4-氯-6-苯基噻吩并[2,3-D]嘧啶 | 35970-79-7

• 物质功能分类: 医药中间体 - 杂环化合物 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 中文名称: 4-氯-6-苯基噻吩并[2,3-D]嘧啶
• 英文名称: 4-chloro-6-phenylthieno[2,3-d]pyrimidine
• CAS: 35970-79-7
• 化学式: C₁₂H₇ClN₂S
• mdl: MFCD02966922
• 分子量: 246.72
• InChiKey: WJFATWIQZZNARY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险品标志：
  Xi,T
• 安全说明：
  S26,S45
• 危险类别码：
  R36,R36/37/38,R25
• 海关编码：
  2934999090

SDS

Name:	4-Chloro-6-phenylthieno[2 3-d]pyrimidine Material Safety Data Sheet
Synonym:	None Known
CAS:	35970-79-7

Section 1 - Chemical Product MSDS Name:4-Chloro-6-phenylthieno[2 3-d]pyrimidine Material Safety Data Sheet
Synonym:None Known

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
35970-79-7	4-Chloro-6-phenylthieno[2,3-d]pyrimidi	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. May cause chemical conjunctivitis.
Skin:
Causes skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause gastrointestinal irritation with nausea, vomiting and diarrhea. May be harmful if swallowed.
Inhalation:
Causes respiratory tract irritation. May be harmful if inhaled.
Chronic:
No information found.

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Section 4 - FIRST AID MEASURES
Eyes: Immediately 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. Wash clothing before reuse.
Ingestion:
Never give anything by mouth to an unconscious person. Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or 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. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or appropriate foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Clean up spills immediately, observing precautions in the Protective Equipment section. Sweep up or absorb material, then place into a suitable clean, dry, closed container for disposal. Avoid generating dusty conditions. Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation. Wash clothing before reuse.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

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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# 35970-79-7: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements or European Standard EN 149 must be followed whenever workplace conditions warrant respirator use.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: white
Odor: slight
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 138-139 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: C12H7ClN2S
Molecular Weight: 246.72

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable at room temperature in closed containers under normal storage and handling conditions.
Conditions to Avoid:
Dust generation.
Incompatibilities with Other Materials:
Oxidizing agents, bases, amines.
Hazardous Decomposition Products:
Hydrogen chloride, chlorine, carbon monoxide, oxides of nitrogen, oxides of sulfur, carbon dioxide.
Hazardous Polymerization: Will not occur.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 35970-79-7 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
4-Chloro-6-phenylthieno[2,3-d]pyrimidine - 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
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing Group:
IMO
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing Group:
RID/ADR
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing group:

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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 22 Do not breathe dust.
S 26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S 36/37/39 Wear suitable protective clothing, gloves
and eye/face protection.
WGK (Water Danger/Protection)
CAS# 35970-79-7: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 35970-79-7 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 35970-79-7 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：

  4-氯-6-苯基噻吩并[2,3-D]嘧啶 在 一水合肼 作用下， 以 乙醇 为溶剂， 生成 4-肼基-6-苯基噻吩[2,3-d]嘧啶
  参考文献：
  名称：

  Arya,V.P.; Ghate,S.P., Indian Journal of Chemistry, 1971, vol. 9, p. 1209 - 1212

  摘要：

  DOI：
• 作为产物：
  描述：

  6-苯基-3H-噻吩并[2,3-d]嘧啶-4-酮 在 五氯化磷 、 三氯氧磷 作用下， 以80%的产率得到4-氯-6-苯基噻吩并[2,3-D]嘧啶
  参考文献：
  名称：

  基于4-氨基噻吩并[2,3-d]嘧啶的新型蛋白激酶CK2抑制剂的设计与合成

  摘要：

  我们先前研究工作的扩展已导致在4-氨基噻吩并[2,3-d]嘧啶衍生物中鉴定出许多新的与ATP竞争的CK2抑制剂。在研究过程中获得的活性最高的化合物是3-（5-对甲苯基-噻吩并[2,3-d]嘧啶-4-基氨基）苯甲酸5e（NHTP23，IC 50  = 0.01μM）， 3-（5-苯基-噻吩并[2,3-d]嘧啶-4-基氨基）-苯甲酸，5g（NHTP25，IC 50  = 0.065μM）和3-（6-甲基-5-苯基-噻吩并[2 ，3-d]嘧啶-4-基氨基）-苯甲酸，5n（NHTP33，IC 50 = 0.008μM）。研究了测试的4-氨基噻吩并[2,3-d]嘧啶衍生物的结构-活性关系，并提出了它们与CK2 ATP受体位点的结合方式。讨论了分子内氢键对化合物结构的负面影响。

  DOI：

  10.1016/j.ejmech.2016.03.004

文献信息

• Pharmacophore Mapping of Thienopyrimidine-Based Monophosphonate (ThP-MP) Inhibitors of the Human Farnesyl Pyrophosphate Synthase
  作者：Jaeok Park、Chun Yuen Leung、Alexios N. Matralis、Cyrus M. Lacbay、Michail Tsakos、Guillermo Fernandez De Troconiz、Albert M. Berghuis、Youla S. Tsantrizos

  DOI：10.1021/acs.jmedchem.6b01888

  日期：2017.3.9

  Recent drug discovery efforts have focused primarily on allosteric inhibition of hFPPS and the discovery of non-bisphosphonate drugs for potentially treating nonskeletal diseases. Hit-to-lead optimization of a new series of thienopyrimidine-based monosphosphonates (ThP-MPs) led to the identification of analogs with nanomolar potency in inhibiting hFPPS. Their interactions with the allosteric pocket of

  人法呢基焦磷酸合酶（hFPPS）是甲羟戊酸途径中的关键调节酶，催化C-15异戊二烯类法呢基焦磷酸（FPP）的生物合成。FPP在执行大量细胞功能的小GTP酶的翻译后异戊烯化中起关键作用。尽管hFPPS是溶骨性疾病的公认治疗靶标，但目前可用的双膦酸酯类药物表现出不良的细胞摄取能力，并分布到非骨骼组织中。最近的药物发现工作主要集中在hFPPS的变构抑制和发现潜在用于治疗非骨骼疾病的非双膦酸酯药物上。一系列基于硫代嘧啶的单膦酸酯（ThP-MPs）的先导性优化导致鉴定出具有纳摩尔浓度抑制hFPPS的类似物。它们与酶的变构口袋的相互作用通过晶体学表征，并且结果提供了对变构抑制的药效团要求的进一步见解。
• Design, Synthesis, and Biological Evaluation of 6-Substituted Thieno[3,2-<i>d</i>]pyrimidine Analogues as Dual Epidermal Growth Factor Receptor Kinase and Microtubule Inhibitors
  作者：Romeo Romagnoli、Filippo Prencipe、Paola Oliva、Stefania Baraldi、Pier Giovanni Baraldi、Santiago Schiaffino Ortega、Mariem Chayah、Maria Kimatrai Salvador、Luisa Carlota Lopez-Cara、Andrea Brancale、Salvatore Ferla、Ernest Hamel、Roberto Ronca、Roberta Bortolozzi、Elena Mariotto、Elena Mattiuzzo、Giampietro Viola

  DOI：10.1021/acs.jmedchem.8b01391

  日期：2019.2.14

  The clinical evidence for the success of tyrosine kinase inhibitors in combination with microtubule-targeting agents prompted us to design and develop single agents that possess both epidermal growth factor receptor (EGFR) kinase and tubulin polymerization inhibitory properties. A series of 6-aryl/heteroaryl-4-(3',4',5'-trimethoxyanilino)thieno[3,2- d]pyrimidine derivatives were discovered as novel

  酪氨酸激酶抑制剂与微管靶向剂成功结合的临床证据促使我们设计和开发具有表皮生长因子受体（EGFR）激酶和微管蛋白聚合抑制特性的单一药物。发现了一系列6-芳基/杂芳基-4-（3'，4'，5'-三甲氧基苯胺基）噻吩并[3,2-d]嘧啶衍生物，它们是新型的双微管蛋白聚合和EGFR激酶抑制剂。4-（3'，4'，5'-三甲氧基苯胺基）-6-（对甲苯基）噻吩并[3,2-d]嘧啶衍生物6g是该系列中最有效的化合物，具有抗增殖作用，其中一半最大抑制浓度（IC50）值在一位或两位数纳摩尔范围内。化合物6g与秋水仙碱位点的微管蛋白结合并抑制微管蛋白组装，IC50值为0.71μM，6g抑制EGFR活性，IC50值为30 nM。我们的数据表明，6g优异的体外和体内特性可能源于其对微管蛋白聚合和EGFR激酶的双重抑制作用。
• SUBSTITUTED BICYCLIC HETEROARYL COMPOUNDS FOR THE TREATMENT OF CARDIOVASCULAR DISEASE
  申请人：Lampe Thomas

  公开号：US20100261736A1

  公开（公告）日：2010-10-14

  The present application relates to novel substituted bicyclic heteroaryl compounds, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular diseases.

  本申请涉及新型取代的双环杂环芳基化合物，其制备方法，它们用于治疗和/或预防疾病的用途，以及它们用于制备治疗和/或预防疾病的药物的用途，特别是用于治疗和/或预防心血管疾病。
• Route selection in the synthesis of C-4 and C-6 substituted thienopyrimidines
  作者：Steffen Bugge、Svein Jacob Kaspersen、Eirik Sundby、Bård Helge Hoff

  DOI：10.1016/j.tet.2012.08.090

  日期：2012.11

  possibilities of selective Suzuki reactions on 6-bromo-4-chlorothienopyrimidine were investigated. The preference for mono arylation at C-6 could be increased, in the case of Pd(PPh3)4 catalysis, by reducing the water content of the reaction, or by using less electron rich Pd-ligands. The highest selectivity was obtained with Pd(OAc)2 or Pd2(dba)3, while reactions with the more electron rich Pd(PPh3)4 and

  已经研究了三种不同的制备6-芳基-N-（1-芳基乙基）噻吩并嘧啶丁-4-胺的途径。首先，研究了在6-溴-4-氯噻吩并嘧啶上进行选择性铃木反应的可能性。在Pd（PPh 3）4催化的情况下，可以通过降低反应的水含量或使用较少的富电子Pd配体来提高C-6处单芳基化的偏好。用Pd（OAc）2或Pd 2（dba）3可获得最高的选择性，而与电子含量更高的Pd（PPh 3）4的反应特别是XPhos产生的单/双耦合产品比率较低。其次，测试了避免该选择性问题的两种替代策略。在二恶烷/水中使用Pd（PPh 3）4时，对6-溴噻吩并嘧啶-4（3 H）-1的C-6的Suzuki反应以70-89％的产率进行。在4-氨基-6-溴-噻吩并嘧啶上的类似条件（八个实例）得到67-95％的收率。该反应可以用在邻，间和对位中含有未保护的酚基的硼酸进行职位。通过延长反应时间，与空间拥挤的芳基硼酸偶联也是有效的。根据芳基硼酸的性质
• The Discovery and Development of Thienopyrimidines as Inhibitors of <i>Helicobacter pylori</i> That Act through Inhibition of the Respiratory Complex I
  作者：Alex K. Mugengana、Nicole A. Vita、Autumn Brown Gandt、Kevin Moran、George Agyapong、Lalit K. Sharma、Elizabeth C. Griffith、Jiuyu Liu、Lei Yang、Ekaterina Gavrish、Kirk E. Hevener、Michael D. LaFleur、Richard E. Lee

  DOI：10.1021/acsinfecdis.0c00300

  日期：2021.5.14

  binding and poor solubility. Although lead compounds in the series demonstrated efficacy in an ex vivo infection model, the compounds had no efficacy in a mouse model of H. pylori infection. Additional optimization of pharmacological properties of the series to increase solubility and free-drug levels at the sequestered sites of H. pylori infection would potentially result in a gain of in vivo efficacy. The

  由于对当前广谱三联疗法的耐药性增加，幽门螺杆菌感染的成功治疗变得越来越困难。在寻找针对幽门螺杆菌的窄谱药物时，高通量筛选确定了两种结构相关的噻吩并嘧啶化合物，它们选择性地抑制幽门螺杆菌而不是肠道微生物群的共生成员。建立噻吩并嘧啶对幽门螺杆菌的构效关系 (SAR)，这项研究采用了四系列修改，其中探索了对噻吩并嘧啶核心的系统取代，最终从两个原始命中优化的侧链元素合并到先导化合物中。在本系列的开发过程中，作用模式研究将幽门螺杆菌的呼吸复合物 I 亚基 NuoD 确定为噻吩并嘧啶铅的靶标。由于这种酶复合物对于 H. pylori 中的 ATP 合成至关重要，因此生成了H. pylori NuoB-NuoD 结合界面的同源模型，以帮助合理化 SAR 并指导该系列的进一步开发。从这些研究中，出现了具有增强的抗幽门螺杆菌效力的先导化合物、改进的安全指数和良好的总体药代动力学特征，但蛋白质结合率高和溶解度