肾上腺酮 | 99-45-6

• 物质功能分类: 原料药 - 血液系统用药 - 止血药
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 肾上腺酮
• 中文别名: 3',4'-二羟基-2-(甲基氨基)苯乙酮；3",4"-二羟基-2-(甲基氨基)苯乙酮
• 英文名称: adrenalone
• 英文别名: Adrenalon；1-(3,4-dihydroxyphenyl)-2-(methylamino)ethanone
• CAS: 99-45-6
• 化学式: C₉H₁₁NO₃
• mdl: MFCD00707523
• 分子量: 181.191
• InChiKey: PZMVOUYYNKPMSI-UHFFFAOYSA-N

物化性质

• 熔点：
  235.5°C (rough estimate)
• 沸点：
  314.29°C (rough estimate)
• 密度：
  1.2375 (rough estimate)
• 溶解度：
  酸水溶液（微溶）
• 稳定性/保质期：
  其盐酸盐的熔点为243℃，易溶于水，可溶于乙醇，而不溶于乙醚。

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 海关编码：
  2922509090
• 储存条件：
  温度：20°C，气体环境：惰性气体

制备方法与用途

简介

肾上腺酮是一种局部血管收缩剂和止血的肾上腺素能激动剂。曾用于延长局部麻醉药物的作用。它实际上是肾上腺素的酮形式。

化学性质

肾上腺酮为针状结晶体，分解温度在235-236℃之间，微溶于水、醇和醚。其盐酸盐熔点为243℃，易溶于水，并溶于乙醇而不溶于乙醚。

用途

肾上腺酮主要用于止血药物安络血以及非甾体激素类药物的中间体。

生产方法

通过弗-克反应将儿茶酚与氯乙酸和三氯氧磷结合生成氯乙酰儿茶酚，再经胺化反应用甲胺处理得到肾上腺酮。

反应信息

• 作为反应物：
  描述：

  肾上腺酮 在 氢气 作用下， 以 甲醇 为溶剂， 生成 肾上腺素
  参考文献：
  名称：

  在手性编码金属表面高度对映选择性合成药物

  摘要：

  纳米结构介孔 Pt-Ir 合金用作药物化合物不对称合成的多相催化剂，以对映选择性氢化肾上腺酮为例，产生所需的肾上腺素立体异构体作为模型化合物，其 ee 高达 95 %。

  DOI：

  10.1002/chem.202302054
• 作为产物：
  描述：

  肾上腺素 在 (R)-epinephrine dehydrogenase 、 还原型辅酶Ⅰ 作用下， 以 aq. phosphate buffer 为溶剂， 生成 肾上腺酮
  参考文献：
  名称：

  Purification and characterization of a novel carbonyl reductase involved in oxidoreduction of aromatic β-amino ketones/alcohols

  摘要：

  Aromatic beta-amino ketones/alcohols such as adrenalone play an important role in some stereoselective synthesis of pharmaceuticals. Unfortunately, the transformation of aromatic beta-amino ketones to their chiral alcohols has been carried out chemically as no corresponding biocatalyst has been available. Here, a novel carbonyl reductase responsible for the reduction of adrenalone to (R)-(-)-epinephrine was identified and characterized from Kocuria rhizophila. This enzyme was purified to homogeneity by ammonium sulfate precipitation followed by ion-exchange column chromatography, hydrophobic chromatography and gel chromatography. The purified enzyme yielded pure (R)-enantiomer product with high activity and utilized NADH as the cofactor. The enzyme had special significance by showing selectivity for many aromatic beta-amino ketones/alcohols such as 2-amino-acetophenone, 2-amino-4'-hydroxyacetophenone, isoproterenol and ephedrine. The maximum reaction rate (V-max) and apparent Michaelis-Menten constant (K-m) for adrenalone and NADH were 14.62 mu mol/(min mg) protein and 0.189 mM, 11.66 mu mol/(min mg) protein and 0.204 mM respectively. These properties ensure the enzyme a promising future for industrial application as a replacement of chemical synthesis of aromatic beta-amino chiral alcohols. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.procbio.2014.03.023

文献信息

• [EN] HETEROCYCLIC COMPOUNDS AS KINASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES EN TANT QU'INHIBITEURS DE KINASES
  申请人：ORIGENIS GMBH

  公开号：WO2012143143A1

  公开（公告）日：2012-10-26

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及一种能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体的化合物的新颖化合物（I）的公式。这些化合物在治疗各种疾病中发挥作用。这些疾病包括自身免疫疾病、炎症性疾病、骨疾病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和与激素相关的疾病。
• Controlled Release of Nitric Oxide And Drugs From Functionalized Macromers And Oligomers
  申请人：Bezwada Rao S.

  公开号：US20120035259A1

  公开（公告）日：2012-02-09

  The present invention provides NO and, optionally, drug releasing macromers and oligomers wherein the drug molecule and NO releasing moiety are linked an absorbable macromer or oligomeric chain susceptible to hydrolytic degradation and wherein the macromer or oligomer comprises of repeat units derived from safe and biocompatible molecules such as glycolic acid, lactic acid, caprolactone and p-dioxanone. Furthermore, the present invention relates to controlled release of nitric oxide (NO) and/or drug molecule from a NO and drug releasing macromer or oligomer. Moreover, the present invention also relates to medical devices, medical device coatings and therapeutic formulations comprising of nitric oxide and drug releasing macromers and oligomers of the present invention.

  本发明提供了一氧化氮(NO)和可选的药物释放的大分子和寡聚物，其中药物分子和一氧化氮释放部分通过可吸收的大分子或可水解降解的寡聚物链连接，并且大分子或寡聚物由来自诸如乙醇酸、乳酸、己内酰胺和对二恶烷等安全且生物相容的分子的重复单元组成。此外，本发明还涉及从一氧化氮和/或药物分子释放的大分子或寡聚物控制释放一氧化氮(NO)。此外，本发明还涉及包含本发明的一氧化氮和药物释放大分子和寡聚物的医疗器械、医疗器械涂层和治疗方法。
• ABSORBABLE BRANCHED POLYESTERS AND POLYURETHANES
  申请人：Bezwada Biomedical, LLC

  公开号：US20140142199A1

  公开（公告）日：2014-05-22

  The present invention relates to the discovery of a new class of hydrolysable isocyanates, hydrolysable branched polyols and branched absorbable polyesters and polyurethanes prepared therefrom. The resultant absorbable polymers are useful for drug delivery, stents, highly porous foam, reticulated foam, tissue engineering, tissue adhesives, adhesion prevention, bone wax formulations, medical device coatings, surface modifying agents and other implantable medical devices. In addition, these absorbable polymers can have a controlled hydrolytic degradation profile.

  本发明涉及一种新型可水解异氰酸酯、可水解支链多元醇及其制备的支链可吸收聚酯和聚氨酯的发现。由此得到的可吸收聚合物可用于药物输送、支架、高孔隙率泡沫、网状泡沫、组织工程、组织粘合剂、防止粘连、骨蜡制剂、医疗设备涂层、表面改性剂以及其他可植入医疗设备。此外，这些可吸收聚合物可以具有受控的水解降解特性。
• Hydroxylated nebivolol metabolites
  申请人：O'Donnell P. John

  公开号：US20070014733A1

  公开（公告）日：2007-01-18

  Hydroxylated nebivolol metabolites increase NO release from human endothelial cell preparations in a concentration dependent fashion following acute administration. In addition, hydroxylated nebivolol metabolites, including but not limited to 4-hydroxy-6,6′difluoro-, 4-hydroxy-5-phenol-6,6′difluoro-, and 4-hydroxy-8-pheno-6,6′difluoro-, have the ability to increase the capacity for NO release in human endothelial cells following chronic administration. This invention provides hydroxylated nebivolol metabolites and compositions comprising nebivolol and/or at least one hydroxylated metabolite of nebivolol and/or at least one additional compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof. In addition, this invention provides methods of treating and/or preventing vascular diseases by administering at least one hydroxylated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one hydroxylated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.

  羟基化奈必洛尔代谢物在急性给药后以浓度依赖性方式增加人内皮细胞制剂的一氧化氮释放。此外，羟基化奈必洛尔代谢物，包括但不限于4-羟基-6,6'-二氟代-、4-羟基-5-苯酚-6,6'-二氟代-和4-羟基-8-苯并-6,6'-二氟代-，在慢性给药后能够增加人内皮细胞的一氧化氮释放能力。本发明提供了羟基化奈必洛尔代谢物和包含奈必洛尔和/或至少一种羟基化奈必洛尔代谢物和/或至少一种用于治疗心血管疾病的附加化合物的组合物，以及可药用的盐。此外，本发明还提供了通过给药至少一种能够释放治疗有效量的一氧化氮到受血管疾病影响的靶向部位的羟基化奈必洛尔代谢物来治疗和/或预防血管疾病的方法。本发明还涉及通过给药至少一种羟基化奈必洛尔代谢物来治疗和/或预防偏头痛。本发明还可以与治疗代谢综合征障碍的其他治疗联合使用，或作为单一治疗。
• [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。

表征谱图