2,3-二氢-5H-噁唑并[2,3-b]喹唑啉-5-酮 | 52727-44-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 2,3-二氢-5H-噁唑并[2,3-b]喹唑啉-5-酮
• 中文别名: 2,3-二氢-5H-恶唑并[2,3-b]喹唑啉-5-酮；2,3-二氢-5H-恶唑并[2,3-B]喹唑啉-5-酮
• 英文名称: 2,3-dihydro-5H-oxazolo<2,3-b>quinazolin-5-one
• 英文别名: 2,3-dihydro-5H-oxazolo(2,3-b)quinazolin-5-one；2H-oxazolo[2,3-b]quinazolin-5(3H)-one；2,3-Dihydro-5H-oxazolo[2,3-b]quinazolin-5-one；2,3-dihydro-[1,3]oxazolo[2,3-b]quinazolin-5-one
• CAS: 52727-44-3
• 化学式: C₁₀H₈N₂O₂
• mdl: MFCD00209576
• 分子量: 188.186
• InChiKey: QBEBJBXQJGORQQ-UHFFFAOYSA-N

物化性质

• 熔点：
  160-163 °C(lit.)
• 密度：
  1.47
• 溶解度：
  >28.2 [ug/mL]
• 稳定性/保质期：
  遵照规定使用和储存，则不会发生分解。

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• WGK Germany：
  3
• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P362,P403+P233,P501
• 危险性描述：
  H315,H319,H335
• 储存条件：
  保持贮藏器密封，并将其放入一个紧密的容器中。应储存在阴凉、干燥的地方。

SDS

Date Updated: 12/FEB/2006
Version 1.2
Regulation (EC) No 1907/2006
________________________________________________________________________
1 - Product and Company Information
________________________________________________________________________
Product Name 2,3-DIHYDRO-5H-OXAZOLO(2,3-B)QUINAZOLIN-
5-ONE, 95%
Product Number 428981
Company
Century Ba-Shi Building 22A-B,
200020 Shanghai
Technical Phone # [phone]
Fax [phone]
E-mail Address
________________________________________________________________________
2 - Hazards Identification
________________________________________________________________________
________________________________________________________________________
3 - Composition/Information on Ingredients
________________________________________________________________________
Product Name CAS # EC no Annex I
Index Number
2,3-DIHYDRO-5H-OXAZOLO(2,3-B)QUINA 52727-44-3 None None
ZOLIN-5-ONE, 95
Formula C10H8N2O2
Molecular Weight 188,1900 AMU
________________________________________________________________________
4 - First Aid Measures
________________________________________________________________________
AFTER INHALATION
If inhaled, remove to fresh air. If not breathing give
artificial respiration. If breathing is difficult, give oxygen.
AFTER SKIN CONTACT
In case of contact, immediately wash skin with soap and copious
amounts of water.
AFTER EYE CONTACT
In case of contact, immediately flush eyes with copious amounts
of water for at least 15 minutes.
AFTER INGESTION
If swallowed, wash out mouth with water provided person is
conscious. Call a physician.
________________________________________________________________________
5 - Fire Fighting Measures
________________________________________________________________________
EXTINGUISHING MEDIA
Suitable: Water spray. Carbon dioxide, dry chemical powder, or
appropriate foam.
SPECIAL RISKS
Specific Hazard(s): Emits toxic fumes under fire conditions.
SPECIAL PROTECTIVE EQUIPMENT FOR FIREFIGHTERS
Wear self-contained breathing apparatus and protective clothing
to prevent contact with skin and eyes.
________________________________________________________________________
6 - Accidental Release Measures
________________________________________________________________________
PROCEDURE(S) OF PERSONAL PRECAUTION(S)
Wear respirator, chemical safety goggles, rubber boots, and
heavy rubber gloves.
METHODS FOR CLEANING UP
Sweep up, place in a bag and hold for waste disposal. Avoid
raising dust. Ventilate area and wash spill site after material
pickup is complete.
________________________________________________________________________
7 - Handling and Storage
________________________________________________________________________
HANDLING
Directions for Safe Handling: Avoid inhalation. Avoid contact
with eyes, skin, and clothing. Avoid prolonged or repeated
exposure.
STORAGE
Conditions of Storage: Keep tightly closed. Store in a cool dry
place.
________________________________________________________________________
8 - Exposure Controls / Personal Protection
________________________________________________________________________
ENGINEERING CONTROLS
Safety shower and eye bath. Mechanical exhaust required.
GENERAL HYGIENE MEASURES
Wash contaminated clothing before reuse. Wash thoroughly after
handling.
PERSONAL PROTECTIVE EQUIPMENT
Respiratory Protection: Use respirators and components tested and
approved under appropriate government standards such as NIOSH (US)
or CEN (EU). Respiratory protection is not required. Where
protection is desired, use multi-purpose combination (US) or type
ABEK (EN 14387) respirator cartridges.
Hand Protection: Compatible chemical-resistant gloves.
Eye Protection: Chemical safety goggles.
________________________________________________________________________
9 - Physical and Chemical Properties
________________________________________________________________________
pH N/A
BP/BP Range N/A
MP/MP Range 160,000. - 163,000 °
C.
Flash Point N/A
Flammability N/A
Autoignition Temp N/A
Oxidizing Properties N/A
Explosive Properties N/A
Explosion Limits N/A
Vapor Pressure N/A
Partition Coefficient N/A
Viscosity N/A
Vapor Density N/A
Saturated Vapor Conc. N/A
Evaporation Rate N/A
Bulk Density N/A
Decomposition Temp. N/A
Solvent Content N/A
Water Content N/A
Surface Tension N/A
Conductivity N/A
Miscellaneous Data N/A
Solubility N/A
________________________________________________________________________
10 - Stability and Reactivity
________________________________________________________________________
STABILITY
Materials to Avoid: Strong oxidizing agents.
HAZARDOUS DECOMPOSITION PRODUCTS
Hazardous Decomposition Products: Carbon monoxide, Carbon dioxide,
Nitrogen oxides.
________________________________________________________________________
11 - Toxicological Information
________________________________________________________________________
SIGNS AND SYMPTOMS OF EXPOSURE
To the best of our knowledge, the chemical, physical, and
toxicological properties have not been thoroughly investigated.
ROUTE OF EXPOSURE
Skin Contact: May cause skin irritation.
Eye Contact: May cause eye irritation.
Inhalation: Material may be irritating to mucous membranes and
upper respiratory tract.
Multiple Routes: May be harmful by inhalation, ingestion, or
skin absorption.
________________________________________________________________________
12 - Ecological Information
________________________________________________________________________
No data available.
________________________________________________________________________
13 - Disposal Considerations
________________________________________________________________________
SUBSTANCE DISPOSAL
Dissolve or mix the material with a combustible solvent and burn
in a chemical incinerator equipped with an afterburner and
scrubber. Observe all federal, state, and local environmental
regulations.
________________________________________________________________________
14 - Transport Information
________________________________________________________________________
RID/ADR
Non-hazardous for road transport.
IMDG
Non-hazardous for sea transport.
IATA
Non-hazardous for air transport.
________________________________________________________________________
15 - Regulatory Information
________________________________________________________________________
Caution: Substance not yet fully tested (EU).
COUNTRY SPECIFIC INFORMATION
Germany
WGK: 3
Self-Classification
________________________________________________________________________
16 - Other Information
________________________________________________________________________
WARRANTY
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
shall not be held liable for any damage resulting from handling or
from contact with the above product. See reverse side of invoice
or packing slip for additional terms and conditions of sale.
unlimitedpaper copies for internal use only.
DISCLAIMER
For R&D use only. Not for drug, household or other uses.

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模块 15 - 法规信息
N/A

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模块16 - 其他信息
N/A

反应信息

• 作为反应物：
  描述：

  2,3-二氢-5H-噁唑并[2,3-b]喹唑啉-5-酮 在 氨 作用下， 生成 3-(2-aminoethyl)-2,4(1H,3H)-quinazolinedione
  参考文献：
  名称：

  Ketanserin类似物：5-HT2和5-HT1C血清素受体结合的结构亲和性关系。

  摘要：

  酮色林是原型5-HT2血清素拮抗剂。尽管它一直是研究5-羟色胺药理学的重要工具，但它对药物设计的影响相对较小，因为对其结构亲和性关系知之甚少。此外，酮色林还与5-HT1C受体结合，对其结构特征对5-HT1C受体亲和力的影响知之甚少。本研究表明，酮色林的4-氟苯甲酰基部分的氟和羰基对5​​-HT2结合的贡献很小，完整的苯甲酰基哌啶部分是重要的特征。哌啶环的开环降低了亲和力。尽管喹唑啉-2,4-二酮部分也有助于结合，它似乎起着较小的作用，并且可以通过保留5-HT2亲和力在结构上简化。例如，N-（4-苯基丁基）-4-（4-氟苯甲酰基）哌啶（39）以与酮色林（Ki = 3.5 nM）几乎相同的亲和力（Ki = 5.3 nM）结合。所有检测到的化合物在5-HT1C位点的结合亲和力均比酮色林低，某些简化的类似物以5-HT2C结合酮色林的5-HT1C选择性结合近十倍。但是，没有显示> 120倍的选择性。

  DOI：

  10.1021/jm00104a017
• 作为产物：
  描述：

  3-(2-羟基乙基)-2,4-(1h,3h)-喹唑啉二酮 在 氯化亚砜 、 sodium carbonate 作用下， 以 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 9.0h， 生成 2,3-二氢-5H-噁唑并[2,3-b]喹唑啉-5-酮
  参考文献：
  名称：

  一种酮色林中间体以及酮色林的制备方法

  摘要：

  本发明公开了一种酮色林中间体2,3‑二氢‑5H‑噁唑并[2,3‑B]喹唑啉‑5‑酮的制备方法和一种酮色林的制备方法，所述酮色林中间体2,3‑二氢‑5H‑噁唑并[2,3‑B]喹唑啉‑5‑酮的制备方法的反应方程式如下：在该反应中，使用碳酸钠和乙腈并且不添加催化剂，反应后热滤除去无机盐，滤液蒸干回收乙腈得到中间体04即酮色林中间体2,3‑二氢‑5H‑噁唑并[2,3‑B]喹唑啉‑5‑酮。该方法操作简便，成本更低，产物性状更好，更有利于最终产物的合成。

  公开号：

  CN112142760A

文献信息

• Synthesis and Discovery of Arylpiperidinylquinazolines: New Inhibitors of the Vesicular Monoamine Transporter
  作者：Brian A. Provencher、Amy J. Eshleman、Robert A. Johnson、Xiao Shi、Olga Kryatova、Jared Nelson、Jianhua Tian、Mario Gonzalez、Peter C. Meltzer、Aaron Janowsky

  DOI：10.1021/acs.jmedchem.8b00542

  日期：2018.10.25

  Methamphetamine, a human vesicular monoamine transporter 2 (VMAT2) substrate, releases dopamine, serotonin, and norepinephrine from vesicles into the cytosol of presynaptic neurons and induces reverse transport by the monoamine transporters to increase extracellular neurotransmitters. Currently available radioligands for VMAT2 have considerable liabilities: The binding of [3H]dihydrotetrabenazine ([3H]DHTB)

  甲基苯丙胺是人囊泡单胺转运蛋白2（VMAT2）的底物，可将多巴胺，5-羟色胺和去甲肾上腺素从囊泡释放到突触前神经元的细胞质中，并诱导单胺转运蛋白逆向转运，从而增加细胞外神经递质。当前可用于VMAT2的放射性配体具有相当大的责任：[ 3 H]二氢丁苯那嗪（[ 3 H] DHTB）与VMAT2上一个位点的结合不依赖于ATP，[ 3 H]利血平几乎不可逆地与VMAT2结合。在这里，我们证明了几种芳基哌啶基喹唑啉（APQs）是[ 3的有效抑制剂。H]利血平与HEK-293细胞中表达的重组人VMAT2结合。这些化合物是生物非对映选择性的和生物对映选择性的。铅标记的APQ具有独特性，因为它可逆地与VMAT2结合，但不结合[ 3 H] DHTB结合位点。此外，实验表明，几种新颖的APQ配体具有抑制HEK-VMAT2细胞和小鼠纹状体小泡摄取的高效力，并且可能是表征药物诱导的对人VMAT2表达和功能的作用的有用工具。
• Reinvestigation of the Synthesis of Ketanserin () and its Hydrochloride Salt () via 3-(2-Chloroethyl)-2,4-(1<i>H</i>,3<i>H</i>)-quinazolinedione () or Dihydro-5<i>H</i>-oxazole(2,3-<i>b</i>)quinazolin-5-one ()
  作者：Hossein Fakhraian、Mehdi Heydary

  DOI：10.1002/jhet.1897

  日期：2014.1

  The synthesis of ketanserin (5) and its hydrochloride salt (5.HCl) using respectively equimolar amounts of 3‐(2‐chloroethyl)‐2,4‐(1H,3H)‐quinazolinedione (2) with 4‐(parafluorobenzoyl)piperidine (3) and dihydro‐5H‐oxazole(2,3‐b)quinazolin‐5‐one (1) with hydrochloride salt of 4‐(parafluorobenzoyl)piperidine (3.HCl) is reinvestigated. The one‐pot reaction of ethyl‐2‐aminobenzoate with ethyl chloroformate

  分别使用等摩尔量的3-（2-氯乙基）-2-，4-（1 H，3 H）-喹唑啉二酮（2）与4-（对氟苯甲酰基）合成酮色林（5）及其盐酸盐（5.HCl））再研究了哌啶（3）和二氢-5 H-恶唑（2,3 - b）喹唑啉-5-酮（1）与4-（对氟苯甲酰基）哌啶（3.HCl）的盐酸盐。2-氨基苯甲酸乙酯与氯甲酸乙酯和乙醇胺的一锅反应得到了3-（2-氯乙基）-2-，4-（1 H，3 H）-喹唑啉二酮（2）（86％），然后在碳酸钠存在下，将其与4-（对氟苯甲酰基）哌啶（3）在乙基甲基酮中回流，得到酮色林的游离碱（87％）。在另一种尝试中，酮色林（非常纯的盐酸盐5.HCl），使用等摩尔量的二氢-5合成ħ恶唑（2,3- b）喹唑啉-5-酮（1）和4-盐酸盐（无溶剂熔融法合成对氟苯甲酰基）哌啶（3.HCl）。因此，在最优化的条件下（180°C和30分钟的反应时间），粉末混合物转化为玻璃状晶体，最初易溶于氯仿，但随时间（2
• Process for preparing ketanserine
  申请人：RAVIZZA S.p.A.

  公开号：EP0098499A1

  公开（公告）日：1984-01-18

  A process for preparing the compound 3-[2-[4-(p.fluorobenzoyl)-1-piperidinyl]ethyl]-2,4(1H,3H)-quinazolinedione, known in the pharmaceutical field as Ketanserine, by reacting 4-(p.fluorobenzoyl) piperidine with 2,3-dihydro-5H-oxazole (2,3-b)quinazolin-5-one.

  一种制备化合物3-[2-[4-(对氟苯甲酰)-1-哌啶基]乙基]-2,4(1H,3H)-喹唑啉二酮的方法，该化合物在制药领域中被称为Ketanserine，通过将4-(对氟苯甲酰)哌啶与2,3-二氢-5H-噁唑(2,3-b)喹唑啉-5-酮反应得到。
• VMAT INHIBITORY COMPOUNDS
  申请人：Oregon Health & Science University

  公开号：US20160031852A1

  公开（公告）日：2016-02-04

  Disclosed herein are compounds that bind to the vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions comprising those compounds, and methods of treatment using said compounds and pharmaceutical compositions.

  本文揭示了与囊泡式单胺转运体2（VMAT2）结合的化合物，包括这些化合物的制药组合物，以及使用这些化合物和制药组合物的治疗方法。
• Rational Design and Lead Optimisation of Potent Antimalarial Quinazolinediones and Their Cytotoxicity against MCF-7
  作者：Sitthivut Charoensutthivarakul、Duangporn Lohawittayanan、Phongthon Kanjanasirirat、Kedchin Jearawuttanakul、Sawinee Seemakhan、Napason Chabang、Patrick Schlaeppi、Varisa Tantivess、Tanapol Limboonreung、Matthew Phanchana

  DOI：10.3390/molecules28072999

  日期：——

  ranges of biological activities including antimalarial, anticancer, and anti-inflammatory. TCMDC-125133 containing a quinazolinedione pharmacophore displays promising antimalarial activity and low toxicity, as described in the GlaxoSmithKline (GSK) report. Herein, the design and synthesis of novel quinazolinedione derivatives is described on the basis of our previous work on the synthesis of TCMDC-125133

  喹唑啉二酮是药物化学中最杰出的杂环化合物之一，因为它具有广泛的生物活性，包括抗疟疾、抗癌和抗炎。正如葛兰素史克 (GSK) 报告中所述，含有喹唑啉二酮药效团的 TCMDC-125133 具有良好的抗疟活性和低毒性。在此，基于我们之前关于 TCMDC-125133 合成的工作描述了新型喹唑啉二酮衍生物的设计和合成，其中尽可能使用低成本化学品和更环保的替代品。最初的 SAR 研究侧重于取代缬氨酸接头部分；根据使用 SwissADME 的计算机预测，开发了针对化合物 4-10 的简明四步合成。对内部合成的化合物 4-10 进行了抗恶性疟原虫 3D7 的抗疟活性测定，结果显示只有含有缬氨酸接头的化合物 2 是耐受的。另一轮先导优化重点在于取代化合物 2 中的间茴香胺部分。制备了 12 种衍生物的库，抗疟试验表明，通过取代化合物间位的甲氧基可以维持有效的抗疟活性带有氟或氯原子的苯基侧链（21：IC50