4-(4-硝基苯氧基)四氢-1(2H)-吡啶羧酸叔丁酯 | 138227-62-0

• 物质功能分类: 医药中间体
• 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: 4-(4-硝基苯氧基)四氢-1(2H)-吡啶羧酸叔丁酯
• 英文名称: tert-butyl 4-(4-nitrophenoxy)piperidine-1-carboxylate
• 英文别名: 4-(4-Nitrophenoxy)piperidine-1-carboxylic acid tert-butyl ester
• CAS: 138227-62-0
• 化学式: C₁₆H₂₂N₂O₅
• 分子量: 322.361
• InChiKey: UNNMTKGKCWNQNU-UHFFFAOYSA-N

物化性质

• 熔点：
  99 °C
• 沸点：
  453.7±35.0 °C(Predicted)
• 密度：
  1.211±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  84.6
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 危险品标志：
  Xi
• 海关编码：
  2933399090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  室温密封保存，并保持干燥。

SDS

Name:	tert-Butyl 4-(4-nitrophenoxy)tetrahydro-1(2H)-pyridinecarboxylate Material Safety Data Sheet
Synonym:	None Known
CAS:	138227-62-0

Section 1 - Chemical Product MSDS Name:tert-Butyl 4-(4-nitrophenoxy)tetrahydro-1(2H)-pyridinecarboxylate Material Safety Data Sheet
Synonym:None Known

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
138227-62-0	tert-Butyl 4-(4-nitrophenoxy)tetrahydr	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 irritation of the digestive tract. 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. Wash mouth out with 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 chemical foam.

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

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Section 7 - HANDLING and STORAGE
Handling:
Minimize dust generation and accumulation. Avoid breathing dust, vapor, mist, or gas. Avoid contact with eyes, skin, and clothing.
Keep container tightly closed. Avoid ingestion and inhalation. Use with adequate ventilation. Wash clothing before reuse.
Storage:
Store in a cool, dry place. Store in a tightly closed container.

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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# 138227-62-0: 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:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Powder
Color: pale-yellow
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 99-101 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: C16H22N2O5
Molecular Weight: 322.36

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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, acids, reducing agents.
Hazardous Decomposition Products:
Carbon monoxide, oxides of nitrogen, carbon dioxide, hydrogen fluoride gas, sulfur oxides (SOx), including sulfur oxide and sulfur dioxide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 138227-62-0 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
tert-Butyl 4-(4-nitrophenoxy)tetrahydro-1(2H)-pyridinecarboxylate - 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 24/25 Avoid contact with skin and eyes.
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# 138227-62-0: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 138227-62-0 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 138227-62-0 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-(4-硝基苯氧基)四氢-1(2H)-吡啶羧酸叔丁酯 在 三氟乙酸 作用下， 反应 1.0h， 以99%的产率得到4-(4-硝基苯氧基)-哌啶
  参考文献：
  名称：

  合成和评估结构受约束的喹唑啉酮衍生物作为有效和选择性的组胺H3受体反向激动剂。

  摘要：

  设计，合成并评价了一系列有效的H 3反向激动剂1的结构受约束的衍生物，并将其评估为组胺H 3受体反向激动剂。结果，如2f中的N-环丁基哌啶-4-基氧基被鉴定为1的柔性1-吡咯烷基丙氧基的最佳替代结构。随后对2f的喹唑啉酮核心的优化表明，在2f的5-位取代。喹唑啉酮环影响效能。代表性衍生物5a和5s在大鼠的组胺释放测定和小鼠的受体占用测定中显示出增强的效力。

  DOI：

  10.1021/jm800569w
• 作为产物：
  描述：

  4-羟基哌啶 在 sodium hydride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 33.5h， 生成 4-(4-硝基苯氧基)四氢-1(2H)-吡啶羧酸叔丁酯
  参考文献：
  名称：

  COMPOUNDS AS NEURONAL HISTAMINE RECEPTOR-3 ANTAGONISTS AND USES THEREOF

  摘要：

  本发明涉及作为H3R拮抗剂的化合物(A)的公式，以及它们的制备和用途，并进一步涉及包含这些化合物的药物组合物及其用途作为组胺3受体（H3R）功能调节剂。本发明还涉及这些化合物或药物组合物在治疗或预防与人类H3R功能相关的某些疾病和疾病中的用途。

  公开号：

  US20200102289A1

文献信息

• Phenoxypiperidines and analogs thereof useful as histamine H3 antagonists
  申请人：Mutahi W. Mwangi

  公开号：US20070167435A1

  公开（公告）日：2007-07-19

  Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein: M is CH or N; U and W are each CH, or one of U and W is CH and the other is N; X is a bond, alkylene, —C(O)—, —C(N—OR 5 )—, —C(N—OR 5 )—CH(R 6 )—, —CH(R 6 )—C(N—OR 5 )—, —O—, —OCH 2 —, —CH 2 O— or —S(O) 0-2 —; Y is —O—, —(CH 2 ) 2 —, —C(═O)—, —C(═NOR 7 )— or —SO 0-2 —; Z is a bond, optionally substituted alkylene or alkylene interrupted by a heteroatom or heterocyclic group; R 1 is optionally substituted alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocycloalkyl, or benzimidazolyl or a derivative thereof; R 2 is optionally substituted alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl or heterocycloalkyl; and the remaining variables are as defined in the specification; compositions and methods for treating an allergy-induced airway response, congestion, diabetes, obesity, an obesity-related disorder, metabolic syndrome and a cognition deficit disorder using said compounds, alone or in combination with other agents.

  揭示了以下化合物的结构式或其药学上可接受的盐或溶剂，其中：M为CH或N；U和W分别为CH，或者U和W中的一个为CH，另一个为N；X为键，烷基，—C(O)—，—C(N—OR5)—，—C(N—OR5)—CH(R6)—，—CH(R6)—C(N—OR5)—，—O—，—O —，—CH2O—或—S(O)0-2—；Y为—O—，—(CH2)2—，—C(═O)—，—C(═NOR7)—或—SO0-2—；Z为键，可选择地取代的烷基或被杂原子或杂环基中断的烷基；R1为可选择地取代的烷基，环烷基，芳基，芳基烷基，杂芳基，杂环烷基或苯并咪唑基或其衍生物；R2为可选择地取代的烷基，烯基，芳基，芳基烷基，杂芳基，杂芳基烷基，环烷基或杂环烷基；其余变量如规范中所定义；使用这些化合物，单独或与其他药剂联合使用，治疗由过敏引起的气道反应、充血、糖尿病、肥胖症、与肥胖有关的疾病、代谢综合征和认知缺陷障碍的组合物和方法。
• Discovery and Development of <i>N</i>-[4-(1-Cyclobutylpiperidin-4-yloxy)phenyl]-2-(morpholin-4-yl)acetamide Dihydrochloride (SUVN-G3031): A Novel, Potent, Selective, and Orally Active Histamine H₃ Receptor Inverse Agonist with Robust Wake-Promoting Activity
  作者：Ramakrishna Nirogi、Anil Shinde、Abdul Rasheed Mohammed、Rajesh Kumar Badange、Veena Reballi、Thrinath Reddy Bandyala、Sangram Keshari Saraf、Kumar Bojja、Sravanthi Manchineella、Pramod Kumar Achanta、Kiran Kumar Kandukuri、Ramkumar Subramanian、Vijay Benade、Raghava Choudary Palacharla、Pradeep Jayarajan、Santoshkumar Pandey、Venkat Jasti

  DOI：10.1021/acs.jmedchem.8b01280

  日期：2019.2.14

  histamine H3 receptor (H3R), physicochemical properties, and pharmacokinetics in rats resulted in identification of N-[4-(1-cyclobutyl-piperidin-4-yloxy)phenyl]-2-(morpholin-4-yl)acetamide dihydrochloride (17v, SUVN-G3031) as a clinical candidate. Compound 17v is a potent (hH3R Ki = 8.73 nM) inverse agonist at H3R with selectivity over other 70 targets, Compound 17v has adequate oral exposures and

  在大鼠中对组胺H3受体（H3R）的体外亲和力，理化性质和药代动力学指导下的一系列化学优化导致鉴定了N- [4-（1-环丁基-哌啶丁-4-基氧基）苯基] -2 -（吗啉-4-基）乙酰胺二盐酸盐（17v，SUVN-G3031）作为临床候选药物。化合物17v在H3R上是一种强效（hH3R Ki = 8.73 nM）反向激动剂，对其他70个靶标具有选择性。化合物17v在大鼠和狗中均具有足够的口服暴露量和良好的消除半衰期。它显示出高的受体占有率和明显的促醒作用，并减少了Orexin-B萨泊林损伤的大鼠的快速眼动睡眠，支持了其在治疗人类睡眠障碍中的潜在治疗作用。剂量比有效剂量高出几倍，对运动活性没有影响。它没有hERG和磷脂病的问题。已经成功完成了对动物的安全性，耐受性和药代动力学的第一阶段评估，以及对动物的长期安全性研究，而无需担心进一步的开发。
• UREIDO-PYRAZOLE DERIVATIVES AND THEIR USE AS KINASE INHIBITORS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1609789A1

  公开（公告）日：2005-12-28

  The present invention provides kinase inhibitors of Formula I: wherein: R1 is hydrogen, methyl, or tolyl; W is piperidinyl, napthyl, or phenyl optionally substituted with halo; X is a bond, -CH2-, -O-(CH2)n-, -O-, or -C(O)-; n is 1 or 2; Y is phenyl, piperidinyl, or piperazinyl; Z is -C(O)-R2, -CH2-R3, or methylsulfonyl; R2 is C1-C4 alkyl, C1-C4 alkoxy, benzyloxy, C3-C5 cycloalkyl optionally substituted with phenyl, pyridyl optionally substituted with 1-2 C1-C4 alkoxy or 1-2 halo, thienyl optionally substituted with halo or C1-C4 alkyl, pyrrolyl, imidazolyl, pyrazolyl optionally substituted with C1-C4, alkyl, or phenyl optionally substituted from the group selected from trifluoromethyl, trifluoromethoxy, and 1-2 halo, and R3 is pyridyl; or a pharmaceutically acceptale salt thereof.

  本发明提供了化合物I的激酶抑制剂： 其中： R1为氢、甲基或甲苯基； W为哌啶基、萘基或苯基，可选择地取代为卤素； X为键、-CH2-、-O-( )n-、-O-或-C(O)-； n为1或2； Y为苯基、哌啶基或哌嗪基； Z为-C(O)-R2、- -R3或甲磺酰基； R2为C1-C4烷基、C1-C4烷氧基、苄氧基、C3-C5环烷基，可选择地取代为苯基，吡啶基，可选择地取代为1-2个C1-C4烷氧基或1-2个卤素，噻吩基，可选择地取代为卤素或C1-C4烷基，吡咯基，咪唑基，吡唑基，可选择地取代为C1-C4烷基，或苯基，可选择地取代为三氟甲基，三氟甲氧基和1-2个卤素中选择的一种，以及 R3为吡啶基； 或其药学上可接受的盐。
• [EN] PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF CANCER<br/>[FR] DÉRIVÉS DE PYRROLO[2,3-D]PYRIMIDINE ET LEUR UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：SENTINEL ONCOLOGY LTD

  公开号：WO2021074251A1

  公开（公告）日：2021-04-22

  The invention provides compounds of the formula (1): or a salt or tautomer thereof wherein A, R1, R2, R3, R4, R5 and R6 are as defined herein. The compounds are inhibitors of Wee1 and/or PLK1 kinase and are envisaged to be useful in the treatment of cancers.

  这项发明提供了式（1）的化合物：或其盐或互变异构体，其中A、R1、R2、R3、R4、R5和R6如本文所定义。这些化合物是Wee1和/或PLK1激酶的抑制剂，预计在癌症治疗中有用。
• Identification of N-phenyl-3-methoxy-4-pyridinones as orally bioavailable H3 receptor antagonists and β-amyloid aggregation inhibitors for the treatment of Alzheimer’s disease
  作者：Minkui Zhang、Li Tang、Liu Jiang、Jun Wei、Yongzhou Hu、Rong Sheng

  DOI：10.1016/j.ejmech.2020.113096

  日期：2021.2

  functional agents for therapy of Alzheimer’s disease, through introducing alkyloxy moiety into 4-pyridinone ring to avoid the possible phase II metabolism of 3-hydroxy-4-pyridinone in lead compound 3-hydroxy-2-methyl-1-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl)-pyridin-4(1H)-one (4). In vitro studies indicated that most of these compounds exhibit excellent H3 receptor antagonistic activities and potent

  根据我们以前的工作，通过将烷氧基部分引入4-吡啶酮环中以避免可能的II期，设计了一系列N-苯基-3-甲氧基-4-吡啶酮衍生物作为口服生物可利用的双重功能药物，用于治疗阿尔茨海默氏病铅化合物的3-羟基-4-吡啶酮的代谢3-羟基-2-甲基-1-（4-（3-（吡咯烷-1-基）丙氧基）苯基） -吡啶-4-（1 ħ） -酮（ 4）。体外研究表明，这些化合物大多数都具有出色的H 3受体拮抗活性和强力的自诱导Aβ1-40 / Aβ1-42聚集抑制活性。特别是，3-甲氧基-1-（4-（3-（吡咯烷基-1-基）丙氧基）苯基）-吡啶-4（1H）-一（7i）在H 3 R拮抗作用中显示IC 50值为0.52 nM。对其他组胺受体亚型具有良好的选择性。透射电子显微镜（TEM）图像显示化合物7i可有效抑制自我介导的Aβ1-40 / Aβ1-42聚集。如预期的那样，它在血浆中表现出理想的药代动力学性质和良好的BBB渗透