3-氰基-N-(1,3-二苯基吡唑-5-基)苯甲酰胺 | 781652-57-1

• 物质功能分类: 有机原料 - 氨基化合物 - 酰胺类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-氰基-N-(1,3-二苯基吡唑-5-基)苯甲酰胺
• 中文别名: 3-氰基-N-(1,3-二苯基-1H-吡唑-5-基)苯甲酰胺
• 英文名称: 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide
• 英文别名: CDPPB；3-cyano-N-(2,5-diphenylpyrazol-3-yl)benzamide
• CAS: 781652-57-1
• 化学式: C₂₃H₁₆N₄O
• 分子量: 364.406
• InChiKey: BKUIZWILNWHFHD-UHFFFAOYSA-N

物化性质

• 熔点：
  210-212°C
• 溶解度：
  DMSO：加热至60℃时≥5mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.7
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : CDPPB
CAS-No. : 781652-57-1
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

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Section 2. HAZARDS IDENTIFICATION
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008 [EU-GHS/CLP]
Acute toxicity, Oral (Category 4)
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Harmful if swallowed.
Label elements
Labelling according Regulation (EC) No 1272/2008 [CLP]
Pictogram
Signal word Warning
Hazard statement(s)
H302 Harmful if swallowed.
Precautionary statement(s) none
Supplemental Hazard none
Statements
According to European Directive 67/548/EEC as amended.
Hazard symbol(s)
R-phrase(s)
R22 Harmful if swallowed.
S-phrase(s) none
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Synonyms : 3-Cyano-N-1,3-diphenyl-1H-pyrazol-5-yl)benzamide
Formula : C23H16N4O
Molecular Weight : 364,40 g/mol
Component Concentration
CDPPB
CAS-No. 781652-57-1 -

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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
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.
Indication of any immediate medical attention and special treatment needed
no data available

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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
Carbon oxides, nitrogen oxides (NOx)
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

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Section 6. ACCIDENTAL RELEASE MEASURES
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure
adequate ventilation. Avoid breathing dust.
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.

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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.
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: 2 - 8 °C
Specific end uses
no data available

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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
Complete suit protecting against chemicals, 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).

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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- log Pow: 4,686
octanol/water
p) Autoignition 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

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Section 10. STABILITY AND REACTIVITY
Reactivity
no data available
Chemical stability
no data available
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

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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 sensitization
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
Potential health effects
Inhalation May be harmful if inhaled. May cause respiratory tract irritation.
Ingestion Harmful if swallowed.
Skin
May be harmful if absorbed through skin. May cause skin irritation.
Eyes Causes eye irritation.
Signs and Symptoms of Exposure
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.
Additional Information
RTECS: Not available

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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
no data available
Other adverse effects
no data available

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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.

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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

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SECTION 15 - REGULATORY INFORMATION
N/A

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

CDPPB 是一种有效、选择性和能够透过脑部的正变构调节剂，能作用于代谢型谷氨酸受体亚型 5 (mGluR5)，在表达人类 mGluR5 的中国仓鼠卵巢细胞中的 EC50 值为 27 nM。CDPPB 可能为开发抗精神病药物提供了一种方法。

靶点

mGluR5	27 nM (EC50)

反应信息

• 作为产物：
  描述：

  5-氨基-1,3-二苯基哌唑 、 3-[chloro(hydroxy)methyl]benzonitrile 以 二氯甲烷 为溶剂， 以73%的产率得到3-氰基-N-(1,3-二苯基吡唑-5-基)苯甲酰胺
  参考文献：
  名称：

  An efficient one-pot synthesis of N-(1,3-diphenyl-1H-pyrazol- 5-yl)amides

  摘要：

  Abstractmagnified image A “one‐pot” method for the synthesis of N‐(1,3‐diphenyl‐1H‐pyrazol‐5‐yl)amides was developed by cyclization of benzoylacetonitrile (1) and phenylhydrazine in neat condition followed by acylation. The corresponding N‐(1,3‐diphenyl‐1H‐pyrazol‐5‐yl)amides were provided in good to excellent yields (70–90%). The significant advantages of the new synthetic method are excellent yields and simple work‐up procedure without isolation and purification of intermediary 5‐amino‐1,3‐diphenyl pyrazol (2). J. Heterocyclic Chem., (2010).

  DOI：

  10.1002/jhet.343

文献信息

• Discovery of Positive Allosteric Modulators for the Metabotropic Glutamate Receptor Subtype 5 from a Series of <i>N</i>-(1,3-Diphenyl-1<i>H</i>- pyrazol-5-yl)benzamides That Potentiate Receptor Function in Vivo
  作者：Craig W. Lindsley、David D. Wisnoski、William H. Leister、Julie A. O'Brien、Wei Lemaire、David L. Williams,、Maryann Burno、Cyrille Sur、Gene G. Kinney、Doug J. Pettibone、Philip R. Tiller、Sheri Smith、Mark E. Duggan、George D. Hartman、P. Jeffrey Conn、Joel R. Huff

  DOI：10.1021/jm049400d

  日期：2004.11.1

  glutamate receptor subtype 5 (mGluR5). Appropriately substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides (e.g., 8) have been identified as a novel class of potent positive allosteric modulators of mGluR5 that potentiate the response to glutamate. An iterative analogue library synthesis approach provided potentiators with excellent potency and selectivity for mGluR5 (vs mGluRs 1-4, 7, 8). Compound 8q demonstrated

  该报告描述了代谢型谷氨酸受体亚型5（mGluR5）的第一个中央活性的变构调节剂的发现。适当取代的N-（1,3-二苯基-1H-吡唑-5-基）苯甲酰胺（例如8种）已被鉴定为mGluR5的新型强力正构构变构剂，可增强对谷氨酸的反应。迭代的类似物文库合成方法为增效剂提供了对mGluR5（相对于mGluRs 1-4、7、8）具有出色的效能和选择性。化合物8q在已知抗精神病药活跃的动物行为模型中证明了其概念的体内证据，支持基于精神分裂症NMDA功能减退模型的新型抗精神病药的开发。
• Pyrazole modulators of metabotropic glutamate receptors
  申请人：Lindsley W. Craig

  公开号：US20060281803A1

  公开（公告）日：2006-12-14

  The present invention is directed to compounds which are allosteric modulators of metabotropic glutamate receptors, including the mGluR5 receptor, and which are useful in the treatment of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.

  本发明涉及化合物，它们是代谢性谷氨酸受体的别构调节剂，包括mGluR5受体，并且在治疗与谷氨酸功能障碍和代谢性谷氨酸受体相关的神经和精神障碍以及相关疾病方面有用。该发明还涉及包含这些化合物的制药组合物以及在预防或治疗代谢性谷氨酸受体相关疾病方面使用这些化合物和组合物。
• Partial mGluR5 antagonists for treatment of anxiety and CNS disorders
  申请人：Conn Jeffrey P.

  公开号：US20070208028A1

  公开（公告）日：2007-09-06

  Provided is a method of treating conditions and disorders for which full mGluR5 antagonists are potentially effective, such as, e.g., anxiety, epilepsy, schizophrenia and other psychotic disorders, Parkinson's disease, addictive disorders, and the like in a subject in need of such treatment, comprising administration to such subject of a therapeutically effective amount of a partial, non-competitive mGluR5 antagonist compound of the invention. Specific examples of partial MgluR5 antagonists provided include those compounds having the formula: wherein: Z is, independently N or —CH—, provided that one, and only one Z is N; R is halogen (e.g., Br, F and the like), alkyl (e.g., methyl), alkenyl (e.g., CH═CH2, aryl (e.g., phenyl), heterocyclic (e.g., thiophenyl).

  提供了一种治疗全mGluR5拮抗剂可能有效的疾病和疾病的方法，例如焦虑、癫痫、精神分裂症和其他精神障碍、帕金森病、成瘾性疾病等，适用于需要此类治疗的患者，包括向该患者施用本发明的部分、非竞争性mGluR5拮抗剂化合物的治疗有效量。所提供的部分MgluR5拮抗剂的具体例子包括具有以下式子的化合物：其中：Z独立地为N或—CH—，但仅有一个Z为N；R为卤素（例如Br、F等）、烷基（例如甲基）、烯基（例如CH═CH2）、芳基（例如苯基）、杂环（例如噻吩基）。
• Methods of treating fragile X syndrome and related disorders
  申请人：Massachusetts Institute of Technology

  公开号：US10682397B2

  公开（公告）日：2020-06-16

  Disclosed herein are novel methodologies of treating fragile X syndrome and related disorders by inhibiting mGlu5-relevant signaling pathways via the reduction of β-arrestin2 protein levels or the diminution of mGlu5 and β-arrestin2 protein interactions.

  本文公开了通过降低β-arrestin2蛋白水平或减少mGlu5和β-arrestin2蛋白相互作用来抑制mGlu5相关信号通路，从而治疗脆性X综合征和相关疾病的新方法。
• A positive allosteric modulator of mGluR5 promotes neuroprotective effects in mouse models of Alzheimer's disease
  作者：Paula Maria Quaglio Bellozi、Giovanni Freitas Gomes、Maria Carolina Machado da Silva、Isabel Vieira de Assis Lima、Carla Ribeiro Álvares Batista、Wellerson de Oliveira Carneiro Junior、Juliana Guimarães Dória、Érica Leandro Marciano Vieira、Rafael Pinto Vieira、Rossimiriam Pereira de Freitas、Claudia Natália Ferreira、Eduardo Candelario-Jalil、Tony Wyss-Coray、Fabíola Mara Ribeiro、Antônio Carlos Pinheiro de Oliveira

  DOI：10.1016/j.neuropharm.2019.107785

  日期：2019.12

  Alzheimer's Disease (AD) is the most prevalent neurodegenerative disorder. Despite advances in the understanding of its pathophysiology, none of the available therapies prevents disease progression. Excess glutamate plays an important role in excitotoxicity by activating ionotropic receptors. However, the mechanisms modulating neuronal cell survival/death via metabotropic glutamate receptors (mGluR5) are not completely understood. Recent data indicates that CDPPB, a positive allosteric modulator of mGluR5, has neuroprotective effects. Thus, this work aimed to investigate CDPPB treatment effects on amyloid-beta (A beta) induced pathological alterations in vitro and in vivo and in a transgenic mouse model of AD (T41 mice). A beta induced cell death in primary cultures of hippocampal neurons, which was prevented by CDPPB. Male C57BL/6 mice underwent stereotaxic surgery for unilateral intra-hippocampal A beta injection, which induced memory deficits, neurodegeneration, neuronal viability reduction and decrease of doublecortin-positive cells, a marker of immature neurons and neuronal proliferation. Treatment with CDPPB for 8 days reversed neurodegeneration and doublecortin-positive cells loss and recovered memory function. Fourteen months old T41 mice presented cognitive deficits, neuronal viability reduction, gliosis and A beta accumulation. Treatment with CDPPB for 28 days increased neuronal viability (32.2% increase in NeuN(+) cells) and reduced gliosis in CA1 region (Iba-1(+) area by 31.3% and GFAP(+) area by 37.5%) in transgenic animals, without inducing hepatotoxicity. However, it did not reverse cognitive deficit. Despite a four-week treatment did not prevent memory loss in aged transgenic mice, CDPPB is protective against A beta stimulus. Therefore, this drug represents a potential candidate for further investigations as AD treatment.