摩熵化学
数据库官网
小程序
打开微信扫一扫
首页 分子通 化学资讯 化学百科 反应查询 关于我们
请输入关键词

reboxetine mesylate | 98769-84-7

中文名称
——
中文别名
——
英文名称
reboxetine mesylate
英文别名
Edronax;(2R)-2-[(R)-(2-ethoxyphenoxy)-phenylmethyl]morpholine mesylate;reboxetine methanesulfonate;(2R)-2-[(R)-(2-ethoxyphenoxy)-phenylmethyl]morpholine;methanesulfonic acid
reboxetine mesylate化学式
CAS
98769-84-7
化学式
CH4O3S*C19H23NO3
mdl
——
分子量
409.503
InChiKey
CGTZMJIMMUNLQD-STYNFMPRSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

物化性质

  • 熔点:
    170-171°C
  • 溶解度:
    H2O:~8 mg/mLat ≤60 °C

计算性质

  • 辛醇/水分配系数(LogP):
    2.7
  • 重原子数:
    28
  • 可旋转键数:
    6
  • 环数:
    3.0
  • sp3杂化的碳原子比例:
    0.4
  • 拓扑面积:
    103
  • 氢给体数:
    2
  • 氢受体数:
    7

ADMET

毒理性
  • 在妊娠和哺乳期间的影响
◉ 母乳喂养期间使用总结:瑞波西汀未获得美国食品药品监督管理局在美国的上市批准,但在其他国家可用。有限的信息表明,母亲每日剂量高达10毫克的瑞波西汀在母乳中产生的水平较低,似乎不会对哺乳婴儿产生任何不良反应。在更多数据可用之前,瑞波西汀在母乳喂养期间应谨慎使用并进行监测。 ◉ 对哺乳婴儿的影响:有四名患有产后抑郁症的母亲在服用平均每日6.5毫克(79微克/千克)瑞波西汀治疗期间,哺乳了1.3到2.1个月(具体程度未说明)。其中一名母亲还每日服用20毫克艾司西酞普兰,另一名每日服用300毫克舍曲林。这些婴儿中没有表现出任何不良反应。其中三名婴儿的丹佛发展评分正常;第四名母亲服用瑞波西汀的婴儿发展年龄仅为正常的71%,但这个问题在母亲服用瑞波西汀之前就已存在。 五名妇女在怀孕和哺乳期间服用了瑞波西汀(具体程度和剂量未说明)。他们的婴儿中没有出现不良反应,并且报告了正常的发展里程碑。 ◉ 对泌乳和母乳的影响:瑞波西汀增加了男性受试者的血清催乳素水平。这一发现对哺乳母亲的意义尚不清楚。已建立泌乳的母亲催乳素水平可能不会影响她的哺乳能力。 一项观察性研究调查了2859名在怀孕前两年内服用抗抑郁药的妇女的结果。与怀孕期间未服用抗抑郁药的妇女相比,整个孕期(三个季度)都服用抗抑郁药的妇女在出院时哺乳的可能性降低了37%。仅在第三季度服用抗抑郁药的妇女在出院时哺乳的可能性降低了75%。仅在第一和第二季度服用抗抑郁药的妇女在出院时哺乳的可能性没有降低。研究中未具体说明母亲使用的抗抑郁药种类。 一项回顾性队列研究比较了2001年至2008年的医院电子医疗记录,研究对象是晚期妊娠期间被开出抗抑郁药的妇女(n = 575)与患有精神疾病但未接受抗抑郁药治疗的妇女(n = 1552)以及没有精神疾病诊断的妇女(n = 30,535)。接受抗抑郁药治疗的妇女在出院时哺乳的可能性比没有精神疾病诊断的妇女低37%,但与未接受治疗的精神疾病母亲相比,哺乳的可能性没有降低。这些母亲中没有人在服用瑞波西汀。 在一项涉及1999年至2008年的80,882对挪威母婴对的研究中,有392名妇女报告在产后新开始使用抗抑郁药,有201名报告从怀孕期间继续使用抗抑郁药。与未暴露的对照组相比,晚期妊娠使用抗抑郁药与哺乳开始的可能性降低7%有关,但对哺乳持续时间和专一性没有影响。与未暴露的对照组相比,新开始或重新开始使用抗抑郁药与在6个月时主要哺乳的可能性降低63%,任何哺乳的可能性降低51%,以及突然停止哺乳的风险增加2.6倍有关。具体抗抑郁药未提及。
◉ Summary of Use during Lactation:Reboxetine is not approved for marketing in the United States by the U.S. Food and Drug Administration, but is available in other countries. Limited information indicates that maternal doses of up to 10 mg daily produce low levels in milk and appear to not result in any adverse effects in breastfed infants. Until more data are available, reboxetine should be used with careful monitoring during breastfeeding. ◉ Effects in Breastfed Infants:Four infants whose mothers had postpartum depression had been breastfed (extent not stated) for 1.3 to 2.1 months during maternal reboxetine therapy at an average dose of 6.5 mg (79 mcg/kg) daily. One of the mothers was also taking escitalopram 20 mg daily and another was taking sertraline 300 mg daily. None of the infants exhibited any adverse reactions. Three of the infants had normal Denver developmental scores; the fourth whose mother was taking reboxetine had a developmental age of only 71% of normal, but the problem predated maternal reboxetine therapy. Five women used reboxetine during pregnancy and lactation (extent not stated) in unspecified doses. No adverse effects were noted in their infants and normal developmental milestones were reported. ◉ Effects on Lactation and Breastmilk:Reboxetine increased serum prolactin in male subjects. The relevance of this finding to nursing mothers is not clear. The prolactin level in a mother with established lactation may not affect her ability to breastfeed. An observational study looked at outcomes of 2859 women who took an antidepressant during the 2 years prior to pregnancy. Compared to women who did not take an antidepressant during pregnancy, mothers who took an antidepressant during all 3 trimesters of pregnancy were 37% less likely to be breastfeeding upon hospital discharge. Mothers who took an antidepressant only during the third trimester were 75% less likely to be breastfeeding at discharge. Those who took an antidepressant only during the first and second trimesters did not have a reduced likelihood of breastfeeding at discharge. The antidepressants used by the mothers were not specified. A retrospective cohort study of hospital electronic medical records from 2001 to 2008 compared women who had been dispensed an antidepressant during late gestation (n = 575) to those who had a psychiatric illness but did not receive an antidepressant (n = 1552) and mothers who did not have a psychiatric diagnosis (n = 30,535). Women who received an antidepressant were 37% less likely to be breastfeeding at discharge than women without a psychiatric diagnosis, but no less likely to be breastfeeding than untreated mothers with a psychiatric diagnosis. None of the mothers were taking reboxetine. In a study of 80,882 Norwegian mother-infant pairs from 1999 to 2008, new postpartum antidepressant use was reported by 392 women and 201 reported that they continued antidepressants from pregnancy. Compared with the unexposed comparison group, late pregnancy antidepressant use was associated with a 7% reduced likelihood of breastfeeding initiation, but with no effect on breastfeeding duration or exclusivity. Compared with the unexposed comparison group, new or restarted antidepressant use was associated with a 63% reduced likelihood of predominant, and a 51% reduced likelihood of any breastfeeding at 6 months, as well as a 2.6-fold increased risk of abrupt breastfeeding discontinuation. Specific antidepressants were not mentioned.
来源:Drugs and Lactation Database (LactMed)

安全信息

  • 安全说明:
    S22,S24/25
  • 储存条件:
    | 2-8°C |

SDS

SDS:4e77db8c3dd7bcfca8cb1688ec87cee6
查看

制备方法与用途

生物活性

Reboxetine mesylate(PNU 155950E,FCE20124)是一种降低肾上腺素重新吸收的抑制剂。其对[3H]小鼠下丘脑突触体对碘化钾的吸收量和[3H]5-HT小鼠纹状体突触对碘化钾吸收的Ki值分别为8.2 nM和1070 nM。

Target Value
去甲肾上腺素再摄取 8.2 nM (Ki)
体外研究

Reboxetine 在计量依赖性下完全抑制[3H]-多巴胺摄取到人去甲肾上腺素转运体(hNET),在MDCK细胞中的Ki值为11 nM。

体内研究
  • Reboxetine 剂量依赖性且有效抑制蓝斑核神经元放电,在大鼠中ED50为191 μg/kg。
  • α2拮抗剂piperoxan(1.5 mg/kg, IV)能够逆转Reboxetine 对蓝斑核神经元的抑制作用。
  • Reboxetine 剂量依赖性逆转小鼠体内reserpine诱导的眼睑痉挛和低体温症。在大鼠中,ED50分别为10 mg/kg 和3 mg/kg (p.o.)。
  • Reboxetine 显著减少DSM-III-R惊恐性障碍症患者惊恐发作的次数和惊恐症状。
  • Reboxetine 也会提高汉米尔顿抑郁评定量表、霍普金斯症状检查表-90,和希恩伤残量表的分数。在复发性DSM-III-R重度抑郁患者的治疗期间,与安慰剂相比,Reboxetine 显著降低复发率(22% vs. 56%),并且具有较大的维持响应的累积概率。
  • Reboxetine 能够有效防止抑郁症状的复发。
去甲肾上腺素和多巴胺
  • Reboxetine 急性全身性给药剂量依赖性增加大鼠额叶皮质中细胞外去甲肾上腺素,而不影响细胞外血清素。
  • Reboxetine (20 mg/kg) 也会增加大鼠额叶皮质中细胞外多巴胺。
  • Reboxetine 长期给药14天,提高大鼠额叶皮质中细胞外去甲肾上腺素和多巴胺的基础浓度,并且大大净增加细胞外去甲肾上腺素和多巴胺,而不影响血清素。
尼古丁自给药
  • Reboxetine 剂量依赖性减少约60%的尼古丁自给药。
  • Reboxetine (5.6 mg/kg) 重复给药减少尼古丁自给药和蔗糖响应。

反应信息

  • 作为反应物:
    描述:
    reboxetine mesylate盐酸 作用下, 以 乙醚乙酸乙酯 为溶剂, 反应 24.0h, 生成 (2R)-2-[(R)-(2-ethoxyphenoxy)-phenylmethyl]morpholine hydrochloride
    参考文献:
    名称:
    US2010/69389
    摘要:
    公开号:
  • 作为产物:
    参考文献:
    名称:
    The use of environmental metrics to evaluate green chemistry improvements to the synthesis of (S,S)-reboxetine succinate
    摘要:
    辉瑞绿色化学指标项目进行了描述,并通过一个案例研究展示了(S,S)-雷博西丁琥珀酸的合成。最初的合成路径采用传统的分离方法,产生了大量废物。随后,该路径被一种对映选择性合成所取代,该合成采用了Sharpless环氧化反应、选择性保护原料醇的酶促反应以及一种新的高效手性莫菲林构建方法作为关键步骤。这些改进使得合成过程中产生的废物减少了90%以上。详细的指标从所有合成路径的共同起始原料(反式肉桂醇)出发进行了呈现。
    DOI:
    10.1039/c1gc15921f
点击查看最新优质反应信息

文献信息

  • [EN] PROCESSES USEFUL FOR THE SYNTHESIS OF (R)-1-{2-[4'-(3-METHOXYPROPANE-1-SULFONYL)-BIPHENYL-4-YL]-ETHYL}-2-METHYL-PYRROLIDINE<br/>[FR] PROCÉDÉS UTILES POUR LA SYNTHÈSE DE LA (R)-1-{2-[4'-(3-MÉTHOXYPROPANE-1-SULFONYL)-BIPHÉNYL-4-YL]-ÉTHYL}-2-MÉTHYL-PYRROLIDINE
    申请人:ARENA PHARM INC
    公开号:WO2009128907A1
    公开(公告)日:2009-10-22
    Processes useful for making a pharmaceutically useful compound according to Formula (I), forms of such a compound, and intermediates useful in such processes are described.
    根据公式(I)制备药用化合物的有用过程,以及该化合物的形式和在这些过程中有用的中间体被描述。
  • [EN] SUBSTITUTED PIPERIDINE COMPOUND AND USE THEREOF<br/>[FR] COMPOSÉ DE PIPÉRIDINE SUBSTITUÉE ET SON UTILISATION
    申请人:TAKEDA PHARMACEUTICALS CO
    公开号:WO2017135306A1
    公开(公告)日:2017-08-10
    Provided is a substituted piperidine compound having an orexin type 2 receptor agonist activity. A compound represented by the formula (I): wherein each symbol is as described in the DESCRIPTION, or a salt thereof has an orexin type 2 receptor agonist activity, and is useful as a prophylactic or therapeutic agent for narcolepsy.
    提供的是一种替代哌啶化合物,具有促进俐克脑肽2型受体激动剂活性。公式(I)所代表的化合物:其中每个符号如描述中所述,或其盐具有促进俐克脑肽2型受体激动剂活性,并且可用作嗜睡症的预防或治疗药物。
  • Novel Bicyclic Pyridinones
    申请人:Pettersson Martin Youngjin
    公开号:US20120252758A1
    公开(公告)日:2012-10-04
    Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I as defined herein. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
    所述化合物及其药用可接受的盐被披露,其中所述化合物具有如本文所定义的Formula I的结构。相应的药物组合物、治疗方法、合成方法和中间体也被披露。
  • HETEROCYCLIC COMPOUND AND USE THEREOF
    申请人:Takeda Pharmaceutical Company Limited
    公开号:US20210198240A1
    公开(公告)日:2021-07-01
    The present invention provides a heterocyclic compound having an orexin type 2 receptor agonist activity. A compound represented by the formula (I): wherein each symbol is as described in the specification, or a salt thereof has an orexin type 2 receptor agonist activity, and is useful as an agent for the prophylaxis or treatment of narcolepsy.
    本发明提供了一种具有orexin类型2受体激动剂活性的杂环化合物。 表示为公式(I)的化合物: 其中每个符号如说明书中所述,或其盐具有orexin类型2受体激动剂活性,并且可用作预防或治疗发作性嗜睡症的药剂。
  • [EN] MODULATORS OF THE HISTAMINE H3 RECEPTOR AND THE TREATMENT OF DISORDERS RELATED THERETO<br/>[FR] MODULATEURS DU RÉCEPTEUR H3 HISTAMINIQUE ET TRAITEMENT DE TROUBLES S'Y RAPPORTANT
    申请人:ARENA PHARM INC
    公开号:WO2014028322A1
    公开(公告)日:2014-02-20
    The present invention relates to compounds of Formula (Ia) and pharmaceutically acceptable salts, solvates, and hydrates thereof, that modulate the activity of the histamine H3 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of histamine H3-associated disorders.
    本发明涉及式(Ia)的化合物及其药用可接受的盐、溶剂和水合物,这些化合物调节组胺H3受体的活性。本发明的化合物和药物组合物用于治疗组胺H3相关疾病的方法。
查看更多