盐酸甲基多巴酯 | 6014-30-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 盐酸甲基多巴酯
• 英文名称: (S)-α-Me-Dopa ethyl ester
• 英文别名: ethyl methyldopate；methyldopate；Methyldopal；ethyl (2S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoate
• CAS: 6014-30-8
• 化学式: C₁₂H₁₇NO₄
• 分子量: 239.271
• InChiKey: SVEBYYWCXTVYCR-LBPRGKRZSA-N

物化性质

• 沸点：
  398.0±37.0 °C(Predicted)
• 密度：
  1.243±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO（微溶，加热）、甲醇（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  92.8
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 储存条件：
  -20°C，密封保存，置于干燥处

制备方法与用途

甲基多巴是α-甲基多巴（α-MD；HY-B0225）的乙酯前药，是一种α-肾上腺素能激动剂，主要对α2-肾上腺素能受体具有选择性作用。研究显示，甲基多巴可能适用于重度高血压治疗。

反应信息

• 作为反应物：
  描述：

  盐酸甲基多巴酯 在 phosphate buffer 、 phosphate buffer (PH = 7.4) 、 potassium hydrogencarbonate 、 potassium hexacyanoferrate(III) 作用下， 以 水 、 苯 为溶剂， 反应 5.0h， 以15%的产率得到(S)-5-Hydroxy-2-methyl-6-oxo-2,6-dihydro-1H-indole-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  Synthetic and preliminary hemodynamic and whole animal toxicity studies on (R,S)-, (R)-, and (S)-2-methyl-3-(2,4,5-trihydroxyphenyl)alanine

  摘要：

  The synthesis, resolution, and absolute configuration assignment of 2-methyl-3-(2,4,5-trihydroxphenyl)alanine (6-OH-alpha-Me-Dopa) are reported. Hemodynamic studies in the rat have shown that this structural analogue and potential metabolite of the clinically useful drug (S)-alpha-Me-Dopa possesses weak hypotensive activity which resides in the R enantiomer. LD50 studies in mice have established that 6-OH-alpha-Me-Dopa is over four times more toxic than alpha-Me-Dopa. Chronic exposure to 6-OH-alpha-Me-Dopa leads to renal and hepatic lesions. The case of oxidation of this hydroquinone to the electrophilic quinone species may contribute to its enhanced toxicity compared to alpha-Me-Dopa.

  DOI：

  10.1021/jm00186a007
• 作为产物：
  描述：

  乙醇 、 甲基多巴 在 盐酸 作用下， 以90%的产率得到盐酸甲基多巴酯
  参考文献：
  名称：

  一种丹酚酸A类似物及其作为抗氧化剂的用途

  摘要：

  本发明提供了一类新的具有抗氧化活性的丹酚酸A类似物，其可通过上调CAT和SOD等抗氧化酶的表达以及增加非酶抗氧化物质GSH的产生，直接或间接地清除ROS，体现了较好的抗氧化能力，拓宽了现有抗氧化剂的范围，并可作为先导化合物继续优化。同时本发明化合物即使在低浓度(10μM/kg·天)下，也可以保护肝脏免受CCl4诱导的氧化应激损伤，具有良好的成药前景。

  公开号：

  CN110642735A

文献信息

• ACYL-HYDRAZONE AND OXADIAZOLE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME AND USES THEREOF
  申请人：Universidade Federal de Santa Catarina

  公开号：US20150191445A1

  公开（公告）日：2015-07-09

  The present invention relates to acyl-hydrazone compounds, in particular 3,4,5-trimethoxyphenyl-hydrazide derivatives, as well as the oxadiazole analogs thereof and other similar compounds, and to the pharmaceutical use of the same for the treatment of various diseases associated with cell proliferation, such as leukemias, including acute lymphoblastic leukemia (ALL), tumours and inflammation. Acyl-hydrazones have been obtained having activity similar to that of the compound used as a standard in experiments (colchicine). The greater selectivity of the compounds according to the invention is an important feature, associated with fewer side effects than the pharmaceuticals used at present in clinical treatments. The synthetised acyl-hydrazones, more particularly the compounds 02 and 07, exhibited important antileukemic activity, which suggests 02 and 07 as candidates to pharmaceutical prototypes, or to pharmaceuticals for the treatment of leukemias, in particular acute lymphoblastic leukemia (ALL), tumours and other proliferative diseases, such as inflammation. The action mechanism of the most active compounds was determined by using DNA microarrays and subsequent tests indicated by the chip, besides selectivity studies in healthy human lymphocytes.

  本发明涉及酰基腙化合物，特别是3,4,5-三甲氧基苯基腙衍生物，以及其噁二唑类似物和其他类似化合物，以及它们在治疗与细胞增殖相关的各种疾病，如白血病（包括急性淋巴细胞白血病（ALL））、肿瘤和炎症方面的药用。已获得具有与实验中使用的化合物（秋水仙碱）相似活性的酰基腙。根据本发明的化合物具有更大的选择性，与目前在临床治疗中使用的药物相比，副作用更少是一个重要特征。合成的酰基腙，尤其是化合物02和07，表现出重要的抗白血病活性，这表明02和07可能成为药物原型的候选，或用于治疗白血病，特别是急性淋巴细胞白血病（ALL）、肿瘤和其他增殖性疾病，如炎症的药物。最活性化合物的作用机制是通过使用DNA微阵列确定的，并且通过芯片指示的后续测试，以及对健康人类淋巴细胞的选择性研究。
• [EN] CARBONATE PRODRUGS AND METHODS OF USING THE SAME<br/>[FR] PROMÉDICAMENTS CARBONATÉS ET LEURS MÉTHODES D'UTILISATION
  申请人：NEUROGESX INC

  公开号：WO2009143297A1

  公开（公告）日：2009-11-26

  The present invention provides carbonate prodrugs which comprise a carbonic phosphoric anhydride prodrug moiety attached to the hydroxyl or carboxyl group of a parent drug moiety. The prodrugs may provide improved physicochemical properties over the parent drug. Also provided are methods of treating a disease or condition that is responsive to the parent drug using the carbonate prodrugs, as well as kits and unit dosages.

  本发明提供了碳酸盐前药，其包括连接到母药基团的羟基或羧基上的碳酸磷酸酐前药基团。这些前药可能比母药具有改进的物理化学性质。还提供了使用碳酸盐前药治疗对母药具有响应的疾病或症状的方法，以及配套工具和单剂量。
• [EN] CLEAVABLE CONJUGATES OF CATECHOL COMPOUNDS AND WATER-SOLUBLE POLYMERS AND METHODS OF TREATMENT USING THE SAME<br/>[FR] CONJUGUÉS CLIVABLES DE COMPOSÉS CATÉCHOLS ET POLYMÈRES SOLUBLES DANS L'EAU ET PROCÉDÉS DE TRAITEMENT LES UTILISANT
  申请人：SERINA THERAPEUTICS INC

  公开号：WO2020023947A1

  公开（公告）日：2020-01-30

  Described are conjugates comprising a water-soluble polymer linked to a compound comprising a catechol moiety via a cleavable linkage, wherein the cleavable linkage is formed between the water-soluble polymer and a first phenolic hydroxyl group of the catechol moiety and a second phenolic hydroxyl group of the catechol moiety is linked to a blocking group wherein the rate of hydrolytic release of the compound comprising the catechol moiety is controlled, at least in part, through structure or design of the blocking group on the second phenolic hydroxyl group of the catechol moiety. Therefore, the rate of hydrolytic release of the compound comprising the catechol moiety can be tuned through structural design of the group on the second phenolic hydroxyl group of the catechol moiety. Compounds used in the synthesis of the described conjugates and methods of using the described conjugate and other compounds in the treatment of dopamine-responsive disorders are also described.

  描述了一种包含水溶性聚合物与含儿茶酚基团的化合物通过可切断连接而形成的共轭物，其中可切断连接形成在水溶性聚合物和儿茶酚基团的第一个酚羟基之间，而儿茶酚基团的第二个酚羟基与阻塞基团相连，其中通过对儿茶酚基团的第二个酚羟基上的阻塞基团的结构或设计，至少部分地控制了含儿茶酚基团的化合物的水解释放速率。因此，通过对儿茶酚基团的第二个酚羟基上的基团的结构设计，可以调节含儿茶酚基团的化合物的水解释放速率。描述了用于合成所述共轭物的化合物以及使用所述共轭物和其他化合物治疗多巴胺敏感性疾病的方法。
• Methods to increase plasma HDL cholesterol levels and improve HDL functionality with probucol monoesters
  申请人：——

  公开号：US20030064967A1

  公开（公告）日：2003-04-03

  It has been discovered that certain selected probucol monoesters, and their pharmaceutically acceptable salts or prodrugs, are useful for increasing circulating HDL cholesterol. These compounds may also improve HDL functionality by (a) increasing clearance of cholesteryl esters, (b) increasing HDL-particle affinity for hepatic cell surface receptors or (c) increasing the half life of apoAI-HDL.

  已经发现某些选择的普布考醇单酯以及它们的药用盐或前药对增加循环高密度脂蛋白胆固醇是有用的。这些化合物还可以通过（a）增加酯化胆固醇的清除、（b）增加高密度脂蛋白颗粒与肝细胞表面受体的亲和力或（c）增加apoAI-HDL的半衰期来改善高密度脂蛋白的功能。
• Memory of Chirality of Tertiary Aromatic Amide: Application to the Asymmetric Synthesis of (<i>S</i>)-α-MethylDOPA
  作者：Thi Thoa Mai、Baby Viswambharan、Didier Gori、Cyrille Kouklovsky、Valérie Alezra

  DOI：10.1021/jo301588t

  日期：2012.10.5

  We describe an original asymmetric synthesis of (S)-α-methylDOPA proceeding by the concept of memory of chirality, the only source of chirality being the starting d-alanine. The initial chirality of the amino acid is temporarily transferred to a dynamic axial chirality of a tertiary aromatic amide. The (S)-α-methylDOPA hydrochloride is obtained after four steps with 98% ee.

  我们通过手性记忆的概念描述了（S）-α-甲基DOPA的原始不对称合成，手性的唯一来源是起始的d-丙氨酸。氨基酸的初始手性被暂时转移至叔芳族酰胺的动态轴向手性。（S）-α-甲基DOPA盐酸盐在四个步骤后以98％ee获得。