莫沙必利 | 112885-41-3

• 物质功能分类: 原料药 - 消化系统用药 - 止吐催吐药
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 莫沙必利
• 中文别名: 莫沙比利；4-氨基-5-氯-2-乙氧基-N-[[4-(4-氟苄基)-2-吗啉基]甲基]苯甲酰胺
• 英文名称: mosapride
• 英文别名: 4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl]benzamide；4-amino-5-chloro-2-ethoxy-N-((4-(4-fluorobenzyl)morpholin-2-yl)methyl)benzamide；(RS)-4-amino-5-chloro-2-ethoxy-N-{[4-(4-fluoro-benzyl)-2-morpholinyl]-methyl}-benzamide；4-amino-5-chloro-2-ethoxy-N-[[4-[(4-fluorophenyl)methyl]morpholin-2-yl]methyl]benzamide
• CAS: 112885-41-3
• 化学式: C₂₁H₂₅ClFN₃O₃
• mdl: MFCD00867430
• 分子量: 421.899
• InChiKey: YPELFRMCRYSPKZ-UHFFFAOYSA-N

物化性质

• 熔点：
  151-153°C
• 沸点：
  549.2±50.0 °C(Predicted)
• 密度：
  1.272±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  76.8
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 危险品标志：
  F+,C,N
• WGK Germany：
  3
• RTECS号：
  LW9100000
• 海关编码：
  2934999090
• 危险类别：
  8
• 安全说明：
  S16,S26,S27,S28,S29,S33,S36/37/39,S45,S61
• 危险类别码：
  R14,R51/53,R34,R12
• 包装等级：
  II
• 危险品运输编号：
  UN 3260 8/PG 2
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  -20°C 冰箱

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Mosapride
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: Mosapride
CAS number: 112885-41-3

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C21H25ClFN3O3
Molecular weight: 421.9

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen chloride, hydrogen fluoride.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

概述

莫沙必利化学名为4-氨基-5-氯-2-乙氧基-N-[[4-(4-氟苄基)-2-吗啉基]甲基]苯甲酰胺，是一种高选择性5-HT4受体激动剂。其主要作用部位为胃和十二指肠。

用途

莫沙必利为选择性的5-羟色胺(5-HT4)受体激动剂，在临床上主要用于慢性胃炎、功能性消化不良、反流性食管炎及手术后的一系列胃肠道症状的缓解。

市场情况

莫沙必利（Mosapride）由住友大日本公司开发，作为选择性的5-羟色胺4(5-HT4)受体激动剂，用于治疗与慢性胃炎相关疾病。1998年10月，该产品首次在日本上市，并随后在阿根廷、印度、中美洲及中国（2001年）、韩国等地市场推出。2006年4月，卫材公司在包括东盟在内的10个亚洲国家获得了莫沙必利的开发、生产和销售权。

目前，国外主要销售公司为住友大日本公司，国内则以康弘药业为主。枸橼酸莫沙必利片拥有四个批准文号，而枸橼酸莫沙必利胶囊、分散片和口服溶液各有一个批准文号。进口药品是住友大日本公司的枸橼酸莫沙必利片（商品名：加斯清）。根据米内网数据显示，康弘药业的莫沙必利片及分散片在2016年的销售额超过3亿元。

生物活性

Mosapride是一种胃动力药，为选择性的5-HT4激动剂。

靶点

Target	Value
5HT4	()

生产方法

2-氨甲基-4-(4-氟苄基)吗啉溶于二氯甲烷，加入4-氨基-5-氯-2-乙氧基苯甲酸和1-乙基-3-(3-二甲氨基丙基)碳化二亚胺盐酸盐，在25%搅拌下反应4小时。反应液依次用水、氢氧化钠水溶液及饱和氯化钠水溶液洗涤，干燥后过滤并减压浓缩。得到的物质用乙醇重结晶以获得莫沙必利。

将莫沙必利溶于乙醇中，加入35%氯化氢的乙醇溶液过滤收集沉淀，再用乙醇进行重结晶，得盐酸莫沙必利。

将莫沙必利溶于热的10%枸橼酸水溶液中，然后缓慢冷却并过滤以收集沉淀，获得枸橼酸莫沙必利二水合物。

反应信息

• 作为反应物：
  描述：

  莫沙必利 在 柠檬酸 作用下， 以 水 为溶剂， 以86%的产率得到4-氨基-5-氯-2-乙氧基-N-[[4-(4-氟苄基)-2-吗啉基]甲基]苯甲酰胺枸橼酸盐
  参考文献：
  名称：

  [EN] PROCESS FOR THE SYNTHESIS OF MOSAPRIDE
  [FR] PROCEDE DE SYNTHESE D'UN DERIVE BENZAMIDE

  摘要：

  公开号：

  WO2003106440A3
• 作为产物：
  描述：

  (RS)-4-(tert-butoxy-carbonyl-amino)-5-chloro-2-ethoxy-N-{[4-(4-fluoro-benzyl)-2-morpholinyl]methyl}-benzamide 在 盐酸 作用下， 以 水 为溶剂， 反应 3.0h， 以100%的产率得到莫沙必利
  参考文献：
  名称：

  [EN] PROCESS FOR THE SYNTHESIS OF MOSAPRIDE
  [FR] PROCEDE DE SYNTHESE D'UN DERIVE BENZAMIDE

  摘要：

  公开号：

  WO2003106440A3

文献信息

• [EN] SULFONYL COMPOUNDS THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN<br/>[FR] COMPOSÉS DE SULFONYLE QUI INTERAGISSENT AVEC LA PROTÉINE RÉGULATRICE DE LA GLUCOKINASE
  申请人：AMGEN INC

  公开号：WO2013123444A1

  公开（公告）日：2013-08-22

  The present invention relates to sulfonyl compounds that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where glucokinase regulatory protein is involved using the compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions that contain the compounds, or pharmaceutically acceptable salts thereof.

  本发明涉及与葡萄糖激酶调节蛋白相互作用的磺酰基化合物。此外，本发明涉及使用这些化合物或其药学上可接受的盐治疗2型糖尿病和其他涉及葡萄糖激酶调节蛋白的疾病和/或症状的方法，以及含有这些化合物或其药学上可接受的盐的药物组合物。
• [EN] INDAZOLE- AND PYRROLOPYRIDINE-DERIVATIVE AND PHARMACEUTICAL USE THEREOF<br/>[FR] DÉRIVÉ D'INDAZOLE ET PYRROLOPYRIDINE ET UTILISATION PHARMACEUTIQUE DE CELUI-CI
  申请人：DAINIPPON SUMITOMO PHARMA CO

  公开号：WO2012169649A1

  公开（公告）日：2012-12-13

  The present invention relates to a novel indazole- or pyrrolopyridine-derivative, represented by the formula (1) below, that has an agonistic action or a partial agonistic action against serotonin-4 receptor, and a pharmaceutical composition comprising the same. Formula (1) [wherein each substituent is as defined in claim 1]

  本发明涉及一种新型吲唑基或吡咯吡啶基衍生物，由下面的式（1）表示，该衍生物对5-羟色胺-4受体具有激动作用或部分激动作用，并且包括含有该衍生物的药物组合物。式（1）[其中每个取代基如权利要求1所定义]
• [EN] LYMPHATIC SYSTEM-DIRECTING LIPID PRODRUGS<br/>[FR] PROMÉDICAMENTS LIPIDIQUES ORIENTANT VERS LE SYSTÈME LYMPHATIQUE
  申请人：ARIYA THERAPEUTICS INC

  公开号：WO2019046491A1

  公开（公告）日：2019-03-07

  The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, as well as methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a provided lipid prodrug or a pharmaceutical composition thereof.

  本发明提供了淋巴系统定向脂质前药，其制药组合物，制备这种前药和组合物的方法，以及改善作为脂质前药一部分的治疗剂的生物利用度或其他性质的方法。本发明还提供了治疗疾病、紊乱或症状的方法，包括向需要的患者施用所提供的脂质前药或其制药组合物。
• 5-Membered heterocyclic compound
  申请人：Nishida Haruyuki

  公开号：US20090156642A1

  公开（公告）日：2009-06-18

  The present invention provides 5-membered heterocycle compounds represented by the following general formula (I): The present compounds have a superior acid secretion inhibitory effect, and shows an antiulcer activity and the like.

  本发明提供了以下通式(I)表示的5元杂环化合物： 本化合物具有优异的抑制胃酸分泌效果，并显示出抗溃疡活性等。
• 8-azabicyclo[3.2.1]octyl-2-hydroxybenzamide compounds as mu opioid receptor antagonists
  申请人：Saito Daisuke Roland

  公开号：US20090062333A1

  公开（公告）日：2009-03-05

  The invention provides 8-azabicyclo[3.2.1]octyl-2-hydroxybenzamide compounds of formula (I): wherein R 2 , R 7 , and m are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are antagonists at the mu opioid receptor. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat conditions associated with mu opioid receptor activity, and processes and intermediates useful for preparing such compounds.

  本发明提供了式(I)的8-氮杂双环[3.2.1]辛基-2-羟基苯甲酰胺化合物： 式中，R2、R7和m如说明书中所定义，或其药用可接受的盐，这些化合物是μ阿片受体的拮抗剂。本发明还提供了包含这些化合物的药物组合物，使用这些化合物治疗与μ阿片受体活性相关病症的方法，以及用于制备这些化合物的过程和中间体。