N-苯甲酰基-5'-O-[二(4-甲氧基苯基)苯基甲基]-2'-脱氧-5-甲基胞苷 | 104579-03-5

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 中文名称: N-苯甲酰基-5'-O-[二(4-甲氧基苯基)苯基甲基]-2'-脱氧-5-甲基胞苷
• 英文名称: 5'-O-(4,4'-dimethoxytriphenylmethyl)-2'-deoxy-N⁴-benzoyl-5-methylcytidine
• 英文别名: 5’-O-(4,4’-dimethoxytrityl)-n4-benzoyl-5-methyl-2’-deoxycytidine；5'-O-(4,4'-Dimethoxytrityl)-N4-benzoyl-5-methyl-2'-deoxycytidine；N-[1-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-5-methyl-2-oxopyrimidin-4-yl]benzamide
• CAS: 104579-03-5
• 化学式: C₃₈H₃₇N₃O₇
• mdl: MFCD00057965
• 分子量: 647.728
• InChiKey: YWHPQMVQHSPNRU-LBFZIJHGSA-N

物化性质

• 密度：
  1.26±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO：41.67 mg/mL（64.33 mM；需要超声波）

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  48
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.236
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  7

安全信息

• 危险性防范说明：
  P261,P280,P305+P351+P338,P304+P340
• 危险性描述：
  H302
• 储存条件：
  -20℃

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: 5’-O-(4,4’-Dimethoxytrityl)-n4-benzoyl-5-methyl-2’-deoxycytidine
Synonyms:

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

---

Section 3. Composition/information on ingredients.
Ingredient name: 5’-O-(4,4’-Dimethoxytrityl)-n4-benzoyl-5-methyl-2’-deoxycytidine
CAS number: 104579-03-5

---

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

---

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.

---

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.

---

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.
Store in closed vessels.
Storage:

---

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.

---

Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C38H37N3O7
Molecular weight: 647.7

---

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.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

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.

---

Section 14. Transportation information
Non-harzardous for air and ground transportation.

---

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.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

5'-O-DMT-N4-Bz-5-Me-dC是一种修饰核苷，而5'-O-DMT-2'-O-TBDMS-rI则用于脱氧核糖核酸或核酸的合成。

反应信息

• 作为反应物：
  描述：

  N-苯甲酰基-5'-O-[二(4-甲氧基苯基)苯基甲基]-2'-脱氧-5-甲基胞苷 在 吡啶 、 盐酸 、 对甲苯磺酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 66.67h， 生成 [(2R,3S,5R)-5-(4-benzamido-5-methyl-2-oxopyrimidin-1-yl)-2-(chloromethoxymethyl)oxolan-3-yl] 2-phenoxyacetate
  参考文献：
  名称：

  Synthesis and binding properties of pyrimidine oligodeoxynucleoside analogs containing neutral phosphodiester replacements: the formacetal and 3'-thioformacetal internucleoside linkages

  摘要：

  The replacement of the phosphodiester linkage with neutral, achiral, nuclease resistant entities is desirable for the development of oligodeoxynucleotide (ODN) analogs as therapeutic agents in either the antisense or antigene modes. Described herein is the use of the formacetal and 3'-thioformacetal connections as phosphodiester backbone analogs. Pyrimidine dimer blocks containing these moieties were synthesized and incorporated into ODNs in an alternating array with phosphodiester bonds, such that the ODNs had seven acetal and seven phosphodiester linkages. The binding properties of the resulting chimeric ODNs to single-stranded (ss) RNA and double-stranded (ds) DNA were then determined. ssRNA binding properties were determined by thermal denaturation (Tm) analysis, and the 3'-thioformacetal ODN/ssRNA duplex showed a 5.5-degrees-C enhancement in Tm relative to the control phosphodiester ODN. The triple helix formation properties of the 3'-thioformacetal and formacetal ODNs were determined by footprint and restriction enzyme inhibition assays. The 3'-thioformacetal ODN binds to dsDNA with an affinity slightly less than the control ODN. The high affinity and specificity of an ODN containing the 3'-thioformacetal for the ssRNA target and dsDNA target suggest that this linkage is a promising analog for both antisense and triple helix therapeutic applications.

  DOI：

  10.1021/jo00063a014
• 作为产物：
  描述：

  beta-胸苷 在 1H-1,2,4-三唑 、 4-二甲氨基吡啶 、 氨 、 potassium carbonate 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 N-苯甲酰基-5'-O-[二(4-甲氧基苯基)苯基甲基]-2'-脱氧-5-甲基胞苷
  参考文献：
  名称：

  2-脱氧核糖相关二糖核苷及其亚磷酰胺的合成

  摘要：

  实现了抗肿瘤药ISIS 183750杂质参比化合物的合成。在该过程中，首次建立了合成2-脱氧核糖基二糖核苷的通用方法。

  DOI：

  10.1016/j.tet.2017.05.052

文献信息

• Site-specific replacement of phosphorothioate with alkyl phosphonate linkages enhances the therapeutic profile of gapmer ASOs by modulating interactions with cellular proteins
  作者：Michael T Migawa、Wen Shen、W Brad Wan、Guillermo Vasquez、Michael E Oestergaard、Audrey Low、Cheryl L De Hoyos、Ruchi Gupta、Susan Murray、Michael Tanowitz、Melanie Bell、Joshua G Nichols、Hans Gaus、Xue-hai Liang、Eric E Swayze、Stanley T Crooke、Punit P Seth

  DOI：10.1093/nar/gkz247

  日期：2019.6.20

  Phosphorothioate-modified antisense oligonucleotides (PS-ASOs) interact with a host of plasma, cell-surface and intracellular proteins which govern their therapeutic properties. Given the importance of PS backbone for interaction with proteins, we systematically replaced anionic PS-linkages in toxic ASOs with charge-neutral alkylphosphonate linkages. Site-specific incorporation of alkyl phosphonates altered the RNaseH1 cleavage patterns but overall rates of cleavage and activity versus the on-target gene in cells and in mice were only minimally affected. However, replacing even one PS-linkage at position 2 or 3 from the 5′-side of the DNA-gap with alkylphosphonates reduced or eliminated toxicity of several hepatotoxic gapmer ASOs. The reduction in toxicity was accompanied by the absence of nucleolar mislocalization of paraspeckle protein P54nrb, ablation of P21 mRNA elevation and caspase activation in cells, and hepatotoxicity in mice. The generality of these observations was further demonstrated for several ASOs versus multiple gene targets. Our results add to the types of structural modifications that can be used in the gap-region to enhance ASO safety and provide insights into understanding the biochemistry of PS ASO protein interactions.

  硫代磷酸修饰的反义寡核苷酸（PS-ASO）与多种血浆、细胞表面和细胞内蛋白质相互作用，这些蛋白质调控其治疗特性。鉴于PS骨架对与蛋白质相互作用的重要性，我们系统性地将毒性ASO中的阴离子PS连接替换为电中性烷基膦酸连接。定点引入烷基膦酸改变了RNaseH1的切割模式，但整体切割速率和针对细胞及小鼠目标基因的活性仅受到轻微影响。然而，即使在DNA间隙的5′侧的第2或第3位替换一个PS连接为烷基膦酸，也能降低或消除几种具有肝毒性的gapmer ASO的毒性。毒性的降低伴随着核仁侧斑蛋白P54nrb的错误定位缺失、细胞中P21 mRNA水平升高和caspase活化的消除，以及小鼠的肝毒性减少。这些观察结果的普遍性在针对多个基因靶点的几种ASO中得到了进一步证明。我们的结果增加了可用于间隙区域以提高ASO安全性的结构修饰类型，并为理解PS ASO蛋白相互作用的生物化学提供了见解。
• [EN] NOVEL PHOSPHOROUS (V)-BASED REAGENTS, PROCESSES FOR THE PREPARATION THEREOF, AND THEIR USE IN MAKING STEREO-DEFINED ORGANOPHOSHOROUS (V) COMPOUNDS<br/>[FR] NOUVEAUX RÉACTIFS À BASE DE PHOSPHORE (V), LEURS PROCÉDÉS DE PRÉPARATION ET LEUR UTILISATION DANS LA FABRICATION DE COMPOSÉS ORGANOPHOSHOREUX (V) STÉRÉODÉFINIS
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2019200273A1

  公开（公告）日：2019-10-17

  The present invention relates to novel phosphorous (V) (P(V)) reagents, methods for preparing thereof, and methods for preparing organophosphorous (V) compounds by using the novel reagents.

  本发明涉及新型磷（V）（P(V)）试剂，其制备方法以及利用这种新型试剂制备有机磷（V）化合物的方法。
• Oligonucleotides having modified nucleoside units
  申请人：——

  公开号：US20040014957A1

  公开（公告）日：2004-01-22

  Disclosed are oligonucleotides and oligonucleosides that include one or more modified nucleoside units. The oligonucleotides and oligonucleosides are particularly useful as antisense agents, ribozymes, aptamer, siRNA agents, probes and primers or, when hybridized to an RNA, as a substrate for RNA cleaving enzymes including RNase H and dsRNase.

  披露的是包括一个或多个修饰核苷单元的寡核苷酸和寡核苷糖。这些寡核苷酸和寡核苷糖特别适用于作为反义剂、核酶、适配体、siRNA试剂、探针和引物，或者当它们与RNA杂交时，作为包括RNase H和dsRNase的RNA切割酶的底物。
• Antisense modulation of cyclin-dependent kinase 6 expression
  申请人：Isis Pharmaceuticals Inc.

  公开号：US20040087523A1

  公开（公告）日：2004-05-06

  Antisense compounds, compositions and methods are provided for modulating the expression of cyclin-dependent kinase 6. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding cyclin-dependent kinase 6. Methods of using these compounds for modulation of cyclin-dependent kinase 6 expression and for treatment of diseases associated with expression of cyclin-dependent kinase 6 are provided.

  提供了用于调节细胞周期依赖性激酶6表达的反义化合物、组合物和方法。这些组合物包括针对编码细胞周期依赖性激酶6的核酸的反义化合物，特别是反义寡核苷酸。提供了利用这些化合物调节细胞周期依赖性激酶6表达以及治疗与细胞周期依赖性激酶6表达相关的疾病的方法。
• Antisense modulation of PTPN12 expression
  申请人：Isis Pharmaceuticals Inc.

  公开号：US20030232434A1

  公开（公告）日：2003-12-18

  Antisense compounds, compositions and methods are provided for modulating the expression of PTPN12. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PTPN12. Methods of using these compounds for modulation of PTPN12 expression and for treatment of diseases associated with expression of PTPN12 are provided.

  提供了用于调节PTPN12表达的反义化合物、组合物和方法。这些组合物包括针对编码PTPN12的核酸的反义化合物，特别是反义寡核苷酸。提供了使用这些化合物调节PTPN12表达和治疗与PTPN12表达相关疾病的方法。