ethyl (p-bromomethyl)benzoylformate | 76590-57-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl (p-bromomethyl)benzoylformate
• 英文别名: Ethyl 2-[4-(bromomethyl)phenyl]-2-oxoacetate
• CAS: 76590-57-3
• 化学式: C₁₁H₁₁BrO₃
• 分子量: 271.111
• InChiKey: JZRMBHRZXFXEFZ-UHFFFAOYSA-N

物化性质

• 沸点：
  350.3±25.0 °C(Predicted)
• 密度：
  1.450±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (p-bromomethyl)benzoylformate 在 氢氧化钾 、 sodium hydroxide 、 1,1-二氯甲醚 、 tetramethylammonium hydrogen difluoride 、 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 8.58h， 生成 (R)-α-hydroxy-α-<4-(fluoromethyl)phenyl>benzeneacetic acid
  参考文献：
  名称：

  Syntheses and Biological Properties of Chiral Fluoroalkyl Quinuclidinyl Benzilates

  摘要：

  Previously, (R)-quinuclidinyl (R)-4-iodobenzilate ((R,R)-IQNB), a muscarinic receptor antagonist, has been labeled with I-123 and I-125 for use in in vitro and in vivo studies in animals and humans. We have prepared fluoroalkyl analogs of QNB, which are amenable to labeling with F-18, for potential imaging applications with positron emission tomography. The enantiomers of (fluoroalkyl)benzilic acids were prepared via an enantioselective Grignard addition reaction. Subsequent coupling of the enantiomeric (fluoroalkyl)benzilic acid with a selected enantiomer of quinuclidinol provides fluorinated analogs of QNB with known stereochemistry at each of the stereogenic centers. These compounds exhibit different affinities for the muscarinic receptor tissue subtypes in vitro. (R,R)-4-(Fluoromethyl)-QNB, (R,R)-IQNB, and (R,R)-4-(fluoroethyl)-QNB exhibit selectivity for the M1 subtype, and (R,S)-4-(fluoromethyl)-QNB exhibits selectivity for the M2 subtype.

  DOI：

  10.1021/jm00010a016
• 作为产物：
  描述：

  2-(4-甲基苯基)-2-氧代乙酸乙酯 在 N-溴代丁二酰亚胺(NBS) 、 过氧化氢苯甲酰 作用下， 以 四氯化碳 为溶剂， 反应 3.0h， 以51%的产率得到ethyl (p-bromomethyl)benzoylformate
  参考文献：
  名称：

  某些苯乙醛酸促进心脏中碳水化合物的氧化。

  摘要：

  描述了一系列苯乙醛酸，其中许多能够促进肌肉组织中碳水化合物的氧化，从而在提高脂肪酸利用率的情况下有利地改变碳水化合物/脂肪酸的平衡。据报道，这种情况发生在缺血性心脏病中，尤其是在心肌感染之后。为了有效地将苯乙醛酸递送至细胞内的作用部位，L-（+）-苯甘氨酸被用作前药。已知这些被氨基转移为苯乙醛酸。已选择L-（+）-2-（4-羟基苯基）甘氨酸（25，奥芬尼辛）进行临床评估。

  DOI：

  10.1021/jm00136a009

文献信息

• Imidazole derivatives, process for their preparation and pharmaceutical compositions thereof
  申请人：Pfizer Limited

  公开号：EP0029742A1

  公开（公告）日：1981-06-03

  Compounds of the general formula: wherein R is hydrogen, C1-C4 alkyl, or halogen; Y is (CH2)n, where n is 1 to 4, benzyl or CH2-(Het)- where Het represents a 5 or 6 membered aromatic heterocyclic ring linkedto Z by a ring carbon atom; Z is CO2R1, CONHR2, CON(R3)2, COCO2R1, COCONHR2, COCON(R')2, CN or 5-tetrazolyl, or, when Y is -CH2-(Het),C1-C4 alkyl, where: R1 is H or C1-C4 alkyl, R2 is H, C1-C4 alkyl, C2-C4 alkanoyl, C1-C4 alkylsulphonyl, CN, benzoyl or benzenesulphonyl, the phenyl ring in said benzoyl or benzenesulphonyl groups being optionally substituted, each R3 is C1-C4 alkyl or two groups R3 together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino or morpholino group; the group -O-Y-Z being attached to the 3 or 5 position of the pyridine ring, and the pharmaceutically acceptable salts thereof and bioprecursors therefor are able to selectively inhibit the action of the thromboxane synethetase enzyme without significantly inhibiting the action of the prostacycline synthetase or cyclooxygenase enzymes and are thus useful in the treatment of ischaemic heart disease, stroke, transient ischaemic attack, thrombosis, migraine and the vascular complications of diabetes.

  通式如下的化合物 其中 R 是氢、C1-C4 烷基或卤素； Y 是 (CH2)n（其中 n 为 1 至 4）、苄基或 CH2-(Het)-（其中 Het 代表通过环碳原子与 Z 连接的 5 或 6 位芳香杂环）； Z 是 CO2R1、CONHR2、CON(R3)2、COCO2R1、COCONHR2、COCON(R')2、CN 或 5-四唑基，或者，当 Y 是-CH2-(Het)时，C1-C4 烷基，其中： R1 是 H 或 C1-C4 烷基、 R2 是 H、C1-C4 烷基、C2-C4 烷酰基、C1-C4 烷基磺酰基、CN、苯甲酰基或苯磺酰基，所述苯甲酰基或苯磺酰基中的苯基环被任选取代、 每个 R3 均为 C1-C4 烷基，或两个基团 R3 与所连接的氮原子一起形成吡咯烷基、哌啶基或吗啉基；基团-O-Y-Z 连接到吡啶环的 3 或 5 位，其药学上可接受的盐及其生物前体能够选择性地抑制血栓素合成酶的作用，而不会显著抑制前列环素合成酶或环氧合酶的作用，因此可用于治疗缺血性心脏病、中风、短暂性脑缺血发作、血栓形成、偏头痛和糖尿病的血管并发症。
• Proton Transfer via π-Interactions from Pyridine Provides a Facilitated Route for Transfer of CO₂ in Its Complex with a Carbanion
  作者：Marc Alexander Zambri、Ronald Kluger

  DOI：10.1021/jacs.3c10403

  日期：2024.1.17

  π-associated species. The formation of the complex of CO2 and the co-formed carbanion also addresses the mechanism of the uncatalyzed exchange of 13CO2 into carboxyl groups discovered by Lundgren. Finally, microscopic reversibility implicates pyridine as a vicinal Brønsted base in thiamin-aldehyde adducts, producing carbanions that could incorporate dissolved CO2 into carboxyl groups.

  芳香族 π 相互作用已被认为可以增强酶催化过程，提供克服熵障碍的有效途径。非酶类似物是质子化吡啶和硫胺素缀合物中苯基取代基的复合物，通过反应复合物中邻位碳负离子的质子化促进CO 2的离开。为了评估来自 π 相关质子供体的催化途径的效率，评估了一个系统，该系统通过由相同的硫胺素衍生碳负离子产生的替代产物的形成速率产生可测量的竞争。确定了在存在和不存在质子化吡啶的情况下对（溴甲基）-扁桃基硫胺脱羧的竞争途径的障碍，从而确定了π相关物种之间邻位质子转移的效率。 CO 2和共形成的碳负离子复合物的形成也解决了Lundgren发现的13 CO 2未催化交换为羧基的机制。最后，微观可逆性表明吡啶作为硫胺素-醛加合物中的邻位布朗斯台德碱，产生可以将溶解的CO 2结合到羧基中的负碳离子。
• Non-Nucleoside Inhibitors of Human Adenosine Kinase: Synthesis, Molecular Modeling, and Biological Studies
  作者：Stefania Butini、Sandra Gemma、Margherita Brindisi、Giuseppe Borrelli、Andrea Lossani、Anna Maria Ponte、Andrea Torti、Giovanni Maga、Luciana Marinelli、Valeria La Pietra、Isabella Fiorini、Stefania Lamponi、Giuseppe Campiani、Daniela M. Zisterer、Seema-Maria Nathwani、Stefania Sartini、Concettina La Motta、Federico Da Settimo、Ettore Novellino、Federico Focher

  DOI：10.1021/jm101438u

  日期：2011.3.10

  Adenosine kinase (AK) catalyzes the phosphorylation of adenosine (Ado) to AMP by means of a kinetic mechanism in which the two substrates Ado and ATP bind the enzyme in a binary and/or ternary complex, with distinct protein conformations. Most of the described inhibitors have Ado-like structural motifs and are nonselective; and some of them (e.g., the tubercidine-like ligands) are characterized by a toxic profile. We have cloned and expressed human AK (hAK) and searched for novel non-substrate-like inhibitors. Our efforts to widen the structural diversity of AK inhibitors led to the identification of novel non-nucleoside, noncompetitive allosteric modulators characterized by a unique molecular scaffold. Among the pyrrolobenzoxa(thia)zepinones (4a-qq) developed, 4a was identified as a non-nucleoside prototype hAK. inhibitor. 4a has proapoptotic efficacy, slight inhibition of short-term RNA synthesis, and cytostatic activity on tumor cell lines while showing low cytotoxicity and no significant adverse effects on short-term DNA synthesis in cells.
• Evidence for the generation of .alpha.-carboxy-.alpha.-hydroxy-p-xylylene from p-(bromomethyl)mandelate by mandelate racemase
  作者：David T. Lin、Vincent M. Powers、Laure J. Reynolds、Christian P. Whitman、John W. Kozarich、George L. Kenyon

  DOI：10.1021/ja00209a069

  日期：1988.1
• US4339583A
  申请人：——

  公开号：US4339583A

  公开（公告）日：1982-07-13