O-6-苄基鸟嘌呤 | 19916-73-5

• 物质功能分类: 生物化工 - 核酸类
• 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: O-6-苄基鸟嘌呤
• 中文别名: 6-苄氧基鸟嘌呤；6-O-苄基鸟嘌呤；6-苄基鸟嘌呤；2-氨基-6-苄氧基嘌呤；苄基鸟嘌呤；2-氨基-6-(苄氧基)嘌呤
• 英文名称: 2-Amino-6-benzyloxypurine
• 英文别名: O⁶-benzylguanine；o6-Benzylguanine；6-phenylmethoxy-7H-purin-2-amine
• CAS: 19916-73-5
• 化学式: C₁₂H₁₁N₅O
• 分子量: 241.252
• InChiKey: KRWMERLEINMZFT-UHFFFAOYSA-N

物化性质

• 熔点：
  193(dec.)
• 沸点：
  459.3±55.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)
• 溶解度：
  溶于甲醇，溶解度20mg/mL
• 稳定性/保质期：

  遵照规定使用和储存，则不会发生分解。

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  89.7
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  2933990090
• 安全说明：
  S26,S36
• 危险标志：
  GHS07
• 危险性描述：
  H315,H319,H335
• 危险性防范说明：
  P261,P305 + P351 + P338
• 储存条件：
  存于阴凉干燥处

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
O6-Benzylguanine
Product Name:
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
Wear protective gloves/protective clothing/eye protection/face protection
P280:
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
P405: Store locked up

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Section 3. Composition/information on ingredients.
O6-Benzylguanine
Ingredient name:
CAS number: 19916-73-5

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Section 4. First aid measures
Immediately wash skin with copious amounts of water for at least 15 minutes while removing
Skin contact:
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.
Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.
Ingestion:

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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.
Storage: Store in closed vessels.

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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
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C12H11N5O
Molecular weight: 241.3

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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.

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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

制备方法与用途

O6-苯基鸟嘌呤简介

O6-Benzylguanine 是一种鸟嘌呤类似物，作为 DNA 修复酶 O6 烷基鸟嘌呤DNA烷基转移酶 (AGT) 的抑制剂。

药理活性

O6-Benzylguanine 可以作为 AGT 底物，在其苄基转移到 AGT 半胱氨酸残基上后，不可逆地灭活 AGT 并阻止 DNA 修复。此外，它还能诱导肿瘤细胞凋亡，并具有抗肿瘤活性。

靶点

Target	Value
AGT

体外研究

• L3.6pl 细胞对 O6-Benzylguanine 的敏感性在剂量和时间上表现出依赖关系，48 小时时的 IC50 值为 50 μg。O6-Benzylguanine 可以调节 p53 下游靶蛋白表达、诱导凋亡并减少细胞增殖。
• O6-Benzylguanine 显著降低了 L3.6pl 细胞中的 MGMT 转录活性。

Western Blot 分析

项目	结果
细胞系:	L3.6pl 和 PANC1 细胞
浓度:	50 μg
孵育时间:	48 小时
表达变化:	MGMT、cyclin B1、cyclin B2、cyclin A、p53 和 ki-67 减少，p21 增加。细胞色素 C 和 caspase 9 的水平增加，而 PARP1 蛋白的水平降低。

RT-PCR

项目	结果
细胞系:	L3.6pl 细胞
浓度:	50 μg
孵育时间:	48 小时
结果:	显著降低了 L3.6pl 中的 MGMT 转录活性。

体内研究

• O6-Benzylguanine (100 μg；i.p.) 在连续 35 天内给药，抑制胰腺癌细胞生长并增加胰腺细胞对吉西他滨 (Gemcitabine) 的敏感性。
• O6-Benzylguanine 可以在体内抑制胰腺癌细胞的增殖，并诱导肿瘤细胞凋亡。

动物模型

项目	结果
实验动物:	雄性无胸腺裸鼠 (NCI-nu)（携带人胰腺癌 L3.6pl 细胞）
剂量:	100 μg
给药方式:	i.p；连续 35 天
结果:	显著减少了肿瘤体积和重量。

用途

用于研究各种 DNA 修复机制。

反应信息

• 作为反应物：
  描述：

  O-6-苄基鸟嘌呤 在 cesium bicarbonate 、 cesium hydroxide 、 甲烷磺酸 、 双氧水 、 乙酸酐 、 对甲苯磺酸 、 sodium fluoride 、 溶剂黄146 、 特丁基对苯二酚 、 potassium hydroxide 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 乙醇 、 水 为溶剂， 反应 98.0h， 生成 entecavir
  参考文献：
  名称：

  恩替卡韦中间体及其制备方法

  摘要：

  本发明公开了一种恩替卡韦中间体及其制备方法。本发明提供了一种恩替卡韦中间体化合物3的制备方法，其包括以下步骤：在溶剂中，将化合物4进行还原反应，得到化合物3。本发明还提供了一种恩替卡韦中间体化合物4的制备方法，其包括以下步骤：在溶剂中，酸性条件下，将化合物5与化合物18进行缩醛交换反应，得到化合物4。本发明的制备方法原料廉价易得，反应条件温和，产品收率较高。原子经济性好，环境友好，适合于工业化生产。

  公开号：

  CN104177397B
• 作为产物：
  描述：

  (6-(benzyloxy)-2-((((4-nitrobenzyl)oxy)carbonyl)amino)-9H-purin-9-yl)methyl pivalate 在 乙二胺四乙酸 、 氨 、 锌 作用下， 以 甲醇 为溶剂， 反应 40.07h， 生成 O-6-苄基鸟嘌呤
  参考文献：
  名称：

  4-Nitrobenzyloxycarbonyl Derivatives of O⁶-Benzylguanine as Hypoxia-Activated Prodrug Inhibitors of O⁶-Alkylguanine-DNA Alkyltransferase (AGT), Which Produces Resistance to Agents Targeting the O-6 Position of DNA Guanine

  摘要：

  A series of 4-nitrobenzyloxycarbonyl prodrug derivatives of O-6-benzylguanine (O-6-BG), conceived as pro-drugs of O-6-BG, an inhibitor of the resistance protein O-6-alkylguanine-DNA alkyltransferase (ACT), were synthesized and evaluated for their ability to undergo bioreductive activation by reductase enzymes under oxygen deficiency. Three agents of this class, 4-nitrobenzyl (6-(benzyloxy)-9H-purin-2-yl)carbamate (1) and its monomethyl (2) and gem-dimethyl analogues (3), were tested for activation by reductase enzyme systems under oxygen deficient conditions. Compound 3, the most water-soluble of these agents, gave the highest yield of O-6-BG following reduction of the nitro group trigger. Compound 3 was also evaluated for its ability to sensitize 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (laromustine)-resistant DU145 human prostate carcinoma cells, which express high levels of AGT, to the cytotoxic effects of this agent under normoxic and oxygen deficient conditions. While 3 had little or no effect on laromustine cytotoxicity under aerobic conditions, significant enhancement occurred under oxygen deficiency, providing evidence for the preferential release of the AGT inhibitor O-6-BG under hypoxia.

  DOI：

  10.1021/jm201115f
• 作为试剂：
  描述：

  <1S-(1α,2β,3β)>-3-<<(4-methylphenyl)sulfonyl>oxy>-1,2-cyclobutanedimethanol dibenzoate ester 、 O-6-苄基鸟嘌呤 在 O-6-苄基鸟嘌呤 作用下， 以51的产率得到<1S-(1α,2β,3α)>-3-<2-amino-6-(phenylmethoxy)-9H-purin-9-yl>-1,2-cyclobutanedimethanol 1,2-dibenzoate ester
  参考文献：
  名称：

  J. Med. Chem. 1991, 34, 1415-1421

  摘要：

  DOI：

文献信息

• [EN] COMPOUNDS AND COMPOSITIONS COMPRISING CDK INHIBITORS AND METHODS FOR THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS ET COMPOSITIONS COMPRENANT DES INHIBITEURS DES CDK ET MÉTHODES DE TRAITEMENT DU CANCER
  申请人：UNIV GEORGIA STATE RES FOUND

  公开号：WO2010129858A1

  公开（公告）日：2010-11-11

  Disclosed herein are compounds suitable for use as antitumor agents, methods for treating cancer wherein the disclosed compounds are used in making a medicament for the treatment of cancer, methods for treating a tumor comprising, administering to a subject a composition comprising one or more of the disclosed cytotoxic agents, and methods for preparing the disclosed antitumor agents.

  本文披露了适用作抗肿瘤药剂的化合物，用于治疗癌症的方法，其中所披露的化合物用于制备治疗癌症的药物，治疗肿瘤的方法包括向受试者施用包含一种或多种所披露的细胞毒性药剂的组合物，以及制备所披露的抗肿瘤药剂的方法。
• [EN] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE TYROSINE KINASE DE BRUTON
  申请人：BIOCAD JOINT STOCK CO

  公开号：WO2018092047A1

  公开（公告）日：2018-05-24

  The present invention relates to a new compound of formula I: or pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: V1 is C or N, V2 is C(R2) or N, whereby if V1 is C then V2 is N, if V1 is C then V2 is C(R2), or if V1 is N then V2 is C(R2); each n, k is independently 0, 1; each R2, R11 is independently H, D, Hal, CN, NR'R", C(O)NR'R", C1-C6 alkoxy; R3 is H, D, hydroxy, C(O)C1-C6 alkyl, C(O)C2-C6 alkenyl, C(O)C2-C6 alkynyl, C1-C6 alkyl; R4 is H, Hal, CN, CONR'R", hydroxy, C1-C6 alkyl, C1-C6 alkoxy; L is CH2, NH, O or chemical bond; R1 is selected from the group of the fragments, comprising: Fragment 1, Fragment 2, Fragment 3 each A1, A2, A3, A4 is independently CH, N, CHal; each A5, A6, A7, A8, A9 is independently C, CH or N; R5 is H, CN, Hal, CONR'R", C1-C6 alkyl, non-substituted or substituted by one or more halogens; each R' and R" is independently selected from the group, comprising H, C1-C6 alkyl, C1-C6 cycloalkyl, aryl; R6 is selected from the group: [formula II] each R7, R8, R9, R10 is independently vinyl, methylacetylenyl; Hal is CI, Br, I, F, which have properties of inhibitor of Bruton's tyrosine kinase (Btk), to pharmaceutical compositions containing such compounds, and their use as pharmaceuticals for treatment of diseases and disorder.

  本发明涉及一种新的化合物，其化学式为I：或其药学上可接受的盐、溶剂化合物或立体异构体，其中：V1为C或N，V2为C(R2)或N，如果V1为C，则V2为N，如果V1为C，则V2为C(R2)，或者如果V1为N，则V2为C(R2)；每个n，k独立地为0或1；每个R2，R11独立地为H，D，Hal，CN，NR'R"，C(O)NR'R"，C1-C6烷氧基；R3为H，D，羟基，C(O)C1-C6烷基，C(O)C2-C6烯基，C(O)C2-C6炔基，C1-C6烷基；R4为H，Hal，CN，CONR'R"，羟基，C1-C6烷基，C1-C6烷氧基；L为CH2，NH，O或化学键；R1从包括的片段组中选择：片段1，片段2，片段3，每个A1，A2，A3，A4独立地为CH，N，CHal；每个A5，A6，A7，A8，A9独立地为C，CH或N；R5为H，CN，Hal，CONR'R"，C1-C6烷基，未取代或被一个或多个卤素取代；每个R'和R"独立地从包括H，C1-C6烷基，C1-C6环烷基，芳基的组中选择；R6从组中选择：[化学式II]每个R7，R8，R9，R10独立地为乙烯基，甲基乙炔基；Hal为CI，Br，I，F，具有布鲁顿酪氨酸激酶（Btk）抑制剂的性质，以及含有这种化合物的药物组合物，以及它们作为治疗疾病和紊乱的药物的用途。
• [EN] TRICYCLIC TRIAZOLE COMPOUNDS THAT MODULATE HSP90 ACTIVITY<br/>[FR] COMPOSÉS TRIAZOLES TRICYCLIQUES MODULANT L'ACTIVITÉ HSP90
  申请人：SYNTA PHARMACEUTICALS CORP

  公开号：WO2009139916A1

  公开（公告）日：2009-11-19

  The present invention relates to substituted tricyclic triazole compounds and compositions comprising substituted tricyclic triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a compound of the invention, or a composition comprising such a compound.

  本发明涉及替代三环三唑化合物和包含替代三环三唑化合物的组合物。该发明还涉及在需要的受体中抑制Hsp90活性的方法，以及预防或治疗高增殖性疾病（如癌症）的方法，其中包括向受体施用本发明的化合物或包含这种化合物的组合物。
• Amino-substituted heterocycles, compositions thereof, and methods of treatment therewith
  申请人：D'Sidocky Neil R.

  公开号：US20080242694A1

  公开（公告）日：2008-10-02

  Provided herein are Heterocyclic Compounds having the following structure: wherein R 1 , R 2 , X, Y and Z are as defined herein, compositions comprising an effective amount of a Heterocyclic Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, metabolic conditions and conditions treatable or preventable by inhibition of a kinase pathway comprising administering an effective amount of a Heterocyclic Compound to a patient in need thereof.

  本文提供具有以下结构的杂环化合物： 其中R1、R2、X、Y和Z如本文所定义，包含有效量杂环化合物的组合物，以及治疗或预防癌症、炎症性疾病、免疫疾病、代谢性疾病以及通过给予患者需要的有效量杂环化合物来抑制激酶途径治疗或预防的疾病的方法。
• [EN] PROTEIN KINASE INHIBITORS AND USE THEREOF<br/>[FR] INHIBITEURS DE PROTÉINE KINASE ET LEUR UTILISATION
  申请人：MERCK SERONO SA

  公开号：WO2009108670A1

  公开（公告）日：2009-09-03

  Disclosed are benzonaphthyridinyl derivative compounds and analogs thereof, pharmaceutical compositions comprising such compounds and processes for preparing the same. The compounds are useful in the treatment of diseases amenable to kinase signal transduction inhibition, regulation or modulation.

  揭示了苯并萘啶衍生物化合物及其类似物，包括含有这些化合物的药物组合物以及制备这些化合物的方法。这些化合物在治疗对激酶信号传导抑制、调节或调控敏感的疾病中很有用。