8-苄基-1,3,8-三氮杂螺[4.5]癸烷-4-酮 | 974-41-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 8-苄基-1,3,8-三氮杂螺[4.5]癸烷-4-酮
• 中文别名: 8-苄基-1-苯基-1,3,8-三氮杂螺[4.5]癸烷-4-酮；8-苄基-1-苯基-1,3,8-三氮杂螺[4.5]-4-癸酮
• 英文名称: 8-benzyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
• 英文别名: 8-Benzyl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one
• CAS: 974-41-4
• 化学式: C₂₀H₂₃N₃O
• mdl: MFCD02929369
• 分子量: 321.422
• InChiKey: QMECPMOWMNRLSL-UHFFFAOYSA-N

物化性质

• 熔点：
  232-238℃
• 沸点：
  538℃
• 密度：
  1.22
• 闪点：
  279℃

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

SDS

Name:	8-Benzyl-4-oxo-phenyl-1 3 8-triazaspiro[4 5]decane 99% Material Safety Data Sheet
Synonym:
CAS:	974-41-4

Section 1 - Chemical Product MSDS Name:8-Benzyl-4-oxo-phenyl-1 3 8-triazaspiro[4 5]decane 99% Material Safety Data Sheet
Synonym:

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
974-41-4	8-Benzyl-4-oxo-phenyl-1,3,8-triazaspir	99%	213-549-8

Hazard Symbols: None Listed.
Risk Phrases: None Listed.

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Not available.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause irritation of the digestive tract. May be harmful if swallowed.
Inhalation:
May cause respiratory tract irritation. May be harmful if inhaled.
Chronic:
Not available.

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Section 4 - FIRST AID MEASURES
Eyes: 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.
Ingestion:
Get medical aid. Wash mouth out with water.
Inhalation:
Remove from exposure and move to fresh air immediately.
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.
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.

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Section 7 - HANDLING and STORAGE
Handling:
Avoid breathing dust, vapor, mist, or gas. Avoid contact with skin and eyes.
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:
Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 974-41-4: Personal Protective Equipment Eyes: Not available.
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: Crystalline powder
Color: light yellow
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: 538 deg C @760mmHg
Freezing/Melting Point: Not available.
Autoignition Temperature: Not available.
Flash Point: 279 deg C ( 534.20 deg F)
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water: slightly soluble
Specific Gravity/Density:
Molecular Formula: C20H23N3O
Molecular Weight: 321.42

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials.
Incompatibilities with Other Materials:
Strong oxidizing agents, acids, bases.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, carbon dioxide.
Hazardous Polymerization: Has not been reported.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 974-41-4 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
8-Benzyl-4-oxo-phenyl-1,3,8-triazaspiro[4, 5]decane - 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
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: Not available.
Risk Phrases:
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
WGK (Water Danger/Protection)
CAS# 974-41-4: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 974-41-4 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 974-41-4 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：

  8-苄基-1,3,8-三氮杂螺[4.5]癸烷-4-酮 在 palladium on activated charcoal 、 氢气 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 异丙醇 为溶剂， 反应 58.0h， 生成 8-(5-chloro-2-((2-methoxy-4-(pyrrolidin-1-yl)phenyl)amino)pyrimidin-4-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 2-arylaminopyrimidine derivatives bearing 1,3,8-triazaspiro[4,5]decan-4-one or piperidine-3-carboxamide moiety as novel Type-I1/2 ALK inhibitors

  摘要：

  Aiming to develop novel Type -I-1/2 inhibitors of ALK to overcome extensive resistance mutations, especially the L1196M mutation surrounding the ATP pocket, two series of 2-arylaminopyrimidine derivatives (11a-f and 22at) were designed based on scaffold hopping. The extensive structural elaboration discovered compound 22o which possessed excellent IC50 values of 0.06 and 0.23 mu M against ALK-positive Karpas299 and H2228 cell lines, respectively. Meanwhile, 22o displayed encouraging inhibitory potency in the ALK(WT) (2.5 nM) and ALK(L1196m )(6.5 nM) enzymatic assays. Furthermore, the AO/EB and Hoechst 33258 assays illustrated 22o could induce cell apoptosis in a dose-dependent manner. Eventually, the molecular docking of 22o with ALK clearly presented the vital interactions within the active site, which was in accordance with Type -I-1/2 inhibitor binding mode.

  DOI：

  10.1016/j.bioorg.2019.103456
• 作为产物：
  描述：

  4-苯胺基-1-苄基-4-氰基哌啶 在 sodium tetrahydroborate 、 硫酸 作用下， 以 甲醇 为溶剂， 反应 36.0h， 生成 8-苄基-1,3,8-三氮杂螺[4.5]癸烷-4-酮
  参考文献：
  名称：

  发现针对F 1 / F O-三磷酸腺苷（ATP）合酶c亚基的新型1,3,8-三氮杂[4.5]癸烷衍生物，用于治疗心肌梗死的再灌注损伤

  摘要：

  近期的心脏病学研究报道了线粒体通透性过渡孔（mPTP）的作用，功能和结构，并表明其打开在继发于再灌注的心肌细胞死亡进程中起关键作用。在本手稿中，我们验证了一种新的药理学方法作为心肌梗塞（MI）治疗中再灌注的辅助手段，并描述了基于a以F 1 / F O的c亚基为靶点的1,3,8-triazaspiro [4.5]癸烷支架-ATP合酶复合物。我们在MI模型中鉴定了三种具有良好mPTP抑制活性和有益作用的潜在化合物，包括全心脏细胞凋亡率降低和再灌注过程中心脏功能的总体改善。所选化合物在细胞和线粒体水平上均未显示脱靶作用。此外，尽管与ATP合酶复合物相互作用，该化合物仍能保持线粒体ATP含量。

  DOI：

  10.1021/acs.jmedchem.8b00278

文献信息

• [EN] 1,3,8-TRIAZASPIRO COMPOUNDS AND THEIR USE AS MEDICAMENTS FOR THE TREATMENT OF REPERFUSION INJURY<br/>[FR] COMPOSÉS 1,3,8-TRIAZASPIRO ET LEUR UTILISATION EN TANT QUE MÉDICAMENTS PERMETTANT LE TRAITEMENT D'UNE LÉSION DE REPERFUSION
  申请人：MARIA CECILIA HOSPITAL S P A

  公开号：WO2020021378A1

  公开（公告）日：2020-01-30

  The present invention relates to a 1,3,8-triazaspiro compound of Formula (I), wherein A is -CH2, -SO2 -, -NH-CO-, -NH-CS- or -CO-; the dashed line represents a single or double bond; R1 is a substituent selected from (C1-C3) alkyl, phenyl, thienyl and cyclohexyl, said substituent being optionally substituted by halogen or (C1 -C3) alkyl; and R2 is a substituent selected from H, (C1-C3) alkyl, (C1-C3) alkoxy, -CF3 and halogen; and wherein, when the dashed line is a double bond, A is -CH2 - and R1 is phenyl, or a pharmaceutically acceptable salt thereof for use in the treatment of reperfusion injury diseases. The 1,3,8-triazaspiro compound of the invention is a selective inhibitor of the C subunit of the F1/Fo-ATP synthase complex and a modulator of the mitochondrial permeability transition pore activity in mammalian cells and tissues, in the treatment of reperfusion injury diseases.

  本发明涉及一种式(I)的1,3,8-三氮杂螺环化合物，其中A为-CH2、-SO2-、-NH-CO-、-NH-CS-或-CO-；虚线代表单键或双键；R1为从(C1-C3)烷基、苯基、噻吩基和环己基中选择的取代基，该取代基可以选择性地被卤素或(C1-C3)烷基取代；R2为从H、(C1-C3)烷基、(C1-C3)烷氧基、-CF3和卤素中选择的取代基；当虚线为双键时，A为- -且R1为苯基，或其在治疗再灌注损伤疾病中的药学上可接受的盐。本发明的1,3,8-三氮杂螺环化合物是F1/Fo-ATP合成酶复合物的C亚基的选择性抑制剂，以及哺乳动物细胞和组织中线粒体通透性转换孔活性的调节剂，在治疗再灌注损伤疾病中。
• [EN] TRIAZA-SPIRODECANONES AS DDR1 INHIBITORS<br/>[FR] TRIAZA-SPIRODÉCANONES UTILISÉES EN TANT QU'INHIBITEURS DE DDR1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2017005583A1

  公开（公告）日：2017-01-12

  The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein L and R1 to R5 are as described herein, as well as processes for their manufacture, pharmaceutical compositions comprising them, and their use as medicaments.

  本发明涉及式(I)的化合物或其药用盐，其中L和R1至R5如本文所述，以及它们的制备方法、包含它们的药物组合物，以及它们作为药物的用途。
• Piperidone derivatives and medical uses thereof
  申请人：Heinrich-Pette-Institut

  公开号：EP2036556A1

  公开（公告）日：2009-03-18

  The present invention relates to compositions comprising 4-Oxo-piperidine-carboxylates and derivatives thereof, for example derivatives substituted with phenyl, nitrophenyl or benzyl groups. It also teaches the medical use of these and related compounds for treatment of retroviral diseases, in particular, HIV and HTLV, proliferative diseases, in particular CML and Trypanosomiasis.

  本发明涉及包含4-氧代哌啶羧酸酯及其衍生物的组合物，例如用苯基、硝基苯基或苄基取代的衍生物。它还教导了这些相关化合物的医药用途，用于治疗逆转录病毒性疾病，特别是HIV和HTLV，增殖性疾病，特别是慢性髓细胞白血病和锥虫病。
• REMEDIES FOR PAIN
  申请人：Meiji Seika Kaisha, Ltd.

  公开号：EP1142587A1

  公开（公告）日：2001-10-10

  The present invention provides a pain control agent, which contains, as an active ingredient, a compound having both µ opioid receptor agonist activity and dopamine D2 receptor antagonist activity. The compound having both of these activities exerts a potent morphine-like analgetic effect and causes no psychological dependence, and even regulates side effects. In particular, a novel compound represented by general formula (I) or a pharmacologically acceptable salt thereof has both µ opioid receptor agonist activity and dopamine D2 receptor antagonist activity, and is useful as pain control agent with regulated side effects.

  本发明提供了一种疼痛控制剂，其包含作为活性成分的化合物具有µ阿片受体激动剂活性和多巴胺D2受体拮抗剂活性。具有这两种活性的化合物具有强效的类鸦片样镇痛作用，并不会导致心理依赖，甚至可以调节副作用。特别是，由通式（I）表示的新化合物或其药理学可接受的盐具有µ阿片受体激动剂活性和多巴胺D2受体拮抗剂活性，并且作为具有调节副作用的疼痛控制剂是有用的。
• Fluorescent Tools for the Imaging of Dopamine D₂‐Like Receptors**
  作者：Martin Nagl、Denise Mönnich、Niklas Rosier、Hannes Schihada、Alexei Sirbu、Nergis Konar、Irene Reyes‐Resina、Gemma Navarro、Rafael Franco、Peter Kolb、Paolo Annibale、Steffen Pockes

  DOI：10.1002/cbic.202300659

  日期：2024.1.15

  The family of dopamine D₂‐like receptors represents an interesting target for a variety of neurological diseases, e. g. Parkinson's disease (PD), addiction, or schizophrenia. In this study we describe the synthesis of a new set of fluorescent ligands as tools for visualization of dopamine D₂‐like receptors. Pharmacological characterization in radioligand binding studies identified UR‐MN212 (20) as a high‐affinity ligand for D₂‐like receptors (pK_i (D_2longR)=8.24, pK_i (D₃R)=8.58, pK_i (D₄R)=7.78) with decent selectivity towards D₁‐like receptors. Compound 20 is a neutral antagonist in a G_o1 activation assay at the D_2longR, D₃R, and D₄R, which is an important feature for studies using whole cells. The neutral antagonist 20, equipped with a 5‐TAMRA dye, displayed rapid association to the D_2longR in binding studies using confocal microscopy demonstrating its suitability for fluorescence microscopy. Furthermore, in molecular brightness studies, the ligand's binding affinity could be determined in a single‐digit nanomolar range that was in good agreement with radioligand binding data. Therefore, the fluorescent compound can be used for quantitative characterization of native D₂‐like receptors in a broad variety of experimental setups.

  摘要多巴胺 D2 样受体家族是治疗各种神经系统疾病（如帕金森病（PD）、成瘾或精神分裂症）的有趣靶点。帕金森病（PD）、成瘾症或精神分裂症。在这项研究中，我们描述了一组新的荧光配体的合成过程，它们是多巴胺 D2 样受体可视化的工具。在放射性配体结合研究中进行的药理学表征发现，UR-MN212（20）是 D2 样受体的高亲和性配体（pKi (D2longR)=8.24, pKi (D3R)=8.58, pKi (D4R)=7.78 ），对 D1 样受体具有良好的选择性。在 D2longR、D3R 和 D4R 的 Go1 激活试验中，化合物 20 是一种中性拮抗剂，这对于使用全细胞进行的研究来说是一个重要特征。中性拮抗剂 20 配有 5-TAMRA 染料，在使用共聚焦显微镜进行的结合研究中显示出与 D2longR 的快速结合，这表明它适用于荧光显微镜。此外，在分子亮度研究中，配体的结合亲和力可在个位数纳摩尔范围内确定，与放射性配体的结合数据十分吻合。因此，该荧光化合物可用于在各种实验装置中对原生 D2 样受体进行定量表征。