1-(4-氯苄基)-1,4-二氮杂烷 | 40389-65-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(4-氯苄基)-1,4-二氮杂烷
• 中文别名: 1-(4-氯苄基)高哌嗪
• 英文名称: 1-(4-chlorobenzyl)homopiperazine
• 英文别名: p-chlorobenzylhomopiperazine；N-p-chlorobenzylhomopiperazine；1-(4-Chlorobenzyl)-1,4-diazepane；1-[(4-chlorophenyl)methyl]-1,4-diazepane
• CAS: 40389-65-9
• 化学式: C₁₂H₁₇ClN₂
• mdl: MFCD03407501
• 分子量: 224.733
• InChiKey: XUFLZPFWTDGFEG-UHFFFAOYSA-N

物化性质

• 熔点：
  75-77 °C
• 沸点：
  114-120 °C(Press: 0.2 Torr)
• 密度：
  1.115±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 1-(4-Chlorobenzyl)-1,4-diazepane
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: 1-(4-Chlorobenzyl)-1,4-diazepane
CAS number: 40389-65-9

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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: C12H17ClN2
Molecular weight: 224.7

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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.

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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：

  1-(4-氯苄基)-1,4-二氮杂烷 在 palladium on activated charcoal 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 为溶剂， 生成 N-((1R,3s,5S)-8-((6-fluoronaphthalen-2-yl)methyl)-8-azabicyclo[3.2.1]octan-3-yl)-4-(2-hydroxybenzoyl)-1,4-diazepane-1-carboxamide
  参考文献：
  名称：

  Discovery and structure–activity relationships of urea derivatives as potent and novel CCR3 antagonists

  摘要：

  The synthesis and structure-activity relationships of ureas as CCR3 antagonists are described. Optimization starting with lead compound 2 (IC50 = 190 nM) derived from initial screening hit compound 1 (IC50 = 600 nM) led to the identification of (S)-N-((1R,3S,5S)-8-((6-fluoronaphthalen-2-yl)methyl)-8-azabicyclo[3.2.1]octan-3-yl)-N-(2-nitrophenyl)pyrrolidine-1,2-dicarboxamide 27 (IC50 = 4.9 nM) as a potent CCR3 antagonist. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.042
• 作为产物：
  描述：

  高哌嗪 、 4-氯氯苄 在 乙醇 、 乙酰氯 、 氢氧化钾 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 20.5h， 以53.4%的产率得到1-(4-氯苄基)-1,4-二氮杂烷
  参考文献：
  名称：

  Diarylalkyl cyclic diamine derivatives as chemokine receptor antagonists

  摘要：

  本文描述了式（I）的环状二胺或其药理学上可接受的酸盐以及它们的医学应用。这些化合物抑制趋化因子如MIP-1a和/或MCP-1对靶细胞的作用，可用作治疗药物和/或预防药物，用于动脉粥样硬化、类风湿性关节炎等疾病，在这些疾病中，血液单核细胞和淋巴细胞浸润组织。

  公开号：

  US06686353B1

文献信息

• Bis(piperazinyl or homopiperazinyl)alkanes
  申请人：Boehringer Ingelheim Ltd.

  公开号：US04725597A1

  公开（公告）日：1988-02-16

  Compounds of the formula ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are independently hydrogen, alkyl of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkanoyloxy of 1 to 4 carbon atoms, halogen, trihalomethyl, di(lower alkyl of 1 to 4 carbon atoms)amino, (alkoxy of 1 to 4 carbon atoms)carbonyl, nitro, cyano or alkanoyl of 1 to 3 carbon atoms; R.sub.7 and R.sub.8 are independently hydrogen, methyl, hydroxyl, carboxyl, (alkoxy of 1 to 4 carbon atoms)carbonyl, hydroxymethyl, phenyl, or p-chlorophenyl; R.sub.9 and R.sub.10 are independently hydrogen or methyl; j and k are independently 0, 1, 2, or 3, their sum being no more than 4; m and n are independently 0, 1, 2, or 3, their sum being no more than 4; A is --CH.sub.2 -- or --CH.sub.2 --CH.sub.2 --; R.sub.7 and R.sub.9 together are oxo, provided k is other than o; R.sub.8 and R.sub.10 together are oxo, provided m is other than o; R.sub.11 and R.sub.12 independently represent hydrogen or one to four methyl substituents on the carbon atoms of the piperazine ring (A=--CH.sub.2 --); R.sub.13, R.sub.14, R.sub.15, and R.sub.16 are independently hydrogen or methyl; R.sub.13 and R.sub.14 together are oxo; R.sub.15 and R.sub.16 together are oxo; and X is alkylene of 1 to 2 carbon atoms, optionally hydroxy-substituted; or a non-toxic, pharmacologically acceptable acid addition salt thereof, are useful as antiallergic and anti-inflammatory agents.

  式为##STR1##的化合物，其中R.sub.1、R.sub.2、R.sub.3、R.sub.4、R.sub.5和R.sub.6独立地为氢、1至4个碳原子的烷基、羟基、1至4个碳原子的烷氧基、1至4个碳原子的烷酰氧基、卤素、三卤甲基、1至4个碳原子的低烷基)氨基、(1至4个碳原子的烷氧基)羰基、硝基、氰基或1至3个碳原子的烷酰基；R.sub.7和R.sub.8独立地为氢、甲基、羟基、羧基、(1至4个碳原子的烷氧基)羰基、羟甲基、苯基或对氯苯基；R.sub.9和R.sub.10独立地为氢或甲基；j和k独立地为0、1、2或3，它们的和不超过4；m和n独立地为0、1、2或3，它们的和不超过4；A为--CH.sub.2 --或--CH.sub.2 --CH.sub.2 --；R.sub.7和R.sub.9一起为氧代，条件是k不等于o；R.sub.8和R.sub.10一起为氧代，条件是m不等于o；R.sub.11和R.sub.12独立地表示对哌嗪环的碳原子上的氢或一个到四个甲基取代基（A=--CH.sub.2 --）；R.sub.13、R.sub.14、R.sub.15和R.sub.16独立地为氢或甲基；R.sub.13和R.sub.14一起为氧代；R.sub.15和R.sub.16一起为氧代；X为1至2个碳原子的烷基，可选地为羟基取代；或其非毒性、药理学上可接受的酸盐，可用作抗过敏和抗炎药物。
• Substituted phenylalkyl-(piperazinyl or homopiperazinyl)alkyl-thiols and
  申请人：Boehringer Ingelheim Limited

  公开号：US04618677A1

  公开（公告）日：1986-10-21

  Compounds of the formula ##STR1## wherein R is hydrogen or ##STR2## A is alkyl of 1 to 8 carbon atoms; cycloalkyl of 3 to 7 carbon atoms; phenyl; or phenyl mono-, di- or tri-substituted independently with alkyl of 1 to 4 carbon atoms, halogen, trihalomethyl, alkoxy of 1 to 3 carbon atoms, carboxylic acyl of 1 to 3 carbon atoms, carboxyl, (alkoxy of 1 to 3 carbon atoms)carbonyl, nitro, cyano or di(alkyl of 1 to 3 carbon atoms)amino; R.sub.1, R.sub.2 and R.sub.3, are independently hydrogen, halogen, alkyl of 1 to 4 carbon atoms, trihalomethyl, nitro, cyano, di(alkyl of 1 to 4 carbon atoms)amino, (alkoxy of 1 to 4 carbon atoms)carbonyl, alkoxy of 1 to 4 carbon atoms or hydroxyl; R.sub.4 and R.sub.5 are independently hydrogen, alkyl of 1 to 4 carbon atoms, or phenyl; R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are independently hydrogen or methyl; Y is --CH.sub.2 -- or --CH.sub.2 --CH.sub.2 --; j is 0 or 1; k and m are independently 0, 1, 2, or 3, their sum being no more than 6 and must be 0 when j is 1; n is 2, 3, or 4, with the proviso that n must be 3 or 4 when R.sub.1 is hydrogen or 2-methyl, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9 and R are each hydrogen and j, k, and m are each 0, and Y is --CH.sub.2 --; and non-toxic, pharmaceutically acceptable acid addition salts thereof are useful for the treatment of immunological, inflammatory and allergic disorders.

  式##STR1##中的化合物，其中R是氢或##STR2## A是1至8个碳原子的烷基；3至7个碳原子的环烷基；苯基；或苯基单独、二独或三独地与1至4个碳原子的烷基、卤素、三卤甲基、1至3个碳原子的烷氧基、1至3个碳原子的羧酰基、羧基、（1至3个碳原子的烷氧基）羰基、硝基、氰基或二（1至3个碳原子的烷基）氨基取代；R.sub.1、R.sub.2和R.sub.3，分别是氢、卤素、1至4个碳原子的烷基、三卤甲基、硝基、氰基、二（1至4个碳原子的烷基）氨基、（1至4个碳原子的烷氧基）羰基、1至4个碳原子的烷氧基或羟基；R.sub.4和R.sub.5分别是氢、1至4个碳原子的烷基或苯基；R.sub.6、R.sub.7、R.sub.8和R.sub.9分别是氢或甲基；Y是--CH.sub.2--或--CH.sub.2--CH.sub.2--；j为0或1；k和m分别为0、1、2或3，它们的和不超过6，当j为1时必须为0；n为2、3或4，但当R.sub.1为氢或2-甲基，R.sub.2、R.sub.3、R.sub.4、R.sub.5、R.sub.6、R.sub.7、R.sub.8、R.sub.9和R分别为氢，j、k和m分别为0，Y为--CH.sub.2--时，n必须为3或4；其无毒、药用酸盐可用于治疗免疫、炎症和过敏性疾病。
• Potent anticonflict activity and lessening of memory impairment with a series of novel [1]benzothieno[2,3-c]pyridines and 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridines
  作者：Hiromu Kawakubo、Katuya Okazaki、Tadasi Nagatani、Katuyuki Takao、Shinichi Hasimoto、Taisuke Sugihara

  DOI：10.1021/jm00173a031

  日期：1990.11

  [1]Benzothieno[2,3-c]pyridines (10a-c, 11, 12a-t, and 13a,b) and 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridines (3a-c, 7, 8a-c, and 9) were synthesized. The compounds are bioisosteres of beta-carbolines and 1,2,3,4-tetrahydro-beta-carbolines where the indole nitrogen is replaced by sulfur. Their pharmacological activity was evaluated in a water lick conflict test in rats and a passive avoidance test

  [1] Benzothieno [2,3-c]吡啶（10a-c，11、12a-t和13a，b）和1,2,3,4-四氢[1]苯并噻吩并[2,3-c]吡啶合成了（3a-c，7、8a-c和9）。该化合物是β-咔啉和1,2,3,4-四氢-β-咔啉的生物等排体，其中吲哚氮被硫取代。在大鼠的水舔冲突试验和小鼠的被动回避试验中评估了它们的药理活性。在1,2,3,4-四氢[1]苯并噻吩并[2,3-c]吡啶系列中，C-3处的乙基酯（3b）或环己基甲酰胺（7）的存在赋予良好的抗冲突活性并减少记忆障碍，而3b N-酰化取消活动。在[1] benzothieno（2,3-c] pyrididine系列中，C-3处的氨乙基羧酰胺（12a）基团也具有活性，但所研究的其他酰胺均无活性。最有效的化合物（3b，7、12a）也口服给药，具有有效的抗冲突和抗东pol碱失忆症活性。这些化合物尽管具有与β-咔啉类似的结构，但并未与
• Novel Small Molecule Inhibitors of Choline Kinase Identified by Fragment-Based Drug Discovery
  作者：Stephan G. Zech、Anna Kohlmann、Tianjun Zhou、Feng Li、Rachel M. Squillace、Lois E. Parillon、Matthew T. Greenfield、David P. Miller、Jiwei Qi、R. Mathew Thomas、Yihan Wang、Yongjin Xu、Juan J. Miret、William C. Shakespeare、Xiaotian Zhu、David C. Dalgarno

  DOI：10.1021/acs.jmedchem.5b01552

  日期：2016.1.28

  activity of novel small molecule inhibitors of ChoKα. Starting from weakly binding fragments, we describe a structure based lead discovery approach, which resulted in novel highly potent inhibitors of ChoKα. In cancer cell lines, our lead compounds exhibit a dose-dependent decrease of phosphocholine, inhibition of cell growth, and induction of apoptosis at low micromolar concentrations. The druglike lead

  胆碱激酶α（ChoKα）是一种参与磷脂合成的酶，因此在调节细胞增殖，致癌转化和人类致癌作用中起着关键作用。由于ChoKα的几种抑制剂在细胞和动物模型中均表现出抗增殖活性，因此这种新型致癌基因作为一种有前景的癌症治疗小分子靶标最近引起了人们的兴趣。在这里，我们总结了为进一步验证ChoKα作为致癌靶点所做的努力，并探讨了新型的ChoKα小分子抑制剂的活性。从弱结合的片段开始，我们描述了一种基于结构的先导发现方法，该方法导致了新型高效的ChoKα抑制剂。在癌细胞系中，我们的先导化合物显示出剂量依赖性的磷酸胆碱减少，抑制细胞生长，在低摩尔浓度下诱导细胞凋亡。此处介绍的类药物前导系列对于改善细胞效力，药物靶标停留时间和药代动力学参数是可优化的。这些抑制剂不仅可以用来进一步证实ChoKα作为致癌靶标，而且还可以作为新化学物质使用，从而可能导致抗肿瘤剂特异性地干扰癌细胞的代谢。
• [EN] DIARYLALKYL CYCLIC DIAMINE DERIVATIVES AS CHEMOKINE RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE DIAMINE CYCLIQUE DE DIARYLAKLYLE UTILISES EN TANT QU'ANTAGONISTES DES RECEPTEURS DE CHIMIOKINES
  申请人：TEIJIN LIMITED

  公开号：WO1997044329A1

  公开（公告）日：1997-11-27

  (EN) Cyclic diamines of formula (I) or their pharmacologically acceptable acid addition salts, and their medical applications are described. These compounds inhibit the action of chemokines such as MIP-la and/or MCP-l on target cells, and are useful as a therapeutic drug and/or preventative drug in diseases, such as atherosclerosis, rheumatoid arthritis, and the like where blood monocytes and lymphocytes infiltrate into tissues.(FR) Diamines cycliques de formule (I) ou leur sels d'addition d'acide pharmaceutiquement acceptables ainsi que leurs applications médicales. Ces composés inhibent l'action de chimiokines telles que MIP-1a et/ou MCP-1 sur des cellules cibles, et sont utiles en tant que médicaments thérapeutiques et/ou préventifs dans les maladies telles que l'athérosclérose, l'arthrite rhumatoïde et similaire dans lesquelles les monocytes et les lymphocytes s'infiltrent dans les tissus.

  (I)式的环状二胺或其药学上可接受的酸盐加合物以及它们的医学应用被描述。这些化合物抑制化学趋化因子如MIP-1a和/或MCP-1在目标细胞上的作用，并且可作为治疗药物和/或预防药物在疾病中使用，例如动脉粥样硬化、类风湿性关节炎等，这些疾病中血液单核细胞和淋巴细胞渗入组织。