2,4-二氧代-1,2,3,4-四氢嘧啶-5-磺酰氯 | 28485-18-9

• 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: 2,4-二氧代-1,2,3,4-四氢嘧啶-5-磺酰氯
• 中文别名: 2,4-二氧代-1,2,3,4-四氢-5-嘧啶磺酰氯
• 英文名称: uracil-5-sulfonyl chloride
• 英文别名: uracil-5-sulphonyl chloride；2,4-Dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonyl chloride；2,4-dioxo-1H-pyrimidine-5-sulfonyl chloride
• CAS: 28485-18-9
• 化学式: C₄H₃ClN₂O₄S
• mdl: MFCD06655485
• 分子量: 210.598
• InChiKey: FQHNJCWWBKYCJW-UHFFFAOYSA-N

物化性质

• 熔点：
  >300 °C
• 沸点：
  301.9±15.0 °C(Predicted)
• 密度：
  1.587±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 危险等级：
  8
• 危险品标志：
  Xi
• 海关编码：
  2933599090
• 储存条件：
  存储条件：2-8°C，密封保存，并保持干燥。

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: 2,4-Dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonyl chloride
Synonyms:

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H314: Causes severe skin burns and eye damage
H318: Causes serious eye damage
P260: Do not breathe dust/fume/gas/mist/vapours/spray
P303+P361+P353: IF ON SKIN (or hair): Remove/Take off immediately all contaminated clothing. Rinse skin with
water/shower
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P301+P330+P331: IF SWALLOWED: Rinse mouth. Do NOT induce vomiting
P405: Store locked up

---

Section 3. Composition/information on ingredients.
Ingredient name: 2,4-Dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonyl chloride
CAS number: 28485-18-9

---

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.

---

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.

---

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.

---

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.

---

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.

---

Section 9. Physical and chemical properties
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C4H3ClN2O4S
Molecular weight: 210.6

---

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 chloride, sulfur oxides.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

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.

---

Section 14. Transportation information
UN Number: UN3261 Class: 8 Packing group: III
Proper shipping name: CORROSIVE SOLID, ACIDIC, ORGANIC, N.O.S. (2,4-Dioxo-1,2,3,4-tetrahydropyrimidine-5-
sulfonyl chloride)

---

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.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  2,4-二氧代-1,2,3,4-四氢嘧啶-5-磺酰氯 在 锌 作用下， 生成 5-[(2,4-二氧代-1H-嘧啶-5-基)二硫基]-1H-嘧啶-2,4-二酮
  参考文献：
  名称：

  Synthesis of Compounds Related to Thymine. III. Chlorosulfonation of Uracil

  摘要：

  DOI：

  10.1021/ja01583a041
• 作为产物：
  描述：

  尿嘧啶 在 氯磺酸 、 氯化亚砜 作用下， 反应 12.5h， 以92.3%的产率得到2,4-二氧代-1,2,3,4-四氢嘧啶-5-磺酰氯
  参考文献：
  名称：

  N-苯基-（2,4-二羟基嘧啶-5-磺酰胺基）苯甲酰肼衍生物作为胸苷酸合酶（TS）抑制剂和潜在抗肿瘤药物的设计，合成和生物学评估。

  摘要：

  抑制细胞核苷酸代谢以促进细胞凋亡是癌症治疗的关键原理。胸苷酸合酶（TS）是细胞DNA合成起始中的关键限速酶。在这里，我们介绍了两种类型的胸苷酸合酶抑制剂，并提取了这两种类型的胸苷酸合酶抑制剂的关键药理特性，并进行了组合，以设计出具有抑制活性的新化合物。因此，通过结合原理设计合成了具有共同生物促凋亡作用的42种新化合物。大多数化合物对A549，OVCAR-3，SGC7901和MDA-MB-231细胞具有良好的抗增殖活性。化合物10l对A549细胞的IC50为1.26μM，优于培美曲塞（PTX，IC50 = 3.31μM），此外，化合物10l的选择指数高于PTX。流式细胞仪分析表明，化合物10l（凋亡率为39.4％）可以诱导A549细胞凋亡，并有效抑制肿瘤细胞的增殖。进一步的蛋白质印迹分析表明，化合物10l可通过激活caspase-3，增加裂解的caspase-3的表达并降低bcl-2 / b

  DOI：

  10.1016/j.ejmech.2018.05.020

文献信息

• Design, synthesis and biological evaluation of novel uracil derivatives bearing 1, 2, 3-triazole moiety as thymidylate synthase (TS) inhibitors and as potential antitumor drugs
  作者：Guo-qing Lu、Xin-yang Li、Kamara Mohamed O、Depu Wang、Fan-hao Meng

  DOI：10.1016/j.ejmech.2019.03.047

  日期：2019.6

  Research on thymidylate synthase inhibitors has been a hot spot for anticancer drug development. Here, based on the structures and pharmacological properties of two types of TS inhibitors, through a molecular assembly principle of drugs design, we designed and synthesized a series of 30 novel uracil derivatives as TS inhibitors. The antiproliferative ability of these compounds was evaluated against

  胸苷酸合酶抑制剂的研究一直是抗癌药物开发的热点。在此，根据两种TS抑制剂的结构和药理特性，通过药物设计的分子组装原理，我们设计合成了30种新颖的尿嘧啶衍生物作为TS抑制剂。通过MTT分析评估了这些化合物对四种癌细胞系（A549，OVCAR-3，SGC-7901和HepG2）的抗增殖能力。它们中的大多数对所有测试的细胞系均表现出优异的活性。此外，hTS分析结果表明，这些化合物具有独特的体外抑制hTS活性的能力。值得注意的是，化合物13j对A549细胞表现出最强的活性（IC 50 = 1.18μM）和极显着的酶抑制（IC 50  = 0.13μM），优于培美曲塞（PTX，IC 50  = 3.29μM和IC 50  = 2.04μM）。流式细胞仪分析表明，化合物13j可以通过将细胞周期阻滞在G1 / S期来抑制A549细胞的增殖，进而诱导细胞凋亡。进一步的蛋白质印迹分析表明化合物13j可能下调周期检查点蛋白cyclin
• 嘧啶类抗肿瘤化合物及其制备方法和应用
  申请人：中国医科大学

  公开号：CN109705045B

  公开（公告）日：2020-07-14

  本发明属于医药领域，具体涉及嘧啶类抗肿瘤化合物及其制备方法和应用。本发明是对嘧啶类似物和TP抑制剂的药效特点进行分析，拟通过拼合原理设计一系列具有二者共同生物作用的新化合物。药理研究显示，本发明化合物对人肺癌A549细胞、人卵巢癌OVCAR‑3细胞、人胃癌SGC‑7901细胞均有一定的抑制活性。
• Discovery of N-phenyl-(2,4-dihydroxypyrimidine-5-sulfonamido) phenylurea-based thymidylate synthase (TS) inhibitor as a novel multi-effects antitumor drugs with minimal toxicity
  作者：Xin-yang Li、Ting-jian Zhang、Mohamed Olounfeh Kamara、Guo-qing Lu、Hai-li Xu、De-pu Wang、Fan-hao Meng

  DOI：10.1038/s41419-019-1773-0

  日期：——

  cell migration and angiogenesis in cancer tissues. Furthermore, in vivo pharmacology evaluations of L14e showed significant antitumor activity in A549 cells xenografts with minimal toxicity. All of these results demonstrated that the L14e has the potential for drug discovery as a multi-effects inhibitor and provides a new reference for clinical treatment of non-small cell lung cancer.

  胸苷酸合酶（TS）是肿瘤化学治疗的热点，其抑制剂是抗肿瘤药物研究的重要方向。据我们所知，目前尚无可抑制癌细胞迁移的胸苷酸合酶抑制剂的报道。因此，出于最佳治疗目的，结合我们以前的报道和发现，我们希望获得一种多效抑制剂。本研究根据展平原理设计并合成了18种N-苯基-（2,4-二羟基嘧啶-5-磺酰胺基）苯基脲衍生物作为多效抑制剂。生物学评估结果表明，目标化合物可以在体外显着抑制hTS酶，BRaf激酶和EGFR激酶活性，并且大多数化合物对6种癌细胞具有出色的抗细胞生存能力。尤其，与培美曲塞相比，候选化合物L14e（IC50 = 0.67μM）具有优于A549和H460细胞的抗细胞活力和安全性。进一步的研究表明，L14e可能导致G1 / S期停滞，然后诱导内在凋亡。Transwell，western blot和管形成结果证明，L14e可以抑制EGFR信号通路的激活，从而最终达到抑制癌组织中癌细胞迁移
• Inhibitory effect of some new uracil and thiouracil derivatives on cercarial penetration enzymes
  作者：O. A. Fathalla、M. E. Haiba、M. M. Anwar、Maha S. Almutairi、A. S. Maghraby、M. M. Bahgat

  DOI：10.1007/s11164-012-0748-x

  日期：2013.5

  Some uracil- and thiouracil-5-sulfonohydrazide derivatives have been synthesized to be evaluated as antischistosomal agents. N-[2-(1,5-Dimethyl-3-oxo-2-phenylpyrazolin-4-yl)-4-oxo-1,3-thiazolidin-3-yl]-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide (3c) was formulated in jojoba oil and used to paint mice tails before infection with Schistosoma mansoni cercariae. Using Boc-Val-Leu-Gly-Arg-PNA, a specific substrate for trypsin-like serine proteinases, compound 3c inhibited cercarial serine protease activity with 50 % inhibition concentration (IC50) of 160 μg. Upon topical application on mice tails before infection with S. mansoni cercariae, it caused a 20 % reduction in worm burden compared with untreated infected mice. Using soluble crude cercarial antigen in enzyme-linked immunosorbent assay (ELISA), no significant changes were observed in the levels of immunoglobulin M (IgM) and IgG in sera from treated infected mice at 2, 4, and 6 weeks postinfection (WPI) compared with the level in sera from infected untreated mice. At 4 WPI, sera from treated infected mice showed significantly low (P < 0.05) IgM reactivity to crude soluble worm antigen compared with infected nontreated ones. IgG levels in sera from treated infected mice at 2 and 4 WPI were significantly lower (P < 0.05) than in sera from infected nontreated mice. At 6 WPI, the IgG response showed no significant differences in sera from both mice groups. Sera from treated infected mice at 2, 4, and 6 WPI had generally lower IgM reactivity to soluble egg antigen when compared with the level in sera from nontreated infected mice. At all time points postinfection, sera collected from treated infected mice showed significantly low IgG reactivity (P < 0.05) compared with infected nontreated mice.

  一些尿嘧啶和硫尿嘧啶-5-磺酸肼衍生物已被合成，并被评估为抗血吸虫剂。N-[2-(1,5-二甲基-3-氧代-2-苯基吡唑啉-4-基)-4-氧代-1,3-噻唑烷-3-基]-4-氧代-2-硫代-1,2,3,4-四氢嘧啶-5-磺酰胺（3c）被配制在荷荷巴油中，并用于感染血吸虫幼虫前涂抹小鼠尾巴。利用Boc-Val-Leu-Gly-Arg-PNA，这是一种特异性基质用于类胰蛋白酶的丝氨酸蛋白酶，化合物3c对幼虫丝氨酸蛋白酶活性产生了50%的抑制浓度（IC50）为160μg。 在感染S. mansoni幼虫前的局部涂抹中，与未处理的感染小鼠相比，它使虫体负担降低了20%。 使用溶解的粗幼虫抗原进行酶联免疫吸附试验（ELISA），在感染后2、4和6周，与未处理感染小鼠的血清水平相比，未观察到治疗感染小鼠IgM和IgG水平的显著变化。 在4周时，治疗感染小鼠的血清对粗溶解虫抗原表现出明显低（P < 0.05）的IgM反应，与未处理的感染小鼠相比。 在2和4周时，治疗感染小鼠的血清IgG水平明显低（P < 0.05）于未处理感染小鼠的血清。 在6周时，两个小鼠组的血清IgG反应没有显著差异。 与未处理感染小鼠的血清水平相比，治疗感染小鼠在2、4和6周时对可溶性卵抗原的IgM反应普遍较低。 在感染后所有时间点，治疗感染小鼠收集的血清与未处理感染小鼠相比，IgG反应显著低（P < 0.05）。
• Uracil derivatives as inhibitors of TNF-alpha converting enzyme (TACE) and matrix metalloproteinases
  申请人：——

  公开号：US20030229081A1

  公开（公告）日：2003-12-11

  The present application describes novel uracil derivatives of formula I: A-W-U-X-Y-Z-U a -X a -Y a -Z a I or pharmaceutically acceptable salt or prodrug forms thereof, wherein A, W, U, X, Y, Z, U a , X a , Y a , and Z a are defined in the present specification, which are useful as inhibitors of TNF-&agr; converting enzyme (TACE), matrix metalloproteinases (MMP), aggrecanase or a combination thereof.

  本申请描述了式I的新颖尿嘧啶衍生物：A-W-U-X-Y-Z-Ua-Xa-Ya-Za或其药用可接受的盐或前药形式，其中A、W、U、X、Y、Z、Ua、Xa、Ya和Za在本规范中有定义，这些衍生物可用作肿瘤坏死因子α转化酶（TACE）、基质金属蛋白酶（MMP）、聚集素酶的抑制剂或其组合。