利诺吡啶 | 105431-72-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 利诺吡啶
• 中文别名: 1,3-二氢-1-苯基-3,3-双(4-吡啶甲基)-2H-吲哚-2-酮双盐酸盐
• 英文名称: linopirdine
• 英文别名: 3,3-bis(pyridin-4-ylmethyl)-1-phenylindolin-2-one；1-phenyl-3,3-bis(pyridin-4-ylmethyl)indol-2-one
• CAS: 105431-72-9
• 化学式: C₂₆H₂₁N₃O
• 分子量: 391.472
• InChiKey: YEJCDKJIEMIWRQ-UHFFFAOYSA-N

物化性质

• 熔点：
  186-186.5 °C
• 沸点：
  655.9±50.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：>10mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  46.1
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933790090
• 储存条件：
  存储条件：2-8°C，密封保存，并确保环境干燥。

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : Linopirdine
CAS-No. : 105431-72-9
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

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Section 2. HAZARDS IDENTIFICATION
Classification of the substance or mixture
Not a hazardous substance or mixture according to Regulation (EC) No. 1272/2008.
This substance is not classified as dangerous according to Directive 67/548/EEC.
Label elements
The product does not need to be labelled in accordance with EC directives or respective national laws.
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Synonyms : DuP 996
1,3-Dihydro-1-phenyl-3,3-bis(4-pyridinylmethyl)-2H-indol-2-one
Formula : C26H21N3O
Molecular Weight : 391,46 g/mol

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Section 4. FIRST AID MEASURES
Description of first aid measures
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration.
In case of skin contact
Wash off with soap and plenty of water.
In case of eye contact
Flush eyes with water as a precaution.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water.
Most important symptoms and effects, both acute and delayed
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.
Indication of any immediate medical attention and special treatment needed
no data available

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Section 5. FIREFIGHTING MEASURES
Extinguishing media
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, nitrogen oxides (NOx)
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

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Section 6. ACCIDENTAL RELEASE MEASURES
Personal precautions, protective equipment and emergency procedures
Avoid dust formation. Avoid breathing vapors, mist or gas.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
Sweep up and shovel. Keep in suitable, closed containers for disposal.
Reference to other sections
For disposal see section 13.

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Section 7. HANDLING AND STORAGE
Precautions for safe handling
Provide appropriate exhaust ventilation at places where dust is formed.Normal measures for preventive fire
protection.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Specific end uses
no data available

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Section 8. EXPOSURE CONTROLS/PERSONAL PROTECTION
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
General industrial hygiene practice.
Personal protective equipment
Eye/face protection
Use equipment for eye protection tested and approved under appropriate government standards
such as NIOSH (US) or EN 166(EU).
Skin protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique
(without touching glove's outer surface) to avoid skin contact with this product. Dispose of
contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and
the standard EN 374 derived from it.
Body Protection
Choose body protection in relation to its type, to the concentration and amount of dangerous
substances, and to the specific work-place., The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
Respiratory protection is not required. Where protection from nuisance levels of dusts are desired,
use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and
approved under appropriate government standards such as NIOSH (US) or CEN (EU).

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Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Information on basic physical and chemical properties
a) Appearance Form: solid
Colour: white
b) Odour no data available
c) Odour Threshold no data available
d) pH no data available
e) Melting point/freezing Melting point/range: 184 - 186 °C
point
f) Initial boiling point and no data available
boiling range
g) Flash point no data available
h) Evaporation rate no data available
i) Flammability (solid, gas) no data available
j) Upper/lower no data available
flammability or
explosive limits
k) Vapour pressure no data available
l) Vapour density no data available
m) Relative density no data available
n) Water solubility no data available
o) Partition coefficient: n- no data available
octanol/water
p) Autoignition no data available
temperature
q) Decomposition no data available
temperature
r) Viscosity no data available
s) Explosive properties no data available
t) Oxidizing properties no data available
Other safety information
no data available

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Section 10. STABILITY AND REACTIVITY
Reactivity
no data available
Chemical stability
no data available
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
Strong oxidizing agents
Hazardous decomposition products
Other decomposition products - no data available

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Section 11. TOXICOLOGICAL INFORMATION
Information on toxicological effects
Acute toxicity
no data available
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitization
no data available
Germ cell mutagenicity
no data available
Carcinogenicity
IARC: No component of this product present at levels greater than or equal to 0.1% is identified as
probable, possible or confirmed human carcinogen by IARC.
Reproductive toxicity
no data available
Specific target organ toxicity - single exposure
no data available
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Potential health effects
Inhalation
May be harmful if inhaled. May cause respiratory tract irritation.
Ingestion May be harmful if swallowed.
Skin May be harmful if absorbed through skin. May cause skin irritation.
Eyes May cause eye irritation.
Signs and Symptoms of Exposure
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.
Additional Information
RTECS: Not available

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Section 12. ECOLOGICAL INFORMATION
Toxicity
no data available
Persistence and degradability
no data available
Bioaccumulative potential
no data available
Mobility in soil
no data available
Results of PBT and vPvB assessment
no data available
Other adverse effects
no data available

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Section 13. DISPOSAL CONSIDERATIONS
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company.
Contaminated packaging
Dispose of as unused product.

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Section 14. TRANSPORT INFORMATION
UN number
ADR/RID: - IMDG: - IATA: -
UN proper shipping name
ADR/RID: Not dangerous goods
IMDG: Not dangerous goods
IATA: Not dangerous goods
Transport hazard class(es)
ADR/RID: - IMDG: - IATA: -
Packaging group
ADR/RID: - IMDG: - IATA: -
Environmental hazards
ADR/RID: no IMDG Marine pollutant: no IATA: no
Special precautions for user
no data available

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SECTION 15 - REGULATORY INFORMATION
N/A

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

Linopirdine (DuP 996) 是一种具有口服活性的、选择性 M 型 K+ 电流 (IM；Kv7；KCNQ Channels) 抑制剂，其 IC50 为 2.4 μM。此外，它也是 TRPV1 激活剂。Linopirdine 已被公认为一种认知增强药物，并能增加大鼠脑组织中乙酰胆碱的释放。

靶点

• IC50: 2.4 μM (M 型 K+ 电流)

体外研究

林普瑞定 (DuP 996) 抑制 IC（通过测量中间后超极化尾部电流 ImAHP 表示），其 IC50 为 16.3 μM。在 100 μM 浓度下，Linopirdine 轻微抑制了 K+ 泄漏电流 (IL)、瞬时外向电流 (IA)、延迟整流 (IK) 和 IAHP 的慢相分量，分别减少了 28%、37%、36% 和 52%。混合的 Na+/K+ 内向整流电流 (IQ) 在 Linopirdine 下几乎不受影响（IC50 >300 μM）。此外，Linopirdine 还作为 TRPV1 的激动剂起作用。

体内研究

静脉注射 Linopirdine (DuP 996; 0.1-6 mg/kg，剂量递增) 短暂地（10-15 分钟）且呈剂量依赖性地增加平均动脉压 (MAP)，最多可增加 15%。

动物模型	雄性 Sprague-Dawley 大鼠 (300-350 g)
剂量	0.1, 0.5, 1, 3, 6 mg/kg
给药方式	五次静脉注射递增剂量
结果	短暂且呈剂量依赖性地增加 MAP，最多 15%

注：结果为通过多次静脉给药在大鼠中观察到的。

反应信息

• 作为反应物：
  描述：

  利诺吡啶 在 吗啉 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 16.33h， 生成 1-phenyl-3-(pyridin-4-yl)-4-(pyridin-4-ylmethyl)quinolin-2(1H)-one
  参考文献：
  名称：

  羟吲哚向喹啉酮的区域发散扩环

  摘要：

  开发不同的方法来加速结构-活性关系研究对于简化发现过程至关重要。我们开发了一个罕见的区域发散环扩展示例，以从共同的起始材料中获得两种区域异构体。为了实现这种区域分歧，我们确定了将羟吲哚转化为喹啉酮异构体的两种不同的反应条件。所提出的方法被证明与多种官能团兼容，从而实现了生物活性羟吲哚的后期多样化，并促进了喹啉酮药物及其衍生物的合成。

  DOI：

  10.1021/jacs.3c12119
• 作为产物：
  描述：

  1-苯基靛红 在 sodium hydroxide 、 sodium tetrahydroborate 、 溶剂黄146 作用下， 以 甲醇 、 溶剂黄146 、 异丙醇 为溶剂， 反应 2.0h， 生成 利诺吡啶
  参考文献：
  名称：

  A Large Scale Preparation of the Cognitive Enhancer Linopirdine

  摘要：

  Linopirdine is a pharmacologically potent drug which stimulates central nervous system neurotransmitter release. A facile process used to synthesize linopirdine on a commercial manufacturing scale consisting of seven chemical steps with only a single isolated intermediate is described.

  DOI：

  10.1080/00397919308011258
• 作为试剂：
  描述：

  1,3-dihydro-3-(4-pyridinylmethylene)-1-phenyl-2H-indole-2-one 、 硼氢化钠 、 sodium hydroxide 、 盐酸 在 sodium hydroxide 、 水 、 利诺吡啶 、 crude product 、 异丙醇 作用下， 以 甲醇 、 水 为溶剂， 反应 4.9h， 以yielded 89.4 g (85%) crude title compound的产率得到利诺吡啶
  参考文献：
  名称：

  Process for preparing 3,3-disubstituted indolines

  摘要：

  本发明提供了制备3,3-二取代吲哚啉的方法，特别是3,3-二吡啶取代的吲哚啉，用于治疗哺乳动物的认知或神经功能障碍。

  公开号：

  US04806651A1

文献信息

• Piperazine-piperidine antagonists and agonists of the 5-HT1A receptor
  申请人：Asselin Magda

  公开号：US20070027160A1

  公开（公告）日：2007-02-01

  The present invention relates to novel piperazine-piperidine compounds. The compounds are useful as 5-HT 1A binding agents, particularly as 5-HT 1A receptor antagonists and agonists. These compounds are useful in treating central nervous system disorders, such as cognition disorders, anxiety disorders, depression and sexual dysfunction.

  本发明涉及新型哌嗪-哌啶化合物。这些化合物可用作5-HT1A结合剂，特别是作为5-HT1A受体拮抗剂和激动剂。这些化合物在治疗中枢神经系统疾病方面很有用，如认知障碍、焦虑症、抑郁症和性功能障碍。
• [EN] PYRAZOLO [4, 3-D] PYRIMIDINES USEFUL AS KINASE INHIBITORS<br/>[FR] PYRAZOLO[4,3-D]PYRIMIDINES UTILES EN TANT QU'INHIBITEURS DE KINASES
  申请人：ORIGENIS GMBH

  公开号：WO2012143144A1

  公开（公告）日：2012-10-26

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及一种能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复的激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体的化合物的新颖化合物（I）的公式。这些化合物在治疗各种疾病中发挥作用。这些疾病包括自身免疫疾病、炎症性疾病、骨疾病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和与激素相关的疾病。
• [EN] HETEROCYCLIC COMPOUNDS AS KINASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES EN TANT QU'INHIBITEURS DE KINASES
  申请人：ORIGENIS GMBH

  公开号：WO2012143143A1

  公开（公告）日：2012-10-26

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及一种能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体的化合物的新颖化合物（I）的公式。这些化合物在治疗各种疾病中发挥作用。这些疾病包括自身免疫疾病、炎症性疾病、骨疾病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和与激素相关的疾病。
• P ^III /P ^V =O Catalyzed Cascade Synthesis of N‐Functionalized Azaheterocycles
  作者：Trevor V. Nykaza、Gen Li、Junyu Yang、Michael R. Luzung、Alexander T. Radosevich

  DOI：10.1002/anie.201914851

  日期：2020.3.9

  the modular synthesis of diverse N-aryl and N-alkyl azaheterocycles (indoles, oxindoles, benzimidazoles, and quinoxalinediones) is reported. The method employs a small-ring organophosphorus-based catalyst (1,2,2,3,4,4-hexamethylphosphetane P-oxide) and a hydrosilane reductant to drive the conversion of ortho-functionalized nitroarenes into azaheterocycles through sequential intermolecular reductive C-N

  报道了一种有机催化方法，用于模块化合成各种N-芳基和N-烷基氮杂杂环（吲哚，羟吲哚，苯并咪唑和喹喔啉二酮）。该方法采用小环有机磷基催化剂（1,2,2,3,4,4-六甲基膦烷P-氧化物）和氢化硅烷还原剂通过顺序的分子间还原性CN交联来驱动邻官能化硝基芳烃转化成氮杂杂环与硼酸偶联，然后进行分子内环化。该方法能够从容易获得的结构单元快速构建氮杂杂环，包括针对N取代的苯并咪唑和喹喔啉二酮的区域特异性方法。
• 4-Arylspirocycloalkyl-2-aminopyrimidine carboxamide KCNQ potassium channel modulators
  申请人：Gillman W. Kevin

  公开号：US20060063790A1

  公开（公告）日：2006-03-23

  The invention encompasses compounds of Formula I, which are blockers of KCNQ channels. Blockers of KCNQ channels are known to enchance cognition in laboratory animals. The invention includes, salts, solvates, compositions, and methods of use.

  这项发明涵盖了Formula I的化合物，这些化合物是KCNQ通道的阻滞剂。已知KCNQ通道的阻滞剂能够增强实验动物的认知能力。该发明包括盐类、溶剂合物、组合物和使用方法。