diethyl [[2-(bromomethyl)phenyl]methyl]phosphonate | 50869-57-3

• 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: diethyl [[2-(bromomethyl)phenyl]methyl]phosphonate
• 英文别名: diethyl 2-(bromomethyl)benzylphosphonate；2-(Diethylphosphonomethyl)benzyl bromide；1-(bromomethyl)-2-(diethoxyphosphorylmethyl)benzene
• CAS: 50869-57-3
• 化学式: C₁₂H₁₈BrO₃P
• 分子量: 321.151
• InChiKey: FMKQTGASIKCHLL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  diethyl [[2-(bromomethyl)phenyl]methyl]phosphonate 在 硫酸 、 sodium ethanolate 、 溶剂黄146 作用下， 反应 49.0h， 生成 triethyl 5-<(diethoxyphosphinyl)methyl>-1,4-dihydro-2,3,3-isoquinolinetricarboxylate
  参考文献：
  名称：

  N-甲基-D-天冬氨酸激动剂和竞争性拮抗剂药效团模型的产生。设计和合成膦酰基烷基取代的四氢异喹啉作为新型拮抗剂。

  摘要：

  描述了一系列四氢异喹啉羧酸在谷氨酸受体的N-甲基-D-天冬氨酸（NMDA）亚型上的制备和结合亲和力，以及对NMDA激动剂和拮抗剂的分子模型分析。使用公开的NMDA配体，在激动剂药效团模型的产生中采用了活性类似物作图方法。尽管可以将已知的竞争性拮抗剂（例如CPP（1））叠加到激动剂模型上，但要克服它们与相同受体位点结合的假设，可以使用独立的建模方法来得出单独的药效团模型。竞争性拮抗剂模型的开发涉及一种逐步方法，其中包括定义PO3H2受体相互作用的优选几何形状，多重构象搜索，以及确定体积和电子公差。对该模型进行了详细描述，与观察到的强效NMDA拮抗剂的亲和力一致，并为已知拮抗剂AP5，AP6和AP7的亲和力观察到的周期性提供了解释。比较了激动剂和拮抗剂模型的特征，并提出了关于这两类化合物的受体相互作用性质的假说。本文报道的药效基团模型与可容纳激动剂和拮抗剂配体的NMDA受体上的单个识别位点一致

  DOI：

  10.1021/jm00086a004
• 作为产物：
  描述：

  1,2-二溴-3,4-二甲基苯 在 亚磷酸三乙酯 作用下， 生成 diethyl [[2-(bromomethyl)phenyl]methyl]phosphonate
  参考文献：
  名称：

  Antagonists of specific excitatory amino acid neurotransmitter receptors

  摘要：

  该发明涉及新型、有效的抗癫痫药、镇痛药和认知增强剂，通过拮抗特定的兴奋性氨基酸神经递质受体来发挥作用。具体来说，该发明涉及具有一般化学式的.ω.-[2-磷酸烷基)苯基]-2-氨基烷酸：其中R.sub.1和R.sub.2相同或不同，选自氢、较低烷基、卤素、--CH.dbd.CH--CH.dbd.CH.dbd.、氨基、硝基、三氟甲基或氰基的群体；n和m=0、1、2或3；以及其药学上可接受的盐和衍生物。一般式的具体优选化合物示例选自以下群体：4-[2-磷酸甲基苯基]-2-氨基丁酸、乙基3-[2-(2-二乙基磷酸乙基)苯基]-2-乙酰氨基-2-羧乙酸乙酯、3-[2-(2-磷酸甲基)苯基]-2-氨基丙酸、乙基3-[2-(3-溴丙基)苯基]-2-乙酰氨基-3-羧乙酸乙酯、乙基3-[2-(3-二乙基磷酸丙基)苯基]-2-乙酰氨基-2-羧乙酸乙酯、乙基3-[2-(3-磷酸丙基)-苯基]-2-氨基丙酸、乙基5-[2-(二乙基磷酸甲基)-苯基]-2-乙酰氨基-2-羧乙氧基戊酸酯和5-[2-磷酸甲基苯基]-2-氨基戊酸。

  公开号：

  US04657899A1

文献信息

• N-substituted .alpha.-amino acids and derivatives thereof having
  申请人：Warner-Lambert Company

  公开号：US05179085A1

  公开（公告）日：1993-01-12

  N-substituted .alpha.-amino acids and derivatives thereof are described, as well as methods for the preparation and pharmaceutical composition of same, which are useful in selectively blocking the N-methyl-D-aspartate (NMDA) excitatory amino acid receptors in mammals and also are useful in treating cerebrovascular disorders such as cerebral ischemia or cerebral infarction resulting from thromboembolic or hemorrhagic stroke, cerebral vasospasm, hypoglycemia, cardiac arrest, status epilepticus and cerebral trauma as well as for treating schizophrenia, epilepsy, neurodegenerative disorders, Alzheimer's disease or Huntington's disease and also additionally useful as anesthetics in surgical procedures where a finite risk of cerebrovascular damage exists.

  本文介绍了N-取代的α-氨基酸及其衍生物，以及制备方法和药物组成物，这些物质在哺乳动物中选择性地阻断N-甲基-D-天门冬氨酸（NMDA）兴奋性氨基酸受体方面有用，也可用于治疗脑血管疾病，如由栓塞性或出血性中风引起的脑缺血或脑梗死、脑血管痉挛、低血糖、心脏停跳、持续性癫痫状态和脑外伤，以及治疗精神分裂症、癫痫、神经退行性疾病、阿尔茨海默病或亨廷顿病，并且还可作为麻醉剂用于存在有限脑血管损伤风险的外科手术中。
• Agent for preventing or treating neuropathy
  申请人：Momose Yu

  公开号：US20060004069A1

  公开（公告）日：2006-01-05

  The present invention provides an agent for preventing or treating neuropathy having superior action and low toxicity. This agent comprises a compound represented by the formula: wherein ring A is a 5-membered aromatic heterocycle containing 2 or more nitrogen atoms, which may further have substituent(s); B is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; X is a divalent acyclic hydrocarbon group; Z is —O—, —S—, —NR 2 —, —CONR 2 — or —NR 2 CO— (R 2 is a hydrogen atom or an optionally substituted alkyl group); Y is a bond or a divalent acyclic hydrocarbon group; R 1 is an optionally substituted cyclic group, an optionally substituted amino group or an optionally substituted acyl group, provided that when the 5-membered aromatic heterocycle represented by ring A is imidazole, then Z should not be —O—, or a salt thereof.

  本发明提供了一种用于预防或治疗神经病的药剂，具有优异的作用和低毒性。该药剂包括以下式子所表示的化合物：其中环A是一个含有2个或更多氮原子的5元芳香杂环，可以进一步具有取代基；B是一个可选取代的碳氢化合物基团或可选取代的杂环基团；X是一个二价的无环碳氢基团；Z是—O—、—S—、—NR2—、—CONR2—或—NR2CO—（其中R2是氢原子或可选取代的烷基基团）；Y是一个键或一个二价的无环碳氢基团；R1是一个可选取代的环基、可选取代的氨基或可选取代的酰基，但当环A所表示的5元芳香杂环是咪唑时，Z不应为—O—，或其盐。
• Synthesis and Biological Studies of Novel Aminophosphonates and Their Metal Carbonyl Complexes (Fe, Ru)
  作者：Aneta Kosińska、David Virieux、Jean-Luc Pirat、Kamila Czarnecka、Małgorzata Girek、Paweł Szymański、Sławomir Wojtulewski、Saranya Vasudevan、Arkadiusz Chworos、Bogna Rudolf

  DOI：10.3390/ijms23158091

  日期：——

  strategy to introduce new drug candidates for the treatment of neurodegenerative diseases. A series of (aminomethyl)benzylphosphonates 8a–c and their metallocarbonyl iron 9a–c and ruthenium 10a–c complexes were designed, synthesized, and evaluated for their inhibitory potentials against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) by determination of IC50. Metallocarbonyl derivatives

  寻找生物相关靶点的新抑制剂被认为是引入新的候选药物治疗神经退行性疾病的重要策略。设计、合成了一系列（氨基甲基）苄基膦酸盐8a - c及其金属羰基铁9a - c和钌10a - c配合物，并通过 IC 50测定评估了它们对乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BuChE) 的抑制潜力。一般来说，金属羰基衍生物对这些酶没有显着的抑制活性，最有效的抑制剂是（氨基甲基）苄基膦酸酯8a（针对 AChE 的 IC 50 = 1.215 µM）。与异构体8b和8c相比，AChE 和（氨基甲基）苄基膦酸酯8a – c的分子对接分析显示8a和 AChE的相互作用最强。还进行并讨论了合成化合物对 V79 细胞系的细胞毒性研究。
• Phosphono-hydroisoquinoline compounds useful in reducing neurotoxic injury
  申请人：G.D. Searle & Co.

  公开号：EP0364996A2

  公开（公告）日：1990-04-25

  A class of phosphono-hydroisoquinoline compounds is described for treatment to reduce neurotoxic injury associated with anoxia or ischemia which typically follows stroke, cardiac arrest or perinatal asphyxia. The treatment includes administration of a phosphono-hydroisoquinoline compound alone or in a composition in an amount effective as an antagonist to inhibit excitotoxic actions at major neuronal excitatory amino acid receptor sites. Compounds of most interest are those of Formula 1: wherein each of R' through R4 is hydrido, wherein each of Z1 and Z2 is hydroxyl, wherein W is a single bond connecting the phosphorus atom with the aromatic ring and wherein the A ring is aromatic. Also disclosed are two classes of intermediate compounds having a fully unsaturated A ring, which intermediate compounds are useful in methods to make product compounds of Formula I.

  描述了一类膦酰基氢化异喹啉化合物，用于治疗减少与缺氧或缺血相关的神经毒性损伤，缺氧或缺血通常发生在中风、心脏骤停或围产期窒息之后。治疗方法包括单独施用或在组合物中施用膦酰基氢化异喹啉化合物，施用量应能有效地作为拮抗剂抑制主要神经元兴奋性氨基酸受体部位的兴奋毒性作用。最令人感兴趣的化合物是式 1： 其中，R'到 R4 中的每一个都是氢基，Z1 和 Z2 中的每一个都是羟基，W 是连接磷原子和芳香环的单键，A 环是芳香环。还公开了两类具有完全不饱和 A 环的中间体化合物，这些中间体化合物在制造式 I 产品化合物的方法中是有用的。
• Exploration of N-phosphonoalkyl-, N-phosphonoalkenyl-, and N-(phosphonoalkyl)phenyl-spaced .alpha.-amino acids as competitive N-methyl-D-aspartic acid antagonists
  作者：Christopher F. Bigge、Graham Johnson、Daniel F. Ortwine、James T. Drummond、Daniel M. Retz、Laura J. Brahce、Linda L. Coughenour、Frank W. Marcoux、Albert W. Probert

  DOI：10.1021/jm00086a005

  日期：1992.4

  A series of N-substituted alpha-amino acids containing terminal phosphonic acid groups has been synthesized as potential N-methyl-D-aspartate (NMDA) receptor antagonists. NMDA receptor affinity was determined by displacement of a known ligand ([H-3]CPP) from crude rat brain synaptic membranes; an antagonist action was demonstrated by the inhibition of glutamate-induced accumulation of [Ca-45(2+)] in cultured rat cortical neurons. Receptor affinity was significantly correlated with antagonist activity (Figure 1). Moderate affinity (IC50 = 1-2-mu-M) was retained for analogues (31 and 32, Table 1; and 59 and 66, Table II) with reduced flexibility in their phosphonate side chains and is consistent with entropy playing a role in determining receptor affinity. Modeling studies suggest a folded conformation that brings the distal phosphonic acid group into close proximity with the alpha-carboxylate is required for binding. Each of the active analogues possess entropy-limiting features (double bonds, phenyl rings) in their side chains that allows the superposition of their key NH2, alpha-COOH, and distal PO3H2 groups with those of known competitive antagonists. Affinity decreased for analogues with alpha-carbon substitution, presumably because the alpha-substituent inhibits the folding of these structures into a bioactive conformation and occupies receptor-excluded volume. A complete description of the NMDA antagonist pharmacophore model is provided in a companion paper. 1