N,N'-(1,2-ethanediyl)-bis-(L-cysteine diethyl ester) | 121251-02-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N,N'-(1,2-ethanediyl)-bis-(L-cysteine diethyl ester)
• 英文别名: N,N'-1,2-ethylenediylbis-L-cysteine diethyl ester；1,2-Bis-(1-Ethoxycarbonyl-2-mercapto-ethylamino)-ethan；Bicisate；ethyl (2R)-2-[2-[[(2R)-1-ethoxy-1-oxo-3-sulfanylpropan-2-yl]amino]ethylamino]-3-sulfanylpropanoate
• CAS: 121251-02-3
• 化学式: C₁₂H₂₄N₂O₄S₂
• 分子量: 324.466
• InChiKey: RZQNBTMGBODDSK-UWVGGRQHSA-N

物化性质

• 沸点：
  444.1±45.0 °C(Predicted)
• 密度：
  1.158±0.06 g/cm3(Predicted)
• 熔点：
  196-198ºC
• 溶解度：
  Insoluble

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  20
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  78.7
• 氢给体数：
  4
• 氢受体数：
  8

ADMET

代谢

Bicisate被酯酶作用代谢生成单酸和二酸。确切的代谢转化尚未阐明。

Bicisate is metabolized to form mono- and di-acids by the action of esterases. The exact metabolic transformation has not been elucidated.

来源:DrugBank

毒理性

• 蛋白质结合

Bicisate及其主要代谢物不与蛋白质结合。

Bicisate and its major metabolites are not protein-bound.

来源:DrugBank

吸收、分配和排泄

• 吸收

静脉给药后，双三嗪显示出非常大的脑提取率。给药后一小时，大约5%的给药剂量仍留在血液中。血液中放射性活性的最高浓度在静脉注射后0.5分钟达到，占注射剂量的13.9%。静脉给予双三嗪后，渗透性表面积为0.48 ml·g/min。

After intravenous administration, bicisate presents a very large brain extraction. About 5% of the administered dose remains in the blood one hour after administration. The highest concentration of radioactivity in blood was attained 0.5 minutes after intravenous injection and it represented 13.9% of the injected dose. After intravenous administration of bicisate, the permeability surface area was 0.48 ml.g/min.

来源:DrugBank

吸收、分配和排泄

• 消除途径

Bicisate主要通过肾脏排泄。据报道，初次给药后两小时内，有50%的剂量通过尿液排出，甚至在24小时后，有74%的给药剂量通过尿液排出。初次给药后48小时，仅有12.5%的给药剂量通过粪便排出。

Bicisate is primarily excreted by the kidneys. It has been reported that 50% of the dose is excreted in urine two hours after initial administration and even 74% of the administered dose is excreted in urine after 24 hours. Fecal excretion just accounts for 12.5% of the administered dose 48 hours after initial administration.

来源:DrugBank

吸收、分配和排泄

• 分布容积

静脉给药双脒酸后，分布体积为0.74升。

After intravenous administration of bicisate, the distribution volume was 0.74 L.

来源:DrugBank

吸收、分配和排泄

• 清除

从1到24小时，作为亲水性示踪剂的损失，bisisate的清除率大约为每小时3.5%。

The clearance of bicisate from 1 to 24 hours, studied as a loss of hydrophilic tracer, is of approximate 3.5% per hour.

来源:DrugBank

反应信息

• 作为产物：
  描述：

  S,S'-bis-benzyl ethylene-bis-L-cysteine 在 盐酸 、 氨 、 sodium 作用下， 生成 N,N'-(1,2-ethanediyl)-bis-(L-cysteine diethyl ester)
  参考文献：
  名称：

  1-噻唑烷-4-甲酸的液氨钠还原反应中间体的二聚反应

  摘要：

  在液氨中用钠将 l-噻唑烷-4-羧酸 (II) 还原，取决于随后的反应程序，生成 N-甲基-l-半胱氨酸 (I) 或 N-甲基-l-半胱氨酸的混合物 ( I) (30%) 和二聚体 (50%)，其结构显示为 VI。与文献中所表达的相反，1,2-二氯乙烷与半胱氨酸 (III) 在 8-10 的 pH 值下反应不会生成化合物 VI，而是生成化合物 VIII。

  DOI：

  10.1139/v67-009

文献信息

• Radiochemical synthesis and preliminary evaluation of anti-bladder cancer monoclonal antibody BDI-1 labeled with rhenium-188
  作者：Rongfu Wang、Chungli Zhang、Lizhang Yu、Yifeng Guo、Ying Bai

  DOI：10.1002/jlcr.470

  日期：2001.5

  The anti-human bladder cancer monoclonal antibody BDI-1 was radio-labeled with rhenium-188 by direct labeling methods using SnCl2 as reductant and MDP as stannous stabilizer or by indirect method using NHS-ECM ester as bifunctional chelator. Radiochemical yields of 30±7.23% and 87.4±5.67% and radiochemical purity of more than 95% were achieved. The inmmunoreactive fraction was 58.7%. The results showed that radionuclide 188Re might be employed using the same labeling methodology with 99mTc labeling of BDI-1 for radiommunoimaging (RII) and radioimmunotherapy (RIT) and that may be useful in radioimmunodetection and RIT of human bladder carcinoma in vivo. Copyright © 2001 John Wiley & Sons, Ltd.

  以SnCl2为还原剂、MDP为亚锡稳定剂的直接标记法或以NHS-ECM酯为双功能螯合剂的间接标记法对抗人膀胱癌单克隆抗体BDI-1进行了铼-188的放射性标记。放射性化学收率分别为 30±7.23% 和 87.4±5.67%，放射性化学纯度超过 95%。非放射性部分为 58.7%。结果表明，放射性核素 188Re 与 BDI-1 的 99mTc 标记方法相同，可用于放射共成像（RII）和放射免疫治疗（RIT），并可用于体内人类膀胱癌的放射免疫检测和 RIT。Copyright © 2001 John Wiley & Sons, Ltd. All Rights Reserved.
• BUTYRYLCHOLINESTERASE LIGANDS AS DIAGNOSTIC TOOLS AND TREATMENT FOR DESEASES OF THE NERVOUS SYSTEM
  申请人：Darvesh Sultan

  公开号：US20110212026A1

  公开（公告）日：2011-09-01

  Compounds useful for the early diagnosis of malignant tumors, multiple sclerosis, and especially Alzheimer's Disease and related dementias; especially compounds of Formula (I) wherein R 1 is selected from the group consisting of hydrogen, cyano, fluoro, iodo, alkyl, and aryl; R 2 is selected from the group consisting of hydrogen, alkyl, and aryl; X is selected from the group consisting of CH 2 , CH 2 O, oxygen, OCH 2 , CH 2 S, SCH 2 , NH, N-alkyl, and N-aryl; Y is an optional spacer group, absent or selected from the group consisting of oxygen, sulfur, NH, N-alkyl, and N-aryl; and Z is selected from the group consisting of alkyl substituted with cyano, fluoro, or iodo and aryl substituted with cyano, fluoro, or iodo. In a preferred embodiment, R 1 and R 2 are hydrogen, X is CH 2 O, Y is absent, and Z is phenyl substituted with fluoro, cyano, or iodo. In some embodiments, Z is more specifically 18 F-phenyl or 123 I-phenyl or 131 I-phenyl. Other compounds are also provided.

  本发明提供了用于早期诊断恶性肿瘤、多发性硬化症，尤其是阿尔茨海默病和相关痴呆症的化合物，特别是式（I）的化合物，其中R1选自氢、氰、氟、碘、烷基和芳基组成的群体；R2选自氢、烷基和芳基组成的群体；X选自CH2、CH2O、氧、OCH2、CH2S、SCH2、NH、N-烷基和N-芳基组成的群体；Y是可选的间隔基团，不存在或选自氧、硫、NH、N-烷基和N-芳基组成的群体；Z选自用氰、氟或碘取代的烷基和用氰、氟或碘取代的芳基组成的群体。在首选实施例中，R1和R2为氢，X为CH2O，Y不存在，Z为用氟、氰或碘取代的苯基。在某些实施例中，Z更具体地为18F-苯基或123I-苯基或131I-苯基。本发明还提供了其他化合物。
• COMPOSITION FOR PREPARATION OF RADIOACTIVE PHARMACEUTICAL FOR DIAGNOSIS OF REGIONAL CEREBRAL BLOOD FLOW
  申请人：Fujifilm RI Pharma Co., Ltd.

  公开号：EP2000154A2

  公开（公告）日：2008-12-10

  An object of the present invention is to provide a composition for effectively labeling ECD with 99mTc within a short period of time. The composition for producing [N,N'-ethylenedi-L-cysteinate(3-)]oxotechnetium(99mTc) diethyl ester is characterized by containing N,N'-(1,2-ethylene)bis-L-cysteine diethyl ester or a salt thereof, a reducing agent, and an acidic substance or a salt thereof.

  本发明的目的是提供一种在短时间内用 99mTc 有效标记 ECD 的组合物。 生产[N,N'-亚乙基-L-半胱氨酸（3-）]氧锝（99m锝）二乙酯的组合物的特征是含有 N,N'-（1,2-亚乙基）双-L-半胱氨酸二乙酯或其盐、还原剂和酸性物质或其盐。
• TERNARY LIGAND COMPLEXES USEFUL AS RADIOPHARMACEUTICALS
  申请人：Du Pont Pharmaceuticals Company

  公开号：EP0984791A1

  公开（公告）日：2000-03-15
• US5280015A
  申请人：——

  公开号：US5280015A

  公开（公告）日：1994-01-18