4-氯-7-三氟甲基喹唑啉 | 16499-65-3

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 4-氯-7-三氟甲基喹唑啉
• 中文别名: 4-氯-7-(三氟甲基)喹唑啉
• 英文名称: 4-chloro-7-(trifluoromethyl)quinazoline
• 英文别名: 4-Chlor-7-trifluormethyl-chinazolin
• CAS: 16499-65-3
• 化学式: C₉H₄ClF₃N₂
• 分子量: 232.592
• InChiKey: IJNDITTYYNJLPT-UHFFFAOYSA-N

物化性质

• 熔点：
  62-64 °C(Solv: ligroine (8032-32-4))
• 沸点：
  285.8±35.0 °C(Predicted)
• 密度：
  1.496±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  储存条件为2-8°C，并需保存在惰性气体中。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4-Chloro-7-(trifluoromethyl)quinazoline
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: 4-Chloro-7-(trifluoromethyl)quinazoline
CAS number: 16499-65-3

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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: C9H4ClF3N2
Molecular weight: 232.6

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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, hydrogen chloride, hydrogen fluoride.

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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-氯-7-三氟甲基喹唑啉 在 苯胺 作用下， 以 乙醇 为溶剂， 生成 4-anilino-7-trifluoromethylquinazoline
  参考文献：
  名称：

  Method of using 4-anilinoquinazoline derivatives as analgesic and

  摘要：

  使用公式（I）中的4-苯胺基喹唑啉衍生物的方法：##STR1##（其中：R.sup.1代表氢原子，卤素原子，三氟甲基基团或硝基基团；R.sup.2代表氢原子，C.sub.1-C.sub.4烷基，烷氧基或卤素原子；R.sup.3代表氢原子或C.sub.1-C.sub.4烷基），以及其药学上可接受的盐，作为镇痛剂和抗炎药在哺乳动物的治疗中。这些化合物可以通过将适当的4-卤代喹唑啉与适当的苯胺或苯胺衍生物加热而制备得到。

  公开号：

  US04322420A1
• 作为产物：
  描述：

  7-(三氟甲基)喹唑啉-4(3H)-酮 在 N,N-二甲基甲酰胺 作用下， 反应 15.0h， 生成 4-氯-7-三氟甲基喹唑啉
  参考文献：
  名称：

  药物性质优化：口服生物利用喹唑啉基多靶点激酶抑制剂的发现。

  摘要：

  为了开发新的癌症疗法，我们已经在MOLM-13和MV4-11白血病模型以及大肠和胰腺动物模型中报告了临床候选药物BPR1K871（1）作为有效的抗癌化合物。由于BPR1K871缺乏口服生物利用度，我们继续通过药物样性质优化来寻找口服生物利用度类似物。我们优化了1的理化特性（PCP）以及体外大鼠肝脏微粒体的稳定性，同时监测了HCT-116细胞系中的极光激酶抑制和细胞抗增殖活性。喹唑啉核心1的6位和7位的结构修饰导致34被鉴定为口服生物利用型（F％= 54）多激酶抑制剂，对多种癌细胞系表现出有效的抗增殖活性。

  DOI：

  10.1016/j.bioorg.2020.103689

文献信息

• Potential Antimalarials. IX. Di-mannich Bases of 4-(7′-trifluoro-methylquinazolin-4′-ylamino)phenol and 4-(7′-Trifluoromethylquinolin-4′-ylamino)phenol
  作者：GB Barlin、C Jiravinyu

  DOI：10.1071/ch9900311

  日期：——

  Syntheses are reported for a series of di-Mannich bases of 4-(7′-trifluoromethylquinazolin-4′-ylamino)phenol derived from 4-chloro-7-trifluoromethylquinazoline with the di-Mannich bases of 4-aminophenol. Some analogous quinolines were prepared similarly. When tested for antimalarial activity against Plasmodium falciparum in vitro, the quinazolines were rather less active than the corresponding quinolines.

  报告了一系列 4-(7′-三氟甲基喹唑啉-4′-基氨基)苯酚二曼尼希碱的合成，这些苯酚二曼尼希碱来自 4-氯-7-三氟甲基喹唑啉和 4-氨基苯酚的二曼尼希碱。一些类似的喹啉类化合物也是用类似方法制备的。在对恶性疟原虫进行体外抗疟活性测试时，这些喹唑啉类化合物的活性比相应的喹啉类化合物低。
• 4-(cinnolinylamino or quinazolinylamino)benzenesulphonamides and
  申请人：John Wyeth & Brother Limited

  公开号：US04640920A1

  公开（公告）日：1987-02-03

  Novel quinazoline and cinnoline derivatives having the formula ##STR1## (wherein one of A and B is CH and the other one of A and B is N; X.sub.1 is halogen or CF.sub.3 and X.sub.3 is one of the groups II, III, IV or V ##STR2## where Q is lower alkylene; R.sub.1 is hydrogen or lower alkyl; R.sub.2 and R.sub.3 are independently lower alkyl or R.sub.2 and R.sub.3 are a divalent radical such that HNR.sub.2 R.sub.3 is a secondary cyclic amine with 5 to 7 ring atoms; R.sub.4 is lower alkyl; n is 0 or 1; the rings shown in formulae III and IV are piperidine or pyrrolidine optionally substituted by lower alkyl; and the ring shown in formula V is piperazine optionally substituted by lower alkyl) and their pharmaceutically acceptable salts are useful as pharmaceuticals particularly as anti-hypertensives. Novel intermediates are also described including the corresponding sulphonic acids of formula I (where A, B and X.sub.1 are defined above and X.sub.3 is OH).

  具有以下结构式的新奎奈唑和咪唑衍生物（其中A和B中的一个是CH，另一个是N；X1是卤素或CF3，X3是II、III、IV或V中的一个基团，其中Q是较低的烷基烯；R1是氢或较低的烷基；R2和R3是独立的较低烷基，或者R2和R3是一种双价基团，使得HNR2R3是具有5至7个环原子的二级环胺；R4是较低的烷基；n为0或1；在III和IV式中显示的环是哌啶或吡咯啉，可以选择地被较低的烷基取代；在V式中显示的环是哌嗪，可以选择地被较低的烷基取代），以及它们的药学上可接受的盐在药物学中特别作为降压药物是有用的。还描述了新的中间体，包括式I的相应磺酸（其中A、B和X1如上所定义，X3是OH）。
• Design and Analysis of the 4‐Anilinoquin(az)oline Kinase Inhibition Profiles of GAK/SLK/STK10 Using Quantitative Structure‐Activity Relationships
  作者：Christopher R. M. Asquith、Tuomo Laitinen、James M. Bennett、Carrow I. Wells、Jonathan M. Elkins、William J. Zuercher、Graham J. Tizzard、Antti Poso

  DOI：10.1002/cmdc.201900521

  日期：2020.1.7

  have been associated with negative clinical outcomes. We have designed and synthesized a series of 4-anilinoquin(az)olines in order to better understand the structure-activity relationships of three main collateral kinase targets of quin(az)oline-based kinase inhibitors: cyclin G associated kinase (GAK), STE20-like serine/threonine-protein kinase (SLK) and serine/threonine-protein kinase 10 (STK10)

  4-苯胺基喹啉和4-苯胺基喹唑啉环系统一直是现有激酶药物发现计划中的重大工作重点，这些计划已开发出获批的药物。随着先进的筛选技术的出现，现在已经评估了这些化合物的广泛的动力学特征。这些环系统最初是为包括表皮生长因子受体（EGFR）在内的特定靶标设计的，但实际上显示了许多有效的附带激酶靶标，其中一些与阴性临床结局有关。我们设计和合成了一系列4-苯胺基喹啉（az）脯氨酸，以便更好地了解基于喹（唑啉的激酶抑制剂的三个主要附带激酶靶的结构-活性关系：细胞周期蛋白G相关激酶（GAK），STE20样丝氨酸/苏氨酸蛋白激酶（SLK）和丝氨酸/苏氨酸蛋白激酶10（STK10）。这是通过一系列定量构效关系（QSAR）分析，激酶ATP结合位点的水位分析以及广泛的小分子X射线结构分析实现的。
• Potential Antimalarials. XII. 4-Chloro-3-(substituted amino)methyl-5-[7-bromo (and 7-trifluoromethyl)-1,5-naphthyridin-4-ylamino]biphenyl-2-ols and 4-Chloro-3-(substituted amino)methyl-5-(7-trifluoromethyl-quinazolin-4-ylamino)biphenyl-2-ols
  作者：GB Barlin、C Jiravinyu

  DOI：10.1071/ch9901367

  日期：——

  The mono- Mannich bases 3-(t- butylamino )methyl-4?-chloro-, 3-(4- benzylpiperidin-1-yl)methyl-4′-chloro-, 3-(4-benzylpiperazin-1- yl )methyl-4′-chloro-, 4′-chloro-3-diethylaminomethyl-, 4′-chloro-3-(pyrrolidin-1-yl)methyl-, 4′-chloro-3-(piperidin-1-yl)methyl- and 4′-chloro-3-(3- and 4- methylpiperidin-1-yl)methyl-5-[7-bromo (and 7- trifluoromethyl )-1,5-naphthyridin-4-ylamino]- biphenyl-2-ol, and the corresponding substituted 5-(7-trifluoromethylquinazolin-4-ylamino)bi- phenyl-2-ols, have been prepared by condensation of the 5-amino-3-(N- substituted aminomethyl )-4′-chlorobiphenyl-2-ols and the appropriate 4-chloro heterocycle. The antimalarial activity of these products against the chloroquine-sensitive isolate (FCQ-27) of Plasmodium falciparum revealed that the 1,5-naphthyridines reported here were less active than the corresponding di-Mannich bases, e.g. (6), derived from 4-[7- bromo (and 7-trifluoromethyl)-1?,5′-naphthyridin-4′-ylamino]phenol, a feature not shared by the corresponding quinazolines.

  单曼尼希碱 3-(叔丁基氨基)甲基-4?-氯-，3-(4-苄基哌啶-1-基)甲基-4′-氯-，3-(4-苄基哌嗪-1-基)甲基-4′-氯-，4′-氯-3-二乙基氨基甲基-、4′-氯-3-(吡咯烷-1-基)甲基、4′-氯-3-(哌啶-1-基)甲基和 4′-氯-3-(3-和 4-甲基哌啶-1-基)甲基-5-[7-溴（和 7-三氟甲基）-1、5-氨基-3-(N-取代的氨基甲基)-4′-氯联苯-2-醇和相应的取代的 5-(7-三氟甲基喹唑啉-4-基氨基)联苯-2-醇，是通过 5-氨基-3-(N-取代的氨基甲基)-4′-氯联苯-2-醇和适当的 4-氯杂环缩合制备的。这些产品对氯喹敏感的恶性疟原虫分离物（FCQ-27）的抗疟活性表明，这里报告的 1,5-萘啶类化合物的活性低于相应的二曼尼希碱，例如从(6)和(7)中提取的二曼尼希碱。例如由 4-[7-溴（和 7-三氟甲基）-1?,5′-萘啶-4′-基氨基]苯酚衍生的 (6)，相应的喹唑啉类不具有这种特征。
• AMINO ACID COMPOUNDS AND METHODS OF USE
  申请人：Pliant Therapeutics, Inc.

  公开号：US20190276449A1

  公开（公告）日：2019-09-12

  The invention relates to compounds of formula (A) and formula (I): or a salt thereof, wherein R 1 , R 2 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , q and p are as described herein. Compounds of formula (A), formula (I), and pharmaceutical compositions thereof are αvβ6 integrin inhibitors that are useful for treating fibrosis such as idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP).

  该发明涉及以下化合物的公式(A)和公式(I)：或其盐，其中R1、R2、R10、R11、R12、R13、R14、R15、R16、q和p如本文所述。公式(A)、公式(I)的化合物及其药物组合物是αvβ6整合素抑制剂，可用于治疗纤维化疾病，如特发性肺纤维化（IPF）和非特异性间质性肺炎（NSIP）。