福多司坦 | 13189-98-5

• 物质功能分类: 生物化工 - 常见氨基酸及蛋白质类
• 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
• 中文名称: 福多司坦
• 中文别名: 福多斯坦；弗多司坦；(-)-(R)-2-氨基-3-(3-羟丙基硫代)丙酸
• 英文名称: Fudosteine
• 英文别名: (2R)-2-azaniumyl-3-(3-hydroxypropylsulfanyl)propanoate
• CAS: 13189-98-5
• 化学式: C₆H₁₃NO₃S
• 分子量: 179.24
• InChiKey: KINWYTAUPKOPCQ-YFKPBYRVSA-N

物化性质

• 熔点：
  200-202°C (dec.)
• 沸点：
  354.5±42.0 °C(Predicted)
• 密度：
  1.301±0.06 g/cm3(Predicted)
• 溶解度：
  可微溶于水

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  11
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P280,P305+P351+P338,P310
• 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: Fudosteine
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: Fudosteine
CAS number: 13189-98-5

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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, refrigerated.
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: C6H13NO3S
Molecular weight: 179.2

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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, sulfur oxides.

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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

祛痰药 福多司坦（Fudosteine）

福多司坦，化学名为(-)-(R)-2-氨基-3-(3-羟丙基硫代)丙酸，是一种具有祛痰作用的半胱氨酸衍生物。它由日本三菱制药株式会社和S.S制药株式会社研制。该药物药效强、副作用小、适应症广且市场潜力大，适用于支气管哮喘、慢性支气管炎、支气管扩张症、肺结核、尘肺症、肺气肿、非典型分枝杆菌感染及弥漫性细支气管炎等慢性呼吸系统疾病的祛痰。

理化性质

福多司坦为白色或淡黄色结晶性粉末状，无臭。

药理作用

1. 抑制分泌粘蛋白的杯状细胞的过量形成。
2. 改善黏液状态的作用。
3. 气道浆液性分泌亢进作用。
4. 气道炎症抑制作用。

制备方法

福多司坦的合成有多种途径，以下是几种常见的方法及其优缺点：

1. 以L-半胱氨酸与3-溴-1-丙醇为原料，在碱性条件下反应合成。该方法存在的缺点是反应时间较长且会产生等摩尔无机盐，产品纯度低、收率较低（71%），成本高，不利于工业化生产。
2. 将L-半胱氨酸与烯丙醇用热引发、光照或在过氧化物等自由基催化剂存在下反应制备福多司坦。该法缺点是光照条件不适合工业化生产；单独使用无机类过氧化物引发剂分解温度较高。
3. 以L-半胱氨酸与烯丙醇为原料，采用K2S2O8-NaHSO3作为氧化-还原催化体系来合成福多司坦。具体操作步骤如下：
   • 将210g L-半胱氨酸投入100mL水中搅拌使其溶解。
   • 在搅拌下依次加入310g 3-溴-1-丙醇、K2S2O8 1g、NaHSO3 0.38g。
   • 加热至50℃，搅拌8小时。 TLC监测反应。
   • 反应完成后，减压除去水与过量的3，加入200mL无水乙醇，搅拌后有白色固体析出；静置2小时后过滤。
   • 滤液浓缩至残余液约20mL，倒入搅拌着的丙酮中，得白色固体10.2g福多司坦。

有关福多司坦的概述、制备方法、用途、用法、注意事项均由Chemicalbook的丁红编辑整理（2016-03-03）。

适应症

福多司坦适用于支气管哮喘、慢性支气管炎、支气管扩张症、肺结核、尘肺症、肺气肿、非典型分枝杆菌感染及弥漫性细支气管炎等慢性呼吸系统疾病的祛痰治疗。

不良反应

• 消化系统：常见（＞1/100，＜1/10）的有食欲不振、恶心、呕吐；少见(＞1/1000，＜1/100)的有腹痛、腹泻、便秘、胸闷、胃痛、胃部不适、胃部烧灼感、腹涨、口干等。
• 感觉器官：耳鸣、味觉异常。
• 肝功能损害患者：可能导致肝功能进一步恶化；
• 心功能障碍患者：可能对心功能不全患者产生不良影响。

用法

成人口服，每次2粒，一日3次。

注意事项

对胃肠的刺激性轻。用途用于治疗支气管哮喘、支气管扩张、慢性支气管炎、肺结核、尘肺、肺气肿等慢性呼吸系统疾病。

反应信息

• 作为反应物：
  描述：

  福多司坦 在 盐酸 、 potassium hydrogencarbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 5.0h， 生成 (R)-2-(tert-butoxycarbonylamino)-3-(3-hydroxypropylsulfonyl)propionic acid benzyl ester
  参考文献：
  名称：

  CN103739526

  摘要：

  公开号：
• 作为产物：
  描述：

  S-formylethylcysteine 在 sodium tetrahydroborate 作用下， 反应 2.0h， 以34.5 g的产率得到福多司坦
  参考文献：
  名称：

  一种福多司坦的合成方法

  摘要：

  本发明涉及一种福多司坦的合成方法，属生物医药产业领域。以L‑半胱氨酸与丙烯醛为原料，在酸性水溶液中，进行Michael加成反应，之后加入硼氢化钠还原，一锅法合成福多司坦，重结晶得到高纯度的福多司坦。本制备方法反应条件温和可控，产品收率95%，液相纯度99.8%。

  公开号：

  CN110922345B

文献信息

• TROPAN COMPOUND
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1785421A1

  公开（公告）日：2007-05-16

  The conventional anticholinergic drugs for administration through inhalation have been considered to have the possibility of aggravating dysuria associated with prostatic hyperplasia mediated by blood, and it has been demanded that the conventional anticholinergic drugs for administration through inhalation will have to show reduced side effects or adverse ractions. The present invention relates to a compound represented by the general formula (I): (wherein A represents; and R1, R2, R3 and R1 each a hydrogen atom or a substituent; R5 is a substituent; X- is an anion;the symbol: denotes an exo-form or endo-form, or their mixture), its salt or solvation product thereof. They are useful as a prophylactic and/or therapeutic agent with reduced side effects or adverse reactions for the diseases mediated by the muscarinic receptor.

  传统的抗胆碱药物通过吸入给药被认为可能加重与前列腺增生相关的排尿困难，并要求传统的抗胆碱药物通过吸入给药必须显示减少副作用或不良反应。 本发明涉及一种由通式（I）表示的化合物： （其中A代表; 和R1、R2、R3和R1分别是氢原子或取代基; R5是取代基; X-是阴离子;符号: 表示外向型或内向型，或它们的混合物），其盐或溶剂化产物。它们可用作通过胆碱受体介导的疾病的预防和/或治疗剂，具有减少副作用或不良反应。
• FUROISOQUINOLINE DERIVATIVE AND USE THEREOF
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1541576A1

  公开（公告）日：2005-06-15

  The present invention provides a compound represented by the formula    wherein A represents (1) a bond, (2) a group represented by the formula -CRa=CRb- (Ra and Rb each represent a hydrogen atom or C1-6 alkyl) and the like; R1 represents (1) cyano or (2) an optionally esterified or amidated carboxyl group; R2 represents (1) a hydrogen atom, (2) an optionally substituted hydroxy group, (3) an optionally substituted amino group and the like; R3 and R4 each represent a hydrogen atom and the like; R5 represents a hydrogen atom and the like; R6 represents an optionally substituted hydroxy group and the like; R7and R8 each represent an optionally substituted hydrocarbon group and the like; R9 and R10 each represent (1) a hydrogen atom and the like; Y represents an optionally substituted methylene group; and n represents 0 or 1, or a salt thereof, which has an excellent phosphodiesterase IV inhibiting action.

  本发明提供了一种化合物，其表示为式中的化合物，其中A代表（1）键，（2）由式 -CRa=CRb-（Ra和Rb分别代表氢原子或C1-6烷基等）表示的基团等；R1代表（1）氰基或（2）可选择酯化或酰胺化的羧基；R2代表（1）氢原子，（2）可选择取代的羟基，（3）可选择取代的氨基等；R3和R4各自代表氢原子等；R5代表氢原子等；R6代表可选择取代的羟基等；R7和R8各自代表可选择取代的碳氢基团等；R9和R10各自代表（1）氢原子等；Y代表可选择取代的亚甲基基团；n代表0或1，或其盐，具有优异的磷酸二酯酶IV抑制作用。
• 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] NEW CCR2 RECEPTOR ANTAGONISTS AND USES THEREOF<br/>[FR] NOUVEAUX ANTAGONISTES DU RÉCEPTEUR CCR2 ET LEURS UTILISATIONS
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2011073154A1

  公开（公告）日：2011-06-23

  The present invention relates to novel antagonists for CCR2 (CC chemokine receptor 2) of Formula (I) and their use for providing medicaments for treating conditions and diseases, especially pulmonary diseases like asthma and COPD.

  本发明涉及一种新型CCR2（CC趋化因子受体2）拮抗剂的化学式（I），以及它们用于提供治疗疾病和病症的药物，特别是肺部疾病如哮喘和慢性阻塞性肺病。
• NEW CCR2 RECEPTOR ANTAGONISTS AND USES THEREOF
  申请人：Ebel Heiner

  公开号：US20120004252A1

  公开（公告）日：2012-01-05

  The present invention relates to novel antagonists for CCR2 (CC chemokine receptor 2) and their use for providing medicaments for treating conditions and diseases, especially pulmonary diseases like asthma and COPD.

  本发明涉及用于治疗疾病和疾病的新型CCR2（CC趋化因子受体2）拮抗剂及其用途，特别是用于治疗哮喘和慢性阻塞性肺病等肺部疾病的药物。