3-(5-氯-2-羟基苄基)-5-(4-(三氟甲基)苯基)-1,3,4-噁二唑-2(3h)-酮 | 202821-81-6

• 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: 3-(5-氯-2-羟基苄基)-5-(4-(三氟甲基)苯基)-1,3,4-噁二唑-2(3h)-酮
• 英文名称: 3-[(5-Chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)-phenyl]-1,3,4-oxadiazol-2(3H)-one
• 英文别名: BMS-191011；3-[(5-chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3H)-one；BMS 191011；3-(5-Chloro-2-hydroxybenzyl)-5-(4-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2(3H)-one；3-[(5-chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-one
• CAS: 202821-81-6
• 化学式: C₁₆H₁₀ClF₃N₂O₃
• 分子量: 370.715
• InChiKey: QKOWACXSXTXRKA-UHFFFAOYSA-N

物化性质

• 沸点：
  444.0±55.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO：可溶，20mg/mL，澄清（加热）

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  62.1
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• 海关编码：
  2934999090
• 危险标志：
  GHS06
• 危险性描述：
  H301,H413
• 危险性防范说明：
  P301 + P310
• 包装等级：
  III
• 危险类别：
  6.1
• 危险品运输编号：
  2811
• 储存条件：
  | 2-8℃ |

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 5-[4-(Trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one
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: 5-[4-(Trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one
CAS number: 202821-81-6

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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.
Storage: Store in closed vessels, refrigerated.

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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
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C9H5F3N2O2
Molecular weight: 230.1

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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 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

生物活性方面，BMS-191011（BMS-A）是一种钙激活的大电导钾通道（Ca2+-activated potassium (maxi-K) channel）激活剂，并已在中风模型中显示出有效性。

反应信息

• 作为反应物：
  描述：

  3-(5-氯-2-羟基苄基)-5-(4-(三氟甲基)苯基)-1,3,4-噁二唑-2(3h)-酮 在 六甲基磷酰三胺 、 磺酰氯 、 sodium hydride 作用下， 以 二氯甲烷 、 苯 为溶剂， 生成 Phosphoric acid dibenzyl ester 4-chloro-2-[2-oxo-5-(4-trifluoromethyl-phenyl)-[1,3,4]oxadiazol-3-ylmethyl]-phenoxymethyl ester
  参考文献：
  名称：

  Synthesis of water-Soluble prodrugs of BMS-191011: A maxi-K channel opener targeted for post-stroke neuroprotection

  摘要：

  A variety of water-soluble prodrugs of BMS-191011 was synthesized and evaluated for solution state stability and rate of conversion to BMS-191011 in rat and human plasma. The deoxycarnitine ester prodrug (11c) was selected for clinical evaluation based on its superior chemical stability, crystallinity and cleavage to BMS-191011 in human plasma. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00296-8
• 作为产物：
  描述：

  5-(4-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2(3H)-one 在 吡啶盐酸盐 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 3-(5-氯-2-羟基苄基)-5-(4-(三氟甲基)苯基)-1,3,4-噁二唑-2(3h)-酮
  参考文献：
  名称：

  3-[(5-Chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl ]-1,3,4-oxadiazol-2(3H)-one, BMS-191011:  Opener of Large-Conductance Ca²⁺-Activated Potassium (Maxi-K) Channels, Identification, Solubility, and SAR

  摘要：

  Compound 8a (BMS-191011), an opener of the cloned large-conductance, Ca2+-activated potassium (maxi-K) channel, demonstrated efficacy in in vivo stroke models, which led to its nomination as a candidate for clinical evaluation. Its maxi-K channel opening properties were consistent with its structural topology, being derived by combining elements from other known maxi-K openers. However, 8a suffered from poor aqueous solubility, which complicated elucidation of SAR during in vitro evaluation. The activity of 8a in in vivo stroke models and studies directed toward improving its solubility are reported herein. Enhanced solubility was achieved by appending heterocycles to the 8a scaffold, and a notable observation was made that inclusion of a simple amino group (anilines 8k and 8l) yielded excellent in vitro maxi-K ion channel opening activity and enhanced brain-to-plasma partitioning compared to the appended heterocycles.

  DOI：

  10.1021/jm061006n

文献信息

• Phosphate derivatives of diaryl 1,3,4-oxadiazolone
  申请人：Bristol-Myers Squibb Company

  公开号：US05939405A1

  公开（公告）日：1999-08-17

  The present invention provides novel phosphate derivatives having the general formula wherein A, R.sup.1 and R.sup.2 are as defined herein, or a nontoxic pharmaceutically acceptable salt or solvate thereof and are useful in the treatment of disorders which are responsive to the opening of potassium channels.

  本发明提供了具有一般式的新型磷酸盐衍生物，其中A、R^1和R^2如本文所定义，或其无毒的药用可接受盐或溶剂，可用于治疗对钾通道开放有响应的疾病。
• Palladium-Catalyzed Oxidative O–H/N–H Carbonylation of Hydrazides: Access to Substituted 1,3,4-Oxadiazole-2(3<i>H</i>)-ones
  作者：Fanghua Ji、Xianwei Li、Wei Guo、Wanqing Wu、Huanfeng Jiang

  DOI：10.1021/acs.joc.5b00664

  日期：2015.6.5

  cyclocarbonylation provides an efficient and direct approach for the construction of valuable 1,3,4-oxadiazole-2(3H)-ones and their derivatives. The reaction also facilitated the convenient synthesis of BMS-191011, an opener of the cloned large-conductance Ca2+-activated potassium channel, providing an attractive method for medicinal chemistry.

  开发了一种新颖的钯催化的C–O，C–N键形成的氧化环化反应。分子内环羰基化为构建有价值的1,3,4-恶二唑-2（3 H）-ones及其衍生物提供了一种有效而直接的方法。该反应还促进了BMS-191011的便捷合成，BMS-191011是克隆的大电导Ca 2+活化的钾通道的开放剂，为药物化学提供了有吸引力的方法。
• Amino acid derivatives of diaryl 1,3,4-oxadiazolone
  申请人：Bristol-Myers Squibb Company

  公开号：US05977150A1

  公开（公告）日：1999-11-02

  The present invention provides novel amino acid derivatives having the general formula ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined herein, or a nontoxic pharmaceutically acceptable salt or solvate thereof and are useful in the treatment of disorders which are responsive to the opening of potassium channels.

  本发明提供了具有一般式##STR1##的新型氨基酸衍生物，其中R.sup.1、R.sup.2和R.sup.3如本文所定义，或其无毒药学上可接受的盐或溶剂，用于治疗对钾通道开放有响应的疾病。
• Derivatives of 1,3,4-oxadiazolone
  申请人：Bristol-Myers Squibb Company

  公开号：US06034113A1

  公开（公告）日：2000-03-07

  The present invention provides novel oxadiazolone derivatives having the general formula ##STR1## wherein A, B, D and R are as defined herein, or a nontoxic pharmaceutically acceptable salt or solvate thereof and are useful in the treatment of disorders which are responsive to the opening of the large conductance calcium-activated potassium channels.

  本发明提供了一种新型的噁唑烷酮衍生物，其具有以下一般式：##STR1## 其中A、B、D和R如本文所定义，或其无毒药学上可接受的盐或溶剂，可用于治疗对大导电钙激活钾通道开放有响应的疾病。
• 一种BMS-191011的合成方法
  申请人：华南理工大学

  公开号：CN104710379B

  公开（公告）日：2017-01-18

  本发明涉及一种BMS‑191011化合物的合成方法。该方法以4‑三氟甲基苯甲酰肼作为原料经氧化羰基化，甲基保护，卤化，胺化和脱保护等步骤制得BMS‑191011。本发明采用CO气球代替光气，降低了反应的毒性，增加了反应的可操作性。该方法具有原料简单易得，反应条件温和，操作工艺简洁的特点。