3-{[6-(苄基氨基)-9-异丙基-9H-嘌呤-2-基]氨基}-1-丙醇 | 189232-42-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 3-{[6-(苄基氨基)-9-异丙基-9H-嘌呤-2-基]氨基}-1-丙醇
• 中文别名: 4-甲基-5-硝基异喹啉
• 英文名称: bohemine
• 英文别名: 2-[(3-hydroxypropyl)amino]-6-benzylamino-9-isopropylpurine；3-[[6-(benzylamino)-9-propan-2-ylpurin-2-yl]amino]propan-1-ol
• CAS: 189232-42-6
• 化学式: C₁₈H₂₄N₆O
• 分子量: 340.428
• InChiKey: OPQGFIAVPSXOBO-UHFFFAOYSA-N

物化性质

• 熔点：
  101-103 °C
• 沸点：
  589.4±60.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)
• 溶解度：
  氯仿：可溶50 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  87.9
• 氢给体数：
  3
• 氢受体数：
  6

安全信息

• WGK Germany：
  3
• 海关编码：
  2933990090

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : Bohemine
CAS-No. : 189232-42-6
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
Caution - substance not yet tested completely.
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Synonyms : 2-(3-Hydroxypropylamino)-6-benzylamino-9-isopropylpurine
Formula : C18H24N6O
Molecular Weight : 340,42 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
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.
Recommended storage temperature: -20 °C
Packaged under inert gas. Air and light sensitive.
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: powder
Colour: white
b) Odour no data available
c) Odour Threshold no data available
d) pH no data available
e) Melting point/freezing no data available
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.
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

Bohemine 是一种 CDK 抑制剂，对 Cdk2/cyclin E、Cdk2/cyclin A 和 Cdk9/cyclin T1 的 IC50 值分别为 4.6 μM、83 μM 和 2.7 μM。

Target	Value
Cdk9/cyclin T1	2.7 μM
Cdk2/cyclin E	4.6 μM
Cdk2/cyclin A	83 μM

体外研究

Bohemine (0-30 µM；72 小时；ME-750 细胞) 处理抑制了细胞生长。在浓度范围为 1-10 µM 的 Bohemine 添加后，出现了短期的生长和单克隆抗体生产的停滞。短期内对细胞功能的抑制随后导致特定生长率和生产率显著暂时增加。

混合瘤细胞在 G1/S 边界和 G2/M 边界上均受到 Bohemine (0-30 µM) 浓度的影响而延迟。

T-淋巴母细胞系 CEM 经过 Bohemine 处理，发现有五种蛋白质下调，分别是 α-烯醇化酶、三磷酸异构酶、起始因子 5A 及 α-和 β-亚单位的 Rho GDP 分离抑制蛋白。这些蛋白质在糖酵解、蛋白质合成及细胞骨架重排中发挥着重要作用。

Bohemine 抑制人肿瘤细胞系生长，IC50 值为 27 µM。

细胞活力测定

细胞系	浓度	孵育时间	结果
鼠杂交瘤 ME-750 细胞	0 μM, 1 μM, 3 μM, 10 μM 和 30 μM	72 小时	在 10 μM 和 30 μM 浓度下，存活细胞计数显著低于对照组，分别为 77% 和 48%。

体内研究

Bohemine (50 mg/kg；静脉注射；BALB/c 小鼠) 处理显示最大浓度 (Cmax) 为 72,308 nM，观察到的清除率为 0.23 L/h，半衰期 (T1/2) 为 1.39 h。

动物模型	肿瘤类型	剂量	给药方式	结果
BALB/c 小鼠携带结肠26小鼠肿瘤	结肠26小鼠肿瘤	50 mg/kg	静脉注射 (药代动力学分析)	Cmax 为 72,308 nM，观察到的清除率为 0.23 L/h，T1/2 为 1.39 h。

反应信息

• 作为反应物：
  描述：

  iron(III) chloride hexahydrate 、 3-{[6-(苄基氨基)-9-异丙基-9H-嘌呤-2-基]氨基}-1-丙醇 以 盐酸 为溶剂， 以60%的产率得到
  参考文献：
  名称：

  金属配合物作为抗癌剂2.具有N 6-苄氨基嘌呤衍生物的铁（III）和铜（II）生物活性配合物

  摘要：

  铁（III）与2-（3-羟丙基氨基）-6-苄氨基-9-异丙基嘌呤（Bohemin，HL 1）的质子化形式（H + HL 1）2 [FeCl 5 ]·2H 2的络合物O（1），（H + HL 1）2 [FeCl 5 ]·3H 2 O（2）已通过两种不同的方法制备。为铜（II）配合物与6-（2-氯苄基氨基）嘌呤（HL的合成的新途径2），[铜2（μ -Cl）2（μ -HL2）2（HL 2）2 Cl 2 ]·2H 2 O（3）以及与6-（3-氯苄氨基）嘌呤（HL 3），[Cu 2（μ- Cl ）2（μ- HL 3）2 Cl 2 ]（4），也有报道。表征基于元素分析，电子，红外，ES +质量和57 FeMössbauer光谱，电导率数据以及在4.5 – 300 K范围内1 –的磁化率温度测量。温度范围分别为3和35–300 K（4个温度范围）。HL 2配体的电子中性形式（HL 2 ·2H 2 O）和HL

  DOI：

  10.1016/s0020-1693(01)00611-9
• 作为产物：
  描述：

  2,6-二氯-9-异丙基-9h-嘌呤 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-{[6-(苄基氨基)-9-异丙基-9H-嘌呤-2-基]氨基}-1-丙醇
  参考文献：
  名称：

  金刚烷取代的嘌呤及其 β-环糊精复合物：合成和生物活性

  摘要：

  细胞周期蛋白依赖性激酶 (CDK) 在细胞分裂周期中发挥重要作用。CDKs 的合成抑制剂基于 2,6,9-三取代嘌呤，被开发为潜在的抗癌药物；然而，它们在水中的溶解度很低。在这项研究中，我们证明了通过适当取代金刚烷部分可以改善基于嘌呤的抑制剂的药物化学性质。我们制备了十种新的具有金刚烷骨架的嘌呤衍生物，这些骨架使用可变几何形状和极性的亚苯基间隔物连接在 6 位。我们证明了金刚烷骨架不会影响生物活性，并且一些新的嘌呤对 CDK2/细胞周期蛋白 E 的抑制活性甚至高于母体化合物。这些发现得到了对接研究的支持，这表明结合口袋内的金刚烷支架参与了非极性相互作用的复杂稳定。此外，我们证明了 β-环糊精 (CD) 增加了药物在水中的溶解度，尽管这是以降低生化和细胞效应为代价的。最有可能的是，靶标参与所必需的药物浓度通过与 β-CD 复合物内的竞争性药物结合而降低。

  DOI：

  10.3390/ijms222312675

文献信息

• Facile and efficient access to 2,6,9-tri-substituted purines through sequential N9, N2 Mitsunobu reactions
  作者：Steven Fletcher、Vijay M. Shahani、Patrick T. Gunning

  DOI：10.1016/j.tetlet.2009.04.137

  日期：2009.7

  both Mitsunobu reactions. Significantly, excellent chemoselectivity and N9-regioselectivity were observed for the first coupling, and reactions were complete within 15 min at room temperature. Our novel methodology may be readily adapted to furnish N9-mono- or N2,N9-di-functionalized guanine analogues, and the utility of our protocol is further demonstrated by the efficient synthesis of the CDK inhibitor

  提出了一种2,6,9-三取代嘌呤的简便，有效和温和的合成方法，从市售的2-氨基-6-氯嘌呤开始，其采用先后顺序的N9然后N2 Mitsunobu反应作为关键步骤。重要的是，我们对嘌呤核进行N2官能化的合成方法消除了用伯胺将2-卤基团进行传统亲核芳香取代所需要的苛刻条件。在两次光延反应中，苯甲酸，烯丙基，炔丙基和脂肪族醇的收率都非常好。显着地，对于第一次偶联观察到优异的化学选择性和N9-区域选择性，并且在室温下15分钟内反应完成。我们新颖的方法很容易适应提供N 9-单-或N2，N 9-二官能化的鸟嘌呤类似物，并且我们的方案的实用性通过CDK抑制剂波西米因的有效合成得到进一步证明。
• [EN] CYCLOBUTAN-1,1 -DICARBOXYLATO COMPLEXES OF PLATINUM WITH N6-BENZYLADENINE DERIVATIVES, METHOD OF THEIR PREPARATION AND APPLICATION OF THESE COMPLEXES AS DRUGS IN ANTITUMOUR THERAPY<br/>[FR] COMPLEXES CYCLOBUTANE-1,1-DICARBOXYLATO DE PLATINE AVEC DES DÉRIVÉS DE N6-BENZYLADÉNINE, LEUR PROCÉDÉ DE PRÉPARATION ET LEUR APPLICATION EN TANT QUE MÉDICAMENTS DANS UN TRAITEMENT ANTITUMORAL
  申请人：UNIV PALACKEHO

  公开号：WO2011029415A1

  公开（公告）日：2011-03-17

  Cyclobutane-1,1-dicarboxylato complexes of platinum in the oxidation state +II and their crystal-solvates including the structural motif I or having the general formula Il expressed by the structural formula [Pt(cbdc)(L)2] Il or the general formula III expressed by the structural formula [Pt(cbdc)(L)(L')] III, where the symbols L and L' stand for N6-benzyladenine derivatives of the general formula IV bound to the platinum atom of the basic motif V through any adenine nitrogen atom independently chosen from the N1, N3, N6, N7 or N9 atoms, depending on the substitution rate of the molecules IV, where the substituents R1, R2 a R3 are independently chosen from the group of: hydrogen atom, halogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, functional group and N-R'R" group, where R' and R" independently symbolize hydrogen atom, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl and functional group.

  铂的氧化态为+II的环丁二酸-1,1-二羧酸配合物及其晶体溶剂包括结构基团I或具有由结构式[Pt(cbdc)(L)2] II表示的一般式Il或由结构式[Pt(cbdc)(L)(L')] III表示的一般式III，其中符号L和L'代表通式IV的N6-苄腺嘌呤衍生物，通过任何腺嘌呤氮原子独立选择自N1、N3、N6、N7或N9原子与基本基团V的铂原子结合，取决于分子IV的取代率，其中取代基R1、R2和R3独立选择自以下组中的: 氢原子、卤素、烷基、取代烷基、烯基、取代烯基、炔基、取代炔基、环烷基、取代环烷基、环杂烷基、取代环杂烷基、环烯基、取代环烯基、环杂烯基、取代环杂烯基、芳基、取代芳基、杂芳基、取代杂芳基、功能基团和N-R'R"基团，其中R'和R"独立表示氢原子、烷基、取代烷基、烯基、取代烯基、炔基、取代炔基、环烷基、取代环烷基、环杂烷基、取代环杂烷基、环烯基、取代环烯基、环杂烯基、取代环杂烯基、芳基、取代芳基、杂芳基、取代杂芳基和功能基团。
• Cyclin dependent kinase inhibitor
  申请人：Institute of Experimental Botany of the Academy of Sciences of the Czech Republic

  公开号：US06221873B1

  公开（公告）日：2001-04-24

  The present invention is based on the method of treating a patient suffering from leukemia comprising administering a therapeutically effective amount of the compound 2-([(3-hydroxypropyl)amino]-6-benzylamino)-9-isopropylpurine or a pharmaceutically acceptable salt thereof.

  本发明基于治疗白血病患者的方法，包括给予治疗有效量的化合物2-[(3-羟基丙基)氨基]-6-苯甲氨基-9-异丙基嘌呤或其药学上可接受的盐。
• Substituted nitrogen heterocyclic derivatives and pharmaceutical use thereof
  申请人：USTAV EXPERIMENTALNI BOTANIKY AV CR

  公开号：US20030191086A1

  公开（公告）日：2003-10-09

  Various substituted nitrogen heterocyclic derivatives and their pharmaceutically acceptable salt derivatives are provided for use as medicaments, and particularly, as antimitotic, anti-viral, anti-cancer, anti-degenerative, immunosuppressive, and anti-microbial drugs or, vaccines. These heterocyclic derivatives can be used as an active agent in a pharmaceutical, as well as a diagnostic utility. To this end, several families of heterocyclic derivatives are provided including pyrrolopyrimidines, pyrazolopyrimidines, purines, and imidazopyridines. In particular, certain tri-substituted and tetra-substituted purines and pyrazolopyrimidines and their deaza analogues are provided for inhibiting cyclin-dependent kinase (“cdk”) proteins, viruses, and immunostimulation.

  提供了各种取代的氮杂环衍生物及其药学上可接受的盐衍生物，用作药物，特别是作为抗有丝分裂、抗病毒、抗癌、抗变性、免疫抑制和抗微生物药物或疫苗。这些杂环衍生物可以用作药物的活性成分，也可以用作诊断工具。为此，提供了几个杂环衍生物家族，包括吡咯吡咯嘧啶、吡唑嘧啶、嘌呤和咪唑吡啶。特别地，提供了某些三取代和四取代的嘌呤和吡唑嘧啶及其去氮类似物，用于抑制细胞周期依赖性激酶（“cdk”）蛋白、病毒和免疫刺激。
• Nouveaux dérivés de purine possédant notamment des propriétés anti-prolifératives et leurs applications biologiques
  申请人：Centre National de la Recherche Scientifique (C.N.R.S.)

  公开号：EP1308447A1

  公开（公告）日：2003-05-07

  Les dérivés de l'invention sont des dérivés de purine substitués en positions 2, 6 et 9. Il s'agit en particulier de la 2-(1-R hydroxyméthylpropylamino)-6-benzylamino-9-isopropylpurine. Ces dérivés présentent notamment des propriétés antiprolifératives et sont utilisables comme médicaments et comme herbicide.

  本发明的衍生物是在第 2、6 和 9 位被取代的嘌呤衍生物。 特别是 2-(1-R-羟甲基丙基氨基)-6-苄基氨基-9-异丙基嘌呤。 这些衍生物具有抗增殖特性，可用作药物和除草剂。