diethyl (acetylamino)<(3-bromophenyl)methyl>propanedioate | 15017-44-4

• 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: diethyl (acetylamino)<(3-bromophenyl)methyl>propanedioate
• 英文别名: 2-acetylamino-2-(3-bromobenzyl)malonic acid diethyl ester；diethyl (acetylamino)(3-bromobenzyl)propanedioate；α-(3-Brom-benzyl)-α-acetamino-malonsaeure-diethylester；Diethyl (acetylamino)(3-bromobenzyl)malonate；diethyl 2-acetamido-2-[(3-bromophenyl)methyl]propanedioate
• CAS: 15017-44-4
• 化学式: C₁₆H₂₀BrNO₅
• mdl: MFCD28505107
• 分子量: 386.243
• InChiKey: AZORFVFAQMAVDQ-UHFFFAOYSA-N

物化性质

• 熔点：
  99-100 °C(Solv: heptane (142-82-5))
• 沸点：
  496.3±45.0 °C(Predicted)
• 密度：
  1.362±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：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl (acetylamino)<(3-bromophenyl)methyl>propanedioate 在 盐酸 、 草酰氯 、 碳酸氢钠 、 二甲基亚砜 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 19.0h， 生成 rac-(2-(3-bromophenyl)-1-formylethyl)carbamic acid tert-butyl ester
  参考文献：
  名称：

  Hydroxyethylene Sulfones as a New Scaffold To Address Aspartic Proteases:  Design, Synthesis, and Structural Characterization

  摘要：

  Hydroxyethylene sulfones were developed as novel scaffolds against aspartyl proteases. A diastereoselective synthesis has been established to introduce the required side chain decoration with desired stereochemistry. Depending on the substitution of the hydroxyethylene-sulfone core, micro- to submicromolar inhibition of HIV-1 protease is achieved for the S-configuration at P, and R-configuration at the hydroxy-group-bearing backbone atom. This stereochemical preference is consistent with the S,R configuration of amprenavir. The racemic mixture of the most potent derivative (K-i = 80 nM) was separated by chiral HPLC, revealing the S,R,S-enantiomer to be more active (K-i = 45 nM). Docking studies suggested this isomer as the more active one. The subsequently determined crystal structure with HIV-1 protease, cocrystallized from a racemic mixture, exclusively reveals the S,R,S-enantiomer accommodated to the binding pocket. The transition state mimicking hydroxy group of the inhibitor is centered between both catalytic aspartates, while either its carbonyl or sulfonyl group forms H-bonds to the structurally conserved water mediating interactions between ligand and Ile50NH/Ile50NH' of both flaps. Biological testing of the stereoisomeric hydroxyethylene sulfones against cathepsin D and beta-secretase did not reveal significant inhibition. Most likely, the latter proteases require inverted configuration at the hydroxy group.

  DOI：

  10.1021/jm050224y
• 作为产物：
  描述：

  氨基丙二酸二乙酯盐酸盐 在 caesium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 diethyl (acetylamino)<(3-bromophenyl)methyl>propanedioate
  参考文献：
  名称：

  α-氨基烷基自由基向异喹啉的有机催化对映选择性加成

  摘要：

  借助手性磷酸和二氰基吡嗪衍生的生色团（DPZ）光敏剂的双重有机催化体系，并在可见光照射下，将α-氨基酸衍生的氧化还原活性酯（RAE）的对映选择性Minisci型加到异喹啉中已经被开发出来。从RAE产生的各种前手性α-氨基烷基已成功引入异喹啉，以高收率提供了一系列有价值的α-异喹啉取代的手性仲胺，具有良好或优异的对映选择性。

  DOI：

  10.1021/acs.orglett.8b02791

文献信息

• Exploration of phenyl-spaced 2-amino-(5-9)-phosphonoalkanoic acids as competitive N-methyl-D-aspartic acid antagonists
  作者：Christopher F. Bigge、James T. Drummond、Graham Johnson、Thomas Malone、Albert W. Probert、Frank W. Marcoux、Linda L. Coughenour、Laura J. Brahce

  DOI：10.1021/jm00127a030

  日期：1989.7

  To investigate the preferred spatial relationship of the distal phosphonic acid to the alpha-amino acid group of the established competitive N-methyl-D-aspartic acid (NMDA) antagonists APH (1) and APV (2), we have prepared a series of ortho-, meta-, and para-substituted (phosphonoalkyl)phenylglycine and -phenylalanine derivatives. With use of a [3H]CPP receptor binding assay, significant binding activity

  为了研究末端膦酸与已建立的竞争性N-甲基-D-天冬氨酸（NMDA）拮抗剂APH（1）和APV（2）的α-氨基酸之间的优选空间关系，我们制备了一系列邻，间和对位取代的（膦酰基烷基）苯基甘氨酸和-苯丙氨酸衍生物。使用[3H] CPP受体结合测定法，观察到显着的结合活性关键取决于取代位置和烷基间隔基团的长度。4-（膦酰基甲基）-苯基甘氨酸（6，PD 129635）和3-（膦酰基甲基）苯丙氨酸（15，PD 130527）这两种化合物显示出与APH相当的受体结合亲和力。像APH一样，这些化合物也可有效拮抗NMDA给药的后球在小鼠中的惊厥作用和致死作用。还提供了将这些化合物与最近公开的有关NMDA拮抗剂18（NPC 451）的结合功效直接进行比较的数据。对显示出良好的受体结合亲和力和体内拮抗剂活性的结构进行初步比较表明，NMDA受体更喜欢“折叠”构象而不是“延伸”构象。
• Experimentally Induced Phenylketonuria. I. Inhibitors of Phenylalanine Hydroxylase
  作者：Joseph I. DeGraw、Michael. Cory、W. A. Skinner、Myna C. Theisen、Chozo. Mitoma

  DOI：10.1021/jm00313a013

  日期：1967.1.1
• Tetrahydroisoquinoline-Based Non-Peptidomimetic Plasmepsin Inhibitors
  作者：Linda Kinena、Vita Ozola

  DOI：10.1007/s10593-020-02623-6

  日期：2020.1

  A series of tetrahydroisoquinoline derivatives containing different aryl substituents were designed and synthesized using Pictet-Spengler reaction as the key step. The synthesized tetrahydroisoquinoline derivatives displayed micromolar inhibitory activity against plasmepsins I and II.
• BIGGE, CHRISTOPHER F.;DRUMMOND, JAMES T.;JOHNSON, GRAHAM;MALONE, THOMAS;P+, J. MED. CHEM., 32,(1989) N, C. 1580-1590
  作者：BIGGE, CHRISTOPHER F.、DRUMMOND, JAMES T.、JOHNSON, GRAHAM、MALONE, THOMAS、P+

  DOI：——

  日期：——