氢溴酸达非那新 | 133099-07-7

• 物质功能分类: 生物化工 - 抑制剂 - 神经信号通路(Neuronal Signaling)
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 氢溴酸达非那新
• 中文别名: 氢溴酸达菲那新；可比司他；{1-[2-(2,3-二氢苯并呋喃-5-基)乙基]-3-吡咯烷基}-2,2-二苯基乙酰胺氢溴酸盐
• 英文名称: (S)-darifenacin hydrobromide
• 英文别名: Darifenacin hydrobromide；3-(S)-(-)-(1-carbamoyl-1,1-diphenylmethyl)-1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]pyrrolidine hydrobromide；darifenacin monohydrobromide；darifenacine hydrobromide；(3S)-1-[2-(2,3-dihydro-5-benzofuranyl)ethyl]-α,α-diphenyl-3-pyrrolidine acetamide hydrobromide；2-[(3S)-1-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]pyrrolidin-3-yl]-2,2-diphenylacetamide;hydron;bromide
• CAS: 133099-07-7
• 化学式: BrH*C₂₈H₃₀N₂O₂
• 分子量: 507.47
• InChiKey: UQAVIASOPREUIT-VQIWEWKSSA-N

物化性质

• 熔点：
  228-2300C
• 比旋光度：
  25D -30.3° (c = 1.0 in methylene chloride)
• 溶解度：
  在DMSO中的溶解度为20mg/mL，澄清

计算性质

• 辛醇/水分配系数(LogP)：
  4.54
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  55.6
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• WGK Germany：
  3
• 海关编码：
  2934990002
• 危险品运输编号：
  NONH for all modes of transport
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  -20°C冷冻室

SDS

---

SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : Darifenacin hydrobromide
REACH No. : A registration number is not available for this substance as the substance
or its uses are exempted from registration, the annual tonnage does not
require a registration or the registration is envisaged for a later
registration deadline.
CAS-No. : 133099-07-7
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

---

SECTION 2: Hazards identification
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008
Skin irritation (Category 2), H315
Eye irritation (Category 2), H319
Specific target organ toxicity - single exposure (Category 3), Respiratory system, H335
For the full text of the H-Statements mentioned in this Section, see Section 16.
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Xi Irritant R36/37/38
For the full text of the R-phrases mentioned in this Section, see Section 16.
Label elements
Labelling according Regulation (EC) No 1272/2008
Pictogram
Signal word Warning
Hazard statement(s)
H315 Causes skin irritation.
H319 Causes serious eye irritation.
H335 May cause respiratory irritation.
Precautionary statement(s)
P261 Avoid breathing dust.
P305 + P351 + P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove
contact lenses, if present and easy to do. Continue rinsing.
Supplemental Hazard none
Statements
Other hazards
This substance/mixture contains no components considered to be either persistent, bioaccumulative and
toxic (PBT), or very persistent and very bioaccumulative (vPvB) at levels of 0.1% or higher.

---

SECTION 3: Composition/information on ingredients
Substances
: (3S)-1-[2-(2,3-Dihydro-5-benzofuranyl)ethyl]-α,α-diphenyl-3-
Synonyms
pyrrolidineacetamide hydrobromide
UK 88525-04
Formula : C28H30N2O2 . HBr
Molecular weight : 507,46 g/mol
CAS-No. : 133099-07-7
Hazardous ingredients according to Regulation (EC) No 1272/2008
Component Classification Concentration
Darifenacin hydrobromide
CAS-No. 133099-07-7 Skin Irrit. 2; Eye Irrit. 2; STOT 50 - 100 %
SE 3; H315, H319, H335
Hazardous ingredients according to Directive 1999/45/EC
Component Classification Concentration
Darifenacin hydrobromide
CAS-No. 133099-07-7 Xi, R36/37/38 <= 100 %
For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16

---

SECTION 4: First aid measures
Description of first aid measures
General advice
Consult a physician. Show this safety data sheet to the doctor in attendance.
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
In case of skin contact
Wash off with soap and plenty of water. Consult a physician.
In case of eye contact
Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician.
Most important symptoms and effects, both acute and delayed
The most important known symptoms and effects are described in the labelling (see section 2.2) and/or in
section 11
Indication of any immediate medical attention and special treatment needed
No data available

---

SECTION 5: Firefighting measures
Extinguishing media
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
No data available
Advice for firefighters
Wear self-contained breathing apparatus for firefighting if necessary.
Further information
No data available

---

SECTION 6: Accidental release measures
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure
adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.
For personal protection see section 8.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed
containers for disposal.
Reference to other sections
For disposal see section 13.

---

SECTION 7: Handling and storage
Precautions for safe handling
Avoid contact with skin and eyes. Avoid formation of dust and aerosols.
Provide appropriate exhaust ventilation at places where dust is formed.
For precautions see section 2.2.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Recommended storage temperature -20 °C
Store with desiccant.
Storage class (TRGS 510): Non Combustible Solids
Specific end use(s)
Apart from the uses mentioned in section 1.2 no other specific uses are stipulated

---

SECTION 8: Exposure controls/personal protection
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and
at the end of workday.
Personal protective equipment
Eye/face protection
Safety glasses with side-shields conforming to EN166 Use equipment for eye protection tested
and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Skin protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique
(without touching glove's outer surface) to avoid skin contact with this product. Dispose of
contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and
the standard EN 374 derived from it.
Body Protection
impervious clothing, The type of protective equipment must be selected according to the
concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher
level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges.
Use respirators and components tested and approved under appropriate government standards
such as NIOSH (US) or CEN (EU).
Control of environmental exposure
Do not let product enter drains.

---

SECTION 9: Physical and chemical properties
Information on basic physical and chemical properties
a) Appearance Form: solid
b) Odour No data available
c) Odour Threshold No data available
d) pH No data available
e) Melting point/freezing No data available
point
f) Initial boiling point and No data available
boiling range
g) Flash point No data available
h) Evaporation rate No data available
i) Flammability (solid, gas) No data available
j) Upper/lower No data available
flammability or
explosive limits
k) Vapour pressure No data available
l) Vapour density No data available
m) Relative density No data available
n) Water solubility No data available
o) Partition coefficient: n- No data available
octanol/water
p) Auto-ignition No data available
temperature
q) Decomposition No data available
temperature
r) Viscosity No data available
s) Explosive properties No data available
t) Oxidizing properties No data available
Other safety information
No data available

---

SECTION 10: Stability and reactivity
Reactivity
No data available
Chemical stability
Stable under recommended storage conditions.
Possibility of hazardous reactions
No data available
Conditions to avoid
No data available
Incompatible materials
Strong oxidizing agents
Hazardous decomposition products
Other decomposition products - No data available
In the event of fire: see section 5

---

SECTION 11: Toxicological information
Information on toxicological effects
Acute toxicity
No data available
Skin corrosion/irritation
No data available
Serious eye damage/eye irritation
No data available
Respiratory or skin sensitisation
No data available
Germ cell mutagenicity
No data available
Carcinogenicity
IARC: No component of this product present at levels greater than or equal to 0.1% is identified as
probable, possible or confirmed human carcinogen by IARC.
Reproductive toxicity
No data available
Specific target organ toxicity - single exposure
No data available
Specific target organ toxicity - repeated exposure
No data available
Aspiration hazard
No data available
Additional Information
RTECS: Not available
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.

---

SECTION 12: Ecological information
Toxicity
No data available
Persistence and degradability
No data available
Bioaccumulative potential
No data available
Mobility in soil
No data available
Results of PBT and vPvB assessment
This substance/mixture contains no components considered to be either persistent, bioaccumulative and
toxic (PBT), or very persistent and very bioaccumulative (vPvB) at levels of 0.1% or higher.
Other adverse effects
No data available

---

SECTION 13: Disposal considerations
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company. Dissolve or mix the material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.
Contaminated packaging
Dispose of as unused product.

---

SECTION 14: Transport information
UN number
ADR/RID: - IMDG: - IATA: -
UN proper shipping name
ADR/RID: Not dangerous goods
IMDG: Not dangerous goods
IATA: Not dangerous goods
Transport hazard class(es)
ADR/RID: - IMDG: - IATA: -
Packaging group
ADR/RID: - IMDG: - IATA: -
Environmental hazards
ADR/RID: no IMDG Marine pollutant: no IATA: no
Special precautions for user
No data available

---

SECTION 15: Regulatory information
This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006.
Safety, health and environmental regulations/legislation specific for the substance or mixture
No data available
Chemical Safety Assessment
For this product a chemical safety assessment was not carried out

---

SECTION 16: Other information
Full text of H-Statements referred to under sections 2 and 3.
Eye Irrit. Eye irritation
H315 Causes skin irritation.
H319 Causes serious eye irritation.
H335 May cause respiratory irritation.
Skin Irrit. Skin irritation
STOT SE Specific target organ toxicity - single exposure
Full text of R-phrases referred to under sections 2 and 3
Xi Irritant
R36/37/38 Irritating to eyes, respiratory system and skin.
Further information
Copyright 2014 Co. LLC. License granted to make unlimited paper copies for internal use
only.
The above information is believed to be correct but does not purport to be all inclusive and shall be
used only as a guide. The information in this document is based on the present state of our knowledge
and is applicable to the product with regard to appropriate safety precautions. It does not represent any
guarantee of the properties of the product. Corporation and its Affiliates shall not be held
liable for any damage resulting from handling or from contact with the above product. See
and/or the reverse side of invoice or packing slip for additional terms and conditions of sale.

制备方法与用途

生物活性

Darifenacin HBr (UK-88525) 是一种选择性的 M3 muscarinic 受体拮抗剂，其 pKi 值为 8.9。

靶点

Target	Value
M3 mAChR	8.9(pKi)

体外研究

Darifenacin 能使激动剂曲线非平行向右位移，并显著抑制 (+)-顺式-二氧戊环在离体大鼠膀胱中产生的浓度依赖性收缩的最大响应。此外，该药物能使 MDCK 细胞中 R123 (P-糖蛋白探针) 的累积产生浓度依赖性增加。Darifenacin 以明显的浓度依赖方式刺激 P-gp 细胞膜中的 ATPase 活性，其估计的 ED50 值为 1.6 μM。在基底侧到顶端方向表现出显著更大的渗透性时，Darifenacin (100 nM) 导致约 2.6 的 BBMEC 单层分子流出率。

体内研究

在体内外试验中，Darifenacin 剂量依赖性地抑制体积诱导的膀胱收缩（VIBC_AMP），283.3 nmol/kg 剂量下产生 35% 的抑制效果，最大抑制约为 50–55%。在雌性 Sprague-Dawley 大鼠体内，Darifenacin (0.1 mg/kg i.v.) 降低膀胱传入神经 Aδ 和 C 纤维活性，C 纤维上传入峰值的减少可能比 Aδ 纤维上的更显著。在膀胱过度活跃症患者中，服用 Darifenacin (7.5 mg 和 15 mg 每日一次) 后每周尿失禁发作次数分别降低至基线水平的 67.7% 和 72.8%，而安慰剂仅能将此数值降至 55.9%。在膀胱过度活跃症患者中，Darifenacin (7.5 mg 和 15 mg 每日一次) 显著改善了排尿频率、膀胱容量、尿急频率及严重性以及尿失禁发生的次数。

用途

治疗伴有急迫性尿失禁、尿急、尿频症状的膀胱过度活跃症（OAB）患者。

反应信息

• 作为反应物：
  描述：

  氢溴酸达非那新 在 sodium hydroxide 作用下， 以 水 为溶剂， 生成 达非那新
  参考文献：
  名称：

  Novel Polymorphs of Darifenacin Free Base and its Hydrobromide Salt

  摘要：

  本发明提供了一种新颖且稳定的达瑞那新无水基固态非晶态形式，其制备方法，制药组合物和治疗方法。本发明还提供了一种新颖且稳定的达瑞那新盐酸盐多晶形式，其制备方法，制药组合物和治疗方法。

  公开号：

  US20100204296A1
• 作为产物：
  描述：

  达非那新 在 氢溴酸 作用下， 以 水 、 丁酮 为溶剂， 生成 氢溴酸达非那新
  参考文献：
  名称：

  [EN] A METHOD FOR THE PREPARATION OF DARIFENACIN HYDROGEN BROMIDE
  [FR] PROCÉDÉ DE PRÉPARATION DE DARIFÉNACINE BROMHYDRIQUE

  摘要：

  一种制备(3S)-l-[2-(2,3-二氢-5-苯并呋喃基)乙基]-α，α-二苯基-3-吡咯烷乙酰胺溴化氢的方法，其中3-(S)-[(I-氨基甲酰)-1,1-二苯甲基]吡咯烷或其与有机酸的盐在无机碱存在下与5-(2-溴乙基)-2,3-二氢苯并呋喃在水和C6到C9脂肪，脂环或芳香族烃类有机溶剂的异相体系中进行烷基化反应，分离两相后得到粗的达瑞那新碱基，再加入C3到C9的酮或C3到C9的醇和浓盐酸转化为溴化氢盐。

  公开号：

  WO2009094957A1
• 作为试剂：
  描述：

  2-{1-[2-(Benzofuran-5-yl)ethyl]-3-pyrrolidinyl}-2,2-diphenylacetamide 、 正丁醇 、 氢溴酸 在 钯 S 、 1-butanol+water 、 氢溴酸 、 正丁醇 、 氢溴酸达非那新 作用下， 以 溶剂黄146 为溶剂， 15.0~60.0 ℃ 、13.51 MPa 条件下， 反应 9.0h， 生成 达非那新
  参考文献：
  名称：

  Processes for preparing darifenacin hydrobromide

  摘要：

  这项发明涵盖了制备达瑞非尼氢溴酸盐的过程。

  公开号：

  US20070197631A1

文献信息

• [EN] N-PYRAZOLYL CARBOXAMIDES AS CRAC CHANNEL INHIBITORS<br/>[FR] CARBOXAMIDES N-PYRAZOLYL EN TANT QU'INHIBITEURS DU CANAL CRAC
  申请人：GLAXO GROUP LTD

  公开号：WO2010122089A1

  公开（公告）日：2010-10-28

  The present invention relates to amide compounds, processes for their preparation, pharmaceutical compositions containing these compounds and to their use in the treatment of disorders, conditions or disorders such as allergic disorders, inflammatory disorders and disorders of the immune system.

  本发明涉及酰胺化合物，其制备方法，含有这些化合物的药物组合物，以及它们在治疗过敏性疾病、炎症性疾病和免疫系统疾病等疾病、状况或障碍中的应用。
• [EN] SUBSTITUTED HETEROARYL COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS HÉTÉROARYLE SUBSTITUÉS ET LEURS MÉTHODES D'UTILISATION
  申请人：CALITOR SCIENCES LLC

  公开号：WO2015148868A1

  公开（公告）日：2015-10-01

  The present invention provides novel heteroaryl compounds, pharmaceutical acceptable salts and formulations thereof useful in preventing, treating or lessening the severity of a protein-mediated disease. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of protein kinase-mediated disease.

  本发明提供了新颖的杂环芳基化合物，其药用盐和制剂，在预防、治疗或减轻蛋白介导的疾病的严重程度方面具有用处。该发明还提供了包括这些化合物的药用组合物以及使用这些组合物治疗蛋白激酶介导的疾病的方法。
• [EN] PYRIMIDINE DERIVATIVES USED AS ITK INHIBITORS<br/>[FR] DÉRIVÉS DE PYRIMIDINE UTILISÉS COMME INHIBITEURS DE LTK
  申请人：GLAXO GROUP LTD

  公开号：WO2010106016A1

  公开（公告）日：2010-09-23

  The invention is directed to certain novel compounds. Specifically, the invention is directed to compounds of formula (I): and salts thereof. The compounds of the invention are inhibitors of kinase activity, in particular ltk activity.

  本发明涉及某些新颖化合物。具体而言，本发明涉及以下公式（I）的化合物及其盐类。发明的化合物是激酶活性的抑制剂，特别是ltk活性的抑制剂。
• [EN] QUINOLINE DERIVATIVES AND THEIR USES FOR RHINITIS AND URTICARIA<br/>[FR] DÉRIVÉS DE QUINOLINE ET APPLICATIONS ASSOCIÉES DANS LA RHINITE ET L'URTICAIRE
  申请人：GLAXO GROUP LTD

  公开号：WO2010094643A1

  公开（公告）日：2010-08-26

  The present invention relates to compounds of formula (I) and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various diseases, such as allergic rhinitis.

  本发明涉及式(I)的化合物及其盐，其制备方法，含有它们的组合物，以及它们在治疗各种疾病（如过敏性鼻炎）中的用途。
• [EN] HETEROARYL COMPOUNDS AND PHARMACEUTICAL APPLICATIONS THEREOF<br/>[FR] COMPOSÉS HÉTÉROARYLES ET LEURS APPLICATIONS PHARMACEUTIQUES
  申请人：SUNSHINE LAKE PHARMA CO LTD

  公开号：WO2016000615A1

  公开（公告）日：2016-01-07

  The present invention provides herein is a heteroaryl compound or a stereoisomer, a geometric isomer, a tautomer, a racemate, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, as well as a pharmaceutical composition containing the compound disclosed herein. The present invention also provides herein is use of the compound or the pharmaceutical composition thereof disclosed herein in the manufacture of a medicine for treating autoimmune diseases or proliferative diseases.

  本发明提供的是一种杂环芳基化合物或其立体异构体、几何异构体、互变异构体、消旋体、N-氧化物、水合物、溶剂合物、代谢物、药学上可接受的盐或其前药，以及含有本文所披露的化合物的药物组合物。本发明还提供的是使用本文所披露的化合物或其药物组合物制造用于治疗自身免疫疾病或增殖性疾病的药物。