4-(乙基氨基)-2-(甲基硫代)嘧啶-5-羧酸乙酯 | 185040-33-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4-(乙基氨基)-2-(甲基硫代)嘧啶-5-羧酸乙酯
• 英文名称: 4-ethylamino-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester
• 英文别名: 4-ethylamino-2-(methylsulfanyl)pyrimidine-5-carboxylic acid ethyl ester；4-ethylamino-2-methanesulfanylpyrimidine-5-carboxylic acid ethyl ester；ethyl 4-(ethylamino)-2-(methylthio)pyrimidine-5-carboxylate；ethyl 4-ethylamino-2-methylthiopyrimidinecarboxylate；ethyl 4-ethylamino-2-methyl-thiopyrimidine-5-carboxylate；4-ethylamino-2-methanesulfanyl-pyrimidine-5-carboxylic acid ethyl ester；ethyl 4-(ethylamino)-2-methylsulfanylpyrimidine-5-carboxylate
• CAS: 185040-33-9
• 化学式: C₁₀H₁₅N₃O₂S
• 分子量: 241.314
• InChiKey: LBZSUTCUDDWYRI-UHFFFAOYSA-N

物化性质

• 沸点：
  380.8±22.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  89.4
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2933599090

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Ethyl 4-(ethylamino)-2-(methylthio)pyrimidine-5-carboxylate
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: Ethyl 4-(ethylamino)-2-(methylthio)pyrimidine-5-carboxylate
CAS number: 185040-33-9

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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.
Store in closed vessels.
Storage:

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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
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C10H15N3O2S
Molecular weight: 241.3

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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, sulfur oxides.

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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

反应信息

• 作为反应物：
  描述：

  4-(乙基氨基)-2-(甲基硫代)嘧啶-5-羧酸乙酯 在 三聚氟氰 、 水 、 sodium hydride 、 三乙胺 、 间氯过氧苯甲酸 、 sodium hydroxide 作用下， 以 N-甲基吡咯烷酮 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 29.67h， 生成 7-Amino-8-ethyl-2-(methylsulfonyl)-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxamide
  参考文献：
  名称：

  5 OXO-5,8-DIHYDROPYRIDO[2,3-d]PYRIMIDINE DERIVATIVES AS CAMKII KINASE INHIBITORS FOR TREATING CARDIOVASCULAR DISEASES

  摘要：

  本发明涉及5-氧代-5,8-二氢吡啶并[2,3-d]嘧啶衍生物，其制备和治疗用途。

  公开号：

  US20120277220A1
• 作为产物：
  描述：

  4-氯-2-甲硫基嘧啶-5-羧酸乙酯 、 乙胺 在 三乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.5h， 以90%的产率得到4-(乙基氨基)-2-(甲基硫代)嘧啶-5-羧酸乙酯
  参考文献：
  名称：

  细胞周期蛋白依赖性激酶的Pyrido [2,3-d] pyrimidin-7-one抑制剂。

  摘要：

  鉴定为Cdk4抑制剂的8-乙基-2-苯基氨基-8H-吡啶并[2，3-d]嘧啶-7-一（1）引发了评估相关吡啶并[2，3- d]嘧啶-7-抑制细胞周期蛋白依赖性激酶（Cdks）的化合物。对60多个类似物的分析已经确定了一些明显的SAR趋势，可在设计更有效的Cdk抑制剂时加以利用。本研究中报告的最有效的Cdk4抑制剂以IC（50）= 0.004 microM（[ATP] = 25 microM）抑制Cdk4。对与相关激酶Cdk2结合的代表性化合物的X射线晶体学分析表明，它们占据了ATP结合位点。一些化合物在Cdk之间表现出适度的选择性，而Cdk4选择性抑制剂在细胞分裂周期的G（1）相中阻断pRb（+）细胞。

  DOI：

  10.1021/jm000271k

文献信息

• 2-Substituted Aminopyrido[2,3-<i>d</i>]pyrimidin-7(8<i>H</i>)-ones. Structure−Activity Relationships Against Selected Tyrosine Kinases and in Vitro and in Vivo Anticancer Activity
  作者：Sylvester R. Klutchko、James M. Hamby、Diane H. Boschelli、Zhipei Wu、Alan J. Kraker、Aneesa M. Amar、Brian G. Hartl、Cynthia Shen、Wayne D. Klohs、Randall W. Steinkampf、Denise L. Driscoll、James M. Nelson、William L. Elliott、Billy J. Roberts、Chad L. Stoner、Patrick W. Vincent、Donald J. Dykes、Robert L. Panek、Gina H. Lu、Terry C. Major、Tawny K. Dahring、Hussein Hallak、Laura A. Bradford、H. D. Hollis Showalter、Annette M. Doherty

  DOI：10.1021/jm9802259

  日期：1998.8.1

  engaged in therapeutic intervention against a number of proliferative diseases, we have discovered the 2-aminopyrido[2, 3-d]pyrimidin-7(8H)-ones as a novel class of potent, broadly active tyrosine kinase (TK) inhibitors. An efficient route was developed that enabled the synthesis of a wide variety of analogues with substitution on several positions of the template. From the lead structure 2, a series

  在从事针对许多增生性疾病的治疗干预时，我们发现了2-氨基吡啶并[2,3-d]嘧啶7（8H）-一类新型有效的，广泛活性的酪氨酸激酶（TK）抑制剂。开发了一种有效的途径，该途径使得能够合成多种类似物，并在模板的多个位置上进行取代。由铅结构2，制得一系列在C-2位带有可变取代基和在N-8位带有甲基或乙基的类似物。该系列化合物可与ATP竞争，并且对包括受体（血小板衍生的生长因子，PDGFr，成纤维细胞生长因子，FGFr，表皮生长因子，EGFr）和非受体（c-Src）在内的一系列TK表现出亚微摩尔至低纳摩尔的效能）类。评估更充分的成员之一是63，IC50值分别为0.079 microM（PDGFr），0.043 microM（bFGFr），0.044 microM（EGFr）和0.009 microM（c-Src）。在细胞研究中，许多细胞系中有63种抑制PDGF介导的受体自身磷酸化，IC5​​0值为0
• Pyrido\x9b2, 3-d!pyrimidines for inhibiting protein tyrosine kinase
  申请人：Warner-Lambert Company

  公开号：US05733914A1

  公开（公告）日：1998-03-31

  6-Aryl pyrido\x9b2,3-d!pyrimidine 7-imines, 7-ones, and 7-thiones are inhibitors of protein tyrosine kinases, and are thus useful in treating cellular proliferation mediated thereby. The compounds are especially useful in treating cancer, atherosclerosis, restenosis, and psoriasis.

  6-芳基吡啶[2,3-d]嘧啶7-亚胺，7-酮和7-硫醚是蛋白酪氨酸激酶的抑制剂，因此在治疗由此介导的细胞增殖方面非常有用。这些化合物在治疗癌症、动脉粥样硬化、再狭窄和牛皮癣方面特别有用。
• [EN] PYRIMIDINE COMPOUNDS AS KINASE INHIBITORS<br/>[FR] COMPOSÉS PYRIMIDINES EN TANT QU'INHIBITEURS DE KINASE
  申请人：ICAHN SCHOOL MED MOUNT SINAI

  公开号：WO2014151682A1

  公开（公告）日：2014-09-25

  This disclosure relates to compounds, methods for their preparation, pharmaceutical compositions including these compounds and methods for the treatment of cellular proliferative disorders, including, but not limited to, cancer.

  这份披露涉及化合物、它们的制备方法、包括这些化合物的药物组合物以及治疗细胞增殖障碍的方法，包括但不限于癌症。
• Chemically Diverse Group I p21-Activated Kinase (PAK) Inhibitors Impart Acute Cardiovascular Toxicity with a Narrow Therapeutic Window
  作者：Joachim Rudolph、Lesley J. Murray、Chudi O. Ndubaku、Thomas O’Brien、Elizabeth Blackwood、Weiru Wang、Ignacio Aliagas、Lewis Gazzard、James J. Crawford、Joy Drobnick、Wendy Lee、Xianrui Zhao、Klaus P. Hoeflich、David A. Favor、Ping Dong、Haiming Zhang、Christopher E. Heise、Angela Oh、Christy C. Ong、Hank La、Paroma Chakravarty、Connie Chan、Diana Jakubiak、Jennifer Epler、Sreemathy Ramaswamy、Roxanne Vega、Gary Cain、Dolores Diaz、Yu Zhong

  DOI：10.1021/acs.jmedchem.6b00638

  日期：2016.6.9

  p21-activated kinase 1 (PAK1) has an important role in transducing signals in several oncogenic pathways. The concept of inhibiting this kinase has garnered significant interest over the past decade, particularly for targeting cancers associated with PAK1 amplification. Animal studies with the selective group I PAK (pan-PAK1, 2, 3) inhibitor G-5555 from the pyrido[2,3-d]pyrimidin-7-one class uncovered

  p21激活的激酶1（PAK1）在几种致癌途径中的信号转导中具有重要作用。在过去的十年中，抑制这种激酶的概念引起了广泛的兴趣，特别是针对与PAK1扩增相关的癌症。使用吡啶基[2,3- d]选择性I组PAK（pan-PAK1，2，3）抑制剂G-5555进行动物研究] pyrimidin-7-一类化合物具有较窄的治疗窗口，未发现急性毒性。为了尝试减轻毒性，我们引入了显着的结构变化，最终发现了有效的吡啶酮侧链类似物G-9791。用这种化合物，该系列其他成员以及两种结构不同的化合物进行的小鼠耐受性研究表明，该化合物具有持续毒性，且最低毒性浓度与PAK1 / 2介导的细胞效能具有相关性。广泛筛选所选的PAK抑制剂显示PAK1、2和3是唯一重叠的靶标。我们的数据表明，PAK2的抑制可能会导致PAK1的抑制，从而加剧急性心血管毒性，并警告在药物开发中不要继续追求泛I类PAK抑制剂。
• Synthesis and Tyrosine Kinase Inhibitory Activity of a Series of 2-Amino-8<i>H</i>-pyrido[2,3-<i>d</i>]pyrimidines:  Identification of Potent, Selective Platelet-Derived Growth Factor Receptor Tyrosine Kinase Inhibitors
  作者：Diane H. Boschelli、Zhipei Wu、Sylvester R. Klutchko、H. D. Hollis Showalter、James M. Hamby、Gina H. Lu、Terry C. Major、Tawny K. Dahring、Brian Batley、Robert L. Panek、Joan Keiser、Brian G. Hartl、Alan J. Kraker、Wayne D. Klohs、Bill J. Roberts、Sandra Patmore、William L. Elliott、Randy Steinkampf、Laura A. Bradford、Hussein Hallak、Annette M. Doherty

  DOI：10.1021/jm980398y

  日期：1998.10.1

  N-8 of the pyrido[2,3-d]pyrimidine core provided several analogues that retained potency, including derivatives that were biased toward inhibition of the TK activity of PDGFr. Analogues of 2a with a 3-thiophene or an unsubstituted phenyl group at C-6 were the most potent inhibitors. Compound 54, which had IC50 values of 31, 88, and 31 nM against PDGFr, FGFr, and c-src TK activity, respectively, was

  化合物库的筛选导致鉴定出2-氨基-6-（2,6-二氯苯基）-8-甲基吡啶并[2,3-d]嘧啶（1）作为血小板衍生的生长因子受体的抑制剂（ PDGFr），成纤维细胞生长因子受体（FGFr）和c-src酪氨酸激酶（TKs）。用4-（N，N-二乙基氨基乙氧基）苯基氨基取代C-2为1的伯氨基得到2a，其对所有三个TK的活性均大大提高。在目前的工作中，吡啶并[2,3-d]嘧啶核的C-6处的芳族基团和N-8处的烷基基团的变化提供了几种保留效力的类似物，包括偏向于抑制甲壳素的衍生物。 PDGFr的TK活性。2a在C-6处带有3-噻吩或未取代的苯基的类似物是最有效的抑制剂。化合物54的IC50值为31，