼠模型（M
• Aromatic β-Amino Acids as Asp-Phg Mimics in LDV Derived VLA-4 Antagonists­
  作者：Volkmar Wehner、Horst Blum、Michael Kurz、Hans Stilz

  DOI：10.1055/s-2002-34389

  日期：——

  Aromatic β-amino acid esters 2a-h were prepared in racemic and enantiomerically pure form by the Radionow reaction or based on the method described by Davis and used as mimics of the Asp-Phg C-terminus in LDV derived VLA-4 antagonists. As a promising β-amino acid ester, 11 was identified and used for the synthesis of the highly potent VLA-4 antagonist S9059 with an IC50 of 1.6 nM in a cell attachment assay.

  芳香性 β-氨基酸酯 2a-h 通过 Radionow 反应或基于 Davis 描述的方法制备成外消旋形式和手性纯形式，并作为模拟 LDV 衍生的 VLA-4 拮抗剂中的 Asp-Phg C 末端。作为一种有前景的 β-氨基酸酯，11 被鉴定并用以合成高效力的 VLA-4 拮抗剂 S9059，其在细胞粘附试验中的 IC50 值为 1.6 nM。
• [EN] PROCESS FOR THE PREPARATION OF beta-AMINOCARBOXYLIC ACIDS<br/>[FR] PROCEDE DE PREPARATION D'ACIDES DOLLAR G(B)-AMINOCARBOXYLIQUES
  申请人：DEGUSSA

  公开号：WO2005095325A1

  公开（公告）日：2005-10-13

  The present invention relates to a method of producing β-aminocarboxylic acids or their derivatives by conversion of compounds of formula (I) with ketene acetals in the presence of a base.

  本发明涉及一种通过在碱存在下将式(I)化合物与酮乙烯缩醛转化而生产β-氨基羧酸或其衍生物的方法。
• β-Styryl- and β-Aryl-β-alanine Products of Phenylalanine Aminomutase Catalysis
  作者：Karin L. Klettke、Sanjit Sanyal、Washington Mutatu、Kevin D. Walker

  DOI：10.1021/ja071328w

  日期：2007.6.6

  The substrate specificity of a Taxus-derived phenylalanine aminomutase (PAM) was investigated, and the enzyme was found to catalyze the conversion of variously substituted vinyl- and aryl-S-alpha-alanines to corresponding beta-amino acids. This study shows the broad substrate specificity of PAM and thus demonstrates a potential, practical biosynthetic route toward unnatural beta-amino acid subunits of Taxol analogues and beta-peptides.
• Synthesis and biological evaluation of 3-phenyl-3-aryl carboxamido propanoic acid derivatives as small molecule inhibitors of retinoic acid 4-hydroxylase (CYP26A1)
  作者：Dongmei Zhao、Bin Sun、Jinhong Ren、Fengrong Li、Shuai Song、Xuejiao Lv、Chenzhou Hao、Maosheng Cheng

  DOI：10.1016/j.bmc.2014.11.036

  日期：2015.3

  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.