2-{[(1,3-二甲基-1H-吡唑-5-基)氨基]亚甲基}丙二酸二乙酯 | 20481-33-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 2-{[(1,3-二甲基-1H-吡唑-5-基)氨基]亚甲基}丙二酸二乙酯
• 英文名称: diethyl 2-{[(1,3-dimethyl-1H-pyrazol-5-yl)amino]methylene}malonate
• 英文别名: diethyl 2-{[(1,3-dimethyl-1H-pyrazol-5-yl)amino]methylidene}malonate；diethyl 2-[[(2,5-dimethylpyrazol-3-yl)amino]methylidene]propanedioate
• CAS: 20481-33-8
• 化学式: C₁₃H₁₉N₃O₄
• mdl: MFCD00067953
• 分子量: 281.312
• InChiKey: PFQPORNTOSYJRQ-UHFFFAOYSA-N

物化性质

• 沸点：
  366.7±42.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.461
• 拓扑面积：
  82.4
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S37/39
• 危险类别码：
  R36/37/38
• 海关编码：
  2933199090

SDS

Name:	Diethyl 2-{[(1 3-dimethyl-1h-pyrazol-5-yl)amino]methylidene}malonate Material Safety Data Sheet
Synonym:	Ethyl 3-(1,3-dimethylpyrazol-5-ylamino)-2-ethoxycarbonyl acrylat
CAS:	20481-33-8

Section 1 - Chemical Product MSDS Name:Diethyl 2-{[(1 3-dimethyl-1h-pyrazol-5-yl)amino]methylidene}malonate Material Safety Data Sheet
Synonym:Ethyl 3-(1,3-dimethylpyrazol-5-ylamino)-2-ethoxycarbonyl acrylat

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
20481-33-8	Diethyl 2-{[(1,3-dimethyl-1H-pyrazol-5	97%	unlisted

Hazard Symbols: XI
Risk Phrases: 36/37/38

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Irritating to eyes, respiratory system and skin.
Potential Health Effects
Eye:
Causes eye irritation.
Skin:
Causes skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause irritation of the digestive tract. May be harmful if swallowed.
Inhalation:
Causes respiratory tract irritation. May be harmful if inhaled.
Chronic:
Not available.

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Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes.
Ingestion:
Get medical aid. Wash mouth out with water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:
Treat symptomatically and supportively.

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or chemical foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container.

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Section 7 - HANDLING and STORAGE
Handling:
Avoid breathing dust, vapor, mist, or gas. Avoid contact with skin and eyes.
Storage:
Store in a cool, dry place. Store in a tightly closed container.

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 20481-33-8: Personal Protective Equipment Eyes: Not available.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: cream
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 85 - 88 deg C
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C13H19N3O4
Molecular Weight: 281

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Not available.
Conditions to Avoid:
Incompatible materials.
Incompatibilities with Other Materials:
Reducing agents.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, carbon dioxide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 20481-33-8 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
Diethyl 2-{[(1,3-dimethyl-1H-pyrazol-5-yl)amino]methylidene}malonate - Not listed by ACGIH, IARC, or NTP.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
No information available.
IMO
No information available.
RID/ADR
No information available.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: XI
Risk Phrases:
R 36/37/38 Irritating to eyes, respiratory system
and skin.
Safety Phrases:
S 26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S 37/39 Wear suitable gloves and eye/face
protection.
WGK (Water Danger/Protection)
CAS# 20481-33-8: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 20481-33-8 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 20481-33-8 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  2-{[(1,3-二甲基-1H-吡唑-5-基)氨基]亚甲基}丙二酸二乙酯 在 氢氧化钾 、 氯化亚砜 、 三氯氧磷 作用下， 以 乙二醇二甲醚 为溶剂， 反应 37.0h， 生成 4-氯-1,3-二甲基吡唑并[3,4-B]吡啶-5-羰酰氯
  参考文献：
  名称：

  Discovery of New Orally Active Phosphodiesterase (PDE4) Inhibitors

  摘要：

  合成了一系列4-氨基吡唑并吡啶衍生物，并对其作为磷酸二酯酶（PDE4）抑制剂进行生物评估。对3这一我们内部库中发现的结构新颖的化学先导物的化学改造主要集中在1-和3-取代基上。本文详细介绍了新型口服活性化学先导物5的发现，以及结构-活性关系数据、药理评估和亚型选择性研究的结果。

  DOI：

  10.1248/cpb.52.1098
• 作为产物：
  描述：

  5-氨基-1,3-二甲基吡唑 、 乙氧基甲叉丙二酸二乙酯 以89%的产率得到2-{[(1,3-二甲基-1H-吡唑-5-基)氨基]亚甲基}丙二酸二乙酯
  参考文献：
  名称：

  具有治疗潜力的新型口服活性PDE4抑制剂。

  摘要：

  已成功进行了吡唑并吡啶衍生物2的结构优化，吡唑并吡啶衍生物2是我们内部库中新发现的PDE4抑制剂的化学前导之一。介绍了有望具有治疗潜力的新型口服活性PDE4抑制剂的发现过程，并讨论了它们的构效关系。

  DOI：

  10.1016/j.bmcl.2003.10.025

文献信息

• Pyrazolo[3,4-<i>b</i>]pyridines: Syntheses, reactions, and nuclear magnetic resonance spectra
  作者：Brian Maurice Lynch、Misbahul Ain Khan、Huk Chia Teo、Francisco Pedrotti

  DOI：10.1139/v88-074

  日期：1988.3.1

  2-Chloro-3-formylpyridine (2-chloronicotinaldehyde) was obtained by reduction of 2-chloro-3-cyanopyridine by Raney nickel and formic acid (3 1); this intermediate is inaccessible by the above N-oxidation route (peroxyacid oxidation of 3-formylpyridine yields pyridine-N-oxide 3-carboxylic acid). In the synthesis of the parent 1 from 2-chloro-3-formylpyridine, the yield was prejudiced by the formation

  2-氯-3-甲酰基吡啶（2-氯烟醛）由雷尼镍和甲酸（3 1）还原2-氯-3-氰基吡啶得到；该中间体无法通过上述 N-氧化途径获得（3-甲酰基吡啶的过氧酸氧化产生吡啶-N-氧化物 3-羧酸）。在由 2-氯-3-甲酰基吡啶合成母体 1 时，收率受到吖嗪物质 11 的形成的影响。
• Discovery of New Orally Active Phosphodiesterase (PDE4) Inhibitors
  作者：Hiroshi Ochiai、Akiharu Ishida、Tazumi Ohtani、Kensuke Kusumi、Katuya Kishikawa、Susumu Yamamoto、Hiroshi Takeda、Takaaki Obata、Hisao Nakai、Masaaki Toda

  DOI：10.1248/cpb.52.1098

  日期：——

  A series of 4-anilinopyrazolopyridine derivatives were synthesized and biologically evaluated as inhibitors of phosphodiesterase (PDE4). Chemical modification of 3, a structurally new chemical lead that was found in our in-house library, was focused on 1- and 3-substituents. Full details of the discovery of a new orally active chemical lead 5 are presented. Structure–activity relationship data, pharmacological evaluation, and the subtype selectivity study are also presented.

  合成了一系列4-氨基吡唑并吡啶衍生物，并对其作为磷酸二酯酶（PDE4）抑制剂进行生物评估。对3这一我们内部库中发现的结构新颖的化学先导物的化学改造主要集中在1-和3-取代基上。本文详细介绍了新型口服活性化学先导物5的发现，以及结构-活性关系数据、药理评估和亚型选择性研究的结果。
• Design, Synthesis, and Pharmacological Properties of New Heteroarylpyridine/Heteroarylpyrimidine Derivatives as CB₂ Cannabinoid Receptor Partial Agonists
  作者：Mojgan Aghazadeh Tabrizi、Pier Giovanni Baraldi、Giulia Saponaro、Allan R. Moorman、Romeo Romagnoli、Delia Preti、Stefania Baraldi、Carmen Corciulo、Fabrizio Vincenzi、Pier Andrea Borea、Katia Varani

  DOI：10.1021/jm301527r

  日期：2013.2.14

  this potential, it is necessary to develop compounds with high affinity for the CB2 receptor. Very recently, we have identified the oxazinoquinoline carboxamides as a novel class of CB2 receptor full agonists. In this paper we describe the medicinal chemistry of a new series of heteroaryl-4-oxopyridine/7-oxopyrimidine derivatives. Some of the reported compounds showed high affinity and potency at the CB2

  最近的发展表明，CB 2受体配体具有成为治疗上重要的潜力。为了探索这种潜力，有必要开发对CB 2受体具有高亲和力的化合物。最近，我们已经确定恶嗪基喹啉羧酰胺为一类新型的CB 2受体完全激动剂。在本文中，我们描述了一系列新的杂芳基-4-氧吡啶/ 7-氧嘧啶衍生物的药物化学。一些报道的化合物对CB 2受体表现出高亲和力和效力，而对中央表达的CB 1仅表现出适度的亲和力大麻素受体。此外，我们发现这些配体的官能度受与吡啶环缩合的杂芳基官能团的性质控制。在3,5-环一磷酸腺苷（cAMP）分析中，该新系列显示出对毛喉素诱导的cAMP产生的调制具有剂量依赖性的作用，揭示了完全激动剂，部分激动剂和反向激动剂的不同行为。
• PYRAZOLO [3, 4-B] PYRIDINE DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS
  申请人：Rudra Sonali

  公开号：US20110130403A1

  公开（公告）日：2011-06-02

  The present invention relates to phosphodiesterase (PDE) type 4, phosphodiesterase (PDE) type 7 and dual PDE type 4/PDE type 7 inhibitors. Compounds disclosed hereinf having the structure of Formula I: can be useful in the treatment, prevention, inhibition or suppression of CNS diseases, for example, multiple sclerosis; various pathological conditions such as diseases affecting the immune system, including AIDS, rejection of transplant, auto-immune disorders such as T-cell related diseases, for example, rheumatoid arthritis; inflammatory diseases such as respiratory inflammation diseases including chronic obstructive pulmonary disease (COPD), asthma, bronchitis, allergic rhinitis, adult respiratory distress syndrome (ARDS) and other inflammatory diseases including but not limited to psoriasis, shock, atopic dermatitis, eosinophilic granuloma, allergic conjunctivitis, osteoarthritis; gastrointestinal inflammation diseases such as Crohn's disease, colitis, pancreatitis as well as different types of cancers including leukaemia; especially in humans. Processes for the preparation of disclosed compounds, pharmaceutical compositions containing the disclosed compounds and their use as PDE type 4, PDE type 7 and dual PDE t e 4/PDE t e 7 inhibitors are rovided.

  本发明涉及磷酸二酯酶（PDE）4型、磷酸二酯酶（PDE）7型和双重PDE类型4/PDE类型7抑制剂。本文所披露的具有I式结构的化合物可用于治疗、预防、抑制或抑制中枢神经系统疾病，例如多发性硬化症；各种影响免疫系统的病理情况，包括艾滋病、移植排斥、自身免疫性疾病，如T细胞相关疾病，例如类风湿性关节炎；炎症性疾病，如呼吸道炎症性疾病，包括慢性阻塞性肺疾病（COPD）、哮喘、支气管炎、过敏性鼻炎、成人呼吸窘迫综合征（ARDS）以及其他炎症性疾病，包括但不限于牛皮癣、休克、特应性皮炎、嗜酸性肉芽肿、过敏性结膜炎、骨关节炎；胃肠道炎症性疾病，如克罗恩病、结肠炎、胰腺炎以及不同类型的癌症，包括白血病；特别是在人类中。本文提供了披露化合物的制备方法、含有披露化合物的制药组合物以及它们作为PDE类型4、PDE类型7和双重PDE类型4/PDE类型7抑制剂的用途。
• Inhibitors of glucocorticoid receptor translocation
  申请人：Sanford Burnham Prebys Medical Discovery Institute

  公开号：US10272074B2

  公开（公告）日：2019-04-30

  Provided herein are compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of Glucocorticoid Receptor (GR) translocation. Furthermore, the subject compounds and compositions are useful for the treatment of diseases involved in the hypothalamic-pituitary-adrenal (HPA) axis.

  本文提供的是包含所述化合物的化合物和药物组合物。所述化合物和组合物可用作糖皮质激素受体（GR）转运的调节剂。此外，所述化合物和组合物还可用于治疗涉及下丘脑-垂体-肾上腺（HPA）轴的疾病。