依托咪酯EP杂质B | 61045-91-8

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 依托咪酯EP杂质B
• 英文名称: (R)-Metomidate
• 英文别名: (R)-(+)-methyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate；(R)-methyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate；methyl ester metomidate；(R)-methomidate；metomidate；methyl 3-[(1R)-1-phenylethyl]imidazole-4-carboxylate
• CAS: 61045-91-8
• 化学式: C₁₃H₁₄N₂O₂
• 分子量: 230.266
• InChiKey: FHFZEKYDSVTYLL-SNVBAGLBSA-N

物化性质

• 溶解度：
  氯仿（微溶）、甲醇（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  依托咪酯EP杂质B 在 sodium hydroxide 、 水 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 1.0h， 以86%的产率得到1-[(1R)-1-苯基乙基]-1H-咪唑-5-羧酸
  参考文献：
  名称：

  WO2007/144725

  摘要：

  公开号：
• 作为产物：
  描述：

  依托咪酯 在 硫酸 、 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 22.0h， 生成 依托咪酯EP杂质B
  参考文献：
  名称：

  CN116354888

  摘要：

  公开号：

文献信息

• [EN] ANESTHETIC COMPOUNDS AND RELATED METHODS OF USE<br/>[FR] COMPOSÉS ANESTHÉSIQUES ET PROCÉDÉS D'UTILISATION AFFÉRENTS
  申请人：GEN HOSPITAL CORP

  公开号：WO2013106717A1

  公开（公告）日：2013-07-18

  Provided herein are compounds according to formula (I): Provided herein is also a pharmaceutical composition comprising a compound according to formula (I) and a pharmaceutically acceptable carrier, and a method for providing anesthesia in a subject by administering such a pharmaceutical composition.

  本文提供了符合以下式(I)的化合物。本文还提供了一种包含符合式(I)的化合物和药用可接受载体的药物组合物，以及通过给予受试者这种药物组合物来提供麻醉的方法。
• Chemoenzymatic Synthesis of Stannylated Metomidate as a Precursor for Electrophilic Radiohalogenations ? Regioselective Alkylation of Methyl 1H-Imidazole-5-carboxylate [1]
  作者：Friedrich Hammerschmidt、Biljana Peric Simov、Susanne Schmidt、Sabine Schneider、Ilse Zolle

  DOI：10.1007/s00706-004-0242-2

  日期：2005.2

  99%) substituted with iodine in the phenyl ring was prepared from ( S )-1-(4-iodophenyl)ethanol ( ee >98%) obtained by lipase-catalysed resolution and methyl 1 H -imidazole- 5-carboxylate. The two fragments were joined highly regioselectively (alkylation only at N-1 of substituted imidazole) with inversion of configuration using the Mitsunobu reaction. Finally, p -iodometomidate was transformed into the

  由（ S ）-1-（4-碘苯基）乙醇（ ee > 98％）通过脂肪酶催化拆分和1 H- 咪唑甲基5-羧酸甲酯制得 在苯环中被碘取代的甲酰胺基（ ee 99％） 。使用 Mitsunobu 反应将两个片段高度区域选择性地连接（仅在取代的咪唑的N-1处烷基化），并且构型反转 。最终， 将对 碘代苯甲酸酯转化为 对 三甲基锡烷基衍生物。
• HPLC Enantioseparation with Cellulose Tris(3,5-dichlorophenylcarbamate) in Aqueous Methanol as a Mobile Phase
  作者：Bezhan Chankvetadze、Chiyo Yamamoto、Yoshio Okamoto

  DOI：10.1246/cl.2000.352

  日期：2000.4

  The appropriate design of mobile and stationary phase combinations allowed the use of cellulose tris(3,5-dichlorophenylcarbamate) (CDCPC) as the chiral stationary phase (CSP) in high-performance liquid chromatography (HPLC). Together with previous data obtained in n-hexane/2-propanol as a mobile phase the present study indicates very high chiral resolving ability of CDCPC.

  适当的移动相和固定相组合设计允许将纤维素三（3,5-二氯苯基氨基甲酸酯）(CDCPC)作为高效液相色谱（HPLC）中的手性固定相（CSP）使用。结合在正己烷/异丙醇作为移动相中获得的先前数据，本研究表明CDCPC具有非常高的手性分离能力。
• New Selective Inhibitors of Steroid 11β-Hydroxylation in the Adrenal Cortex. Synthesis and Structure–Activity Relationship of Potent Etomidate Analogues
  作者：Ilse M. Zolle、Michael L. Berger、Friedrich Hammerschmidt、Stefanie Hahner、Andreas Schirbel、Biljana Peric-Simov

  DOI：10.1021/jm800012w

  日期：2008.4.1

  functionalized MTO analogues. Our results indicated that (1) ( R)-configuration is essential for high affinity, (2) highest potency resides in the ethyl, 2-propyl, and 2-fluoroethyl esters, and (3) substitution of the phenyl ring is well tolerated. The clinically used inhibitors metyrapone and ketoconazole inhibited (131)I-IMTO binding with low affinity. Incubation of selected analogues with human adrenocortical

  依托咪酯的衍生物被评估为肾上腺类固醇11β-羟基化的抑制剂。Mitsunobu的立体选择性偶联产生了手性纯的类似物，以研究酯的构型，修饰和苯环中的取代作用，目的是探查引入放射性核素的特定位点。标记有碘131的碘代乙二胺碘酸盐（IMTO）用作放射性配体，用于结构亲和关系研究。我们已经表征了大鼠肾上腺膜上特异性（131）I-IMTO结合的动力学参数，并使用（131）I-IMTO结合的置换来评估功能化的MTO类似物。我们的结果表明，（1）（R）-构型对于高亲和力至关重要，（2）最高效力在于乙基，2-丙基和2-氟乙基酯，（3）对苯环的取代具有良好的耐受性。临床上使用的抑制剂甲吡酮和酮康唑以低亲和力抑制（131）I-IMTO结合。选定的类似物与人肾上腺皮质NCI-h295细胞的孵育表明与对皮质醇分泌的抑制作用高度相关。
• Development of [18F]FAMTO: A novel fluorine-18 labelled positron emission tomography (PET) radiotracer for imaging CYP11B1 and CYP11B2 enzymes in adrenal glands
  作者：Salvatore Bongarzone、Filippo Basagni、Teresa Sementa、Nisha Singh、Caleb Gakpetor、Vincent Faugeras、Jayanta Bordoloi、Antony D. Gee

  DOI：10.1016/j.nucmedbio.2018.11.002

  日期：2019.1

  Introduction: Primary aldosteronism accounts for 6-15% of hypertension cases, the single biggest contributor to global morbidity and mortality. Whilst similar to 50% of these patients have unilateral aldosterone-producing adenomas, only a minority of these have curative surgery as the current diagnosis of unilateral disease is poor. Carbon-11 radiolabelled metomidate ([C-11]MTO) is a positron emission tomography (PET) radiotracer able to selectively identify CYP11B1/2 expressing adrenocortical lesions of the adrenal gland. However, the use of [C-11]MTO is limited to PET centres equipped with on-site cyclotrons due to its short half-life of 20.4 min. Radiolabelling a fluorometomidate derivative with fluorine-18 (radioactive half life 109.8 min) in the para-aromatic position ([F-18]FAMTO) has the potential to overcome this disadvantage and allow it to be transported to noncyclotron-based imaging centres.Methods: Two strategies for the one-step radio-synthesis of [F-18]FAMTO were developed. [F-18]FAMTO was obtained via radiofluorination via use of sulfonium salt (1) and boronic ester (2) precursors. [ 18 F]FAMTO was evaluated in vitro by autoradiography of pig adrenal tissues and in vivo by determining its biodistribution in rodents. Rat plasma and urine were analysed to determine [F-18]FAMTO metabolites.Results: [F-18]FAMTO is obtained from sulfonium salt (1) and boronic ester (2) precursors in 7% and 32% nonisolated radiochemical yield (RCY), respectively. Formulated [F-18]FAMTO was obtained with >99% radiochemical and enantiomeric purity with a synthesis time of 140 min from the trapping of [F-18]fluoride ion on an anionexchange resin (QMA cartridge). In vitro autoradiography of [F-18]FAMTO demonstrated exquisite specific binding in CYP11B-rich pig adrenal glands. In vivo [F-18]FAMTO rapidly accumulates in adrenal glands. Liver uptake was about 34% of that in the adrenals and all other organs were <12% of the adrenal uptake at 60 min post-injection. Metabolite analysis showed 13% unchanged [F-18]FAMTO in blood at 10 min post-administration and rapid urinary excretion. In vitro assays in human blood showed a free fraction of 37.5%.Conclusions: [F-18]FAMTO, a new F-18-labelled analogue of metomidate, was successfully synthesised. In vitro and in vivo characterization demonstrated high selectivity towards aldosterone-producing enzymes (CYP11B1 and CYP11B2), supporting the potential of this radiotracer for human investigation. (C) 2018 The Authors. Published by Elsevier Inc.